摘要:

AlCl3-Catalysed trans N-acylation of Acetanilides with-Chloropropionyl Chloride$%H. R. Sonawane,* A. V. Pol, B. S. Nanjundiah and A. Sudalai*National Chemical Laboratory, Pune, 411008, Indiatrans N-acylation of acetanilides with -chloropropionyl chloride catalysed byAlCl3 has been shown to occur efficiently, affording2-chloro-N-phenylpropanamides in preparative yields.Friedel¡ÓCrafts acylation reactions of aromatic compoundswith acid chlorides and anhydrides, catalysed by Lewisacids, have been extensively employed for the synthesis ofaryl ketones.1 There is growing interest in recent yearsin the synthesis of potential drug intermediates such asa-chloropropiophenones (2) as they can be readily re-arranged, either photochemically2 or by Lewis acids,3 to a-arylpropionic acids, a class of non-steroidal and anti-inammatory drugs.4 In our continuing eorts to providea practical route to Flurbiprofen, an important anti-inammatory agent, we required p-amino substituted a-chloropropiophenone (2) as the starting material.Accordingly, when acetanilide 1 (R = H) was subjected toFriedel¡ÓCrafts acylation with a-chloropropionyl chloridein the presence of 1.1 mol of anhyd.AlCl3, a polymericmaterial was obtained. However, when the AlCl3 employedwas catalytic (0.3 mol), the reaction proceeded exceedinglywell to aord the trans N-acylated product 3 instead of theexpected p-acylated one (2) (Scheme 1). In this context, it ispertinent to note that the only example of C-acylation ofacetanilides was reported some time ago.1trans N¡Óacylation, in which one amide function is directlyconverted into another, is an important reaction, ndingwidespread application both in amino sugars5 and in peni-cillin and cephalosporin derivatives.6 However, a fewmethods of trans N-acylation with either acids or anhydridesat high temperatures have been reported using highlyacidic catalysts such as triuoroacetic acid¡Ótriuoroaceticanhydride (TFAA),6 TFAA¡ÓDBN7 and AlCl3.8 The utilityof zeolites as ecient catalysts has been recently reportedby our group.9 In view of the synthetic applications of a-chloroanilides, particularly in the synthesis of agrochemicals(as herbicides),10 we wish to report a new catalytic methodfor the trans N-acylation of anilides with a-chloropropionylchloride, catalysed by AlCl3.The results are summarized in Table 1.Evidently, thescope and generality of the reaction is wide; even the NO2group has increased the substrate reactivity (entry f).Thelow yield of product formation in the case of cyclohexyl-acetamide is due to the formation of many unidentiedproducts.Mechanistically, it may be reasoned that the acyl cationMeCHClCO+ attacks the nitrogen of the amide preferen-tially to form the diacylated product 4, which in turn equili-brates with the acetanilide, leading to the formation of thetrans acylated product (Scheme 2). The overall low yieldmay be explained in terms of the reversible nature of thereaction.These results thus establish the synthetic utility of theprocess toward the synthesis of a variety of trans N-acylatedproducts in preparative yields in most of the examplesstudied. However, it may be mentioned that this method isunsatisfactory as far as aliphatic acetamides are concerned,e.g.cyclohexylacetamide (entry j).ExperimentalAll mps are uncorrected. IR spectra were recorded on a PerkinElmer Model 137E spectrometer. 1H and 13C NMR spectra (d inppm from TMS) were obtained on Varian 60 MHz, Varian FT/80A80MHz and Bruker FT 200MHz spectrometers.Mass spectra wererecorded on an automated Finnagan-MAT 1020C mass spectrometer.General Procedure.To a mixture of acetanilide (1.35 g, 10 mmol)and anhyd. AlCl3 (400 mg, 3 mmol) in dichloroethane (20 ml)was added slowly -chloropropionyl chloride (1.4 g, 11 mmol) in5¡Ó10 min. The mixture was boiled under reux for 16 h, cooled anddecomposed with cold water.The organic layer was separated,washed with NaHCO3 and H2O and dried over anhyd. Na2SO4.The crude product was puried by column chromatography.2-Chloro-N-phenylpropanamide (3a).Mp 82¡Ó83 8C; max/cm£¾1(Nujol) 3280, 1680 (CONH), 1620, 1560, 1460, 1210, 1090, 1010,850, 650; H (80 MHz, CDCl3) 1.88 (d, 3 H, CH3 J 8 Hz,), 4.5 (q, 1H, CHCl, J 7.5 Hz), 7.1¡Ó7.8 (m, 5 H, ArH); m/z 183 (M+, 5%), 148(3), 120 (100), 119 (65), 93 (85), 92 (84), 77 (19), 65 (8).2-Chloro-N-(2-methylphenyl)propanamide (3b).Mp 101¡Ó102 8C;max/cm£¾1 (Nujol) 3260, 1660 (CONH), 1620, 1550, 1460, 1370,1250, 1200, 1080, 1000, 760; H (80 MHz, CDCl3) 1.82 (d, 3 H, CH3J 8 Hz), 2.26 (s, 3 H, ArCH3), 4.55 (q, 1 H, CHCl, J 6 Hz), 6.93¡Ó7.33 (m, 3 H, ArH), 7.78 (dd, 1 H, ArH , J 2Hz each), 8.22 (br, 1H, NH); m/z 197 (M+, 4%), 134 (72), 133 (56), 107 (53), 106 (100),105 (54), 91 (27), 90 (26), 71 (13), 63 (2).2-Chloro-N-(2-uorophenyl)propanamide (3a).Mp 74¡Ó76 8C;max/cm£¾1 (Nujol) 3260, 1680, 1550, 1500, 1460, 1370, 1300, 1250,1000, 810, 770; H (80 MHz, CDCl3) 1.8 (d, 3 H, CH3, J 7.5 Hz), 4.5(q, 1 H, CHCl, J 8 Hz), 6.9¡Ó7.32 (m, 3 H, ArH), 8.25 (m, 1 H,ArH), 8.51 (br, 1 H, NH); C (200 MHz, CDCl3) 22.7, 56.2 (CH),J.Chem. Research (S),1998, 90¡Ó91$Scheme1Scheme 2$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).%NCL Communication No. 6213.*To whom the correspondence should be addressed.90 J. CHEM. RESEARCH (S), 1998115.0, 115.3, 121.8, 124.7, 124.8, 125.3, 150.4 (CF), 167.7 (CO); m/z 203 (M +2, 51%), 202 (M+1, 12), 201 (M+, 100), 138 (38), 111 (30), 109 (21), 90 (12), 83 (42), 63 (10). 2-Chloro-N-(2-chlorophenyl)propanamide (3d).�¢Mp 60¡¾62 8C; max/cm¢§1 (Nujol) 3260, 1670, 1600, 1540, 1450, 1200, 1060, 1000, 770; H (60 MHz, CDCl3) 1.88 (d, 3 H, CH3, J 8 Hz), 4.56 (q, 1 H, CHCl, J 8 Hz), 6.88¡¾7.44 (m, 3 H, ArH), 8.31 (d, 1 H, ArH, J 6 Hz), 8.88 (br, 1 H, NH); m/z 219 (M +2, 16%), 218 (M+ 1, 1), 217 (M+, 20); 184 (27), 182 (100), 154 (39), 146 (15), 129 (20), 127 (66), 126 (55), 99 (33), 90 (20), 63 (34). 2-Chloro-N-(2-bromophenyl)propanamide (3e).�¢mp 73¡¾76 8C; max/cm¢§1 (Nujol) 3260, 1675, 1600, 1550, 1450, 1050, 770; H (80 MHz, CDCl3) 1.88 (d, 3 H, CH3, J 7.5 Hz), 4.5 (q, 1 H, CHCl, J 6 Hz), 6.82¡¾7.56 (m, 3 H, ArH), 8.25 (dd, 1 H, ArH, J 2Hz each), 8.87 (br, 1 H, NH); m/z 263 (M+2, 7%), 261 (M+, 5), 200 (16), 198 (19), 184 (30), 182 (100), 173 (23), 172 (17), 171 (23), 170 (10), 146 (29), 119 (9), 90 (8). 2-Chloro-N-(2-nitrophenyl)propanamide (3f ).�¢Mp 68¡¾70 8C max/ cm¢§1 (Nujol) 3360, 1700, 1610, 1600, 1510, 1350, 810, 760; H (60 MHz, CDCl3) 1.76 (d, 3 H, CH3, J 8 Hz), 4.4 (q, 1 H, CHCl, J 7.5 Hz), 6.73¡¾8.0 (m, 4 H, ArH), 10.45 (br, 1 H, NH); m/z 230 (M+2, 15%), 229 (M +1, 5), 228 (M+, 46), 184 (31), 182 (100), 165 (47), 145 (23), 138 (76), 121 (41), 92 (29), 91 (36), 90 (29), 65 (25), 63 (50). 2-Chloro-N-(4-methoxyphenyl)propanamide (3g).�¢Mp 101¡¾ 102 8C; max/cm¢§1 (Nujol) 3280, 1670, 1560, 1520, 1400, 1260, 950, 850; H (60 MHz, CDCl3) 1.76 (d, 3 H, CH3, J 8 Hz), 3.75 (s, 3 H, OCH3), 4.43 (q, 1 H, CHCl, J 7 Hz), 6.75 (d, 2 H, ArH, J 10 Hz), 7.26 (d, 2 H, ArH, J 10 Hz); 8.0 (br, 1 H, NH); C (200 MHz, CDCl3) 22.6, 55.6, 56.1, 114.3, 122.2, 130.2, 157.2, 167.7; m/z 215 (M+2, 15%), 214 (M +1, 5), 213 (M+, 52), 178 (8), 150 (20), 123 (52), 122 (100), 108 (47), 95 (13), 63 (8). 2-Chloro-N-(4-chlorophenyl)propanamide (3h).�¢Mp 112¡¾114 8C; max/cm¢§1 (Nujol) 3220, 1650, 1580, 1520, 1480, 1385, 1220, 1180, 1080, 1060, 800, 820; H (80 MHz, CDCl3) 1.82 (d, 3 H, CH3, J 7.5 Hz), 4.5 (q, 1 H, CHCL, J 6 Hz), 7.25¡¾7.5 (AB quartet, 4 H, ArH, J 10 Hz), 8.25 (br, 1 H, NH); m/z 219 (M+ 2, 70%), 218 (M +1, 10), 217 (M+, 98), 182 (10), 156 (32), 154 (100), 129 (29), 127 (77), 126 (29), 99 (8). 2-Chloro-N-(4-bromophenyl)propanamide (3i).�¢Mp 122¡¾125 8C; max/cm&cenujol) 3230, 1675, 1600, 1550, 1500, 1410, 1310, 1250, 1200, 1085, 1020, 820; H (80 MHz, CDCl3) 1.81 (d, 3 H, CH3, J 7.5 Hz), 4.5 (q, 1 H, CHCl, J 6 Hz), 7.44 (s, 4 H, ArH), 8.25 (br, 1 H, NH); m/z 265 (M+ 4, 26%), 263 (M +2, 100), 261 (M+, 90), 200 (75), 198 (80), 173 (94), 172 (50), 171 (96), 170 (41), 147 (5). 2-Chloro-N-cyclohexylpropanamide (3j).�¢Mp 104 8C; max/cm¢§1 (Nujol) 3250, 1640, 1550, 1450, 1370; H (80 MHz, CDCl3) 1.25¡¾ 2.15 (m, 10 H, cyclohexyl CH2), 1.88 (d, 3 H, CH3, J 8 Hz), 3.81 (br, 1 H, CHNH), 4.5 (q, 1 H, CHCl, J 7 Hz), 6.56 (br, 1 H, NH).Received, 7th August 1997; Accepted, 24th October 1997 Paper E/7/05770I References 1 Friedel¡¾Crafts and Related Reactions, ed. G. A. Olah, Wiley¡¾ Interscience, New York, 1963, p. 65; H. Heaney in Comprehensive Organic Synthesis, ed. B. M. Trost and I. Fleming, Pergamon Press, New York, 1991, vol. 2, p. 733. 2 H. R. Sonawane, D. G. Kulkarni and N.R. Ayyangar, Tetrahedron Lett., 1990, 31, 7495. 3 C. Giordano, G. Castaldi, F. Casagrande and L. Abis, Tetrahedron Lett., 1982, 23, 1385; G. Giordano, G. Castaldi, F. Uggeri and F. Gurzoni, Synthesis, 1985, 436. 4 H. R. Sonawane, B. S. Nanjundiah, J. R. Ahuja and D. G. Kulkarni, Tetrahedron: Asymmetry, 1992, 3, 163; J. P. Rieu, A. Boucharle, H. Cousse and G. Mouzin, Tetrahedron, 1986, 42, 4095. 5 C. Erbing, K. Granath, L. Kenne and B. Lindberg, Carbohydr. Res., 1976, 47, C5. 6 A. G. M. Barrett, J. Chem. Soc., Perkin Trans. 1, 1979, 1629. 7 B. Nilsson and S. Svensson, Carbohydr. Res., 1978, 62, 377. 8 M. Michman, S. Patai and I. Shen¢çeld, J. Chem. Soc. C, 1967, 1337; M. Michman and D. Meider, J. Chem. Soc. Perkin Trans. 2, 1972, 300. 9 H. R. Sonawane, A. V. Pol, P. P. Moghe, A. Sudalai and S. S. Biswas, Tetrahedron Lett., 1994, 35, 8877. 10 K. Kobayashi and S. Yamagiwa, Jpn. Kokai Tokkyo Koho, 1990, JP 02,225,648 (Chem. Abstr., 1991; 114, 142 892p); T. Yoshimoto, K. Igarashi and Y. Takasawa, CHEMTECH, 1989, 19, 431; H. Yang, X. Li, Z. Zhang and M. Chang, Chem. Abstr., 1993, 119, 8873h. 11 G. Snatzke and M. M. El-Abadelah, Chem. Ber., 1973, 106, 2072. Table 1 AlCl3-catalysed trans N-acylation of anilides with a-chloropropionyl chloride Substrates Product (3) Mp(lit.c )11 No. (1) R yielda(%) ( 8C) a H 57c 82^83 (82) b 2-CH3 67 101^102 (101^102) c 2-F 32d 74^76 (74^76) d 2-Cl 33c,d 60^62 (62) e 2-Br 45 73^76 (73^76) f 2-NO2 60 68^70 (70) g 4-OMe 44c 101^102 (101^102) h 4-Cl 68 112^114 (112) i 4-Br 35 122^125 (124) j Cyclohexylacetamide 10 104 (105) aIsolated after column chromatographic purification; the rest is essentially unreacted anilide. b20%Yield obtained in the absence of catalyst. cEven with the use of 2molar equivalent of -chloropropionyl chloride, no significant improvement in yield was realised. dNo reaction took place in the absence of catalyst. J. CHEM. RESEARCH (S), 1998

ISSN:0308-2342    

DOI:10.1039/a705770i

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Reaction of Ethyl 7-Aminoindole-2-carboxylate with -Diketone and -Oxo Ester Compounds{ Mohamed El Ouar,a Nousedine Knouzia and Jack Hamelin*b aLaboratoire de Chimie Organique et Bioorganique, Faculte ¡§ des Sciences, B.P. 20, 24000, ElJadida, Morocco bSynthe �Ï se et Electrosynthe�Ï se Organiques 3, UMR 6510, Campus de Beaulieu, 35042, Rennes, France Reaction of ethyl 7-aminoindole-2-carboxylate has been investigated: 1H-pyrrolo[3,2-h]quinoline and 6-hydroxy-1H-pyrrolo- [3,2-h]quinoline derivatives are obtainedwith -diketones and -oxo esters, respectively.It has been reported recently that the reaction of 7-amino- indoles with acetylacetone gives 1H-pyrrolo[3,2-h]quino- lines,1 corresponding to a Combes synthesis.2 In this paper, we report the synthesis of 1H-pyrrolo- [3,2-h]quinoline and 6-hydroxy-1H-pyrrolo[3,2-h]quinoline derivatives (3) by condensation of ethyl 7-aminoindole-2- carboxylate (1) with b-diketones and b-oxo-esters, respect- ively.The starting material (1) was prepared from 7-nitroindole- 2-carboxylic acid, which was purchased from Janssen Chimica. Esteri¢çcation followed by catalytic hydrogenation on Pd¡¾charcoal gave the amino compound 1 in 71% yield.3 The reaction of the amine 1 with b-diketones (R1=Me, Ph, R2=Ph) in 1:1.2 ratio gave the crotonic derivatives 2 in the presence of catalytic amounts of toluene-p-sulfonic acid ( p-TSA) at 80 8C.4 The 1H NMR spectra exhibit a singlet at 5.83 (R1=Me) and 6.21 (R1=Ph) ppm for the vinylic protons. When the reaction temperature was raised to 220 8C, the quinolinic derivatives 3a,b were isolated as the major products together with minor amounts of 2a,b5 (Scheme 1).To prove that the indole nitrogen was not su.ciently nucleophilic to react with the carbonyl groups of crotonic and acrylic compounds, we carried out the Conrad¡¾ Limpach reaction6 of amine 1 with the appropriate b-oxo esters. Under acid catalysis at 80 8C, only anils 2 (R1=Me, Ph, R2=OEt) and 6,7,8,9-tetrahydro-1H-pyrrolo[3,2-h]- quinoline 4 (Scheme 2) were isolated.7 However, at 160 8C, 6-hydroxy-1H-pyrrolo[3,2-h]quinoline derivatives 3c¡¾e8¡¾10 (R1=Me, Ph, CF3, R2=OH) were obtained.The structural assignment of compounds 3 and 4 was based on IR, NMR and mass spectroscopic data. Experimental Mps are uncorrected and were measured with a Digital Melting Point Apparatus. IR spectra were recorded on a Perkin Elmer 1310 spectrophotometer, and NMR spectra with a Bruker AC 300 P (300MHz for 1H and 75MHz for 13C) spectrometer (shifts in ppm relative to TMS).Mass spectra were performed with a Varian Mat 311 spectrometer (C.R.M.P.O. Rennes). Reaction of Ethyl 7-Aminoindole-2-carboxylate (1) with -Di- ketones.�¢(a) A mixture of 1 (0.2 g), -diketone (1.17 mmol, 1.2 equivalents) and p-TSA 0.02 g) was heated to 80 8C for 90 min. After cooling the products were puri¢çed by chromatography on silica gel using CH2Cl2 as eluent to yield compound 2.Ethyl 7-[N-(1-methyl-3-oxo-3-phenylbut-1-enylamino]indole-2-car- boxylate (2a). Starting from benzoylacetone the reaction leads to 2a. Yield 60%; mp 160 8C (ether); max/cm¢§1 (KBr) 3240 (NH), 1710 (C=O ester), 1600 (C=O chelated); dH (CDCl3) 1.33 (t, 3 H, 3J 7.1 Hz), 1.77 (s, 3 H), 4.37 (q, 2 H, 3J 7.1 Hz), 5.83 (s, 1 H, vinyl) 7.96 and 7.42 (dd and m, 5 H, R2=Ph) 7.07 (dd, 1 H, Jo 7.5, Jm 1.0 Hz), 7.12 (t, 1 H, Jo 7.5 Hz), 7.29 (d, 1 H, J 2.0 Hz), 7.61 (dd, 1 H, Jo 7.5, Jm 1.0 Hz); m/z 348 (M+) (Found: 348.147. C21H20N2O3 requires 348.147).Ethyl 7-[N-(1,3-diphenyl-3-oxoprop-1-enyl)amino]indole-2-carboxy- late (2b). Starting from dibenzoylmethane the reaction leads to 2b. Yield 65%; mp= 179 8C (ether); max/cm¢§1 (KBr) 3200 (NH), 1720 (C=O ester), 1610 (C=O chelated). H (CDCl3) 1.41 (t, 3 H, J 7.2 Hz), 4.42 (q, 2 H, J 7.2 Hz), 6.21 (s, 1 H, vinyl), 6.55 (dd, 1 H, Jo 7.6, Jm 2.0 Hz), 6.84 (t, 1 H, Jo 7.6 Hz), 7.34¡¾8.01 (m, 12 H, R1, R2=Ph and H3, H4); m/z 410 (M+) (Found: 410.165.C6H22N2O3 requires 410.163). (b) A mixture of ethyl 7-aminoindole-2-carboxylate (1) (0.5 g), - diketone (2.45 mmol) and a catalytic amount of p-TSA (0.04 g) was heated to 220 8C for 90 min. After cooling, the reaction products were separated by chromatography on silica gel using dichloro- methane as eluent to yield compound 3 as the ¢çrst fraction. Ethyl 8-methyl-6-phenyl-1H-pyrrolo[3,2-h]quinoline-2-carboxylate 3a, starting from benzoyl acetone.Yield 38%; mp 151 8C (ether); max/cm¢§1 1670 (C=O ester); H (CDCl3) 1.40 (t, 3 H, 3J 7.1 Hz), 2.68 (s, 3 H), 4.40 (q, 2 H, 3J 7.1 Hz), 7.30 (s, 1 H) 7.48 (m, 4 H), 7.61 (dd, 1 H, Jo 7.5, Jm 1.0 Hz), 7.63 (d, 2 H, Jo 7.5 Hz), 8.15 (d, 1 H, Jo 7.4 Hz), 10.40 (broad s, NH); C (CDCl3) 14.43, 1958, 60.92, 109.70, 116.53, 119.30, 121.34, 124.82, 126.05, 126.91, 127.38, 128.70, 129.11, 133.64, 138.0, 139.47, 145.17, 155.28, 161.61; m/z 330 (M+) (Found: 330.137.C21H18N2O2 requires 330.137). Ethyl 6,8-diphenyl-1H-pyrrolo[3,2-h]quinoline-2-carboxylate 3b, starting from dibenzoymethane. Yield 34%; mp 114¡¾116 8C (ether); max/cm¢§1 (KBr) 1670 (C=O ester); H (CDCl3) 1.41 (t, 3 H, 3J 7.2 Hz), 4.42 (q, 2 H, 3J 7.1 Hz), 7.32 (s, 1 H), 7.50 (m, 9 H), 7.61 (d, 1 H, Jo 9.0 Hz), 7.79 (s, 1 H), 8.19 (d, 2 H, Jo 8.4 Hz), 10.70 (broad s, NH); C (CDCl3) 14.42, 61.0, 109.70, 118.38, 119.0, 121.72, 123.46, 126.21, 127.20, 127.50, 128.33, 128.53, 128.78, J.Chem. Research (S), 1998, 92¡¾93$ Scheme1 Reagents and conditions: i, R1COCH2COR2, p-TSA, 80 8C; ii, R1COCH2CO2Me, Et, p-TSA,160 8C Scheme 2 $This is a Short Paper as de¢çned in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1997, Issue 1]; there is there- fore no corresponding material in J. Chem. Research (M). *To receive any correspondence (e-mail: Jack.Hamelin@univ- rennes1.fr). 92 J. CHEM. RESEARCH (S), 1998129.28, 129.55, 133.45, 138.77, 138.84, 139.36, 149.53, 155.34,161.65; m/z 392 (M+) (Found: 392.150.C26H20N2O2 requires392.152).Reaction of Ethyl 7-Aminoindole-2-carboxylate (1) with -OxoEsters.A mixture of ethyl 7-aminoindole-2-carboxylate (1) (0.5 g),-oxo-ester (1.5 equiv., 3.7 mmol) and a catalytic amount of p-TSA(0.04 g) was heated at 160 8C for 1 h. After cooling, the precipitatewas ltered o and recrystallized from dimethylformamide.Ethyl 6-hydroxy-8-methyl-1H-pyrrolo[3,2-h]quinoline-2-carboxylate(3c), starting from ethyl acetoacetate.Yield 45%; mp 151¡Ó153 8C(DMF); max/cm£¾1 (KBr) 3200 (OH), 4.15 (q, 2 H, 3J 7.5 Hz), 6.71(s, 1 H), 7.09, (s, 1 H), 7.51 (d, 1 H, Jo 7.5 Hz), 7.57 (d, 1 H, Jo7.5 Hz); m/z 270 (M+) (Found: 270.100. C15H14N2O3 requires270.10.Ethyl 6-hydroxy-8-phenyl-1H-pyrrolo[3,2-h]quinoline-2-carboxylate(3d), starting from ethyl benzoylacetate. Yield 43%; mp 284 8C(DMF, dec.); max/cm£¾1 (KBr) 3200 (OH), 1700 (C=O); dH([2H6]DMSO/TFA) 1.04 (t, 3 H, 3J 7.4 Hz), 4.10 (q, 2 H, 3J 7.4 Hz),7.02 (m, 2 H), 7.26 (m, 3 H), 7.44 (m, 4 H); dC ([2H6]DMSO/TFA)14.27, 65.33, 106.23, 116.40, 125.34, 12602, 129.02, 130.80, 131.58,131.80, 132.25, 133.31, 134.74, 155.68, 165.12; m/z =332 (M+)(Found: 332.115.C20H16N2O3 requires 332.116).Ethyl 6-hydroxy-8-triuoromethyl-1H-pyrrolo[3,2-h]quinoline-2-car-boxylate (3e), starting from ethyl triuoromethylacetoacetate. Yield46%; mp 320¡Ó322 8C (DMF); max/cm£¾1 (KBr) 3300 (OH), 1710(C=O); dH ([2H6]DMSO/TFA) 1.12 (t, 3 H, 3J 7.5 Hz), 4.16 (q, 2 H,3J 7.4 Hz), 7.04 (s, 1 H), 7.10 (s, 1 H), 7.32 (d, 1 H, Jo 8.2 Hz), 7.44(d, 1 H, Jo 8.8 Hz), 10.53 (broad s, NH); m/z 324 (M+) (Found:324.073. C15H11N2O3F3 requires 324.072).Reaction of Ethyl 7-Aminoindole-2-carboxylate (1) with Ethyl Tri-uoromethylacetoacetate.A mixture of amine 1 (1.47 mmol), ethyltriuoromethylacetoacetate (1.5 equiv.) and a catalytic amount ofp-TSA (0.03 g) was heated at 80 8C for 1 h.After cooling, theprecipitate was ltered o and recrystallized from ethanol.Ethyl 8-hydroxy-8-triuoromethyl-6,7,8,9-tetrahydro-1H-pyrrolo-[3,2-h]quinolin-6-one-2-carboxylate (4).Yield 40%; mp 230 8C(EtOH); max/cm£¾1 (KBr) 3310 (NH), 1700 (C=O ester), 1630 (C=O); dH ([2H6]DMSO) 1.42 (t, 3 H, 3J 7.1 Hz), 3.03 and 3.14 (d,HA, HB, JAB 16.8 Hz), 4.39 (q, 2 H, 3J 7.2 Hz), 6.45 (broad s, OH),7.12 (s, 1 H), 7.36 (d, 1 H, Jo 8.5 Hz), 7.43 (d, 1 H, Jo 8.3 Hz),10.36 (broad s, NH), 11.45 (broad s, NH); dC ([2H6]DMSO) 14.37,60.86, 72.55, 108.00, 115.03, 116.25, 119.01, 123.81, 125.80, 129.0,129.37, 161.72, 167.71; m/z 342 (M+) (Found: 342.092.C15H13N2O4F3 requires 342.082).Received, 2nd July 1997; Accepted, 9th October 1997Paper E/7/07410GReferences1 M. El Ouar, N. Knouzi, A. El Kihel, E. M. Essassi, M.Benchidmi, J. Hamelin, R. Carrie and R. Danion-Bougot,Synth. Commun., 1995, 25, 1601.2 G. Jones, Chem. Heterocycl. Compd., 1977, 32, 93.3 K. Moustaid, Doctorat de l'Universite , Franche Comte , 1991.4 E. V. Brown, J. Org. Chem., 1965, 30, 1607.5 J. C. Perche, G. Saint-Ruf and N. P. Buu-Ho , J. Chem. Soc.,Perkin Trans. 1, 1972, 260.6 R. Madhav, R. Dufresne and P. Southwick, J. Heterocycl.Chem., 1973, 10, 225.7 C. F. Spencer, H. R. Snyder Jr. and R. J. Alaimo, J. Heterocycl.Chem., 1975, 12, 1319.8 S. Ichiwata and Y. Shiokawa, Chem. Pharm. Bull., 1969, 17,1153.9 S. Ichiwata and Y. Shiokawa, Chem. Pharm. Bull., 1969, 17,2455.10 A. Marcos, C. Pedregal and C. Avendan o, Tetrahedron, 1991,47, 7459.J. CHEM. RESEARCH (S), 1998 93

ISSN:0308-2342    

DOI:10.1039/a707410g

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Synthesis of 1,1-Diacetates from Aldehydes using Trimethylchlorosilane and Sodium Iodide as Catalyst{ Nabajyoti Deka, Ruli Borah, Dipok J. Kalita and Jadab C. Sarma* Regional Research Laboratory, Natural Products Chemistry Group, Organic Chemistry Division, Jorhat, 785006, Assam, India A variety of aldehydes react with acetic anhydride in the presence of trimethylchlorosilane and sodium iodide or trimethylchloro- silane alone to afford1,1-diacetates in excellent yields. Aldehydes may be protected as their 1,1-diacetates by a var- iety of methods. These diacetates are synthetically useful as protecting groups1 having stability towards aqueous acids as well as mild bases,2 and are useful as important building blocks for the synthesis of dienes for Diels�}Alder cyclo- addition reactions.3 Diacetates of some aldehydes are reported to be good cross-linking reagents for cellulose in cotton.4 One European patent claims the peroxygen com- pounds of the type 1,1,5-triacetoxypent-4-ene as activators in the composition of a bleaching mixture for wine stained fabrics.5 Kula has successfully demonstrated in his patent6 the utility of this protecting group in the synthesis of an intermediate for chrysenthemic acid.Recently, several reports have appeared on the synthesis of diacetates from aldehydes using di€erent catalysts.7 Some other methods employed for the preparation of 1,1-diace- tates from aldehydes include the use of protic acids,8 Lewis acids such as BF3,9 PCl3,10 FeCl3,2 etc.and the super acid NaRon-H.11 But in most cases, either a long reaction time (up to 120 h in the case of 2-furaldehyde with PCl3 10), or a low product yield (4% in the case of 4-nitrobenzaldehyde10) is incurred. Herein we wish to report a high yielding method for the preparation of 1,1-diacetates from aldehydes using TMCS�}NaI as catalyst. When an aldehyde was treated with acetic anhydride (1 ml of dry CHCl3 or CH3CN was added to solubilise, if needed) at room temp.[at 0�}5 8C in case of hydroxycitronel- lal (1)] in the presence of a catalytic amount of TMCS (20 mol%) and sodium iodide (20 mol%) it yielded the cor- responding diacetate in excellent yield (Table 1). The same reaction took longer to complete in TMCS alone (reaction in re�Puxing acetonitrile giving a comparable result). A blank reaction of aldehyde, acetic anhydride and sodium iodide failed to react even after 8 h of stirring at room temp.Because of its high yield and short reaction time at ambient temperature this method will better many existing ones.7,11 The catalyst is also easily available, cheap and easy to handle. Experimental Mps were determined on a Buchi capillary apparatus. IR spectra were recorded on a Perkin Elmer 237B IR spectrophotometer. NMR spectra were recorded on a Varian 360L instrument. Mass spectra were recorded on a INCOS 50 GC-MS instrument. General Procedure.DIn a typical reaction a mixture of 2 mmol of benzaldehyde was treated at room temp.with 4 mmol of acetic anhydride followed by 0.4 mmol of TMCS and 0.4 mmol of NaI. J. Chem. Research (S), 1998, 94�}95$ Table 1a Reaction Yield Mp (8C) Entry Substrate time (t/min) (%) found/reported 1 Benzaldehyde 25 87 45^46 (44^452) 2 4-Cl-C6 H4CHO 40 92 79^80 (79^807) 3 4-NO2 -C6H4CHO 40 96 125 (1257) 4 4-MeO-C6 H4CHO 50 96 67^68 (67^6810) 5 Furfural 60 70 55(52^547 ) 6 Butyraldehyde12 40 84 7 Cinnamaldehyde 30 70 85^86 (84^862) 8 Crotonaldehyde12 50 90 9 Gluteraldehydeb 10 Acrolein2 50 60 12 Hydroxycitronellalc 60 70 (2 + 3) aAll the compounds give satisfactory spectral analysis for IR, NMR (60MHz) and MS.Yields are of isolated pure products and mps are uncorrected. bNo reaction in 25% water solution. cThis reaction was carried out at 0^5 8C in 60min. The major products isolatedwere triacetate (2) (50% yield) and diacetate (3) (20% yield) along with a complex mixture ofminor products.$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. 94 J. CHEM. RESEARCH (S), 1998When the reaction was over (TLC monitoring) excess water was added and the product extracted with CH2Cl2. The organic layer was washed with a dilute solution of sodium thiosulfate followed by water, dried over anhydrous sodium sulfate and evaporated under reduced pressure.In most cases pure solid products were obtained. We are grateful to the DST, Government of India for ®nancial assistance (grant no. SP/SL/G-34/93) and to their Director for providing the necessary facilities. D.J.K. thanks CSIR, New Delhi for a fellowship. Thanks are also due to Dr N. C. Barua for helpful discussions. Received, 20th May 1997; Accepted, 13th October 1997 Paper E/7/03477F References 1 S. V. Leibermann and R.Connor, Org. Synth. Coll. Vol. III, 1955, 441. 2 K. S. Kochhar, B. S. Bal, R. P. Deshpande, S. N. Rajadhyaksha and H. W. Pinnick, J. Org. Chem., 1983, 48, 1765. 3 B. B. Snider and S. G. Amin, Synth. Commun., 1978, 8, 117. 4 J. G. Frick Jr. and R. J. Harper Jr., J. Appl. Polym. Sci., 1984, 29, 1433. 5 W. R. Sanderson, Eur. Pat. Appl., EP. 125, 781 (1984) (Chem. Abstr. 102, p64010k). 6 J. Kula, Pol. Pat. PL143, 824 (1988) (Chem. Abstr. 112, p216290y). 7 P. Kumar, V. R. Hegde and T. P. Kumar, Tetrahedron Lett. 1995, 36, 601; C. Pereira, B. Gigante, M. J. Marcelo-Curoto, H. Carreyre, G. Perot and M. Guisnet, Synthesis, 1995, 1077; B. P. Bandgar, N. P. Mahajan, D. P. Mulay, J. L. Thote and P. P. Wadgaonkar, J. Chem. Res. (S), 1995, 470. 8 M. J. Gregory, J. Chem. Soc. (B), 1970, 1201. 9 J. March, Advanced Organic Chemistry, Wiley Eastern, New Delhi, 3rd edn., 1986, p. 861. 10 J. K. Michie and J. A. Miller, Synthesis, 1981, 824. 11 G. Olah and A. K. Mehrotra, Synthesis, 1982, 962. 12 N. Deka, D. J. Kalita, R. Borah and J. C. Sarma, J. Org. Chem., 1997, 1563. J. CHEM. RESEARCH (S

ISSN:0308-2342    

DOI:10.1039/a703477f

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

EPR of Powder Copper Phthalocyaninate Substituted with Eight Tetraazamacrocycles and its Nonanuclear Ni2+, Co2+, Zn2+ and Cu2+ Complexes{ Fevzi Ko ¡ì ksal,a Fatih Ucun,a Erbil AgI ar*b and I . brahim Kartala aDepartment of Physics, Faculty of Arts and Sciences, OndokuzMayis University, Samsun,Turkey bDepartment of Chemistry, Faculty of Arts and Sciences, OndokuzMayis University, Samsun,Turkey Variations of the electron paramagnetic resonance parameters of the copper phthalocyaninates due to the paramagnetic and diamagnetic metal ions substituted into the outer cells of eight 12-membered tetraazamacrocycles are found to be very slight and this slight difference is attributed to the electronegativity of the substitutedmetal.Electron paramagnetic resonance (EPR) spectra of the copper phthalocyanine (CuPc) have been studied pre- viously.1¡¾3 However, so far, Cu2+ phthalocyaninate sub- stituted with eight 12-membered tetraazamacrocycles and its nonanuclear Ni2+, Co2+, Zn2+ and Cu2+ complexes have not been studied.It is the purpose of this study to investi- gate the EPR parameters of these complexes. The cells and the synthesis of the complexes shown in Fig. 1 are given in an earlier study.4 The energy level picture of the CuPc5 is shown in Fig. 2. According to this orbital picture, the unpaired electron of the Cu2+ ion of CuPc is in the antibonding dx2¢§y2 orbital. If a is the coe.cient of dx2¢§y2 in the antibonding orbital and l is the spin¡¾orbit coupling constant for a 3d electron, the Ak and A? components of the hyper¢çne structure constant are given as:5 Ak a P 4 7 a2 ¢§ Ogk ¢§ 2U ¢§ 3 7 Og? ¢§ 2U a K A? a P 2 7 a2 a 11 14 Og? ¢§ 2U ¢§ K O1U where K is the Fermi contact parameter describing the s-electron e€ect on the Cu nucleus and P =2bgNbNhr¢§3i is the dipolar hyper¢çne coupling parameter of the unpaired electron (P = 0.036 cm¢§1).In this study, assuming both Ak and A? are negative and assuming P = 0.036 cm¢§1 5,6 and the experimental gk, g? values, we obtained the K and a2 values from eqn.(1). Figure 3 shows the EPR spectrum of CuPc with eight 12-membered tetraazamacrocycles that are devoid of metal ions; the spectra in the presence of various paramagnetic and diamagnetic ions in the centres of the outer cells (Fig. 1) are similar to this. The upper spectrum is a simulation of the lower one. The spectra are axially symmetric and exhibit the nine superhyper¢çne structure lines from the four nearest N nuclei with an approximate intensity distribution of 1:4:10:16::19:16:10:4:1.The superhyper¢çne coupling con- stant of N is approximately 16 G. The CuPcCu8 sample gives only one EPR line, g= 2.146, without hyper¢çne and J. Chem. Research (S), 1998, 96¡¾97$ Fig. 1 NonanuclearM2+ complexes of copper phthalocyaninate substitutedwith eight tetraazamacrocycles Fig. 2 Bonding picture of CuPc $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. 96 J. CHEM. RESEARCH (S), 1998superhyper®ne lines and has a width of 0200 G. The line- width does not change very much with decreasing tempera- ture (down to 113 K) and should be the result of the dipolar and exchange interactions between the copper ions. Neimann and Kivelson7 have shown that even in the presence of only diamagnetic metal ions the Pc complexes exhibit a strong characteristic EPR line, which they attributed to a free radical.We have also observed this line for all of our samples and it is indicated with an arrow in Fig. 3. The g value of this line is g32.0037 and is in complete agreement with that of the literature.7 The EPR parameters were obtained by simulating the spectra with the Bruker Win-EPR program. The results for the various copper phthalocyaninates are given in Table 1.As seen from Table 1, the hyper®ne coupling (a) values decrease slightly as the substituted ion is varied, in the order f, Zn, Co and Ni. This order is the same as the electro- negativity order Cu (1.9) >Co3Ni (1.8) >jn (1.6) > f. The numbers in parentheses are the electronegativities of the elements.8 Therefore, it may be stated that the ions in the outer cells of the CuPcs in this study attract the central unpaired electron according to their electronegativity. Within the limits of the experimental errors, the values of g in Table 1 do not appear to vary.The calculated results of K and a2 values given in Table 2 seem to support the above conclusion since they decrease as the electronegativity increases, indicating an increase in the covalent character of the unpaired electron. Experimental The spectra were recorded at room temperature with a Varian E-109C model EPR spectrometer using 100 kHz modulation.The modulation amplitude was 0.6 G and the microwave power was around 2 mW. The low temperature measurements were made using a Varian temperature controller. The g factors were determined by comparison with a diphenylpicrylhydrazyl sample of g =2.0036. Received, 21st April 1997; Accepted, 22nd October 1997 Paper E/7/02705B References 1 E. M. Roberts and W. S. Koski, J. Am. Chem. Soc., 1961, 83, 1865. 2 M. Abkowitz, I. Chen and J. H. Sharp, J. Chem. Phys., 1967, 48, 4561. 3 S. E. Harrison and J. M. Assour, J. Chem. Phys., 1964, 40, 365. 4 E. Ag Ï ar, B. Bat , E. Erdem and M. O È zdemir, J. Chem. Res. (S), 1995, 16. 5 T. F. Gibson, D. J. E. Ingram and D. Scholand, Discuss. Faraday Soc., 1958, 26, 72. 6 J. M. Assour, J. Chem. Phys., 1965, 43, 2477. 7 R. Neimann and D. Kivelson, J. Chem. Phys., 1961, 35, 162. 8 L. Pauling, 1960, The Nature of the Chemical Bond, Cornell University Press. Table 1 The experimental EPR parameters of powder copper phthalocyaninate substitutedwith eight tetraazamacrocycles and its nonanuclear Zn2+, Co2+, Ni2+ and Cu2+ complexes (Dg = 0.002, Da = 0.4G) Acronym M' gk g? Ak/G A?/G g aG CuPc(f) f 2.154 2.052 212.0 17.0 2.086 82.0 CuPcZn8 Zn 2.152 2.053 209.3 16.8 2.086 81.0 CuPcCo8 Co 2.148 2.052 209.3 16.0 2.084 80.4 CuPcNi8 Ni 2.148 2.052 209.3 16.0 2.084 80.4 CuPcCu8 Cu ^ ^ ^ ^ 2.146 ^ Table 2 The calculated EPR parameters of powder copper phthalocyaninate substituted with eight tetraazamacrocycles and its nonanuclear Zn2+, Co2+ and Ni2+ complexes Complex K a2 CuPc(f) 0.314 0.797 CuPcZn8 0.311 0.785 CuPcCo8 0.308 0.781 CuPcNi8 0.308 0.781 Fig. 3 EPR spectrumof CuPcwith empty outer cells at room temperature; the upper spectrumis a simulation of the lower using the BrukerWin-EPR program J. CHEM. RESEARCH (S), 1998 97

ISSN:0308-2342    

DOI:10.1039/a702705b

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Redox Chemistry of [Fe2(CN)10]4£¾. Part 4.$ Reactionwith L-Cysteine%Floyd A. Beckford,a Deon Bennet,a Tara P. Dasgupta*a andGeoffrey StedmanbaDepartment of Chemistry, University of theWest Indies,Mona, Kingston 7, JamaicabChemistryDepartment, University ofWales Swansea, Singleton Park, Swansea SA2 8PP, UKL-Cysteine reduces [Fe2(CN)10]4£¾ to [Fe2(CN)10]6£¾ in a two stage process, a rapid reduction to [Fe2(CN)10]5£¾ followed by aslower second order reaction involving HSCH2CH(NH3+)CO2£¾ and a conjugate base.The binuclear FeIIIFeIII complex [Fe2(CN)10]4£¾ is a moderateoxidising agent with successive one electron reduction poten-tials1 (against NHE) of 0.55 and 0.36 V respectively.It is an inert, diamagnetic complex and reacts with manyreducing agents; with iodide reaction proceeds2 to theFeIIIFeII compound, but with ascorbic acid the additionalstage to form FeIIFeII has also been observed.3 When thereductant contains a nucleophilic sulfur centre as in S2O3 2£¾and (NH2)2CS then the binuclear complex may be cleavedand the iron(III) species [Fe(CN)5(Snuc)]n£¾ where n =4 forthiosulfate4 and n =2 for thiourea can be observed in theproducts.These species are readily recognised by a strongabsorption in the 550¡Ó650nm range, giving rise to a pro-nounced blue colour. The present paper describes a study ofthe reaction with L-cysteine, which is a powerful reducingagent (E 8=£¾ 0.34 V at pH 7) and also contains a nucleo-philic sulfur.Reaction was followed by monitoring the decrease inabsorbance at 560 nm, the wavelength of the visible maxi-mum for [Fe2(CN)10]4£¾.Preliminary work showed that therewere two steps, an initial fast reaction which was too rapidto follow under our conditions in which the [Fe2(CN)10]4£¾peak at 560nm disappeared and was replaced by the nearinfra-red peak of [Fe2(CN)10]5£¾ at 1200 nm. This was fol-lowed by a much slower process forming a pale yellow/green species with the spectrum5 of [Fe2(CN)10]6£¾.Thischange could readily be followed by stopped ow. The reac-tion was studied over the ranges 25¡Ó35 8C, pH 3.6¡Ó6.4.Individual runs for this second process gave good rst orderplots, yielding kobs/s£¾1 values that are directly proportionalto [L-cysteine] as shown in Table 1. The kobs values variedwith pH as shown in Table 2. At the higher acidities stu-died, pH 3.63¡Ó4.63, the change of kobs with pH is very slow,but at higher pH values the rate constant rises rapidly.Measurements made at 29.7 and 35 8C showed similar beha-viour.In view of the observations of Wilson et al.6 that traceamounts of copper catalyse the cysteine¡Ó[Fe(CN)6]3£¾ reac-tion we extended our original measurements to see if coppercatalysis is important here also.Wilson comments on thelack of reproducibility in earlier work on the ferricyanideoxidation of thiols, and inspection of the data in Table 1does show some scatter. We have analysed our reactants,buers and distilled water for copper by AAS and concludethat the copper concentration is less than 20 ppb (our esti-mated detection limit); this corresponds to 3.1510£¾7 moldm£¾3.In an attempt to complex copper (or other tracemetal ions) we added Na2[EDTAH2] over the concentrationrange 2¡Ó13010£¾7 mol dm£¾3, but did not observe any eecton kobs. Added copper (CuSO4) did produce a marked cata-lytic eect, plots of kobs vs. [Cu2+] being linear, with a welldened intercept on the [Cu2+]= 0 axis.Two other dier-ences from the work of Wilson et al. may be noted. For thereaction of [Fe(CN)6]3£¾ with cysteine pseudo second orderkinetics {w.r.t. [Fe(CN)6]3£¾} were observed whereas in ourcase all runs gave good rst order kinetics. Also for the[Fe(CN)6]3£¾ oxidations with cysteine, N-acetylcysteine and3-sulfanylpropionic acid Wilson found an apparent order in[thiol] that was greater than one.£¾dFeCN 3£¾ 6 =dtthiol ka kbthiol 1Our data in Table 1, though scattered, show no sign of anysystematic trend in kobs/[cysteine] with [cysteine].We con-clude that catalysis by adventitious copper has only a minoreect in our system, though with the addition of signicantamounts of copper there is undoubtedly some catalysis.Our oxidant, [Fe2(CN)10]4£¾, is a low spin, inert complex,and so we propose that the very fast initial reaction is dueto an outer sphere electron transfer to form [Fe2(CN)10]5£¾.This is followed by a slower outer sphere reaction to form[Fe2(CN)10]6£¾.The reduction potential for [Fe2(CN)10]4£¾is 0.55 V, considerably higher than the 0.36 V for[Fe2(CN)10]5£¾ thus providing much more driving force forthe rst reaction. While we conclude that there is little or noJ. Chem. Research (S),1998, 98¡Ó99$Table 1 Values of kobs for the reaction of L-cysteinewith[Fe2(CN)10]5£¾. [Fe2(CN)105£¾] = 1.710£¾4 mol dm£¾3; I = 1.0moldm£¾3(NaClO4); pH = 5.41 (acetate buffers); y = 30.0 8C103[Cysteine]/mol dm£¾3 kobs/s£¾1 kobs/[cysteine]10 3.21 3.2112 4.36 3.6314 4.59 3.2818 6.09 3.3822 7.18 3.0624 8.66 3.6126 9.46 3.64Table 2 Values of kobs for the reaction of L-cysteinewith[Fe2(CN)10]5£¾.[L-cysteine] = 0.020mol dm£¾3;[Fe2(CN)10]5£¾= 1.710£¾4 mol dm£¾3; I = 1.0mol dm£¾3 (NaClO4).y = 25 8CpH kobs/s£¾13.63 0.594.14 0.524.36 0.664.53 0.694.72 0.884.93 1.275.10 1.985.32 3.285.54 4.955.63 5.385.94 8.73$Part 3: see ref. 3.%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.98 J. CHEM. RESEARCH (S), 1998copper catalysis for the second reaction we cannot excludethe possibility that it may contribute to the rst reaction,though the fact that the rst reaction was still fast in thepresence of added edta argues against it. In the absenceof kinetic data we cannot go further in discussing the rstreaction.For the second reaction the variation in kobs with pHmust surely be due to the acid/base equilibria of L-cysteine.It has three ionisable groups, carboxyl (CO2H), amino(NH3) and sulfhydryl (SH).In aqueous solution L-cysteinecan exist in ve dierent forms depending on the pH of thesolution [eqns. (2)¡Ó(6)]. The values for the respective dis-sociation constants7 are pK1=2.0; pK2=8.53; pK3=8.86;pK4=10.36; pK5=10.03.HSCH2CHNH3CO2H£¾£¾* )£¾£¾K1HSCH2CHNH3CO2£¾ H 2HSCH2CHNH3CO2£¾£¾£¾* )£¾£¾K2 £¾SCH2CHNH3CO2£¾ H 3HSCH2CHNH3CO2£¾£¾£¾* )£¾£¾K3HSCH2CHNH2CO2£¾ H 4£¾SCH2CHNH3CO2£¾£¾£¾* )£¾£¾K4 £¾SCH2CHNH2CO2£¾ H 5HSCH2CHNH2CO2£¾£¾£¾* )£¾£¾K5 £¾SCH2CHNH2CO2£¾ H 6Over our pH range it is clear from the pKa values thatthe main component of cysteine, more than 98%, isHSCH2CH(NH3)CO2£¾ with only minor contributions fromother species.The fact that kobs is almost constant frompH 3.63 to 4.36 at 25 8C suggests that the bimolecular rateconstant for HSCH2CH(NH3)CO2£¾ must be close to 0.59/0.02= 29.5 mol£¾1 dm3 s£¾1 and that undissociated cysteinehas negligible reactivity under our experimental conditions.The increase in kobs with pH must be due to contributionsfrom conjugate base species.Scheme 1 shows the proposed mechanism, and fromthis rate law (7) may be written, where A, B and Care HSCH2CH(NH3+)CO2£¾, £¾SCH2CH(NH3)CO2£¾ andHSCH2CH(NH2)CO2£¾ respectively.Rate k1A k2B k3CFe2CN105£¾ 7Now in our pH range [A] =[cys]T[H+]/([H+] + K2+K3),[B]= [cys]TK2/([H+] + K2+K3) and [C] =[cys]TK3/([H+] + K2+K3) where [cys]T is the total, stoichiometricconcentration of L-cysteine.On substituting into eqn. (7)and rearranging eqn. (8) was obtained.kobsH K2 K3=cysT k1H k2K2 k3K3 8When eqn. (8) is plotted using the data in Table 2 astraight line plot is obtained, and least squares analysisyields k1=27.020.9 mol£¾1 dm3 s£¾1 and 104(kK2+k3K3) =4.421.5 s£¾1. Treatment of the data by non-linear regressionanalysis yields 26.821.0 and 4.521.0 respectively. As theconcentrations of the tautomeric species B and C mustalways be in the constant ratio K2/K3 we cannot obtain sep-arate values for k2 and k3 except by some ad hoc postulatesuch as assuming that one of the tautomers is very muchmore reactive than the other.Thus if k2wk3 then k2 is1.5105 mol£¾1 dm3 s£¾1 at 25 8C. It should be noted thatalthough we have assigned k1 to HSCH2CH(NH3+)CO2£¾there must also be a small concentration of the tautomer£¾SCH2CH(NH3+)CO2H. From the fact that the pKa valuesfor CO2H and SH dissociation dier by some 6.5 log unitssuggests the concentration of this tautomer may be some106.5 times smaller than the main carbohydrate ionisedtautomer.However this would still give a bimolecular rateconstant well below the encounter limit. A similar argumentapplies to HSCH2(NH2)CO2H. Further analysis of the datais not justied. With other reductants that contain a nucleo-philic sulfur centre reaction with [Fe2(CN)10]4£¾ can give riseto coloured pentacyanoferrate(III) complexes with a sixthligand bound to iron through sulfur.We do not see thiswith L-cysteine, possibly because over our pH range the sulf-hydryl group is only slightly ionised, and reduction to[Fe2(CN)10]6£¾ is faster than nucleophilic substitution.ExperimentalMaterials.The complex, [Fe2(CN)10]4£¾, was prepared asdescribed previously.4 Solutions had max 560nm and concen-trations were calculated using = 1600 M£¾1 cm£¾1.L-cysteine hydro-chloride was supplied by Aldrich Chemical Co., USA and usedwithout further purication.Kinetic Studies.Reactions were followed by stopped-ow spec-trophotometry using a Hi-Tech Scientic SF-51 stopped-owattached to a Hi-Tech Scientic SU-40 spectrophotometer unit. Themachine was attached to a Haake GH constant temperature waterbath tted with a Haake D8 circulating pump. The pH was variedusing acetate and disodium hydrogen orthophosphate¡Ócitric acidbuers, the pH being measured with an Orion Research ExpandableIon Analyzer EA 920 tted with a Cole-Parmer combination elec-trode.Ionic strength was maintained at 1.0 mol dm£¾3 usingNaClO4. In all cases, the reaction was investigated under pseudorst order conditions with [cysteine]r[complex].Analysis for Copper.This was carried out using a Perkin Elmer2380 AAS instrument, calibrated with standard copper sulfate sol-ution. A good Beer Lambert Law plot was obtained up to 10 ppmof copper. All reagents including reactants, buers and distilledwater were checked and found to contain less than 20 ppb, ourdetection limit.This work was supported by the Board of PostgraduateStudies, University of the West Indies through scholarshipsto F.A.B. and D.B. We thank a referee for valuablecomments.Received, 15th September 1997; Accepted, 22nd October 1997Paper E/7/06692IReferences1 A. D. James, W. C. E. Higginson and R. S. Murray, J. Chem.Res., 1977, (S) 85; (M) 1084.2 G. Stedman, M. E. Pena and J. R. Leis, Transition Met. Chem,1992, 17, 123.3 F. A. Beckford, T. P. Dasgupta and G. Stedman, J. Chem. Soc.,Dalton Trans., 1995, 2561.4 T. P. Dasgupta, F. A. Beckford and G. Stedman, J. Chem. Soc.,Dalton Trans, 1993, 3605.5 G. Emschwiller and C. K. Jrgensen, Chem. Phys. Lett., 1979, 5,561.6 G. J. Bridgart, M. W. Fuller and I. R. Wilson, J. Chem. Soc.,Dalton Trans., 1973, 1274.7 R. E. Benesch and R. Benesch, J. Am. Chem. Soc., 1955, 77,5877.Fe2(CN)104¡V + cysteineFe2(CN)105¡V + AFe2(CN)105¡V + BFe2(CN)105¡V + C2A+¡E (or B+¡E or C+¡E)Fe2(CN)105¡V + cysteine+¡EFe2(CN)106¡V + A+¡EFe2(CN)106¡V + B+¡EFe2(CN)106¡V + C+¡Ecystinefastk1k2k3Scheme1J. CHEM. RESEARCH (S), 1998 99

ISSN:0308-2342    

DOI:10.1039/a706692i

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Oxidation of Benzylic and Secondary Alcohols to Carbonyl Compounds by NaBrO3^NH4Cl Reagent in Aqueous Acetonitrile$ Ahmad Shaabani* and Majid Ameri Chemistry Department, Shahid BeheshtiUniversity, P.O. Box19396-4716,Tehran, Iran NaBrO3 combined with NH4Cl is found to be an efficient reagent for the conversion, in aqueous acetonitrile and under mild conditions, of benzylic and secondary alcohols into aldehydes and ketones, respectively. The oxidation of alcohols to carbonyl compounds is a fundamental transformation of organic chemistry which is attracting much current interest.1¡¾4 A great number of oxidizing agents can e€ect the conversion of alcohols into carbonyl compounds, and synthetic chemists are faced with an wide choice of methods for this reaction.However, the susceptibility of aldehydes to further oxidation narrows the choice of reagents for the oxidation of primary alcohols to aldehydes in good yield, and if the alcohol group is part of a complex molecule that is sensitive to acidic or basic reagents then the choice of e€ective oxidants is narrowed still further. The discovery of new oxidants for the trans- formation of alcohols to carbonyl compounds under mild conditions with a variety of alcohols is of prime importance in synthetic organic chemistry.Oxidations of alcohols by NaBrO3 in the presence of cerium(IV) ammonium nitrate (CAN),5 bromine,6 NaHSO3,7 HBr,8 H2SO4,9 HClO4 10 and HOAc,11 have been reported, most of the reactions having occurred in relatively strong acidic solutions.We report here the oxidation of benzylic and secondary alcohols with NaBrO3¡¾NH4Cl into the corresponding aldehydes and ketones. We have found that this method of oxidation is very con- venient for the conversion of alcohols into carbonyl com- pounds because of its simplicity and use of mild reaction conditions. Furthermore, NH4Cl and NaBrO3 are both cheap and easily available compared to most other oxidizing agents that have so far been employed.As shown in Table 1, a wide variety of secondary alcohols and some benzylic alcohols could be easily oxidized to the corresponding carbonyl compounds. However, other primary alcohols (Table 1, entries 3¡¾5) were recovered practically unchanged. In order to obtain some information about the reaction pathway, cyclohexanol was allowed to react with (a) NaBrO3¡¾NH4OAc [5 mmol NaBrO3 and 7 mmol NH4OAc in 10 ml solvent mixture (acetonitrile¡¾water 7:3)] and (b) NaBrO3 (5 mmol NaBrO3 in 10 ml same solvent mixture) in the absence of NH4Cl.Neither NaBrO3¡¾NH4OAc nor bromate ion alone was capable of oxidizing cyclohexanol. This fact excludes the possibility of the alcohols being oxidized with just BrO¢§3 ion and also when bromate ion exists in the presence of NH+4 ion in a solution which does not have any acidic property (the pH of 5 mmol NaBrO3 and 7 mmol NH4OAc in 3ml of H2O is 7.20). However, in a solution in which both bromate and NH+4 ions co-exist, NH+4 ion hydrolysis gives an acidic solution (the pH of 5 mmol NaBrO3 and 7 mmol NH4Cl in 3ml of H2O is 4.00) while the BrO¢§3 ions are capable of oxidizing the alcohols.In order to illustrate the role of NH4Cl in providing an acidic solution, we performed experiments in various bu€er solutions in the absence of chloride ion. Thus we repeated the oxidation of cyclohexanol in HOAc¡¾NaOAc (7 ml CH3CN+3 ml bu€er solution with pH =4.62), potassium hydrogen phthalate (7 ml CH3CN+ 3 ml bu€er solution with pH = 3.99) and NaH2PO4 (7 ml CH3CN+ 3 ml bu€er solution with pH= 3.86). No reaction occurred in any of these experiments after 3 h at 80 8C.These experiments showed that the reaction is not only pH-dependent, but also requires the de¢çnite presence of Cl¢§ from NH4Cl in order to proceed. The chloride ion mentioned above is suggested to generate bromine and chlorine via the following reaction:12 2BrO¢§3 a 2X¢§ a 12Ha4Br2 a X2 a 6H2O X a Cl; Br and can in turn oxidize alcohols.13 We have found that Br2 is generated after ca. 2.5 h when NaBrO3 (5 mmol) is added to a solution of NH4Cl (7 mmol, in 7ml CH3CN +3 ml H2O) at room temperature. Also, a of NH4Br¡¾NaBrO3 mixture was observed to release bromine and we suggest that this system could be a good candidate for the oxidation of alcohols or as a bromi- nating agent of alkenes. In conclusion, NaBrO3¡¾NH4Cl is an excellent oxidizing agent which promises to be economical with high yields, employs simple and mild reaction conditions, and is thus a convenient reagent for selective oxidation of secondary and benzylic alcohols. Experimental All products are known compounds and were identi¢çed by com- parison of their physical and spectral data with those of authentic samples.Melting points were determined in open capillaries using an oil-bath and are uncorrected. IR spectra were recorded as neat ¢çlms or as KBr pellets on a Shimadzu 470 spectrometer. 1H NMR spectra were recorded at 90MHz on a JEOL EX-90 instrument with CDCl3 as solvent and Me4Si as an internal standard. pH Measurements were carried out with a Schott CG model 825 pH meter equipped with a combined glass¡¾calomel electrode; all the pH measurements were performed in aqueous solution. All alcohols are commercial materials and were purchased from Fluka, Aldrich or Merck. Reagent-quality solvents were used without further puri¢çcation. Yields reported refer to isolated products or 2,4-di- nitrophenylhydrazone derivatives (2,4-DNP)14,15 of the carbonyl compounds.General Procedure.�¢Alcohol (5 mmol) was added to a mixture of NaBrO3 (0.755 g, 5 mmol) and NH4Cl (0.4 g, 7.5 mmol) in aqueous acetonitrile (CH3CN¡¾H2O= 7/3 v/v; 10 ml). The mixture was stirred at 80 8C for 1¡¾3 h. When the reaction was complete, the resulting solution was extracted with methylene dichloride (20 ml2). The combined organic layers were washed with a satu- rated aqueous solution of NaHCO3 and dried over MgSO4.After ¢çltration, the solution was concentrated to a€ord the crude carbo- nyl compound, which was frequently of good purity without further treatment, although, if necessary, it could be puri¢çed by distillation, crystallization or chromatography, as appropriate. Financial support by the Research Council of Shahid Beheshti University is gratefully acknowledged. J. Chem. Research (S), 1998, 100¡¾101$ $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. 100 J. CHEM. RESEARCH (S), 1998Received, 10th March 1997; Accepted, 28th October 1997 Paper E/7/01647F References 1 R. C. Larock, Comprehensive Organic Transformation, VCH, Weinheim, 1989. 2 M. Hudlicky, Oxidation in Organic Chemistry (ACS Monograph 186), American Chemical Society, Washington, DC, 1990. 3 A. H. Haines, Methods for Oxidation of Organic Compounds: Alcohols, Alcohol Derivatives, Alkyl Halides, Nitroalkanes, Alkyl Azides, Carbonyl Compounds, Hydroxy Arenes and Aminoarenes, Academic Press, London, 1988. 4 I. Yavari and A. Shaabani, J. Chem. Res. (S), 1994, 274. 5 (a) T-L. Ho, Synthesis., 1978, 936; (b) H. Tomidca, K. Oshima and H. Nozaki, Tetrahedron Lett., 1982, 23, 539. 6 L. Farkas and O. Schachter, J. Am. Chem.Soc., 1949, 71, 2827. 7 K. Takase, H. Masuda, O. Kaf, Y. Nishiyama, S. Sakaguchi and Y. Ishii, Chem. Lett., 1995, 871. 8 S. Kajigaeshi, T. Nakayama, N. Nagasaki, H. Yamasaki and S. Fujisaki, Bull. Chem. Soc. Jpn., 1986, 59, 747. 9 G. Hoist, Kgl. Fysiogrof. Sallskap. Lund, 1940, 10, 63 (Chem. Abstr., 1941, 35, 78089). 10 A. C. Chatterji and S. K. Roy, Z. Phys. Chem. (Leipzig) 1972, 250, 137 (Chem. Abstr., 1972, 77, 139201z). 11 Vijayalaxmi and E. V. Sundaram, J. Indian Chem. Soc., 1978, 55, 567. 12 N. N. Greenwood and A. Earnshaw, Chemistry of the Elements., Pergamon Press, Oxford, 1984, p. 1012. 13 For an excellent riew of the oxidizing power of bromine in aqueous solution, see: J. Palou, Chem. Soc. Rev., 1994, 357. 14 R. M. Roberts, J. C. Gilbert, L. B. Rodwald and A. S. Wingrove, Modern Experimental Organic Chemistry, Saunders, Philadelphia, 4th edn., 1985, pp. 700±701. 15 J. Zhang, R. L. Hertzler and E. J. Eisenbraun, J. Chem. Educ., 1992, 69, 1037. 16 W. J. Criddle and G. P. Ellis, Spectral and Chemical Characterization of Organic Compounds: A Laboratory Handbook, Wiley, Chichester, 3rd edn., 1990. 17 R. L. Wear, J. Am. Chem. Soc., 1951, 73, 2390. 18 Aldrich Catalogue/Handbook of Fine Chemicals, 1994±1995. Table 1 Oxidation of alcohols to carbonyl compounds by NaBrO3^NH4Cl in acetonitrile^water (7:3 v/v) at 80 8C Reaction Yield (%) Bp of carbonyl product at Mp of carbonyl Mp of Entry Reactant Product time (t/h) 2,4-DNP Isolated 760 Torr (T/ 8C) product (T/ 8C) 2,4-DNP (T/ 8C) 1 CH3 CH2CH2CH(OH)CH3 CH3CH2CH2COCH3 3.0 75 80 102 (100^101a) ö 142 (144b) 2 (CH3 )2CHCH(OH)CH3 (CH3)2CHCOCH3 3.30 90 88 94 (94^95a) ö 120 (117b) 3 2.30 50 49 ö ö 118 (118.5^119.5c) 4 Octan-1-ol No reaction 6.0 5 Hexan-1-ol No reaction 6.0 6 Cyclopentanol Cyclopentanone 1.0 90 85 127^139 (131a) ö 144 (142b) 7 Cyclooctanol Cyclooctanone 3.0 90 83 185^193 (195a) ö 162 (163b) 8 Cyclohexanol Cyclohexanone 2.0 90 91 150^155 (155a) ö 160^161 (162b) 9d 4-tert-Butylcyclohexanol 4-tert-Butylcyclohexanone 3.0 70 72 ö 48^49(47^50c) 10d 2-tert-Butylcyclohexanol 2-tert-Butylcyclohexanone 3.0 50 53 62f 11g 4.0 80 81 202^203 (207a) ö 146 (146b) 12 PhCH2OH PhCHO 2.0 86 80 175 (179a) ö 230 (237b) 13 PhCH(OH)Me PhCOMe 2.0 95 88 199^201 (202a) ö 240 (250b) 14 4-O2NC6H4CH2OH 4-O2NC6H4CHO 2.0 80 78 ö 104^105 (106b) 315 dec (320 decb) 15h 1.0 60 62 ö 93^95 (94^96e) 125 (125^126j) 16j 1.0 60 61 ö 93^95 (94^96e) ö 17 Me3COH No reaction 19k Cyclohexanol No reaction aFrom ref. 16 at 760 Torr (1101080 Pa). bFromref. 16. cFrom ref. 17. dcis and trans isomers. eFromref. 18. fAt 5 Torr (1665 Pa)(lit.,15 62.5, 4 Torr1532 Pa). g(¡)-Menthol. h(+)-endo-Norborneol. iFromref. 4. j(+)-exo-Norborneol. kIn the absence of NH4Cl. J. CHEM. RESEARCH (S), 1998 101

ISSN:0308-2342    

DOI:10.1039/a701647f

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Reactivity of Some Unsaturated 17-Oxo Steroids under Conditions of Diimide Reduction{ Ljubinka Lorenc,a Lidija Bondarenko-Gheorghiub and Mihailo Lj. Mihailovic � *a aFaculty of Chemistry, University of Belgrade, Studentski trg12^16, P.O. Box158,YU-11001, Belgrade, Yugoslavia bCenter for Chemistry, ICTM, P.O. Box 815,YU-11001, Belgrade,Yugoslavia The olefinic double bond in 17-oxo steroids 1, 5 and 7 is either reduced with diimide very slowly (compound 1) or it cannot be reduced at all (compounds 5 and 7), thus enabling hydrazine (accumulated by disproportionation of the diimide) to react with their respective17-oxo groups to give hydrazones 3, 6 and 8.It is known that the diimide reduction of a carbon±carbon multiple bond can be selectively carried out in the presence of a variety of reactive functional groups,1 including allylic halides,2,3 ethers,2 amines,2 disul®des,4 unsaturated ketones,2,5 peroxides6,7 and some other functions.1 A limi- tation of the use of diimide as a reducing agent is the com- petition between hydrogenation of the carbon±carbon multiple bond and disproportionation,1,8 i.e., hydrogenation of the diimide nitrogen±nitrogen double bond by another diimide molecule to form nitrogen and hydrazine (Scheme 1). Which of these processes will prevail depends on the relative rate at which diimide reacts with the unsaturated substrate.If the rate of reduction is su�ciently slower than the rate of disproportionation of diimide, the latter reaction will dominate and no reduction will be accomplished.For these particular cases it was anticipated1 that if the substrate contains any other functional group capable of reacting with hydrazine, reaction at that function with hydrazine formed by diimide disproportionation would occur. In this paper we report on the diimide reactions of some unsaturated 17-oxo steroids, i.e., 17-oxo-5,8a-epidioxy-5a- androst-6-en-3b-yl acetate (1), 17-oxoandrost-5-en-3b-yl acetate (5) and 17-oxo-7-norandrost-5-en-3b-yl acetate (7) (Schemes 2 and 3), which illustrate the reactivity of such substrates.When the 17-oxo epidioxide 1 was treated with an excess of diimide, generated in situ from dipotassium azodicarboxy- late and acetic acid (for details see Experimental section), it gave, after column chromatography on SiO2 (Scheme 2), the expected saturated 17-oxo epidioxide 2 in only 16% yield, the major reaction product being a Z±E mixture of the cor- responding hydrazone 3 (isolated in 58% yield).The 17-oxo compound 2 was identi®ed by comparison with an authentic sample,7 while the structure 3 was deduced as follows. In product 3 the original ole®nic D6-double bond (1H NMR: AB quartet centred at d 6.42) and the ®ve-membered-ring 17-oxo group (IR: absorption at 1748 cm¡1) were missing, indicating that both these functions had participated in the diimide reaction. In accordance with the proposed structure, the IR spectrum of 3 contained new absorptions at 3450 and 1661 cm¡1 assignable to the hydrazone NH2 group and C1N bond, respectively, while its 1H NMR spectrum, con- taining parts of two singlets for the CH3-18 group (at d 0.92 and 0.98), indicated that this product consisted of the Z and E stereoisomers. In an attempt to purify the hydrazone 3 by recrystal- lization from an acetone±methanol mixture, it was spontaneously transformed to the corresponding isopropyli- denehydrazono derivative 4.This compound was obtained in only one, Z or E, stereoisomeric form, and its identi®- cation based on elemental microanalysis (C24H36N2O4) and spectral characteristics (see Experimental section) con®rmed the hydrazone structure 3. On the other hand, when the D5-unsaturated androstene and B-norandrostene derivatives 5 and 7, respectively, were subjected to the diimide reaction as above, they gave (Scheme 3) the D5-unsaturated hydrazones 6 and 8, respect- ively, in quantitative yield.Signals for the ole®nic HC(6) protons in the 1H NMR spectra of 6 and 8 (at d 5.39 for the former and at d 5.44 for the latter compound) clearly indicated that the D5-double bond in both substrates remained unattacked by the diimide molecule.9 Other spec- tral data were also in full agreement with the structures 6 and 8, respectively. These results have unequivocally con®rmed the validity of the above mentioned assumption. Since the ole®nic double bond in the investigated 17-oxo steroids is either reduced with diimide very slowly (compound 1) or it cannot be reduced at all (compounds 5 and 7), reaction of their J.Chem. Research (S), 1998, 102±103$ Scheme 1 O AcO O O 1 HN NH O AcO O O 2 (~16%) N AcO O O 4 one isomer acetone NNH2 AcO O O Z and E isomer 3 (~58%) N C Me Me •• •• + Scheme 2 $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. 102 J. CHEM. RESEARCH (S), 1998respective 17-oxo groups with hydrazine (accumulated by diimide disproportionation) is the main process. Experimental Mps are uncorrected. IR spectra were recorded on a Perkin- Elmer 337 spectrometer and NMR spectra on a Varian Gemini 2000 spectrometer (1H at 200 MHz, 13C at 50MHz) in CDCl3 solution at room temperature, using SiMe4 as internal standard (d in ppm, J in Hz).Mass spectra were measured on a Finnigan- MAT 8230 spectrometer at 70 eV. Column chromatography was carried out on silica gel 0.063¡¾0.200mm. TLC (control of reactions and separation of products) was performed on silica gel G (Stahl) (detection with 50% aqueous H2SO4). 17-Oxo-5,8 -epidioxy-5 -androst-6-en-3 -yl Acetate (1)11.�¢Mp 239¡¾240 8C (from acetone¡¾methanol); [ ]D=+ 66.0 (c, 0.50 in CHCl3); max/cm¢§1 (KBr) 1748, 1735, 1248; H 0.93 (3 H, s, H-18), 1.00 (3 H, s, H-19), 2.03 (3 H, s, OCOCH3), 5.00 (1 H, m, H-3), 6.32, 6.52 (2 H, AB, J 8.6 Hz, H-6, H-7) (Found: C, 69.75: H, 7.79.C21H28O5 requires C, 69.98; H, 7.83%). Diimide Reduction of 17-Oxo-5,8 -epidioxy-5 -androst-6-en-3 -yl Acetate (1).�¢To a stirred solution of 1 (1.08 g, 3 mmol) in CH2Cl2 (50 ml) and absolute MeOH (70 ml) dipotassium azodicarboxylate (5 g, 13.5 mmol) was added and the suspension cooled in an ice- bath. To this mixture was added dropwise a solution of AcOH (3 ml) in absolute MeOH (30 ml) within ca. 1 h. Stirring was continued at room temperature for an additional 20 h, when the yellow colour disappeared. The mixture was taken up in water (250 ml) and extracted twice with CH2Cl2, the combined organic extract was washed with saturated aq. NaHCO3 solution and water, dried (Na2SO4) and evaporated and the residue (01.2 g) was chromatographed on SiO2 (50 g). Elution with toluene¡¾EtOAc 9:1 and 8:2 a€orded 5,8 -epidioxy-17-oxo-5 -androstan-3 -yl acetate (2) (182 mg, 16.1%), mp (141 8C), IR and 1H NMR identical with those of an authentic sample.7 Toluene¡¾EtOAc 2:8 and EtOAc eluted a mixture of (Z)- and (E)- hydrazone 3 (655 mg, 58.1%): max/cm¢§1 (KBr) 3450, 1733, 1661, 1252; dH 0.92, 0.98 (3 H, parts of two s, H-18 of Z and E isomers), 1.03 (3 H, s, H-19), 2.00 (3 H, s, OCOCH3), 4.81 (1 H, m, H-3).Upon recrystallization from acetone¡¾methanol, hydrazone 3 a€orded 5,8a-epidioxy-17-isopropylidenehydrazono-5a-androstan-3b- yl acetate 4 (384 mg), mp 205 8C; max/cm¢§1 (KBr) 1742, 1670, 1254; dH 0.98 (3 H, s, H-18), 1.04 (3 H, s, H-19), 1.81, 1.99 [6 H, 2 s, N=C(CH3)2],, 2.00 (3 H, s, OCOCH3), 4.82 (1 H, m, H-3); dC 17.3 (q, C-18), 17.5 (q, C-19), 18.0 (q, CH3C=N), 19.3 (t, C-11), 20.9 (t, C-2), 21.0 (q, OCOCH3), 21.5 (t, C-15), 24.7 (q, CH3C=N), 25.7 (t, C-1), 26.4 (t, C-6), 27.9 (t, C-16), 33.5 (t, C-4) 35.4 (t, C-7), 35.5 (s, C-10), 36.0 (t, C-12), 44.8 (s, C-13), 51.7 (s, C-9), 51.9 (d, C-14), 69.4 (d, C-3), 78.5 (s, C-8), 80.4 (s, C-5), 159.3 [s, N=C(CH3)2], 169.7 (s, OCOCH3), 173.2 (s, C-17); m/z 416 (M+) (Found: C, 68.83; H, 8.50; N, 7.11. C24H36N2O4 requires C, 69.20; H, 8.71; N, 7.44%).Diimide Reaction of 17-Oxoandro3 -yl Acetate (5).�¢To a stirred solution of 5 (200 mg, 0.6 mmol) in CH2Cl2 (10 ml) and absolute MeOH (15 ml) dipotassium azodicarboxylate (1.0 g, 2.7 mmol) was added and the suspension cooled in an ice-bath. To this mixture was added dropwise a solution of AcOH (0.6 ml) in MeOH (6 ml) within ca. 30 min and stirring was continued overnight at room temperature.Work-up as above a€orded a crystalline solid (220 mg) which was chromatographed on SiO2 (12 g). Elution with EtOAc gave a mixture of (Z)- and (E)- hydrazones 6 (167 mg, 80.1%), mp 275¡¾276 8C (decomp.); max/ cm¢§1 (KBr) 3344, 1733, 1669, 1250; H 0.87, 0.92 (3 H, parts of two s, H-18 of Z and E isomers), 1.05 (3 H, s, H-19), 2.04 (3 H, s, OCOCH3), 4.61 (1 H, m, H-3), 5.39 (1 H, d, J 5.0 Hz, H-6); C 16.4, 16.6 (q, C-18), 19.2 (q, C-19), 20.5 (t, C-11), 21.3 (q, OCOCH3), 23.2, 23.3 (t, C-15), 24.3 (t, C-2) 27.6 (t, C-7), 31.2 (d, C-8), 31.2 (t, C-12), 33.7, 33.9 (t, C-16), 36.6 (t, C-1), 36.8 (s, C-10), 38.0 (t, C-4), 43.7, 43.9 (s, C-13), 50.2 (d, C-9), 53.5, 53.8 (d, C-14), 73.7 (d, C-3), 122.0 (d, C-6), 139.8 (s, C-5), 170.5 (s, OCOCH3), 165.9 173.6 (s, C-17); m/z 344 (M+).Diimide Reaction of 17-Oxo-7-norandrost-5-en-3 -yl Acetate (7).�¢ A stirred ice-cooled suspension of 7 (200 mg, 0.63 mmol) and potassium azodicarboxylate (1.0 g, 2.7 mmol) in CH2Cl2 (10 ml) and MeOH (15 ml) was treated with a solution of AcOH (0.6 ml) and MeOH (15 ml) as above.The mixture was left overnight at room temperature and worked up as above. The residue (210 mg) was puri¢çed by column chromatography on SiO2 (12 g). Toluene¡¾ EtOAc (6:4 and 1:1) eluted the hydrazone 8 (201 mg, 96.2%), mp 224¡¾225 8C (decomp.); max/cm¢§1 3445, 1733, 1662, 1245; H 0.92 (3 H, s, H-18), 0.93 (3 H, s, H-19), 2.04 (3 H, s, OCOCH3), 4.64 (1 H, m, H-3), 5.44 (1 H, br, s, H-6); C 14.4 (q, C-18), 17.1 (q, C-19), 20.5 (t, C-11), 21.3 (q, OCOCH3), 23.5 (t, C-15), 27.8 (t, C-2), 29.6 (t, C-12), 32.7 (t, C-4), 34.1 (t, C-16), 36.7 (t, C-1), 44.7 (d, C-14), 45.6 (s, C-10), 45.7 (s, C-13), 51.3 (d, C-8), 62.5 (d, C-9), 73.5 (d, C-3), 125.1 (d, C-6), 148.5 (s, C-5), 170.4 (s, OCOCH3), 173.1 (s, C-17); m/z 330 (M+).We thank the Serbian Academy of Sciences and Arts and the Ministry of Sciences and Technology of Serbia for ¢çnan- cial support. Received, 9th September 1997; Accepted, 31st October 1997 Paper E/7/06570A References 1 D. J. Pasto, Reduction of C1C and C2C by Noncatalytic Chemical Methods in Comprehensive Organic Synthesis, ed. B. M. Trost and I. Fleming, Pergamon, Oxford, 1991, vol. 8, p. 471. 2 E. E. van Tamelen, M. Davis and M. F. Deem, Chem. Commun., 1965, 71. 3 S. Uemura, A. Onoe, H. Okazaki, M. Okano and K. Ichikawa, Bull. Chem. Soc. Jpn., 1976, 49, 1437. 4 E. E. van Tamelen, R. S. Dewey, M. F. Lease and W. H. Pirkle, J. Am. Chem. Soc., 1961, 83, 4302. 5 G. Dauben and C. H. Schallhorn, J. Am. Chem. Soc., 1971, 93, 2254. 6 W. Adam and H. J. Eggelte, J. Org. Chem., 1977, 42, 3987. 7 Lj. Lorenc, L. Bondarenko, V. PavlovicA , H. Fuhrer, G. Rihs, J. Kalvoda and M. Lj. MihailovicA , Helv. Chim. Acta, 1989, 72, 608. 8 R. Tang, M. L. McKee and D. M. Stanbury, J. Am. Chem. Soc., 1995, 117, 8967. 9 A successful diimide reduction of the ole¢çnic double bond in some 5-B-nor-steroids has been recently reported,10 using toluene-p-sulfonyl hydrazide in collidine at 150 8C. 10 A. Kasal, H. Chodounska and W. J. Szczepek, Tetrahedron Lett., 1996, 37, 6221. 11 L. Bondarenko-Gheorghiu, Ph.D. Thesis, University of Belgrade, 1986. Scheme 3 J. CHEM. RESEARCH (S), 1998

ISSN:0308-2342    

DOI:10.1039/a706570a

出版商:RSC    

年代:1998

数据来源: RSC