摘要:

Reaction of Symmetric N1,N2-Diarylamidines with a-Bromoacetophenone and Ethyl 2-Bromoethanoate$ Mohsen Abdel-Motaal Gomaa Chemistry Department, Faculty of Science, Minia University, 61519 El-Minia, Egypt 2-Bromo-1-faryl[1-(arylimino)ethyl]aminog-1-phenylethanol derivatives 3a, 3b were obtained from the reaction of N1,N2-diarylacetamidines 1a, 1b with -bromoacetophenone 2, while 1a, 1b with ethyl 2-bromoethanoate 4 afforded 2-f[1-(arylimino)]ethylgaminoethanoic acid derivatives 5a, 5b; N1,N2-diarylformamidines 6a, 6b reacted with 2 and 4 to give the arylaminoacetophenones 8a, 8b and N-arylglycine ethyl esters 11a, 11b respectively together with the corresponding formanilides 9a, 9b.N1,N2-Disubstituted formamidines condensed with active methylene compounds leading to enamines and the corre- sponding free amines.1 This condensation was utilized to synthesize quinoline derivatives by treating N1,N2-diaryl- formamidines with ethyl malonate.2 On the other hand b-cyanoesters condensed with free acetamidines to give 2-amino-4-hydroxypyridine.3 Previously it was reported that N,N,N'-triarylamidines when treated with tetrahalogeno- benzoquinones underwent cleavage into 2-(arylamino)-3,5,6- trihalogeno-1,4-benzoquinones and their 2,5-bis(arylamino) analogues together with the corresponding formanilides.4 N1,N2-Diarylformamidines reacted with dichloro-1,4- naphthoquinone (DC1NQ) and tetrachlorobenzoquinone (CHL) to give 2-(arylamino)-3-(formylarylamino)-1,4- naphthoquinones and benzimidazolinones respectively as substitution products.5 On the other hand N1,N2-diarylacet- amidines reacted with DC1NQ and CHL to a€ord the new chiral compounds 3-aryl-2-(arylimino)-9b-hydroxy-1H- benz[e]indol-5-ones and 1-aryl-2-(arylimino)-3a-hydroxy-1H- indol-6-ones respectively as substitution¡¾addition products.5 In this paper the results of the interaction of the N1,N2- diaryl-formamidines and -acetamidines with a-bromoaceto- phenone and ethyl 2-bromoethanoate are presented.N1,N2-Diarylacetamidines have two reactive sites for nucleophilic addition. When a solution of N1,N2-diarylacet- amidines 1a, 1b and a-bromoacetophenone 2 in ethanol was heated for 2 h, 2-bromo-1-{aryl[1-(arylimino)ethyl]amino}-1- phenylethanol derivatives 3a, 3b were isolated in 47¡¾50% yield. The structures of the products 3a, 3b were assigned on the basis of their elemental analysis and spectral data. In their IR spectrum the carbonyl absorption bands were not observed but the hydroxyl absorption bands were. The 1H decoupled 13C NMR spectra revealed signals between d 93.52 and 94.10 for an aliphatic quaternary carbon atom bearing a hydroxyl group.6 13C DEPT spectra exhibited negative signals between d 66.51 and 67.34 at lower ¢çeld for the methylene group attached to the bromine atom.The 1H NMR spectra showed AB patterns with dA 4.51¡¾4.61 and dB 4.71¡¾4.98 with coupling constants between 12.80 and 12.90 Hz, which indicates that a methylene group is present adjacent to a chiral carbon atom.These unexpected results indicate that the addition of the imino nitrogen atom to the carbonyl group is preferred rather than substitution on the methylene carbon atom of 2. On the other hand when the solutions of acetamidines 1a, 1b and ethyl 2-bromoethanoate 4 were heated in ethanol for 1 h, 2-{aryl[1-(arylimino)]ethyl}aminoethanoic acid deriva- tives 5a, 5b were obtained in 61¡¾64% yield.Acids 5a, 5b are formed via a replacement of the bromine atom by the amidine molecule, followed by hydrolysis by taking up a molecule of water from the ethanol used, with liberation of an ethanol molecule. This is probably due to the presence of the liberated HBr which catalyses this hydrolysis. The structures of compounds 5a, 5b were assigned on the basis of the following data. Their IR spectra showed sharp bands at 3297¡¾3295 and 1662¡¾1660 cm¢§1 for the OH and C.O of the carboxylic group respectively.In their 13C NMR spectra the characteristic signal of the carboxylic ester group at d 166.60 was replaced by signals at d 172.5 which are characteristic for the carboxylic acid carbon atom.6 The replacement of the bromine atom was also con¢çrmed from the mass spectra (m/z a 296 and 328 for 5a and 5b respect- ively) and the correct elemental analysis. N1,N2-Diarylformamidines 6a, 6b were investigated with both a-bromoacetophenone 2 and ethyl 2-bromoethanoate 4.Heating solutions of 6a, 6b and 2 in ethanol for 1 h gave the arylaminoacetophenones 8a, 8b together with the corresponding formanilides 9a, 9b. The structures of 8a, 8b7,8 and 9a, 9b9,10 were identi¢çed by comparison of their melting points with those previously reported. Also compound, 6a, 6b reacted with the ethyl 2-bromo- ethanoate in ethanol to a€ord N-arylglycine ethyl esters 11a, 11b together with the corresponding formanilides 9a, 9b. J.Chem. Research (S), 1998, 654¡¾655$ Scheme 1 Scheme 2 Scheme 3 $This is a Short Paper as de¢çned in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there- fore no corresponding material in J. Chem. Research (M). 654 J. CHEM. RESEARCH (S), 1998The structures of compounds 11a, 11b were identied bycomparison of their melting points with those previouslyreported.11 Thus it is obvious that the reaction of the form-amidines with 2 and 4 replaces the bromine atom to give theintermediates 7a, 7b and 10a, 10b followed by spontaneoushydrolysis (by absorption of water from the ethanol used),probably due to the presence of the liberated HBr to 8a, 8b,11a, 11b and 9a, 9b respectively.ConclusionN1,N2-Diaryl-formamidines and -acetamidines react withthe bromo-active methylene derivatives by nucleophilic sub-stitution rather than by condensation,1¡Ó3 while acetamidines1a, 1b with bromoacetophenone 2 they undergo nucleophilicaddition.This is probably due to electronic eects, where inthe case of 2 the carbonyl group is attached to a benzenering, which leads to faster addition than in the saturatedanalogues.ExperimentalGeneral experimental details have been described previously.12Reaction of N1,N2-Diarylacetamidines 1a, 1b with -Bromoaceto-phenone 2 and Ethyl 2-bromoethanoate 4.Solutions of compounds1a, 1b (1.0 mmol) in ethanol (10 cm3) were added to a solution of 2or 4 (1.0 mmol) in ethanol (5 cm3) and heated to reux temperaturefor 1 h.The reaction mixtures were then concentrated and the resi-dues subjected to PLC using toluene¡Óethyl acetate (1: 2) as the devel-oping solvent to give one main zone which contained 3a, 3b or 5a,5b. The zones were extracted, crystallized and identied as follows:2-Bromo-1-{(4-methylphenyl )[1-(4-methylphenylimino)ethyl ]amino}-1-phenylethanol 3a.Colourless crystals (204 mg, 47%), MP 218 8C(from ethyl acetate¡Ócyclohexane); IR (KBr) 3413 cm£¾1 (OH); 1HNMR (CDCl3) 2.15 (3 H, s, CH3), 2.27 (3 H, s, CH3 aryl), 2.41(3 H, s, CH3 aryl), 4.61 (1 H, d, 1a'-H), 4.98 (1 H, d, 1b'-H, j2Jj 12.90 Hz, CH2Br), 7.06, 7.32, 7.38, 7.57, 7.58 and 7.82 (13 H, all m,aryl H), 8.48 (1 H, br, OH); 13C NMR (CDCl3) 13.72 (CH3),21.19 (CH3 aryl), 21.29 (CH3 aryl), 67.34 (CH2Br), 94.10 (COH),126.09, 126.86, 128.57, 129.39, 129.92 and 132.85 (all aryl CH),129.38 and 132.0 (aryl CCH3), 138.98 (aryl CCOH), 140.16 and140.47 (aryl NC), 164.62 (C.N); MS m/z (%) 438 (M2, 1), 436(M, 1), 393 (3), 356 (M-HBr, 4), 250 (25), 132 (83), 106 (100),81 (14), 79 (10) (Found: C, 65.81; H, 5.70; N, 6.30.Calc. forC24H25BrN2O: C, 65.91; H, 5.76; N, 6.41%).2-Bromo-1-{(4-methoxyphenyl )[1-(4-methoxyphenylimino)ethyl ]-amino}-1-phenylethanol 3b.Colourless crystals (234 mg, 50%), mp205¡Ó207 8C (from ethyl acetate¡Ócyclohexane); IR (KBr) 3414 cm£¾1(OH); 1H NMR [(CD3)2SO] 2.07 (3 H, s, CH3), 3.71 (3 H, s,OCH3), 3.83 (3 H, s, OCH3), 4.51 (1 H, d, 1a'-H), 4.71 (1 H, d, 1b'-H, j2Jj 12.80 Hz, CH2), 6.93, 7.16, 7.27, 7.35, 7.40, 7.40, 7.73 and7.75 (13 H, all m, aryl H), 8.48 (1 H, s, OH); 13C NMR [(CD3)2SO] 13.61 (CH3), 55.27 and 55.55 (OCH3), 66.51 (CH2Br), 93.52(COH), 114.25, 114.88, 126.8, 127.64, 128.0, 128.92 and 129.87 (allaryl CH), 128.26 (aryl CCOH), 138.0 (aryl NC), 159.57 and 159.65(aryl COCH3), 164.63 (C.N); MS m/z (%) 471 (M2, 1), 469(M, 1), 425 (8), 407 (34), 389 (M-HBr, 9), 370 (19), 283 (8), 148(6), 136 (29), 108 (100), 81 (15), 80 (24), 79 (15) (Found: C, 61.50;H, 5.37; N, 6.35.Calc. for C24H25BrN2O3: C, 61.41, H, 5.37;N, 5.97%).N-(4-Methylphenyl )-N-[1-(4-methylphenylimino)ethyl ] glycine 5a.Colourless crystals (190 mg, 64%), mp 154 8C (from ethyl acetate¡Ócyclohexane); IR 3295 (OH), 1662 cm£¾1 (CO); 1H NMR (CDCl3) 2.12 (3 H, s, CH3), 2.30 (3 H, s, aryl CH3), 2.33 (3 H, s, arylCH3), 4.40 (2 H, s, CH2), 7.01¡Ó7.40 (8 H, all m, aryl H), 8.70 (1 H,s, CO2H); MS m/z (%) 296 (M, 70), 189 (60), 136 (20), 107 (49)(Found: C, 72.59; H, 7.24; N, 9.35.Calc. for C18H20N2O2: C, 72.96;H, 7.04; N, 9.45%).N-(4-Methoxyphenyl )-N-[1-(4-methoxyphenylimino)ethyl ]glycine 5b.Colourless crystals (200 mg, 61%), mp 144¡Ó145 8C (from ethylacetate¡Ócyclohexane); IR (KBr) 3297 (OH), 1660 cm£¾1 (CO); 1HNMR (CDCl3) 1.94 (3 H, s, CH3), 3.77 (3 H, s, OCH3), 3.81 (3 H,s, OCH3), 4.86 (2 H, s, CH2), 6.80¡Ó4.73 (8 H, all m, aryl H), 8.62(1 H, s, CO2H); 13C NMR (CDCl3) 22.32 (CH3), 55.34 (CH2),55.50 (OCH3), 55.53 (OCH3), 114.13, 115.06, 121.64 and 128.68 (allaryl H), 131.11 and 136.06 (aryl CN), 156.39 and 159.41 (arylCOCH3), 172.50 (CO2H); MS m/z (%) 328 (M, 28), 206 (55), 178(21), 136 (100), 123 (50), 108 (13) (Found: C, 65.65; H, 6.10; N,8.58. Calc.for C18H20N2O4; C, 65.84; H, 6.14; N, 8.53%).Reaction of N1,N2-Diarylformamidines 6a, 6b with -Bromoaceto-phenone 2.Solutions of compounds 6a, 6b (1.0 mmol) in ethanol(10 cm3) were added to a solution of 2 (199 mg, 1.0 mmol) in etha-nol (5 cm3) and heated to reux temperature for 1 h.After thisperiod yellow crystals of 8a, 8b were precipitated which were lteredo and recrystallized from ethanol. The ltrates were concentratedand the residues subjected to PLC using toluene¡Óethyl acetate (10:1)as the developing solvent to give two zones. The faster moving onecontained 8a, 8b while the more slowly moving one contained 9a,9b. The zones were extracted, crystallized and identied as follows:-(4-methylphenylamino)acetophenone 8a, 90 mg (40%), yellowcrystals (from ethanol), mp 126¡Ó127 8C (lit.,7 128¡Ó129 8C); -(4-methoxyphenylamino)acetophenone 8b, 88 mg (37%), yellow crys-tals (from ethanol), mp 90¡Ó92 8C (lit.,8 93 8C); 4'-methylformanilide9a, 61 mg (45%), colourless crystals (from light petroleum, bp40¡Ó60 8C), mp 53 8C (lit.,9 52 8C); 4'-methoxyformanilide 9b, 70mg(46%), colourless crystals (from light petroleum), mp 83 8C (lit.,1084¡Ó85 8C).Reaction of N1,N2-Diarylformamidines 6a, 6b with Ethyl 2-Bromo-ethanoate 4.A solution of compound 4 (167 mg, 1.0 mmol) inethanol (5 cm3) was added dropwise to a solution of formamidines6a, 6b (1.0 mmol) in ethanol (10 cm3) at room temperature, giving ayellow colour.The reaction mixture was left standing for 1 h, con-centrated and subjected to PLC using toluene¡Óethyl acetate (10:1)as developing solvent to give two zones. The faster moving one con-tained 11a, 11b while the second zone contained the correspondingformanilides 9a, 9b.The zones were extracted, crystallized andidentied as follows: N-(4-methylphenyl)glycine ethyl ester 11a,100 mg (52%), colourless crystals (from cyclohexane), mp 50 8C(lit.,11 51 8C); N-(4-methoxyphenyl)glycine ethyl ester 11b, 120 mg(57%), colourless crystals (from cyclohexane), mp 58¡Ó59 8C (lit.,1159 8C).The author is indebted to Professor Dr. D. Do pp,Division of Organic Chemistry Grhard-Mercator Universita tGH Duisburg, for the elemental analyses, NMR and massspectra.Received, 16th April 1998; Accepted, 25th June 1998Paper E/8/02858CReferences1 F. B. Dains, O. O. Malleis and J. T. Meyers, J. Am. Chem. Soc.,1946, 68, 1251.2 R. M. Roberts, J. Org. Chem., 1949, 14, 297.3 G. W. Kenner, B. Lythgoe, A. R. Todd and A. Toppham,J. Chem. Soc., 1943, 388.4 A. M. Nour El-Din, A. E. Mourad, A. A. Hassan and M. A.Gomaa, Bull. Chem. Soc. Jpn., 1991, 64, 1966.5 D. Do pp, M. A.-M. Gomaa, G. Henkel and A. M. NourEl-Din, J. Heterocycl. Chem., 1995, 32, 603.6 H. O. Kalinowski, S. Berger and S. Braun, in 13C NMRSpectroscopy, Georg Thieme, Stuttgart, 1984, pp. 155 and 207.7 K. Heyns and W. Stumme, Chem. Ber., 1956, 89, 2833.8 M. Bush and G. Hefele, J. Prakt. Chem., 1911, 83, 524.9 M. D. Farnow and C. K. Ingold, J. Chem. Soc., 1924, 125,2534.10 F. Benington, R. D. Morin and L. C. Clark Jr, J. Org. Chem.,1958, 23, 19.11 A. Bryson, N. R. Davies and E. P. Serjeant, J. Am. Chem. Soc.,1963, 85, 1933.12 M. A.-M. Gomaa, S. K. Mohamed and A. M. Nour El-Din,J. Chem. Res. (S ), 1997, 284.Scheme 4J. CHEM. RESEARCH (S), 1998 655

ISSN:0308-2342    

DOI:10.1039/a802858c

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Ammonium Chlorochromate Adsorbed on Montmorillonite K-10: Selective Oxidation of Alcohols under Solvent-free Conditions$ Majid M. Heravi,* Reza Kiakojoori and K. Tabar Hydar Chemistry and Chemical Engineering Research Center of Iran, P.O. Box 14335-186, Tehran, Iran A simple and selective oxidation of alcohols to carbonyl compounds on clay supported ammonium chlorochromate under solventless conditions is expedited by microwave irradiation. Prompted by stringent environment protection laws in recent years, there has been increasing emphasis on the use and design of environmentally friendly solid acid±base cata- lysts to reduce the amount of toxic waste and by-products arising from the chemical processes.1 The oxidation of alcoholic groups to carbonyl functional- ities continues to receive attention from chemists in search of newer and selective methods of oxidation.2 Chromium-based reagents have extensively been used in organic synthesis.3 The utility of chromium(VI) reagents in oxidative transformation is compromised due to their inherent toxicity, cumbersome preparation and potential danger (ignition or explosion) in terms of product isolation and waste disposal.Introduction of reagents4 on solid sup- ports has circumvented some of these problems and pro- vided an attractive alternative in organic synthesis in view of the selectivity and associated ease of manipulation. Therefore it is not surprising that a large number of chro- mium-based oxidants impregnated on solid supports have been explored.5 These supported reagents in solvents oxidize primary and secondary alcohols.6 Organic solvents are not only expensive, but are often �ammable, toxic and environmentally hazardous.Consequently, there is scope for the development of rapid and solventless methods that have manipulative advantages over heterogeneous reactions. In continuation of our investi- gations on organic reactions in solventless systems,7,8 we now report a facile and selective oxidation of alcohols to carbonyl compounds using ammonium chlorochromate adsorbed on montmorillonite K-10 under solvent-free conditions that is accelerated in most cases by exposure to microwaves.The reagent is easily prepared by addition of a weighed amount of montmorillonite K-10 to a solution of am- monium chlorochromate9 in water and rotary evaporating to dryness. The reaction is conducted by mixing ®nely ground supported reagent with neat alcohols.In the absence of the clay the reactions are slow and considerable amounts of alcohols are recovered unchanged at room temperature or even upon microwave irradiation for an extended period. As an example the reaction of 5-methyl-2-nitrobenzyl alcohol with ammonium chlorochromate results in the formation of only 30% of 5-methyl-2-nitrobenzaldehyde, whereas the yield increases to almost to quantitative in the case of the clay-supported reagent. In a few cases, the reac- tions are completed upon simple mixing; gentle warming by microwaves accelerates some others (Table 1).The reactions are relatively clean with no tar formation typical of many CrO3 reactions. Primary alcohols were oxidized to the corresponding alde- hydes and an overoxidation of aldehydes to the correspond- ing acid derivative was not observed even after prolonged irradiation and with excess of supported chromium reagent. On the other hand the oxidations of aryl-substituted unsatu- rated alcohols were less than satisfactory. The carbon± carbon double bond was partially cleaved under the above conditions.Cinnamaldehyde for example was obtained in only 61% yield along with 39% of benzaldehyde in the oxidation of cinnamyl alcohol. In conclusion, oxidation with ammonium chlorochromate supported on montmorillonite K-10 under solvent-free con- ditions is a rapid, manipulatively simple and selective proto- col which avoids the drastic conditions usually employed.Experimental All products are known compounds and their physical data were essentially identical with those of authentic samples. Microwave irradiations were carried out in a National oven, Model 5250 at 900 W. J. Chem. Research (S), 1998, 656±657$ Table 1 Oxidation of alcohols to carbonyl compounds using ammonium chlorochromate adsorbed on montmorillonite K-10 Entry Alcohol Product Yield (%)a 1 Benzyl Benzaldehyde 92 (85) 2 4-Methylbenzyl 4-Methylbenzaldehyde 93 (85) 3b 5-Methyl-2-nitrobenzyl 5-Methyl-2-nitrobenzaldehyde 90 (81) 4b 4-Nitrobenzyl 4-Nitrobenzaldehyde 95 (83) 5b Salicyl Salicylaldehyde 95 (82) 6 a-Phenylethyl Acetophenone 94 (88) 7 Benzhydrol Benzophenone 90 (81) 8b Benzoin Benzil 90 (80) 10b Cyclohexanol Cyclohexanone 88 (72) 11b 2-Methylcyclohexanol 2-Methylcyclohexanone 85 (75) 12b (±)-Menthol Menthone 85 (74) aYields are based on GLC analysis; figures in parentheses refer to isolated yields.bReaction completed under microwave irradiation.Preparation of Ammonium Chlorochromate/Montmorillonite K-10. �To a solution of chromium trioxide (40 g, 0.4 mol) in water (100 mL) was added ammonium chloride (21.4 g, 0.4 mol) within 15 min at 40 8C. The mixture was cooled until a yellow-orange solid $This is a Short Paper as de®ned in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there- fore no corresponding material in J. Chem. Research (M). *To receive any correspondence. 656 J. CHEM. RESEARCH (S), 1998formed. Reheating to 40 8C gave a solution. Montmorillonite K-10 (200 g) was then added with stirring at 40 8C. After evaporation in a rotary evaporator, the orange solid was dried in vacuum for 2 h at 70 8C. It can be kept for several months in air at room tempera- ture without losing its activity. Oxidation of Alcohols in the Solventless System.DThe above reagent (1.7 g, 2.6 mmol) was added to an appropriate neat alcohol (1.3 mmol).This mixture was thoroughly mixed using a pestle and mortar. An exothermic reaction ensued with darkening of the orange reagent and was complete almost immediately as conRrmed by TLC (hexane�}AcOEt, 8: 2). The product was extracted into CH2Cl2 and passed through a small bed of silica gel (1 cm) to a€ord the corresponding pure carbonyl compounds (Table 1). Oxidation of Alcohols under Microwave Irradiation and Solvent- free Conditions (General Procedure).DThe above reagent (1.7 g, 2.6 mmol) was added to an appropriate neat alcohol using a beaker and mixed thoroughly by a spatula. The reaction mixture was placed in a beaker inside a microwave oven and irradiated for 1 min.On completion of the reaction (TLC; hexane�}ethyl acetate, 8: 2) the crude product was directly charged onto a silica gel column. Elution with hexane�}ethyl acetate a€orded the pure carbonyl compound (Table 1). Received, 8th June 1998; Accepted, 29th June 1998 Paper E/8/04309D References 1 C.B. Khouv, C. B. Dartl, J. A. Lalenger and M. E. Davis, J. Catal., 1994, 149, 195. 2 S. V. Pitre, M. V. R. Reddy and Y. D. Vankar, J. Chem. Res. (S), 1997, 462; R. S. Varma, R. K. Sami and R. Dahiya, J. Chem. Res. (S), 1998, 120. 3 A. J. Fatiadi, in Organic Synthesis by Oxidation with Metal Compounds, ed. C. R. H. I. de Jonge Miys, Plenum, New York, 1986, pp. 119�}260. 4 Preparative Chemistry Using Supported Reagents, ed. D. Laszlo, Academic Press, San Diego, 1987; A. Mckillop and D. W. Young, Synthesis, 1979, 401, 481. 5 T. Brunelet, C. Jouitteau and G. Gellbard, J. Org. Chem., 1986, 51, 4016; J. W. Suggs and L. Yluarte, Tetrahedron Lett., 1986, 27, 437. 6 Y. Shia Cheng, W. L. Liu and Shia H. Chen, Synthesis, 1986, 223. 7 M. M. Heravi, K. Aghapoor, M. A. Nooshabadi and M. M. Mojtahidi, Monatsh. Chem., 1997, 128, 1143. 8 K. Aghapoor, M. M. Heravi and M. A. Nooshabadi, Indian J. Chem., Sect. B, 1998, 37, 84. 9 G. Sh. Zharg, Q. Z. Shi, M. F. Chem and K. Cai, Synth. Commun., 1997, 27, 3691. J. CHEM. RESEARCH (

ISSN:0308-2342    

DOI:10.1039/a804309d

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Unusual Azetidine or Oxazine Formation upon Reaction of O-Ethyl Dithiocarbonate with 1,2,3-Triphenyl-3-Phthalimidopropyl Iodides; Erythro Selectivity in the Reaction of Iodotrimethylsilane with Phthalimidopropanols$ M. E. Ivanova, V. B. Kurteva, M. J. Lyapova* and I. G. Pojarlieff Institute of Organic Chemistry, Bulgarian Academy of Sciences, ul. Acad. G. Bonchev block 9, So�¡a 1113, Bulgaria Reaction of isomeric 1,2,3-triphenyl-3-phthalimidopropanols with hexamethyldisilane and iodine gave highly selectively iodides 3 with 1,2-erythro configuration which treated with O-ethyl dithiocarbonate yielded from ET-3 the xanthate ester 4, the trans,trans-dihydrooxazine 5 and the olefin 6 as major products while from EE-3 the cis,trans-azetidine 7 was obtained in 75% yield.Our long standing interest in diastereomers with three adjacent chiral centers has been focused on amino- propanols.1 In an extention to aminothiols we attempted to prepare 1,2,3-triphenyl-3-phthalimidopropyl dithiocarbo- nates from the respective alcohols 1 via the chlorides 2.The latter proved too unreactive to O-ethyl dithiocarbonate and for this reason the iodides, 3, were prepared from 1 with iodotrimethylsilane. High yields were obtained and, contrary to the usually observed inversion of con¢çguration,2 this reaction showed high erythro selectivity with the sterically hindered alcohols studied by us: EE-1 gave a single 3-phthalimido iodide of retained con¢çguration while both TT- and ET-1 gave ET-3.This stereochemical result can be rationalized by the involvement of a carbenium ion. As is the case with methine protons next to sp2 carbons,3 the preferred conformation for the cation should be the one with eclipsed hydrogen and a partial double bond. With such a model (A) the preferred attack should be from the side of the smaller substituent Ph, compared to C-3. Reaction of the iodides 3 with ethyl dithiocarbonate in dry ethanol gave the desired phthalimidopropyl dithio- carbonate 4 as a major product only in the case of ET-3 accompanied by considerable amounts of the unexpected oxazine 5 and the elimination product 6.With the EE iso- mer of 3, however, a high yield of the cis,trans-azetidine 7 was obtained. The structure of the cyclic products was deduced from their spectral properties indicating opening of the phthal- imide ring and formation of an ester function. Acid hydro- lysis of oxazine 5 to TT-3-amino-1,2,3-triphenylpropanol con¢çrmed reliably its structure.The 13C NMR signals for C-2 and C-4 of the azetidine 7 coinciding at d 61.88 are incompatible with an oxazine structure where one carbon is bonded to O and the other one to N and thence a large di€erence in the chemical shifts is expected. For oxazine 5 the resonances of the two carbons are separated by 18 ppm. Heating the iodides in ethanol in the absence of dithio- carbonate brought about degradation but none of the cyclic products, implying that dithiocarbonate is involved by adding to a carbonyl.The intermediate forms the oxazine ring by rear attack followed by ethanolysis. For azetidine formation the intermediate breaks down to produce an amide anion. The conformations of the iodides on Scheme 1 are the preferred ones6 and correlate with cyclization reac- tivities: in the ET isomer O¢§ can be trapped by direct attack, in the EE isomer changing to an unfavourable J. Chem. Research (S), 1998, 658¡¾659$ Scheme 1 conformation presumably allows time for break down to amide anion.Cyclization of addition intermediates has been observed in the reaction of aldimine anions with N-(2- $This is a Short Paper as de¢çned in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there- fore no corresponding material in J. Chem. Research (M). *To receive any correspondence. 658 J. CHEM. RESEARCH (S), 1998bromoethyl)phthalimides.4 The involvement of the amideanion in the formation of the azetidine is supported bythe presence of stilbene observed in the fragmentation of asimilar system.1The relative congurations at C-2, C-3 are not aectedin these reactions and so are known from the startingphthalimido propanols 1.5 Azetidine 7 shows vicinal protoncouplings of 5.4 and 9.9 Hz thus revealing a cis,trans con-guration because with equal substituents in positions 2 and4 the other alternative, the cis,cis isomer, would show equalconstants. Slow rotation on the NMR timescale can beexcluded as it would have doubled the signals of cis,trans-7.The oxazine 5 shows the characteristic large couplingsof the trans,trans isomer.The most likely intramolecularcyclization by inversion at C-1 assigns the relative con-gurations of the idodides as given in Scheme 1.The congurations of the dithiocarbonates 4 were onlytentatively assigned. In the case EE-3 the conguration ofthe ether 8 was unequivocally assigned by synthesis fromthe alcohol EE-1 and ethyl iodide and its conguration canbe explained by the model given for the iodides.The samepathway will provide EE-dithiocarbonate from EE-3 andthe ET isomer for ET-3.ExperimentalThe melting points were measured in capillaries, the IR spectraon a Specord IR 75 or Bruker IFS 113v instrument in chloro-form unless stated otherwise, UV spectra on a Specord UV Visspectrometer in ethanol, NMR spectra on a Bruker DRX 250 indeuteriochloroform (chemical shifts are quoted in ppm as d values)and mass spectra on a JEOL JMS-D 300 spectrometer.EE-1,2,3-Triphenyl-3-phthalimidopropanol 1.A solution of EE-3-amino-1,2,3-triphenylpropanol7 (303 mg, 1 mmol) and phthalicanhydride (148 mg, 1 mmol) in dry pyridine (1 ml) was reuxed for2 h.After cooling the mixture was poured onto ice and allowedto stand overnight. The separated material was triturated with10% HCl (50 ml), the solid formed was collected and recrystallizedfrom ethanol to give compound EE-1 (516 mg, yield 95%), mp217¡Ó218 8C; ~max 1710, 1760, 3400 cm£¾1; MS (Cl) [M 1] m/z 434,416, 374, 270, 254, 210 (Found: C, 80.12; H, 5.35; N, 3.18.C29H23NO3, requires C, 80.35; H, 5.35; N, 3.23%).Diastereomeric 1,2,3-Triphenylpropyl-3-phthalimido Iodides (3):General Procedure.Iodine (254 mg, 1 mmol) and hexamethyl-disilane (0.2 ml, 1 mmol) were added to a stirred solution of theappropriate phthalimidopropanol (434 mg, 1 mmol) in dry chloro-form (5 ml) under argon.After 4 h of stirring at room temperaturethe reaction mixture was rapidly extracted with 10% Na2S2O3 (aq),the organic layer was washed with brine, dried (Na2SO4) andevaporated to dryness under reduced pressure.EE-3. From EE-1, as a single diastereoisomer (NMR), yield 95%,mp 145¡Ó147 8C (decomp.); ~max 1710, 1760 cm£¾1; MS (Cl) [M 1]m/z 544, 416, 269, 254, 236, 180, 150, 128.ET-3. (a) From ET-1,5 crude yield 420 mg, mp 177¡Ó179 8C(chloroform¡Óhexane, 59%); ~max 1710, 1760 cm£¾1; MS (EI) [M£¾ I]415, 269, 268, 254, 236, 180, 150, 128, 127.(b) From TT-1, as a mixture of ET-3/ET-1/TT-1 in a ratio of4.4:1:1.2 (NMR) 480 mg.Reaction of Phthalimido Iodide ET-3 with Potassium O-ethylDithiocarbonate.ET-3 (4.9 g, 9 mmol) and KS2C(OEt) (4.3 g,27 mmol) in dry ethanol (400 ml) was reuxed for 6 h.Afterremoval of the solvent in vacuo the residue was extracted withCH2Cl2¡Ówater, the organic layer washed with brine, dried (Na2SO4)and evaporated.The crude reaction product which showed onTLC more than eight closely moving spots was separated byash chromatography on Silica gel (ether¡Óhexane 1:4 as eluent)giving four major products: trans,trans-5,6-dihydro-4H-2 (2-ethoxy-carbonylphenyl)-4,5,6-triphenyl-1,3-oxazine 5 (800 mg, 22%), mp128¡Ó130 8C (diisopropyl ether); ~max 1673, 1715 cm£¾1; 13C NMR(DEPT) C-2 157.21, C-4 64.29, C-5, 53.33, C-6 81.83, COO167.63, CH2 61.10, CH3 14.17; MS (CI) [M 1] m/z 462, 416, 284,236, 180, 149 (Found: C, 80.82; H, 5.74; N, 3.18.C31H27NO3,requires C, 80.67; H, 5.90; N, 3.03%); ET S-O-ethyl-1,2,3-triphenyl-propyl-3-phthalimido dithiocarbonate 4 (1.4 g, 38%), mp 162¡Ó163 8C(ether¡Ópentane); ~max 1050, 1710,760 cm£¾1; max 385 nm(SCSOC2H5); MS(EI) [M£¾ SCSOC2H5] m/z 416, 268, 236, 180,122(SCSOCH2H5) (Found: C, 71.54; H, 5.20; N, 2.50; S, 11.81.C32H27NO3S requires C, 71.48; H, 5.06; N, 2.60; S, 11.92%);z-1,2,3-triphenyl-3-phthalimidoprop-1-ene 6 (864 mmg, 24%), mp197¡Ó199 8C (chloroform¡Óhexane); ~max 1710, 1760 cm£¾1; MS(CI)416, 268, 236, 180 (Found: C, 83.89; H, 5.00; N, 3.59.C29H21NO2requires C, 83.83; H 5.09; N, 3.37).Reaction of Phthalimido Iodide EE-3 with Potassium O-ethylDithiocarbonate.A solution of EE-3 (2.71 g, 5 mmol) andKS2C(OEt) (2.7 g, 15 mmol) in absolute ethanol (150 ml) wastreated in a manner to that described for ET-3 to leave a residue,which was recrystallized from diisopropyl ether to give 1.04 gof cis,trans-N-(2-ethoxycarbonylbenzoyl )-2,3,4-triphenylazetidine 7.A further 0.69 g could be isolated from the evaporated mother-liquor after separation on Silica gel (ether¡Óhexane 1:4 as eluent),total yield 75%, mp 145¡Ó147 8C; ~max 1660, 1715 cm£¾1, 13C NMRC-2 and C-4 61.88 (common signal), C-3, 48.52, CO 156.93, COO168.30, CH2 61.23, CH3 14.17; MS (CI) [M 1] m/z 462, 282, 177(Found: C, 80.54; H, 5.92; N, 3.24.C31H27NO3, requires C, 80.67;H, 5.90; N, 3.03%).Four other products were isolated from thecolumn: EE-O-ethyl S-1,2,3-triphenyl-3-phthalimidopropyl dithio-carbonate 4 (90 mg, 3.4%), mp 182¡Ó184 8C (diisopropyl ether);~max 1050, 1710, 1760 cm£¾1; max 385 nm (SCSOC2H5); MS(EI)[M-CS2] m/z 460, [M-SCSOC2H5] 415, 324, 268, 236, 178,151, 77(CS2); EE-ethyl 1,2,3-triphenyl-3-phthalimidopropyl ether 8(120 mg, 5.2%), mp 222¡Ó224 8C (diisopropyl ether); ~max 1100,1710, 1760 cm£¾1; ESI-FTICR MS m/z 462.2049 (M 1, theoreti-cally 462.2064, C31H28NO3) identical with the product obtainedfrom EE-1 (1 mmol), NaH (4 mmol) and ethyl iodide (4 mmol) inTHF (5 ml) for 6 h at room temperature in 83% yield; 6 (30 mg,1.4%), identical with the product obtained from ET-3 in the samereaction; trans-stillbene (60 mg, 6.7%), identical with an authenticsample.Received, 8th April 1998; Accepted, 30th June 1998Paper E/8/02677GReferences1 V.B. Kurteva, M. J. Lyapova and I. G. Pojarlie, J. Chem. Res.(S), 1993, 270 and references cited therein.2 G.A. Olah and S. C. Narang, Tetrahedron, 1982, 38, 2225.3 U. Berg, T. Liljefors, M. Roussel and J. Sandstrom, Acc. Chem.Res., 1985, 18, 80.4 N. De Kimpe, Z. Yao, L. De Buyck, R. Verhe and N. Schamp,Bull. Soc. Chim. Belg., 1986, 95, 197.5 M. J. Lyapova and M. E. Ivanova, Compt. Rend. Acad. Bulg.Sci., 1982, 35, 1669.6 V. S. Dimitrov, V. B. Kurteva, M. J. Lyapova, B. P. Mikhovaand I. G. Pojarlie, Magn. Reson. Chem., 1988, 26, 564.7 M. J. Lyapova and B. J. Kurtev, Chem. Ber., 1969, 102, 3739;1971, 104, 131.Table 1 1H NMR chemical shifts (d) and coupling constants(in Hz, in parentheses)Compound H-1(J12) H-2a H-3(J23)EE-1b 4.82(2.8) 4.69 6.21 (13.2)ET-1c 5.08(4.20) 4.77 6.11(12.2)TT-1d 5.083(4.5) 4.956 6.076(11.9)EE-3 5.084(3.1) 4.021 5.931(11.9)ET-3 5.525(6.9) 4.665 5.810(11.6)EE-4e 5.136(3.6) 5.250 5.490(12.6)ET-4f 5.421(3.6) 5.319 5.666(12.3)trans,trans-5g 5.030(10.4)h 3.136i 5.491(10.7)jZ-6 6.415(1.9)k,l 6.484(1.9)k,lcis,trans-7m 5.033(5.4)n 3.812o 5.590(9.9)pEE-8q 4.280(2.9) 4.432 6.213(12.3)aCouplings not shown. bOH 1.78(6.0). cOH 1.98(4.6). dOH2.096(4.5). eCH2 4.504, CH3 1.232. fCH2 4.470, CH3 1.225.gCH2 4.237, CH3 1.282. hH-4(J45). iH-5. jH-6(J56). kJ13.lNo NOE enhancement was observed. mCH2, 4.202, CH3 1.230.nH-2(J23). oH-3. pH-4(J45). qCH2 3.203, CH3 1.960.J. CHEM. RESEARCH (S), 1998 659

ISSN:0308-2342    

DOI:10.1039/a802677g

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Regioselective Introduction of Ethoxycarbonylmethyl and Cyanomethyl Groups into Quinoline and Isoquinoline$ Micheline Grignon-Dubois* and Fa�â za Diaba Laboratoire de Chimie Organique et Organome�Ê tallique, CNRS UMR 5802, Universite�Ê Bordeaux I, 351, Cours de la Libe�Ê ration, F-33405 Talence-Cedex, France A new regioselective route to ethoxycarbonylmethyl- and cyanomethyl-1,2-dihydro-N-methyl-quinolines and -isoquinolines starting from methyl-quinolinium or -isoquinolinium iodides and commercially available trimethylsilyl reagents is presented. As part of a programme directed toward the synthesis of new drugs from functionalized heterocyclic derivatives, we needed to introduce ethoxycarbonylmethyl and cyanomethyl groups on the C-2 position of the quinoline ring.Ethoxy- carbonylmethyl-N-methoxycarbonyldihydroquinolines have previously been obtained by treating ethyl(tributylstannyl) acetate with quinoline and methyl chloroformate.1 However, organostannyl reagents are often dicult to eliminate and are toxic and polluting.Moreover, this process seems to be limited to quinolines activated by alkyl chloroformate, whereas we needed an alkyl group on the nitrogen atom. In the case of 1-methylquinoliniums, Fukuzumi et al.2 obtained the C-2 alkoxycarbonylmethylene adduct as the only pro- duct or in a mixture with the C-4 regioisomer when using a large excess of ketene silyl acetal. Reaction of ethyl bromo- acetate with Reissert compounds3 has also been said to lead to 1-ethoxycarbonylmethyl-1-cyano-2-carbophenyl-1,2- dihydroisoquinoline, but in low yields.Concerning the cyanoalkyl dihydroquinoline derivatives, the C-4 (a-cyano- benzyl) adduct was obtained by treating quinolinium methiodide with phenylacetonitrile and sodium ethoxide.4 In contrast, there is no reference in the literature related to the introduction of cyanoalkyl groups on the C-2 position of quinolines. We report here a new regioselective route to ethoxycarbonylmethyl- and cyanomethyl-1,2-dihydro-N- methyl-quinolines and -isoquinolines starting from methyl- quinolinium or -isoquinolinium iodides (1, 2) and commer- cially available trimethylsilyl reagents.Results and Discussion Nucleophilic addition to quinolinium salts is well known for the functionalization of the quinoline ring.5 However, the regiochemistry of the addition is reported to be depen- dent on substituent e€ects as well as on the nature of the nucleophilic reagent, leading to a competition between C-2 and C-4 additions.5,6 We have recently demonstrated that sonochemical activation allows regiospeciRc C-2 addition of anions to quinolinium iodides in good to quantitative yields.7 In particular, the C-2 addition of the acetonyl anion, prepared in situ from acetone and sodium hydroxide, was systematically obtained when treating with N-methyl- quinolinium iodides.7a From these results we Rrst tried to generate ethoxycarbonylmethyl or cyanomethyl moieties using sodium hydroxide and ethyl acetate or acetonitrile.All our attempts to functionalize 1 in this way failed, and the 1-methyl-2-qinolone 3 was systematically obtained as the only product (68�}75% yield). In contrast with the behaviour of methyl ketones,7a and despite the sonochemical activation, the pKa of ethyl acetate or acetonitrile (24�}25 compared to 20 in the case of methyl ketones8) does not allow the proton abstraction leading to the anion to compete with the addition of the hydroxide anion to the methiodide (Scheme 1).This led us to use trimethylsilyl reagents. As expected, trimethylsilyl acetate (ETSA) alone did not react with com- pound 1.9 The same reaction conducted with 1 equivalent of sodium hydroxide led to 4a, but in only 8% yield along with 3 (34%). In order to avoid the quinoline formation, we decided to replace sodium hydroxide by �Puoride. Indeed, the formation of a Si�}F bond (142 kcal mol1) is usually a highly exothermic process, which provides the driving force for a number of useful synthetic reactions.10 This is the case of active-methylene silylated compounds like ETSA or tri- methylsilylacetonitrile (TMSAN), which are well known to add to the carbonyl double bond in the presence of �Puoride leading to silyl-Reformatsky products.11 When quinolinium methiodide 1 was treated with ETSA or TMSAN in the presence of dried alkali metal �Pouride in acetonitrile solution the nucleophilic addition of the methylene anion was systematically observed (Scheme 1).As expected on the basis of their respective nucleophilic power, caesium �Puoride led to better yields than potassium �Puoride (86 and 40% respectively). Attempts to replace acetonitrile by methylene chloride or THF and alkali metal �Puoride by tetrabutylammonium �Puoride were unsuccessful. These observations are consistent with a charge-controlled process. The reactions were also conducted with 2, leading to the C- 1 adducts 5a, 5b.Examination of Table 1 shows that yields are better with ETSA than with TMSAN, and with quino- line compared to isoquinoline. From a mechanistic point of view, these results are consistent with formation of the methylene anion by nucleophilic attack at the silicon, and its addition to the ortho position versus nitrogen, which is the most electrophilic site. It can be suggested that the process J. Chem. Research (S), 1998, 660�}661$ Scheme 1 Reagents and conditions: i, CH3Y, NaOH, CH3CN, ultrasound; ii, Me3SiCH2Y, CsF, CH3CN, reflux or sonochemical activation $This is a Short Paper as deRned in the Instructions for Authors, Section 5.0 [see J.Chem. Research (S), 1998, Issue 1]; there is there- fore no corresponding material in J. Chem. Research (M). *To receive any correspondence (e-mail: m.grignon@lcoo.u-bor- deaux.fr). 660 J. CHEM. RESEARCH (S), 1998is concerted and takes place in close proximity to the quino-linium iodide as depicted in Scheme 2.Compounds 4b, 5a, 5b are original.Compound 4a hadbeen previously isolated by Fukuzumi et al.2 when treating1 with the ketene triethylsilyl acetal of ethyl acetate andBu4NF. Only the NMR yield was reported (100%), andthe experimental protocol was not described. Moreover,it appears that 10 equivalents of the silyl reagent werenecessary for the reaction to occur. Our process, which iseasy to handle and only needs 1 equivalent of commerciallyavailable silyl reagents, constitutes a real improvement forsynthesizing 4a.ExperimentalFlash column chromatography techniques (302 cm column)were employed to purify crude products using 70¡Ó230 mesh alumina(activity II-III, CH2Cl2) under positive air pressure.Ultrasound-promoted reactions were carried out in a common ultrasoniclaboratory cleaner lled with thermostatted water at 0¡Ó5 8C.Synthesis grade acetonitrile (Aldrich) was dried on molecularsieves.Commercial caesium and potassium uorides (Aldrich, re-agent ACS) were dried prior to use in a domestic microwave oven.Methiodides 1, 2 were prepared according to literature procedures12by alkylation of quinoline or isoquinoline with methyl iodidein acetone solution.To a stirred solution of quinolinium iodide (2.02 g, 7.4 mmol)in acetonitrile (20 mL) was added uoride (KF or CsF, 8.1 mmol)and the trimethylsilyl reagent (Me3SiCH2Y, 8.1 mmol). The mixturewas then stirred at reux or sonicated at 0¡Ó5 8C until the startingmaterial completely reacted as monitored by TLC (SiO2, MeOH¡ÓMe2CO, 10: 90).The reaction mixture was ltered through Celiteand the ltrate evaporated to dryness. The residue was taken upwith cyclohexane (R CH2COOEt, 100 mL) or dichloromethane(R CH2CN, 100 mL) and insoluble materials, if present, wereremoved by ltration and analysed separately. The solution wasevaporated to dryness leading to an oil, which was chromato-graphed eluting typically with CH2Cl2 (Al2O3, activity II-III,70¡Ó230 mesh).2-Ethoxycarbonylmethyl-1-methyl-1,2-dihydroquinoline 4a.H(250 MHz, CDCl3) 1.22 (3 H, t, J 7.1 CH2CH3), 2.44 (1 H, dd,J 14.4, 7.6, CH2CO), 2.56 (1 H, dd, J 14.4, 5.3, CH2CO), 2.91 (3 H,s, NCH3), 4.05 and 4.12 (2 H, dq, J 10.7 and 7.1, CH3CH2), 4.47(1 H, ddd, J 7.6, 5.5 and 5.3, H-2), 5.78 (1 H, dd, J 9.5 and 5.5,H-3), 8 (1 H, d, J 8.1, H-8), 6.66 (1 H,dd, J 7.3 and 7.2, H-6), 6.93 (1 H, dd, J 7.2, and 1.5, H-5), 7.12(1 H, ddd, J 8.1, 7.3 and 1.5 Hz, H-7); C (62.89 MHz, CDCl3)14.2 (CH2CH3), 36.5 (NCH3), 38.0 (COCH2), 57.6 (C-2), 60.6(CH3CH2), 111.0 (C-8), 117.1 (C-6), 123.8 (C-3), 126.3 (C-4), 126.9(C-5), 129.2 (C-7), 121.8, 144.2 (C), 171.4 (CO); m/z 231 (M, 6.4),144 (M£¾ CH2COOEt, 100%); IR (neat) ~max/cm£¾1 1630 (C.C),1725 (C.O) (Found: C, 72.45; H, 7.52; N, 6.0; O, 14.01. C14H17NO2requires C, 72.70; H, 7.41; N, 6.06; O, 13.83%).2-Cyanomethyl-1-methyl-1,2-dihydroquinoline 4b.H (250 MHz,CDCl3) 2.37 (1 H, dd, J 16.3, 6.8, CH2CN), 2.47 (1 H, dd, J 16.3and 5.5, CH2CN), 3.01 (3 H, s, NCH3), 4.40 (1 H, ddd, J 6.8, 5.6and 5.5, H-2), 5.82 (1 H, dd, J 9.6 and 5.6, H-3), 6.56 (1 H, d, J9.5, H-4), 6.56 (1 H, d, J 7.6, H-8), 6.74 (1 H, dd, J 7.5 and 7.4, H-6), 7.00 (1 H, dd, J 7.4, and 1.4, H-5), 7.18 (1 H, ddd, J 7.6, 7.5and 1.4 Hz, H-7); C (62.89 MHz, CDCl3) 21.1 (CNCH2), 37.1(NCH3), 57.5 (C-2), 111.4 (C-8), 117.9 (C-6), 121.3 (C-3), 127.4(C-5), 127.7 (C-4), 129.8 (C-7), 122.0, 143.1 (C) 117.7 (C/N); m/z184 (M, 5.8), 144 (M£¾ CH2CN, 100%); IR (neat) ~max/cm£¾1 1640(C.C), 2240 (C/N) (Found: C, 78.48; H, 6.51; N, 14.99.C12H12N2requires C, 78.22; H, 6.57; N, 15.21%).1-Ethoxycarbonylmethyl-2-methyl-1,2-dihydroisoquinoline 5a.H(250 MHz, CDCl3) 1.17 (3 H, t, J 7.1, CH2CH3), 2.50 (1 H, dd,J 14.1 and 7.1, CH2CO), 2.71 (1 H, J 14.1, 6.2, CH2CO), 2.94 (3 H,s, NCH3), 4.04 (2 H, q, J 7.1), 4.80 (1 H, ddd, J 7.1, 6.2 and1.1, H-1), 5.35 (1 H, d, J 7.3 H-3), 6.03 (1 H, dd, J 7.3 and 1.3,H-4), 6.80¡Ó6.96 (2 H, m), 6.98 (1 H, ddd, J 7.5, 7.2 and 1.3),7.10 (1 H, ddd, J 7.3, 7.2, and 1.8 Hz); C (62.89 MHz, CDCl3)14.1 (CH2CH3), 36.3 (COCH2), 40.5 (NCH3), 59.3 (C-1), 60.5(CH3CH2), 97.6, 122.7, 124.7, 125.6, 127.6, 136.1 (6 CH), 128.1,132.4 (C), 171.7 (CO); m/z 231 (M, 7.6), 144 (M£¾ CH2COOEt,100%); IR (neat) ~max/cm£¾1 1610 (C.C), 1725 (C.O) (Found:C, 72.61; H, 7.43; N, 6.12; O, 13.63.C14H17NO2 requires C, 72.70;H, 7.41; N, 6.06; O, 13.83%).1-Cyanomethyl-2-methyl-1,2-dihydroisoquinoline 5b.H (250MHz,CDCl3) 2.46 (1 H, dd, J 16.4, 6.7, CH2CN), 2.63 (1 H, dd, J 16.4,6.7, CH2CN), 3.02 (3 H, s, NCH3), 4.69 (1 H, dd, J 6.7 and 6.1,H-1), 5.40 (1 H, d, J 7.3, H-3), 6.04 (1 H, d, J 7.3 Hz, H-4),6.90¡Ó7.40 (4 H, m); C (62.89 MHz, CDCl3) 19.2 (CNCH2),40.9 (NCH3), 59.4 (C-1), 98.3, 125.3, 126.0, 126.2, 132.0, 135.2(6 CH), 126.9, 132.1 (C), 118.7 (C/N); m/z 184 (M, 8.9), 144(M£¾ CH2CN, 100); IR (neat) ~max/cm£¾1 1625 (C.C), 2320 (C/N)(Found: C, 78.29; H, 6.49; N, 14.89.C12H12N2 requires C, 78.22;H, 6.57; N, 15.21%).We thank the Conseil Re gional d'Aquitaine for nancialsupport.Received, 9th April 1998; Accepted, 30th June 1998Paper E/8/02694GReferences1 T. G. Murali Dhar and C. Gluchowski, Tetrahedron Lett., 1994,35, 989.2 S. Fukuzumi, M. Fujita, S. Noura and J. Otera, Chem. Lett.,1993, 1025.3 J. Ezquerra and J. Alvarez-Builla, J. Chem. Soc., Chem.Commun., 1984, 54.4 N.J. Leonard and R. L. Foster, J. Am. Chem. Soc., 1952, 74, 3671.5 For reviews, see N. Y. Sidgewick and F. R. S. Sidgewick, TheOrganic Chemistry of Nitrogen, Clarendon Press, Oxford, 1966,p. 718; S. F. Dyke, Adv. Heterocycl. Chem., 1972, 14, 279;J. Gurnos, Quinolines, Wiley, New York, 1982.6 See, for example, N. J. Leonard and R. L. Foster, J. Am. Chem.Soc., 1951, 73, 3325; 1952, 74, 2110; J. Metzgzer, H. Larive ,E.-J. Vincent, R. Dennilauler, R. Baralle and C.Gaurat, Bull.Soc. Chim. Fr., 1967, 30; J. Metzgzer, H. Larive , E.-J. Vincentand R. Dennilauler, Bull. Soc. Chim. Fr., 1967, 46; G. T.Pilygun and B. M. Gutsulyak, Russ. Chem. Rev., 1963, 32, 167;J. W. Bunting and W. G. Meathrel, Tetrahedron Lett., 1971,133; S. Fukuzumi and S. Noura, J. Chem. Soc., Chem. Commun.,1994, 287; M. Maeda, Chem. Pharm. Bull., 1990, 38, 2577.7 (a) F. Diaba, I. Lewis, M. Grignon-Dubois and S. Navarre,J. Org. Chem., 1996, 61, 4830; (b) M. Grignon-Dubois, F.Diabaand M.-C. Grelier-Marly, Synthesis, 1994, 800; (c) M. Grignon-Dubois and A. Meola, Synth. Commun., 1995, 25, 2999.8 J. March, Advanced Organic Chemistry, Wiley Interscience, NewYork, 4th edn., 1992, ch. 8, p. 249.9 Silicon reagents are known to be weaker nucleophiles than tinreagents: see for example, Hosomi, Chem. Lett., 1979, 977.10 For reviews, see W. P. Weber, Silicon Reagents for OrganicSynthesis, Springer, Berlin, 1983; E. W. Colvin, Silicon OrganicSynthesis, Butterworths, London, 1981; G. G. Yakobson andN. E. Akhmetova, Synthesis, 1983, 169; J. H. Clark, Chem. Rev.,1980, 80, 429.11 R. Latouche, F. Texier-Boullet and J. Hamelin, Bull. Soc. Chim.Fr., 1993, 130, 535; S. Jolivet, S. Abdallah-El-Ayoubi, D. Mathe,F. Texier-Boullet and J. Hamelin, J. Chem. Res., 1996, 300;E. Nakamura, M. Shimizu and I. Kuwajima, Tetrahedron Lett.,1976, 1699.12 O. Doebner and W. Miller, Ber. Bunsenges. Phys. Chem., 1883,16, 2464; C. F. Dun, Adv. Heterocycl. Chem., 1964, 3, 1.Scheme 2Table 1 Condensation of Me3SiCH2Y/CsF/CH3CN withcompounds 1 and 2Substrate Reagent Y Conditions Product yield (%)1 COOEt 2 h, )))) 4a : 861 COOEt 2 h, reflux 4a : 841 CN 2 h, )))) 4b : 431 CN 3.5 h, reflux 4b : 272 COOEt 2 h, )))) 5a : 562 COOEt 2 h, reflux 5a : 772 CN 3 h, )))) 5b : 482 CN 3 h, reflux 5b : 51J. CHEM. RESEARCH (S), 1998 661

ISSN:0308-2342    

DOI:10.1039/a802694g

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Kaolin-assisted Aromatic Chlorination and Bromination$ Masao Hirano,* Hiroyuki Monobe, Shigetaka Yakabe and Takashi Morimoto Department of Applied Chemistry, Faculty of Technology, Tokyo University of Agriculture and Technology, Koganei, Tokyo 184-8588, Japan Moist kaolin catalyses the regioselective and high-yielding chlorination and bromination of C6H5OR (R a C1�}C8 alkyl, But, allyl, cyclohexyl, benzyl) to 4-XC6H4OR (X a Cl and Br, respectively) with NaClO2 and Mn(acac)3 in CH2Cl2 in the absence and presence of NaBr, respectively, under mild and neutral conditions.Use of supported reagents and catalysts for organic synthesis has gained general acceptance as a new, environ- mentally benign protocol.1 Aluminosilicate clays are well characterised by their surface acidities, which render them ecient, versatile supports or catalysts.1c,2 Somewhat sur- prisingly, while montmorillonites (bentonites) have achieved very wide use, kaolin-based reagents or kaolin-assisted reac- tions appear to be extremely limited.2 We felt from our own experiments on the oxidation of sulRdes to sulfones3a and to sulfoxides3b that kaolin is slightly inferior as a catalyst to bentonite.However, a marked catalysis of natural kaolins has recently been observed upon the protection reaction of carbonyl compounds4a and the alkylation of benzene.4b It might therefore be of considerable interest to Rnd further use of kaolin as a solid catalyst in a variety of organic reactions.We chose the electrophilic halogenation5 of aromatic ethers as a target, since certain alkyl 4-halogenophenyl ethers exhibit bioactivity and are useful intermediates en route to many Rne chemicals; for example, 4-chlorophenyl octyl ether 2h is a very active plant growth regulator.6 Thus, treatment of anisole 1a with a combination of sodium chlorite (NaClO2) and a catalytic amount of Mn(acac)3 (1 mole % with respect to 1a)7 in CH2Cl2 at 25 8C in the presence of kaolin preloaded with a small amount of water (moist kaolin)% a€orded monochloroanisoles with high selectivity to p-isomer 2a (System A in Scheme 1).System A can successfully be used for the selective chlorin- ation of a series of alkyl phenyl ethers 1b�}1k, irrespective of chain length or steric bulk of the alkyl groups. During this study, we have fortunately found that nuclear bromination is readily achieved by simple addition of NaBr to System A (System B), giving good to quantitative yield of alkyl p-bromophenyl ethers 3a�}3k, along with minor amounts of p-chloro derivatives 2 (<4%).GLC analyses of reaction mixtures showed that Systems A, B achieved 100% regio- speciRcity, except for halogenations of 1a where o-chloro- anisole 4a (4.9%) and o-bromoanisole 5a (1.0%) were formed. Moreover, Systems A, B have proved to be appli- cable to gram scale halogenation of 1a with the use of the same quantity of Mn(acac)3 (0.1 mole % in this case) as that in the small scale experiment (see Table 1).An independent experiment with compound 1a carried out in the absence of moist kaolin brought about no halo- genation even after a prolonged period (1a recovery 99% by GLC), clearly indicating that the clay eciently catalyses the halogenation. Comparative halogenations of 1a using a common acidic clay, Montmorillonite K10, and a mildly acidic support, silica gel, in place of kaolin, revealed that kaolin is superior to the others in its catalytic activity, selectivity or yield of the product (see Table 1).Another set of experiments showed that neither NaClO2/NaBr/moist kaolin nor Mn(acac)3/NaBr/moist kaolin can halogenate 1a, and also that 2a does not change to 3a under bromination conditions. Consequently, it could be likely that a positive chlorine species responsible for the chlorination oxidises bromide ion quickly to generate an electrophilic Bra species. The kaolin-based biphasic systems favorably aided the regiospeciRc halogenation of multisubstituted benzenes 6�}10 (Scheme 2).Although highly activated arenes such as veratrole 8 and pyrogallol trimethyl ether 10 are vulnerable to polyhalogenations,8 the present procedures can be con- trolled to stop at the monohalogenation stage. Like halogenations of simple alkyl phenyl ethers, the tendency that hydrogens attached to the more nucleophilic carbon atoms on the benzene rings5a are preferentially displaced by chlorine and bromine is quite general. J.Chem. Research (S), 1998, 662�}663$ Scheme 1 Scheme 2 $This is a Short Paper as deRned in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there- fore no corresponding material in J. Chem. Research (M). %The e€ect of water on surface-mediated reactions has been described elsewhere.7 *To receive any correspondence. 662 J. CHEM. RESEARCH (S), 1998Surface-mediated reactions a€ord excellent product yield and selectivity often unattainable by solution phase counterparts.9 For fascinating instances, CuCl2/alumina (100 8C, 2�}3 h),9b ButOCl/zeolite (25 8C, 1 h�}2 weeks),9c and Br2/zeolite (ambient, 1�}5 h)9d systems have elegantly achieved high-yielding, regio-controlled nuclear chlorina- tion9b,c and bromination9d of a number of arenes.Simple, inexpensive procedures demonstrated here accomplish e- cient halogenations under mild conditions and their regio- speciRcities are impressive.In addition, NaBr is more attractive as the bromine source than Br2. They could therefore be added to a list of synthetically useful halogena- tion methodologies.9 In view of the easy accessibility and excellent reaction performance of the new biphasic system, we are now looking for another synthetic target to make use of the remarkable catalysis by kaolin. Experimental Sodium chlorite (available chlorine ca. 82% by iodometry), Mn(acac)3, and substrates 1a, b, d, j, k, 6�}10 were used as received from commercial sources.Ethers 1c, 1e�}1h10 and 1i11 were prepared by known methods. Moist kaolin (H2O content, 13 wt. %) was prepared by adding deionised water (0.15 g) in portions to commer- cial kaolin (Kukita; 1.0 g), followed by vigorous shaking of the mixture after every addition for a few minutes until a free-�Powing powder was obtained. Montmorillonite K10 (Aldrich) and predried silica gel (Merck silica gel 60) were treated with deionised water as above.Chlorination Procedure.DA representative procedure was as follows. A 30 ml, two-necked, round bottom �Pask, equipped with a Te�Pon-coated stirrer bar and re�Pux condenser, was charged with anisole 1a (1 mmol), freshly prepared moist kaolin (1 g), Mn(acac)3 (0.01 mmol) and dried (molecular sieves) CH2Cl2 (10 ml), and the mixture stirred for a few minutes. Sodium chlorite (1.7 mmol as available chlorine) was then added in one portion with stirring.The cloudy suspension was kept at 25 8C while ecient stirring was continued in order to ensure smooth reaction and to attain re- producible results. After 100 min (agitation periods after complete addition of NaClO2 are indicated in Table 1) the whole material was transferred to a sintered glass funnel and the Rlter cake washed thoroughly with portions of dry diethyl ether (ca. 100 ml). Rotary evaporation of the solvent, followed by chromatography on a silica gel column (Merck silica gel 60, hexane�}AcOEt), gave p-chloroanisole 2a in 94% yield.Bromination Procedure.DThe bromination was carried out by adding NaClO2 and NaBr both in one portion to a stirred mixture of ether, Mn(acac)3, and moist kaolin CH2Cl2. After a given time, work-up and chromatographic isolation as above gave the pure bromination product. Halogenoethers thus obtained were fully characterised by MS and NMR spectroscopies. Received, 29th May 1998; Accepted, 30th June 1998 Paper E/8/04043E References 1 (a) J.H. Clark, A. P. Kybett and D. J. Macquarrie, Supported Reagents. Preparation, Analysis, and Applications, VCH, New York, 1992; (b) J. H. Clark, Catalysis of Organic Reactions by Supported Inorganic Reagents, VCH, New York, 1994; (c) M. Balogh and P. Laszlo, Organic Chemistry Using Clays, Springer, Berlin, 1993; (d) Preparative Chemistry Using Supported Reagents, ed. P. Laszlo, Academic Press, San Diego, 1987; (e) Solid Supports ands, ed.K. Smith, Ellis Horwood, Chichester, 1992; ( f ) Supported Reagents and Catalysts in Chemistry, ed. B. K. Hodnett, A. P. Kybett, J. H. Clark and K. Smith, The Royal Society of Chemistry, Cambridge, 1998. 2 Ref. 1(d), Part VIII; J. A. Ballantine, in ref. 1(e), ch. 4; P. Laszlo, Acc. Chem. Res., 1986, 19, 121; A. Cornelis and P. Laszlo, Synthesis, 1985, 909. 3 (a) M. Hirano, J. Tomaru and T. Morimoto, Chem. Lett., 1991, 523; Bull. Chem. Soc. Jpn., 1991, 64, 3752; (b) M.Hirano, H. Kudo and T. Morimoto, Bull. Chem. Soc. Jpn., 1992, 65, 1744. 4 (a) D. Ponde, H. B. Borate, A. Sudalai, T. Ravindranathan and V. H. Deshpande, Tetrahedron Lett., 1996, 37, 4605; (b) K. R. Sabu, R. Sukumar and M. Lalithambika, Bull. Chem. Soc. Jpn., 1993, 66, 3535. 5 (a) R. Taylor, Electrophilic Aromatic Substitution, Wiley, Chichester, 1990, ch. 9; (b) J. March, Advanced Organic Chemistry. Reactions, Mechanisms, and Structure, 4th edn., Wiley, New York, 1992, pp. 531�}534. 6 S. R. McLane, E. W. Dean, J. W. Brown, C. R. Connell, W. H. Howard and C. E. Minarik, Weeds, 1953, 2, 288. 7 M. Hirano, S. Yakabe, J. H. Clark and T. Morimoto, J. Chem. Soc., Perkin Trans. 1, 1996, 2693; M. Hirano, S. Yakabe, H. Monobe, J. H. Clark and T. Morimoto, J. Chem. Soc., Perkin Trans. 1, 1997, 3081. 8 S. Kajigaeshi, Y. Shinmasu, S. Fujisaki and T. Kakinami, Chem. Lett., 1989, 415; D. Friedman and D. Ginsburg, J. Org. Chem., 1958, 23, 16. 9 (a) L.Delaude, P. Laszlo and K. Smith, Acc. Chem. Res., 1993, 26, 607; (b) M. Kodomari, S. Takahashi and S. Yoshitomi, Chem. Lett., 1987, 1901; (c) K. Smith, M. Butters and B. Nay, Synthesis, 1985, 1157; (d) K. Smith and D. Bahzad, Chem. Commun., 1996, 467. 10 R. A. Smith, J. Am. Chem. Soc., 1933, 55, 3718. 11 M. Siskin, G. Brons, A. R. Katritzky and R. Murugan, Energy Fuels, 1990, 4, 482. Table 1 Aromatic mono-chlorination and -bromination of aromatic ethersa Chlorination Bromination Ether NaClO2 (mmol) t/min Product (%)b NaClO2 (mmol) NaBr (mmol) t/min Product (%)b 1a 1.7 100 2a (94), 4a (4.9) 1.2 3.0 110 3a (98), 5a (1.0) 1ac 2.1 60 2a (67), 4a (7.5)d 1.4 3.0 60 3a (99) 1ae 2.1 60 2a (72), 4a (13)f 1.4 3.0 120 3a (90)g 1a 14h 50 2a (94) 12h 30 130 3a (95) 1b 1.5 60 2b (96) 1.2 3.0 100 3b (95) 1c 1.6 80 2c (98) 1.2 3.0 160 3c (97) 1d 1.7 100 2d (quant.) 1.2 3.0 100 3d (96) 1e 1.5 70 2e (93) 1.2 3.0 140 3e (92) 1f 1.6 80 2f (99) 1.2 3.0 130 3f (97) 1g 1.6 100 2g (quant.) 1.2 3.0 110 3g (97) 1h 1.5 70 2h (99) 1.2 3.0 90 3h (95) 1i 1.5 60 2i (96) 1.2 3.0 90 3i (98) 1j 1.9 60 2j (99) 1.2 4.0 80 3j (98) 1k 2.2 120 2k (60)i 1.5 4.5 150 3k (66)j 6 1.5 110 11a (93) 1.0 4.5 120 11b (95) 7 2.0 70 12a (96) 1.3 4.5 60 12b (quant.) 8 1.5 60 13a (94) 1.0 3.5 120 13b (quant.) 9 1.2 80 14a (95) 1.1 4.5 90 14b (92) 10 1.3 80 15a (98) 1.0 3.5 120 15b (97) aAt 25 8C; 1 mmol ether, 0.01 mmol Mn(acac)3, 1 g moist kaolin, 10 ml CH2Cl2.bYield of chromatographically purified product based on the starting ether. cMoist montmorillonite K10 used as support. dca. 20% of 1a remained. eSilica gel as support. fca. 13% (GLC area ratio) of a unknown product was formed. gca. 3% of 2a was formed. hAt 30 8C; 10 mmol 1a, 0.01 mmol Mn(acac)3, 3 g moist kaolin, 30 ml CH2Cl2. iGLC yield. jGLC yield; 2.4% of 1k remained. J. CHEM. RESEARCH (S), 1998 6

ISSN:0308-2342    

DOI:10.1039/a804043e

出版商:RSC    

年代:1998

数据来源: RSC

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Tungsten Hexachloride (WCl6) as a Mild and Efficient Reagent for Deprotection of Acetals and Ketals$ Habib Firouzabadi,* Nasser Iranpoor* and Babak Karimi Department of Chemistry, College of Sciences, Shiraz University, Shiraz 71454, Iran A variety of acetals and ketals are efficiently and rapidly converted to the corresponding carbonyl compounds by using WCl6 in dichloromethane or acetonitrile at room temperature. Acetals are one of the most useful and versatile protecting groups in organic syntheses.They Rnd widespread appli- cation for example in the protection of carbonyl, hydroxy, and diol functions.1 Therefore, regeneration of the parent carbonyl group from their masked form seems to be a useful synthetic process. There are several methods for the deprotection of acetals and ketals such as aqueous acid hydrolysis,1 and K-10 montmorillonite in aqueous methanol,2 and non-aqueous methods including those based on TeCl4,3 [Ru(CH3CN)3(triphos)](OTf )2,4 silica-supported guanidinium chloride�}acetyl chloride,5 SiCl4�}NaI,6 K-10 montmorillonite,7 DDQ,8 Ph3P�}CBr4,9 SnCl2 2H2O,10 CuSO4�}SiO2,11 CeCl3 7H2O,12 oxidation methods13 etc.1 But the synthetic application of this transformation is so important that the introduction of improved methods continues to attract attention.New applications of tungsten hexachloride (WCl6) have been of interest to us in recent years. Halo-dehydroxylation, dihalo-de-bisubstitution reac- tions and chemoselective dithioacetalization of carbonyl compounds and transthioacetalization of acetals have been reported.14 In continuation of our studies we have found that tungsten hexachloride eciently converts various types of acetals and ketals (dimethyl, diethyl and cyclic acetals) to the corresponding carbonyl compounds under mild reaction conditions (Scheme 1).As shown in Table 1 a variety of dimethyl acetals (entry 1) and diethyl acetals (entries 2�}6), of structurally di€erent carbonyl compounds as well as 1,3-dioxolanes of aldehydes (entries 7�}10) can be cleanly deprotected at room tempera- ture using 0.15�}0.2 equivalent of WCl6 in dry CH2Cl2.On the other hand, cleavage of 1,3-dioxolanes derived from aromatic and aliphatic ketones was achieved in dry CH3CN in the presence of 0.5�}0.8 equivalent of WCl6 (entries 11�}16). Nitro and methoxy groups are conserved in this method (entries 5, 8). In conclusion, mild reaction con- ditions, easy work-up, and excellent yields of the desired products are worthy of mention as advantages of the present method.J. Chem. Research (S), 1998, 664�}665$ Scheme 1 Table 1 Deprotection of acetals and ketals with WCl6 Entry R1 R2 XX Subst. :WCl6 ratio Solvent Time/min Yielda (%) 1 Ph H (OMe)2 1:0.15 CH2Cl2 5 92 2 Ph H (OEt)2 1:0.15 CH2Cl2 5 93 3 p-MeC6H4 H (OEt)2 1:0.15 CH2Cl2 3 94 4 p-ClC6H4 H (OEt)2 1:0.15 CH2Cl2 5 91 5 p-NO2C6H4 H (OEt)2 1: 0.2 CH2Cl2 7 98 6 (OEt)2 1: 0.2 CH2Cl2 5 98 7 p-MeC6H4 H -OCH2CH2O- 1: 0.2 CH2Cl2 5 90 8 p-MeOC6H4 H -OCH2CH2O- 1: 0.2 CH2Cl2 5 89 9 PhCH.CH H -OCH2CH2O- 1: 0.2 CH2Cl2 5 86 10 n-C6H13 H -OCH2CH2O- 1:0.25 CH2Cl2 15 81 11 Ph Me -OCH2CH2O- 1: 0.7 CH3CN 10 94 12 p-ClC6H4 Me -OCH2CH2O- 1: 0.8 CH3CN 10 89 13 p-PhC6H4 Me -OCH2CH2O- 1: 0.8 CH3CN 10 82 14 PhCH2CH2 Me -OCH2CH2O- 1: 0.6 CH3CN 10 91 15 -OCH2CH2O- 1: 0.6 CH3CN 20 75 16 -OCH2CH2O- 1: 0.8 CH3CN 15 90 aThe yields refer to isolated pure products. Experimental General Procedure for Deprotonation of Acetals with WCl6.DTo a solution of acetal 1 (2 mmol) in dry CH2Cl2 or CH3CN (10 ml), WCl6 (0.3�}1.6 mmol) was added.The solution was stirred at room $This is a Short Paper as deRned in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there- fore no corresponding material in J. Chem. Research (M). *To receive any correspondence. 664 J. CHEM. RESEARCH (S), 1998temperature, and the progress of the reaction was monitored by TLC.On completion (3±20 min), the reaction was quenched with NaOH aqueous solution (10%; 15 ml), and extracted with CH2Cl2 (330 ml). The organic layer was washed successively with saturated NaCl solution (215 ml), and water (15 ml) and dried over anhydrous Na2SO4. Evaporation of the solvent under reduced pressure gave almost pure product. Further puri®cation was achieved by column chromatography on silica gel or recrystalliza- tion from the appropriate solvent to give the desired product in good to excellent yields (Table 1).Financial support by the Shiraz University Research Council is gratefully acknowledged. Received, 27th May 1998; Accepted, 23rd June 1998 Paper E/8/03977A References 1 T. W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis, Wiley, New York, 1991, pp. 178±186. 2 J. Asakura, M. J. Robins, Y. Asaka and T. H. Kim, J. Org. Chem., 1996, 61, 9026. 3 H. Tani, T. Inamasu, K. Masumoto, R.Tamura, H. Shimizu and H. Suzuki, Phosphorus, Sulfur, and Silicon, 1992, 67, 261. 4 S. Ma and L. M. Venanzi, Tetrahedron Lett., 1993, 34, 8071. 5 P. Gros, P. L. Perchec and J. P. Senet, J. Chem. Res. (S), 1995, 196. 6 S. S. Elmorsy, M. V. Bhatt and A. Pelter, Tetrahedron Lett., 1992, 33, 1657. 7 E. C. L. Gautier, A. E. Graham, A. McKillop, S. P. Standen and R. J. K. Taylor, Tetrahedron Lett., 1997, 38, 1881 and references cited therein. 8 K. Tanemura, T. Suzuki and T. Horaguchi, J. Chem. Soc., Chem. Commun., 1992, 979; A. Oku, M. Kinugasa and T. Kamada, Chem. Lett., 1993, 165. 9 C. Johnstone, W. J. Kerr and J. S. Scott, Chem. Commun., 1996, 341. 10 K. L. Ford and E. J. Roskamp, J. Org. Chem., 1993, 58, 4142 and references cited therein. 11 G. M. Caballero and E. G. Gros, Synth. Commun., 1995, 25, 395. 12 E. Marcantoni, F. Nobili, G. Bartoli, M. Bosco and L. Sambri, J. Org. Chem., 1997, 62, 4183. 13 H. Firouzabadi, A. Shari® and B. Karimi, Iran J. Chem., Chem. Eng., 1993, 12, 32 and references cited therein; H. Firouzabadi, N. Iranpoor and M. A. Zol®gol, Bull. Chem. Soc. Jpn., in press; T. Nishiguchi, T. Ohosima, A. Nishida and S. Fujisaki, J. Chem. Soc., Chem. Commun., 1995, 1121. 14 H. Firouzabadi and F. Shiriny, Tetrahedron, 1996, 52, 14929; H. Firouzabadi, N. Iranpoor and B. Karimi, Synlett, 1998, 739. J. CHEM.

ISSN:0308-2342    

DOI:10.1039/a803977a

出版商:RSC    

年代:1998

数据来源: RSC

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Stereoselective Synthesis of Enantiopure AminoCompounds, via Mitsunobu Azidation of(2S,RS)-1-(p-Tolylsulfinyl)butan-2-ol$Pierfrancesco Bravo,*a Giancarlo Cavicchio,*b Marcello Crucianelli,aAndrea Poggiali,a Alessandro Volonterioa and Matteo ZandaaaCentro di Studio sulle Sostanze Organiche Naturali, Dipartimento di Chimica del Politecnico,C.N.R., via Mancinelli 7, I-20131 Milano, Italy,bIngegneria Chimica e Materiali, Coppito, Dipartimento di Chimica, Universita di L'Aquila, ViaVetoio, I-67010 Coppito, Italy,Azidation of (2S,RS)-1¡Ó(p-tolysulfinyl)butan-2-ol under Mitsunobu conditions is the key step for a highly stereoselectivepreparation of enantiomerically pure amino compounds via chiral sulfoxide chemistry.The stereocontrolled synthesis and the reactivity of chiralamines are topics of great interest in modern organicchemistry,1 owing to the remarkable biological propertiesconnected with this class of molecule.Our recent atten-tion towards the development of new stereocontrolledapproaches to chiral amines led us to investigate theazidation of uorosubstituted b-sulnyl alcohols underMitsunobu conditions2 as a new tool for preparing enantio-merically pure b-uoro a-amino acids.3 Since, to our knowl-edge, no reports dealing with Mitsunobu-type reactions ofuorine-free b-sulnyl alcohols are extant in the literature, afurther aim of this study was to investigate the compatibilityof the stereogenic sulnyl group with the Mitsunobuconditions, to extend this methodology to the synthesis ofuorine-free chiral amines.In this paper we describethe Mitsunobu azidation of enantiopure (2S,RS)-1-( p-tolyl-sulnyl)butan-2-ol 1, and the transformation of the resultingazide (2R,RS)-2 into several amino compounds (4¡Ó7)(Scheme 1).The starting b-sulnyl alcohol (2S,RS)-1 was stereoselec-tively prepared by reduction with diisobutylaluminiumhydride (DIBAH) of the corresponding (R)-1-( p-tolyl-sulnyl)butan-2-one.4 Transformation of (2S,RS)-1 into theb-sulnyl azide (2R,RS)-2 was accomplished by treatmentwith NaN3¡ÓPPh3¡ÓCBr4 (method A, 76%)5 or, alternatively,with HN3¡ÓPPh3¡ÓDEAD (method B, 57%). As expected thedesired product (2R,RS)-2 was formed with clean inversionof conguration at C-2, as a single diastereoisomer, isolatedin pure form by ash chromatography on silica gel.The b-sulnyl azide (2R,RS)-2 can be considered as aversatile synthetic intermediate.In fact its sulnyl andazide moieties were submitted to several chemoselectiveelaborations, as described in Scheme 1.Oxidation of(2R,RS)-2 to the corresponding b-tosylazide (R)-3 wasachieved by reaction with m-chloroperbenzoic acid(m-CPBA) at 0 8C (96%). Furthermore, the azide functionof (2R,RS)-2 could be reduced to amine by treatment withHS[CH2]3SH¡Ótriethylamine,6 providing the b-sulnyl amine(2R,RS)-4 in almost quantitative yield, without aecting thestereogenic sulnyl centre.The amino group of (2R,RS)-4 was subsequently protectedupon treatment with DCC¡Óbenzoic acid (72%).The sulnylgroup of the resulting N-benzoyl derivative (2R,RS)-5 wasdeoxygenated with NaI¡Ótriuoroacetic anhydride (TFAA),according to the Oae¡ÓDrabowicz protocol,7 which deliveredthe N-benzoyl b-( p-tolylthio)amine (R)-6 in 83% yield.Finally, N-benzoyl sec-butylamine (S)-7 was obtained byreductive desulfenylation of (R)-6, with Raney-Ni in ethanolat 60 8C (94%). Since the enantiomeric compound (R)-7,having [a]20D £¾21.5 (c 1.15, CH2Cl2), has been previouslydescribed in the literature,8 polarimetric analysis of oursample, having [a]20D 24.7 (c 1.12, CH2Cl2), allowedus to conrm both its (S)-conguration, as well as theenantiomeric purity of all the precursor compounds 2¡Ó6,represented in the Scheme 1.In conclusion, we have reported a synthetically usefulprotocol for the synthesis of enantiomerically pure aminocompounds from b-sulnyl alcohols, which uses azidationunder Mitsunobu conditions as the key step.This methodfeatures both high overall yields and stereoselectivity, andcould therefore be successfully exploited for the preparationof many other biologically interesting, enantiopure aminocompounds.ExperimentalGeneral Procedure.The instrumentation and general exper-imental and analytical procedures were recently described in detail.9The -sulnyl alcohol (2S,RS)-1 was prepared according to aliterature procedure.4-Sulnyl Azide (2R,RS)-2.Method A. To a stirred solution of(2S,RS)-1 (1.22 g, 5.75 mmol) in DMF (50 ml) cooled at 0 8C wereadded NaN3 (5.61 g, 86.3 mmol), Ph3P (5.53 g, 17.3 mmol) andnally CBr4 (5.74 g 17.3 mmol).The mixture was stirred at r.t. for4 h, then water and diethyl ether were added and the phases wereseparated. The organic phase was repeatedly washed with water inorder to remove DMF, then dried over anhydrous Na2SO4, lteredand the solvent removed at reduced pressure. The crude mixturewas submitted to ash chromatography (FC) (1:1 n-hexane¡ÓethylJ. Chem.Research (S),1998, 666¡Ó667$Scheme 1 Reagents, conditions and yields: i Method A: NaN3,Ph3P, CBr4 (76%); Method B: HN3, Ph3P, DEAD (57%);ii, m-CPBA, 0 8C (96%); iii, HS[CH2]3SH¡ÓNEt3 (97%);iv, PhCO2H¡ÓDCC (72%); v, (CF3CO)2O¡ÓNaI (83%);Raney-Ni¡ÓH2, 608C (94%)$This is a Short Paper as dened in the Instructions for Authors,Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there-fore no corresponding material in J. Chem. Research (M).*To receive any correspondence (e-mail: bravo@dept.chem.poli-mi.it).666 J. CHEM.RESEARCH (S), 1998acetate), which a€orded 1.02 g of the desired azide (2R,RS)-2 (76%), as a yellowish oil. Method B. A solution of (2S,RS)-1 (212 mg, 1 mmol) and Ph3P (524 mg, 2 mmol) in anhydrous benzene (11 mL) and HN3 (4.0 mL of 1.0 M solution in anhydrous benzene, 4 mmol) was cooled with an ice¡¾water bath under nitrogen. To the stirred solution DEAD (0.63 ml, 4 mmol) diluted with the same solvent (5 mL) was added dropwise.The bath was removed and, after ca. 15 min, TLC control revealed that all (2S,RS)-1 had been consumed. The reaction mixture was ¢çltered, the solvent was removed in vacuo, and ¢çnally the crude was puri¢çed ¢çrst by FC on silica gel, then on neutral alumina (4 :6 n-hexane¡¾ethyl acetate), providing 135 mg of the desired azide (2R,RS)-2 (57%). (2R,RS)-2: Rf (6:4 n-hexane¡¾ethyl acetate) 0.31; [a]D 20a140.4 (c 0.88, CHCl3); dH (CDCl3) 7.56 (2 H, d, J 8.1 Hz), 7.36 (2 H, d, J 8.1 Hz), 3.6¡¾3.4 (1 H, m), 3.08 (1 H, dd, J 13.1 and 7.0 Hz), 2.84 (1 H, dd, J 13.1 and 6.3 Hz), 2.42 (3 H, s), 2.0¡¾1.5 (2 H, m), and 1.01 (3 H, t, J 7.3 Hz); dC (CDCl3) 142.0, 139.9, 130.2, 124.1, 61.0, 58.3, 27.3, 21.5, 10.1 (Found: C, 55.3; H, 6.8; N, 17.4.C11H15N3OS requires C, 55.7; H, 6.4; N, 17.7%). -Tosyl Azide (R)-3.�¢To a solution of sul¢çnyl azide (2R,RS)-2 (44 mg, 0.18 mmol) in CH2Cl2 (2 ml), cooled at 0 8C, a solution of commercial m-CPBA (57¡¾86%) (84 mg, 0.27¡¾0.41 mmol) in CH2Cl2 (3 ml) was added dropwise.After 1 h at 0 8C (TLC monitoring) the reaction mixture was washed with aqueous 10% sodium sul¢çte, then with saturated aqueous NaHCO3, ¢çnally with brine. The aqu- eous phases were washed with CH2Cl2, the collected organic phases were dried over anhydrous sodium sulfate, ¢çltered and the solvent was removed in vacuo. FC of the crude (n-hexane¡¾ethyl acetate 8:2) provided pure (R)-3 as a yellowish oil (45 mg, 96%). (R)-3.Rf 0.35 (4:1 n-hexane¡¾ethyl acetate); [a]D 20+40.1 (c 0.33, CHCl3); dH (CDCl3) 7.83 (2 H, d, J a 8.4 Hz), 7.37 (2 H, d, J 8.4 Hz), 3.87¡¾3.78 (1 H, m), 3.26 (1 H, dd, J 14.5 and 8.2 Hz), 3.16 (1 H, dd, J 14.5 and 4.0 Hz), 2.47 (3 H, s), 1.8¡¾1.5 (2 H, m), and 1.00 (3 H, t, J 7.3 Hz); dC (CDCl3) 145.8, 137.3, 130.7, 128.7, 60.5, 59.3, 28.7, 22.4, 10.6; FT IR max/cm¢§1 (KBr) 2972, 2121, 2070, 1598, 1319, 1303, 1146; m/z (EI, 70 eV) 226 (Maa1 ¢ect; C2H5, 18), 211 (Ma ¢§N3) (Found: C, 52.5; H, 6.4; N, 16.4.C11H15N3O2S requires C, 52.2; H, 6.0; N, 16.6%). -Sul¢çnyl Amine (2R,RS)-4.�¢To a solution of azide (2R,RS)-2 (200 mg, 0.84 mmol) in methanol (5 mL) at r.t. under nitrogen were added propane-1,3-dithiol (847 L, 8.44 mmol) and triethylamine (1.17 mL, 8.44 mmol). After ca 4 h (TLC monitoring) the mixture was submitted to prolonged evaporation in vacuo, then the residue was puri¢çed by FC (ethyl acetate¡¾isopropanol 95:5 to 5:95).The desired amine (2R,RS)-4 was obtained as a yellowish oil (172 mg, 97%). (2R,RS)-4. Rf 0.30 (5:95 ethyl acetate¡¾isopropanol); [a]D 20a166.5 (c 1.02, CHCl3); dH (CDCl3) 7.56 (2 H, d, J 8.0 Hz), 7.33 (2 H, d, J 8.0 Hz), 3.24 (1 H, m), 2.88 (1 H, dd, J 8.3 and 13.2 Hz), 2.73 (1 H, dd, J 4.2 and 13.2 Hz), 2.41 (3 H, s), 1.71 (2 H, s), 1.61 (1 H, m), 1.47 (1 H, m), 0.95 (3 H, t, J 7.3 Hz); m/z (EI, 70 eV) 212 (Maa1, 85), 148 (46), 91 (25), 72 (100); FT IR max/cm¢§1 (KBr) 3365 (br), 3270, 1597, 1495, 1459, 1399, 1087, 1034.N-Benzoyl -sul¢çnyl amine (2R,RS)-5.�¢A mixture of -sul¢çnyl amine (2R,RS)-4 (130 mg, 0.62 mmol), benzoic acid (144 mg, 1.18 mmol), DCC (243 mg, 1.18 mmol) and p-dimethylaminopyri- dine (13 mg, 0.11 mmol) in CH2Cl2 (6 ml) was stirred at r.t. for 90 min (TLC monitoring). The mixture was diluted with 10 ml of diethyl ether, ¢çltered, and the solvent was removed in vacuo. FC (n-hexane¡¾ethyl acetate 1:1) provided the desired N-benzoyl amine (2R,RS)-5 as a white solid (202 mg, 72%).(2R,RS)-5. Rf 0.30 (1:1 n-hexane¡¾ethyl acetate); mp 151.5¡¾ 153.0 8C (ethyl acetate); [a]D 20a79.1 (c 0.61, CHCl3); dH (CDCl3) 7.82 (2 H, d, J 8.0 Hz), 7.58 (2 H, d, J 8.0 Hz), 7.50¡¾7.27 (5 H, m), 7.23 (1 H, br d, J 7.4 Hz), 4.32 (1 H, m), 3.23 (1 H, dd, J 8.7 and 13.4 Hz), 3.12 (1 H, dd, J 4.8 and 13.4 Hz), 2.40 (3 H, s), 1.94¡¾1.50 (2 H, m), 0.92 (3 H, t, J 7.3 Hz); dC (CDCl3) 167.4, 141.8, 140.3, 134.2, 131.5, 130.1, 128.4, 127.1, 124.2, 61.9, 48.3, 27.8, 21.4, 10.2; m/z (EI, 70 eV) 316 (Maa1, 10), 176 (100), 105 (70), 77 (32); FT IR max/cm1 (KBr) 3303, 1634, 1530, 1029 (Found: C, 68.0; H, 7.1; N, 4.9, C18H21NO2S requires C, 68.4; H, 6.7; N, 4.5%).N-Benzoyl p-Tolylthioamine (R)-6.�¢To a mixture of N-benzoyl -sul¢çnyl amine (2R,RS)-5 (107 mg, 0.32 mmol) and NaI (145 mg, 0.97 mmol) in acetone (2 ml) at ¢§20 8C, a solution of TFAA (0.23 ml, 1.62 mmol) in acetone (1 ml) was added dropwise.The mixture immediately became dark green. After 5 min at ¢§20 8C (TLC monitoring) the reaction was quenched with a saturated aqu- eous sodium sul¢çte solution, then a saturated aqueous NaHCO3 sol- ution was added until neutral pH was reached. The mixture was allowed to warm at room temperature, then the mixture was extracted with ethyl acetate, the collected organic phases were dried over anhydrous sodium sulfate and ¢çltered and the solvent was removed in vacuo.FC (n-hexane¡¾ethyl acetate 7:3) provided the desired N-benzoyl amine (R)-6 (80 mg, 83%). (R)-6. Rf 0.45 (7:3 n-hexane¡¾ethyl acetate); dH (CDCl3) 7.59 (2 H, m), 7.52¡¾7.29 (5 H, m), 7.06 (2 H, d, J 7.8 Hz), 6.12 (1 H, brd, J 8.1 Hz), 4.30 (1 H, m), 3.21 (2 H, br signal), 2.28 (3 H, s), 1.88¡¾1.58 (2 H, m), 0.96 (3 H, t, J 7.3 Hz); m/z (EI, 70 eV) 299 (Ma, 68%), 178 (46), 105 (100), 77 (67). FT IR max/cm¢§1 (KBr) 3308, 1639, 1535, 1490 (Found: C, 71.2; H, 7.2; N, 4.6.C18H21NOS requires C,72.2; H, 7.1; N, 4.7%). N-Benzoyl sec-Butylamine (S)-7.�¢To a stirred solution of the thioamine (R)-6 (72 mg, 0.24 mmol) in absolute ethanol (5.0 ml) Raney-Ni (ca. 0.4 g) was added and the slurry was vigorously stirred for 3 h at 80 8C under a hydrogen atmosphere. The Raney- Ni was removed by ¢çltration on a Celite pad and the solvent was removed under reduced pressure. FC (n-hexane¡¾ethyl acetate 4:1 to 7.3) provided the desired N-benzoyl amine (S)-7 (40 mg, 94%) as a white solid.(S)-7. Rf 0.40 (75:25 n-hexane¡¾ethyl acetate); [a]D 20a24.7 (c 1.12, CH2Cl2); in the literature the enantiomer (R)-7 is reported to have [a]D 20 ¢§ 21.5 (c 1.15, CH2Cl2)8; dH (CDCl3) 7.81¡¾7.78 (2 H, m), 7.52¡¾7.36 (3 H, m), 6.10 (1 H, br signal), 4.20¡¾4.03 (1 H, m), 1.57 (2 H, dq, J ca. 7.3 Hz both), 1.22 (3 H, d, J 6.8 Hz), 0.96 (3 H, t, J 7.3 Hz); dC (CDCl3) 166.9, 135.0, 131.2, 128.4, 126.8, 47.0, 29.7, 20.5, 10.4. Received, 24th February 1998; Accepted, 16th July 1998 Paper E/8/01562G References 1 (a) J.Klein, in The Chemistry of Double-Bonded Functional Groups: Supplement A, ed. S. Patai, Wiley, Chichester, 1989, Vol. 2, Part 1, ch. 10; (b) Methods of Organic Chemistry (Houben- Weyl): Stereoselective Synthesis, eds. G. Helmchen, R. W. Ho€mann, J. Mulzer and E. Schaumann, Georg Thieme, Verlag: Stuttgart, 1995, Vol. E 21b. 2 (a) O. Mitsunobu, Synthesis, 1981, 1; (b) D. L. Hughes, Organic Reactions, 1992, Vol. 42, ch. 2; (c) E. Fabiano, B. T. Golding and M. M. Sadeghi, Synthesis, 1987, 190. 3 P. Bravo, G. Cavicchio, M. Crucianelli, A. Poggiali and M. Zanda, Tetrahedron: Asymmetry, 1997, 8, 2811. 4 (a) G. SolladieA , C. Greck, G. Demailly and A. SolladieA -Cavallo, Tetrahedron Lett., 1982, 23, 5047; (b) G. SolladieA , G. Dmailly and C. Greck, Tetrahedron Lett., 1985, 26, 435. 5 (a) I. Yamamoto, M. Sekine and T. Hata, J. Chem. Soc., Perkin Trans. 1, 1980, 306; (b) S. Shuto, S. Ono, Y. Hase, N. Kamiyama, H. Takada, K. Yamashita and A. Matsuda, J. Org. Chem., 1996, 61, 915. 6 H. Bayley, D. N. Standring and J. R. Knowles, Tetrahedron Lett., 1978, 19, 3633. 7 J. Drabowicz and S. Oae, Synthesis, 1977, 404. 8 (a) F. Foubelo and M. Yus, Tetrahedron Lett., 1994, 35, 4831; (b) F. Foubelo and M. Yus, Tetrahedron: Asymmetry, 1996, 7 2911. 9 A. Volonterio, M. Zanda, P. Bravo, G. Gronza, G. Cavicchio and M. Crucianelli, J. Org. Chem., 1997, 62, 8031. J. CHEM. RESEARCH (S),

ISSN:0308-2342    

DOI:10.1039/a801562g

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Microwave Promoted Epoxidation of a,b-Unsaturated Ketones in Aqueous Sodium Perborate$ Ali Sharifi,* Mohammad Bolourtchian and Farshid Mohsenzadeh Chemistry & Chemical Engineering Research Center of Iran, P.O. Box 14335-186, Tehran, Iran A series of ,-unsaturated ketones has been treated with sodium perborate in water and 1,4-dioxane under microwave irradiation to produce ,-epoxyketones in good yields. Recently, there has been growing interest in applying micro- wave dielectric heating to accelerate organic reactions.1 Oxidation reactions are less considered under microwave irradiation due to unsafe and uncontrollable experimental conditions.2 Sodium perborate is a very cheap and widely used industrial chemical which is utilized as an oxidizing agent in organic chemistry:3 oxidation of anilines, sulRdes, ketones, hydroquinones, aromatic aldehydes, iodoarenes, aromatic nitriles, azines, sulfur heterocycles, benzylic alco- hols, a-hydroxycarboxylic acids, 1,2-diketones, a-hydroxy- ketones, 1,2-diols, unsaturated compounds and oximes under di€erent conditions have been reported.4 a,b-Unsaturated ketones react with sodium perborate in water and a cosolvent to produce the corresponding epoxides over a long period of time.5 Tetrahexylammonium hydrogensulfate is used as a phase transfer catalyst for these reactions, in both biphasic solvent mixtures6 and monophasic aqueous solutions7 at di€erent temperatures to enhance the rate and the yield of products.In this paper, we report epoxidation of a,b-unsaturated ketones by sodium perborate in water and a cosolvent (1,4-dioxane) under microwave irradiation for 2�}3 min to produce the corre- sponding epoxides in good yields (Scheme 1, Table 1). As seen in Table 1, the isolated yield under micro- wave conditions is higher than in thermal reactions. Regio- J. Chem. Research (S), 1998, 668�}669$ Scheme 1 Table 1 Epoxidation of a,b-unsaturated ketones with sodium perborate under microwave irradiation Entry Substrate Product Sodium perborate/substrate (mole ratio) Irradiation time/min Microwave yielda (%) Thermal yieldb (%) 1 3 2 92c (85)d 88c(55)d 2 3 2 100(73) 67(38) 3 2 51(43) 3 3 3 79(68) 78(60) 4 2 84(75) 4 3 3 88(82) 91(56) 5 3 2 83(79) 100(26) 3 3 86(80) 6 3 2 100(93) �} aAll products were characterized by IR, 1H NMR and their spectroscopic data were similar to those reported.bFrom ref. 5. The time of thermal reactions were 5�}26 h.cGC yield. dIsolated yield. speciRcity is observed for entry 4; the spectral data are identical to those of the known compound.5 Other co- solvents such as THF, DMSO, DMF were examined along $This is a Short Paper as deRned in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there- fore no corresponding material in J. Chem. Research (M). *To receive any correspondence (e-mail: ccerci@neda.net) 668 J. CHEM. RESEARCH (S), 1998with water.We observed a lower yield with those solvents than with 1,4-dioxane, under the same conditions. The opti- mum amount of sodium perborate is found to be 3 molar equivalents with respect to the substrate. Irradiation was carried out 3 or 4 times (each time for 15±20 s with 5 min intervals), in order to avoid increase of pressure in the closed Te�on vessel. In conclusion, we have reduced the reaction time com- pared with the thermal method.5 The isolated yields are higher than previously reported.5±7 The reaction constitutes a safe, mild, easy to work-up and convenient method for the synthesis of a,b-epoxyketones.Experimental IR spectra were obtained on a Perkin-Elmer 833 spectrometer, 1H NMR spectra on a Bruker 80 MHz in CDCl3 using Me4Si as internal standard. Microwave induced reactions were carried out in a Moulinex MICRO-CHEF, 900 W at 2450 MHz. General Procedure for Epoxidation of ,-Unsaturated Ketones.� A mixture of ketone (3 mmol) and sodium perborate (9 mmol) in water (9 mL) and 1,4-dioxane (6 mL) in a closed Te�on vessel (volume 250 mL) was irradiated for 2 min (four times, each time 30 s with 5 min intervals). After cooling, the mixture was extracted with dichloromethane (320 mL).The organic layer was separated and dried over magnesium sulfate. After ®ltration the solvent was evaporated and the residue analysed by GC and puri®ed with a short column (eluent: light petroleum±dichloromethane, 10:1).Received, 21st May 1998; Accepted, 14th July 1998 Paper E/8/03846E References 1 S. Galema, Chem. Soc. Rev., 1997, 26, 233; F. Langa, P. De la Cruz, A. De la Hoz, A. Diaz-Ortiz and E. Diez-Barra, Con- temporary Org. Synth., 1997, 373; R. A. Abramovitch, Org. Prep. Proc. Int., 1991, 23, 683; D. M. P. Mingos and D. R. Baghurst, Chem. Soc. Rev., 1991, 20, 1; S. Caddick, Tetrahedron., 1995, 51, 10403; C. R. Strauss and R. W. Trainer, Aust. J. Chem., 1995, 48, 1665. 2 R. Gedye, F. Smith, K. Westaway, A. Humera, L. Baldisera and L. R. Laberge, Tetrahedron Lett., 1986, 26, 279. 3 Leo A. Paquette, Encyclopedia of Reagents for Organic Chemistry, Wiley, Chichester, 1995. 4 A. McKillop and J. A. Tarbin, Tetrahedron, 1987, 43, 1753; Tetrahedron Lett., 1983, 24, 1505; A. McKillop and D. Kemp, Tetrahedron, 1989, 45, 3299; J. Muzart and A. N. Ajjou, Synth. Commun., 1991, 21, 575; A. Banrrjee, B. Harza, A. Bhattacharya, S. Banerjee, G. C. Banerjee and S. Sengupta, Synthesis, 1989, 765; W. W. Zajac, M. G. Darcy, A. P. Subong and J. H. Buzby, Tetrahedron Lett., 1989, 30, 6495; G. A. Olah, P. Ramaiah, C. S. Lee and G. K. S. Prakash, Synlett, 1992, 337; K. L. Reed, J. T. Gupton and T. L. Solarz, Synth. Commun., 1990, 20, 563. 5 K. L. Reed, J. T. Gupton and T. L. Solarz, Synth. Commun., 1989, 19, 3579. 6 E. V. Dehmlow and B. Vehre, New J. Chem., 1989, 13, 117. 7 T. S. Straub, Tetrahedron Lett., 1995, 36, 663. J. CHEM. RESEARCH

ISSN:0308-2342    

DOI:10.1039/a803846e

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Kinetics of the Deamination of Amides by Nitrous Acid$ Khawla Al-Mallah and Geoffrey Stedman* Chemistry Department, University of Wales Swansea, Singleton Park, Swansea SA2 8PP, UK The kinetic profile of the rate constant for the nitrous acid¡¾amide reaction in sulfuric acid as a function of acidity for a range of aliphatic and aromatic primary amides has been interpreted in terms of the HNO2/NOa and the amide/ amide Ha equilibria. The mechanism of the deamination of primary amides by nitrous acid, eqn.(1), was originally thought1¡¾3 to involve a rate-determining N-nitrosation reaction, as had been estab- lished4 for primary amines. Primary aliphatic and aromatic amides are much weaker bases than the corresponding primary amines, and in order to get the reaction to proceed at a reasonable rate much higher concentrations of mineral acid are necessary. In these concentrated solutions activity e€ects are important. Attempts to account quantitatively for the pro¢çle of rate constant versus acid concentration in terms of a single mechanism1 were unsuccessful.Subsequent work by a number of groups5 has established that with the presence of a strongly electron attracting group such as the carbonyl function the initial nitrosation is reversible, and the rate-determining stage involves proton loss. Furthermore the site of the initial nitrosation may be the oxygen of the carbonyl group; this is certainly the site for protonation. The mechanism is summarised in eqns. (2)¡¾(6).RCONH2 a HNO24RCO2H a N2 a H2O O1U NOa a H2O N HNO2 a Ha KNO O2U RCONH2Ha N RCONH2 a Ha KA O3U RCONH2 a NOa N RCONH2 NOa KE O4U RCONH2 NOa a B4RCONHNO a BHa k3 slow O5U RCONHNO4RCO2H a N2 fast O6U We summarise in this paper the results of kinetic studies on a group of aliphatic and aromatic amides reacting with nitrous acid over the range [H2SO4] a 2.8 to 10.5 mol dm¢§3, at 25 8C. Reactions were run with a large excess of amide over nitrous acid, and gave good ¢çrst order plots of ln[nitrite] versus time, k1/min¢§1.Values of k1 were directly proportional to [amide], yielding second order rate con- stants k2/dm3 mol¢§1 min¢§1 in terms of stoichiometric concen- trations. ¢§danitritea=dt a k2aamideaanitritea O7U All amides studied showed a similar dependence of k2 on [H2SO4]; k2 increased with acidity and passed through a sharp maximum close to 8 mol dm¢§3 sulfuric acid, and then decreased sharply. A typical plot is shown in Fig. 1. The decrease in k2 at higher acidities was always markedly steeper than the increase at lower acid concentrations. In order to check that there was no di€erence in mechanism for reaction at acidities on each side of the rate maximum, Arrhenius activation energies were measured on each side of the maximum for two of the aliphatic amides, giving the following results at the molar concentrations of sulfuric acid speci¢çed in parentheses, E/kJ mol¢§1: Ra (CH3)3C, 74.221.4 (4.5); 76.924.8 (9.3); R a CNCH2, 60.124.4 (6.8), 64.022.4 (8.0).The activation energies are constant to within one standard deviation. The results for trimethyla- cetamide were used to correct the rate pro¢çle data measured at 0 to 25 8C, in order to compare the results with those for the other amides studied. The rate maximum is due to the opposing e€ects of acidity on equilibria (2) and (3), combined with the e€ect of sulfuric acid concentration on KE and k3.Equilibrium (2) is described formally by the HR acidity function for which DHR/D[H2SO4] is on average ca. ¢§1.05 dm3 mol¢§1. The pKNO for (2) determined spectro- photometrically using the HR function is ¢§8.11. At [H2SO4] a 8 mol dm¢§3 HR=¢§ 7.59, and thus at higher acidities conversion of nitrite into NOa is virtually com- plete. Equilibrium (3) is described by the HA acidity func- tion for which DHA/D[H2SO4] is only ca. ¢§0.28 dm3 mol¢§1. Thus at lower acidities the increase in [NOa] dominates over the decrease in [RCONH2], while as we approach the con- ditions where HR becomes close to pKNO the fraction of NOa, hR/(KNOahR), levels o€ and tends to 1, while the fraction of free amide, KA/(KAahA), continues to decrease.However the decrease in k2 is very much faster than the decrease in 1/hA and the rate of proton loss is a sensitive function of sulfuric acid concentration. This is presumably because of variation in the activity of the various proton acceptors such as SO4 2 ¢§, H2O and possibly HSO4¢§.In seeking for an empirical measure of this e€ect we used the H0 acidity function, with the idea that as the proton donating power measured by h0 increased so the ability of the medium to remove a proton would decrease. The mechanism in eqns. (2)¡¾(6) requires the rate law (8). rate a k3KEaNOaaaRCONH2a O8U To relate this to eqn. (2) we write a a the fraction of nitrite present as NOa, and b a the fraction of amide present as RCONH2, where a and b have been de¢çned in J.Chem. Research (S), 1998, 670¡¾671$ Fig. 1 Variation of k2 with sulfuric acid concentration for trimethylacetamide at 0 8C $This is a Short Paper as de¢çned in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there- fore no corresponding material in J. Chem. Research (M). *To receive any correspondence. 670 J. CHEM. RESEARCH (S), 1998terms of KNO, hR, KA and hA in the previous paragraph.To allow for the variation of k3KE with 1/h0 we write k3KE=k4/h0. With these substitutions, and the assumption that there is only a small fraction of the amide present as RCONH2NOa, we obtain eqn. (9). logOk2=abU a log k4 a H0 O9U Plots of this type yielded good straight lines with slopes between 0.92 and 1.27 over the range of acidities speci¢çed in Table 1. Values of pKA for aliphatic amides are due to Liler6 and for aromatic amides come from the review7 by Boyd.The value for (CH3)3CONH2 comes from our own work8 based upon NMR measurements, and is very close to Liler's value. Although our model gives a reasonably satisfactory description of the data the choice of H0 was arbitrary. However most acidity functions vary in an approximately linear manner with [H2SO4] in the higher range of acid concentrations, and so the choice of other acidity functions to describe the variation of KEk3 would still have yielded linear plots, though with di€erent slopes.Since of the use of 1/h0 is a purely empirical measure of the ability of the medium to accept a proton we do not o€er any comment on the variation of the slopes. There must be considerable di€erences in the solvation of the aliphatic amides in view of the di€erences in R; for the aromatic amides which all have a phenyl ring the slopes are quite similar. An alternative explanation of the dependence of k2/ab upon 1/h0 would be an acid¡¾base equilibrium for (5) followed by a rate-determining rearrangement as in eqn.(6). However as Williams5 points out the evidence for a rate- determining loss of a proton is very strong, so we reject this alternative. Although the present model gives a reasonable description of the data in terms of the generally accepted mechanism, it is important to realise its limitations. One concerns the value used for pKNO. Various values have been suggested,9,10 and in his interpretation of the kinetics of diazotisation in dilute acid Ridd used11 a value of ca.¢§6.5, which yields limiting rates in good agreement with the calcu- lated value of the encounter rate between NOa and ArNH2. As we are concerned with data over a wide range of sulfuric acid concentration, using the HR data to describe (2) we prefer to use the more negative ¢çgure of ¢§8.11 deduced by Deno et al.12 when ¢çtting spectrophotometric estimates of [NOa]/[HNO2] to his HR data obtained by the ionisation of arylcarbinol indicators. At lower [H2SO4] changing the value of pKNO merely displaces the line of log (k2/ab) versus H0 without signi¢çcantly changing the slope.As HR approaches pKNO the choice is more important. We tried using pKNO=¢§ 6.5, but found deviations at sulfuric acid concentrations greater than 6.5 mol dm¢§3, whereas with Deno's value linearity was observed up to the speci¢çed con- centrations shown in Table 1. We have also extended a few measurements to higher acidities, [H2SO4] a 13.1 mol dm¢§3, and there are deviations from eqn.(9); values of log (k2/ab) are greater than predicted from the equations in Table 1 for the aliphatic amides. The measurements for the aromatic amides were not extended to such high acidities. It is poss- ible that an extra pathway comes into play at high acidities. Finally we turn to a consideration of the di€ering reactivities of the amides studied. Since there are variations in the slopes of the plots of eqn.(9) it is simplest to make comparisons at a given sulfuric acid concentration by substi- tuting the appropriate value of H0. The same reactivity sequence is obtained over our range of acidities. For the aliphatic amides it is (CH3)3C>ClCH2>CNCH2>Cl2CH, which is the same as the sequence of pKA values. For the aromatic amides the sequence is p-CH3O>p-CH3>p-Br> p-Cl>p-NO2, again the same sequence as the pKA values, except for the interchange of positions of chlorine and bromine which are very close together anyway. Clearly the greater the electron releasing power of R in RCONH2 the higher is the reactivity.The addition of NOa to the free amide may be expected to vary with R in the same sense as the addition of Ha, and this is undoubtedly favoured by electron release by R. Step (5) however involving proton loss will be reduced in rate by increase in electron release by R. We conclude therefore that the reactivity in the reaction of nitrous acid with primary amides is controlled by the basicity of the amide, by favouring the formation of an amide NOa species, and that this is more important than the e€ect on the rate of proton loss.Experimental Materials.�¢The amides used were either commercially available materials (Aldrich, BDH, Koch-Light) or were prepared from the acid chlorides by addition to stirred, ice-cold 0.88 ammonia. In some cases the acid chlorides were prepared by reaction of thionyl chloride with the carboxylic acid.The amides were recrystallised from water to constant melting point. Kinetic Methods.�¢Some reactions were followed by colorimetric analysis for nitrous acid involving diazotisation of sulfanilic acid and coupling with alkaline 2-hydroxynaphthol-3,6-disulfonic acid. Other reactions were followed by direct UV spectrophotometry at wavelengths where nitrite absorbed. For slow runs a blank exper- iment was carried out to correct for the self-decomposition of nitrous acid.Thanks are due to the University of Mosul for study leave (to K. A.-M.) Received, 17th June 1998; Accepted, 10th July 1998 Paper E/8/04600J References 1 M. N. Hughes and G. Stedman, J. Chem. Soc., 1964, 5840. 2 M. L. Bender and H. Ladenheim, J. Am. Chem. Soc., 1960, 82, 1895. 3 J. Jaz and A. Bruylants, Bull. Soc. Chim. Belges, 1961, 70, 99. 4 J. H. Ridd, Q. Rev. Chem. Soc., 1961, 15, 418. 5 D. L. H. Williams, in Nitrosation, Cambridge University Press, Cambridge, 1988, p. 101. 6 M. Liler, J. Chem. Soc. B, 1969, 385. 7 J. H. Boyd, in Solute¡¾Solvent Interactions, ed. J. F. Coetzee and C. D. Ritchie, Marcel Dekker, New York, 1969, vol. 1, ch. 3, p. 97. 8 K. Al-Mallah, Ph.D. Thesis, University of Wales, 1974. 9 Stability Constants, Special Publication No. 17, The Chemical Society, London, 1964, p. 163. 10 Stability Constants, Special Publication No. 25, The Chemical Society, London, 1971, p. 91. 11 J. H. Ridd, Adv. Phys. Org. Chem., 1978, 16, 1. 12 N. C. Deno, H. E. Berkheimer, W. L. Evans and H. J. Peterson, J. Am. Chem. Soc., 1959, 81, 2344. Table 1 Parameters used for plots of eqn. (9) R Slope Intercept [H2SO4]/ mol dm¢§3 pKA (CH3)3C* 1.2120.02 7.2220.08 2.8 to 9.3 ¢§ 1.40 ClCH2 1.0120.03 5.8420.12 2.8 to 9.3 ¢§ 2.74 CNCH2 0.9220.04 5.2120.16 3.4 to 9.1 ¢§ 3.73 Cl2CH 1.0320.06 5.1220.23 2.8 to 9.3 ¢§ 4.18 p-MeC6H4 1.2220.04 7.4020.16 5.5 to 10.4 ¢§ 1.67 p-BrC6H4 1.2920.07 7.4720.27 5.5 to 10.5 ¢§ 2.02 p-ClC6H4 1.3220.04 7.5420.13 3.2 to 10.5 ¢§ 1.97 p-MeOC6H4 1.2820.02 7.9020.07 3.1 to 9.1 ¢§ 1.54 p-NO2C6H4 1.2520.05 6.9920.19 5.5 to 10.2 ¢§ 2.70 *Corrected from 0 to 25 8C. J. CHEM. RESEARCH (S), 1998

ISSN:0308-2342    

DOI:10.1039/a804600j

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Synthesis of Metallophthalocyanines under Solvent-free Conditions using Microwave Irradiation$ Ahmad Shaabani Chemistry Department, Shahid Beheshty University, P.O. Box 1939-4716, Tehran, Iran The phthalocyanine complexes of Cu, Co, Ni, and Fe are easily prepared upon exposure to microwave radiation under solvent-free conditions and reaction times are considerably reduced. Phthalocyanines are of interest not only as model com- pounds for the biologically important porphyrins but also because the intensely colored metal complexes are of commercial importance as dyes and pigments.1 Preparation of metallophthalocyanines from the reaction between metal salts, particularly CuCl, phthalic anhydride and urea is carried out on a large scale industrially, the copper derivatives being an important blue pigment.2 Typically, temperatures around 200 8C and reaction times of hours are needed.3 The reaction is sometimes described as followings: It is not clear what the reducing reagent is in this process.4 Such syntheses because of long reaction times and high temperature are often of low yield and giving mixtures of products from which the pure phthalocyanines may be di�cult to obtain.Microwave (MW) irradiation using commercial domestic ovens has recently been used to accelerate organic reactions, the e�cient heating giving rise to remarkable rate enhance- ments.5,6 Nevertheless, these procedures are seriously limited because of the use of solvents in microwave ovens which gives rise to elevated temperatures and consequently high pressures, thus leading in some cases to dangerous explosions.Here I describe a facile preparation of phthalocyanine complexes of Cu, Co, Ni and Fe in the absence of any solvent (``dry media'' conditions) which reduces consider- ably reaction times in a process that is accelerated by micro- wave irradiation. The experimental procedure involves a simple mixing and grinding of reactants and irradiating the reaction mixture in a microwave oven for about 4 to 7 min in the absence of any solvent.The reaction occurred instantly as the melting of the mixture started after about 3 min. The microwave oven was a domestic (Maximum 900 W) National model NN-6653 with ®ve select power levels (two of which were used for this experiment; high 100% wattage, medium 70% wattage). This extremely rapid, manipulatively simple, and inexpensive protocol avoids the use of excess and toxic solvents.The results for various metallophthalocyanines are summarized in Table 1. In conclusion, I have developed a convenient and rapid procedure for the synthesis of metallophthalocyanines using domestic microwave ovens for a few minutes under solvent-free conditions including ``dry'' media. Investi- gations toward extension of this procedure to other metals are in progress. Experimental Elemental analyses were performed using a Heraeus CHn-O rapid analyser. IR spectra were measured on a Shimadzu IR-470 spectro- meter.All starting solids used were anhydrous. The IR spectra of these compounds were in excellent agreement with those reported.10 The preparation of copper phthalocyanines is representative of the general procedure employed. Phthalic anhydride (26.50 g, 0.18 mol), urea 955.40 g, 0.92 mol), copper chloride (5.00 g, 0.05 mol), and ammonium molybdate (0.75 g, 3.80 mmol) were ground together until homogeneous, placed in a beaker and irra- diated in a microwave oven at high power for 6 min.Upon completion of the reaction the product was ground and washed with 5% caustic soda, water, 2% hydrochloric acid and again with water respectively. The dried phthalocyanine thus obtained weighed 23.3 g, 91% of the theoretical amount based on phthalic anhydride. [Cu(pc)] was subsequently recrystallized two times from con- centrated H2SO4. Usually during recrystallization the solution of phthalocyanine in concentrated H2SO4 was poured into distilled water.11 After complete recrystallization the [Cu(pc)] obtained was puri®ed by Soxhlet extraction using in succession methanol and methylene chloride, yield 86%. After two vacuum sublimations (Found: C, 66.69; H, 2.52; Cu, 11.00; N, 19.18. Calc.for C32H16CuN8: C, 66.74; H, 2.78; Cu, 11.03; N, 19.45%). ~max J. Chem. Research (S), 1998, 672±673$ Table 1 Synthesis of metallophthalocyanines, M(pc), using MW Time/min Yield (%)a Entry Product Found Reported Found Reported T/8C Ref 3a [Cu(pc)] from CuCl 6b 480 91 (86)c 91.8 190±195 7,8 3b [Co(pc)] from CoCl2 5b 480 86 (81) 90 180±190 7,9 3c [Ni(pc)] from NiCl2 4.5b 360 90 (86) 86.5 178 8 3d [Fe(pc)] from FeCl2 7d 660 89 (85) 95 180±190 7,9 aBased on the phthalic anhydride.bAt high power (100% wattage). cAfter Soxhlet extraction. dAt medium power (70% wattage). (KBr)/cm¡1 728 vs, 754 s, 779 m, 874 w, 894 m, 1048 m, 1081 s, 1114 s, 1157 m, 1277 m, 1324 s, 1409 m, 1452 w, 1495 m, 1602 w, 3025 vw.$This is a Short Paper as de®ned in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there- fore no corresponding material in J. Chem. Research (M). 672 J. CHEM. RESEARCH (S), 1998[Co(pc)] (Found: C, 67.30; H, 2.69; Co, 10.08; N, 19.47. Calc. for C32H16CoN8; C, 67.28; H, 2.80; Co, 10.32; N, 19.61%): ~max (KBr)/cm¡1 733 vs, 756 s, 780 m, 870 m, 910 m, 1056 m, 1089 vs, 1118 vs, 1157 m, 1283 s, 1327 s, 1419 m, 1458 w, 1515 s, 1598 w, 3040 vw.[Ni(pc)] (Found: C, 67.23; H, 2.71; N, 19.55; Ni, 10.20. Calc. for C32H16N8Ni; C, 67.30; H, 2.80; N, 19.61; Ni, 10.27%). ~max (KBr)/cm¡1 727 vs, 752 s, 771 m, 861 w, 907 m, 1055 (sh), 1084 s, 1114 s, 1157 m, 1277 m, 1320 s, 1415 m, 1457w, 1517 m, 1596 w, 3025 vw. [Fe(pc)] (Found: C, 67.59; H, 2.78; Fe, 9.76; N, 19.57. Calc. for C32H16FeN8; C, 67.64; H, 2.82; Fe, 9.83; N, 19.71%): ~max (KBr)/cm¡1 734 vs, 756 s, 780 m, 871 w, 904 m, 1076 s, 1117 s, 1156 m, 1279 m, 1327 s, 1411 m, 1456w, 1501 m, 1598 w, 3035 vw.The support of this work by the ministry of Science and Higher Education research council is gratefully acknowledged. Received, 9th December 1998; Accepted, 13th July 1998 Paper E/708858B References 1 A. B. P. Lever, Adv. Inorg. Chem. Radiochem., 1965, 7, 27. 2 F. H. Moser and A. L. Thomas, The Phthalocyanines, CRC Press, Boca Raton, FL, 1983; K. Venkataraman, Synthetic Dyes, Academic Press, 1952, vol. 2, pp. 1118±1142. 3 F. H. Moser and A. L. Thomas, Phthalocyanine Compounds, Reinhold, New York, 1963; Br. Pat., 909 375, 1962; Swiss Pat., 428 046, 1967; Br. Pat., 991 419, 1965. 4 F. A. Cotton and G. Wilkinson, Advanced Inorganic Chemistry, 4th ed, Wiley, New York, vol. 134, 1980. 5 E. Gutierrez, A. Loupy, G. Bram and E. Ruiz-Hitzky, Tetrahedron Lett., 1989, 30, 945; D. R. Baghurst and D. M. P. Mingos, J. Organomet. Chem., 1990, 384, C57; D. M. P. Mingos and D. R. Baghurst, Chem. Soc. Rev., 1991, 20, 1; D. R. Baghurst and D. M. P. Mingos, J. Chem. Soc., Chem. Commun., 1988, 829. 6 S. Caddick, Tetrahedron, 1995, 51, 10403. 7 Allied Chemical Corportion, Br. Pat., 991 419, 1961. 8 Czech Pat., 215 594, 1984. 9 Allied Chemical Corporation, Belg. Pat., 611 062, 1961. 10 A. A. Ebert and H. B. Gottlieb, J. Am. Chem. Soc., 1952, 74, 2806; A. N. Sidorov and I. P. Kotlyar, Opt. Spectrosc., 1961, 11, 92; H. F. Shurvell and L. Pinzuti, Can. J. Chem., 1966, 44, 125. 11 H. Lubs, in The Chemistry of Synthetic Dyes and Pigments, Hafner Publishing Corp., Darrien, CT, 1970. J. CHEM. RESEARCH (S), 1998

ISSN:0308-2342    

DOI:10.1039/a708858b

出版商:RSC    

年代:1998

数据来源: RSC