摘要:

X O– O R X O O R X O O– R – A B C (X = O, NMe) X OH O R X O R X O R O O OH OH ClCH2CHO i 2a–d 3 H 8-Me 6-Me H OOO NMe 1.5 3.5 3.0 5.0 73 75 70 60 R X Time ( t/h) Yield (%) 2a 2b 2c 2d 1 + X O R O 4a–d X = O X = NMe 4a–c 4d 2a–d i X O O – R + H C Cl O H OH X O O R H OH Cl OH – 5 2 A X = O, NMe 244 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 244–245 J. Chem. Research (M), 1997, 1701–1707 Regioselective Synthesis of Furo[3,2-c][1]benzopyran-4-one and Furo[3,2-c]quinolin-4-one Krishna C.Majumdar* and Trijit Bhattacharyya Department of Chemistry, University of Kalyani, Kalyani-741 235, W.B. India 4-Hydroxycoumarins and 4-hydroxy-1-methyl-2-quinolone react with chloroacetaldehyde in the presence of aqueous potassium carbonate to give 3-hydroxy-2,3-dihydrofuro derivatives (60–75%) which on treatment with aqueous hydrochloric acid provide furo[3,2-c]coumarins and the hitherto unreported 5-methylfuro[3,2-c]quinolin-4-one in nearly quantitative yields.Recently we have reported1 a simple route to the regioselective synthesis of 2-alkylfuro[3,2-c][1]benzopyran-4-ones and 2-alkylfuro[3,2-c]quinolin-3-ones. This prompted us to undertake a study to synthesise furo[3,2-c][1]benzopyran- 4-ones and furo[3,2-c]quinolin-4-ones devoid of any substitution on the furan ring from the reaction of 4-hydroxycoumarins and 4-hydroxyquinolones, respectively, with chloroacetaldehyde. The results are reported here. The compound 1 in the presence of a base may exist as an ambident anion (canonical forms A, B and C).It is widely known to undergo O-alkylation1–3 under classical (acetone– K2CO3) conditions and partial C-alkylation4 in phase-transfer- catalysed reactions with hydroxide base. Thus initially it was a reasonable expectation that we would obtain product 2 through O-alkylation and cyclisation and/or product 3 through C-alkylation and cyclisation. To this end, 4- hydroxycoumarin (1a) in water was treated with chloroacetaldehyde in the presence of potassium carbonate at room temperature for 1.5 h.A white solid was obtained in 73% yield which was characterised as 3-hydroxy-2,3-dihydrofuro[ 3,2-c][1]benzopyran-4-one (2a). Other substrates 1b–d were similarly treated to give the products 2b-d in 60–75% yields. Products 2a–c were then treated with hydrochloric acid (1 M) to provide the furo[3,2-c][1]benzopyran-4-ones 4a–c in almost quantitative yields (Scheme 2). It was necessary to use 6 M hydrochloric acid in the case of 2d to convert it (in 96% yield) into the product furo[3,2-c]quinolin-4-one 4d.The formation of products 2 from 1 may easily be explained by the reversible nucleophilic addition of a coumarin- 4-olate anion to the carbonyl group of chloroacetaldehyde to give an intermediate 5 (not isolated) followed by base-catalysed intramolecular cyclisation leading to products 2 (Scheme 3). It may be noted that the nucleophilic addition to the carbonyl group of the chloroacetaldehyde is facilitated by the electron-withdrawing inductive effect of the chlorine, and that in water the equilibrium is strongly in favour of the hydrate.This methodology failed when reactions were attempted with substrates such as 3-hydroxycoumarin, 3-hydroxy-2-quinolone and 7-hydroxycoumarin. Perhaps the reversible nucleophilic addition step from 1 to 5 is important. In the case of 3-hydroxycoumarin and 3-hydroxy-2-quinolone, the equilibrium is perhaps not in favour of the intermediate and thus cyclisation is precluded.Furo[3,2-c][1]benzopyran-4-one (4a) has been prepared6 earlier from the reaction of 4-hydroxycoumarin and malic acid in four steps. Furo[3,2-c][1]benzopyran-4-one and furo[3,2-c]quinoline-4-one derivatives obtained from the thermal rearrangement always carry a substituent at the furan ring (2-position). Thus the present procedure provides a simple method for the regioselective synthesis of furo[3,2-c][1]benzopyran-4-one and furo[3,2-c]quinolin-4- one devoid of any substitution on the furan ring.We thank the CSIR (New Delhi) for financial assistance and the UGC (New Delhi) for providing a junior research fellowship (to T. B.). We also thank one of the referees for helpful suggestions. Techniques used: UV, IR, 1H and 13C NMR, mass spectrometry, elemental analysis, TLC, column chromatography *To receive any correspondence (e-mail: kcm@klyuniv.ernet.in). Scheme 1 Reagents and conditions: i, K2CO3–H2O, room temperature Scheme 2 Reagents and conditions: i, HCl–H2O, heat Scheme 3J. CHEM.RESEARCH (S), 1997 245 References: 7 Received, 5th November 1996; Accepted, 14th April 1997 Paper E/6/07538J References cited in this synopsis 1 K. C. Majumdar, A. T. Khan and D. P. Das, Synth. Commun., 1989, 19, 917; K. C. Majundar and P. K. Chowudhury, Heterocycles, 1991, 32, 73. 2 V. N. Dholakia and K. N. Trivedi, J. Indian Chem. Soc., 1971, 48, 344; Y. A. Shaikh and K. N. Trivedi, Curr. Sci., 1969, 17, 409; R. R. Shah and K. N. Trivedi, Indian J. Chem., 1979, 17B, 395; V. K. Ahluwalia, M. C. Gupta and S. Mehta, Indian J. Chem., 1979, 17B, 395; A. Patra, A. K. Mukhopadhyay and A. K. Mitra, Indian J. Chem., 1979, 17, 638; A. K. Mitra, A. K. Mukhopadhyay, S. K. Misra and A. Patra, Indian J. Chem., 1982, 21, 834. 3 K. C. Majumdar, A. T. Khan and R. N. De, Synth. Commun., 1988, 18, 1589; K. C. Majumdar, D. P. Das and A. T. Khan, Synth. Commun., 1988, 18, 2027. 4 K. C. Majumdar, A. T. Khan and S. K. Chattopadhyay, Indian J. Chem., 1990, 29B, 483; K. C. Majumdar, A. T. Khan and S. K. Chattopadhyay, Heterocycles, 1989, 29, 1573; J. Reisch and A. Bethe, Arch. Pharm. (Weinheim), 1987, 320, 737 (Chem. Abstr., 1988, 108, 55862). 6 V. N. Dholakia and K. N. Trivedi, Chem. Ind. (London), 1966, 4, 160.

ISSN:0308-2342    

DOI:10.1039/a607538j

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

OMe OMe MeO MeO NH 1 2 3 4 5 6 7 8 9 10 11 Isopavine NMe2 Amitriptyline R R R R CH2 + CH2OH R CH2CH2 CH2OH R a R = H b R = Bu t 13 Nafion-H benzene reflux for 2 h a R = H (40%) b R = Bu t (28%) 5 a R = H (46%) b R = Bu t (66%) 16 CH2Cl R CH2CH2 CH2Cl R a R = H b R = Bu t 14 TiCl4 benzene 0 °C for 1 h a R = H (95%) b R = Bu t (95%) 16 R R + CH2 O H B –H+ –HCHO 5 CH2 R CH2CH2 CH2OH R + +H+ –H2O 13 A 246 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 246–247 J. Chem. Research (M), 1997, 1708–1735 Selective Preparation of Polycyclic Aromatic Hydrocarbons.Part 7.1 A Preparative Route to 10,11-Dihydro- 5H-dibenzo[a,d]cycloheptenes using Friedel–Crafts Intramolecular Cyclobenzylation Takehiko Yamato,*a Naozumi Sakaue,a Masayasu Kominea and Yoshiaki Naganob aDepartment of Applied Chemistry, Faculty of Science and Engineering, Saga University, Honjo-machi 1, Saga 840, Japan bTohwa Institute for Science, Tohwa University, 1-1 Chikushigaoka, Minami-ku, Fukuoka 815, Japan A convenient, mild, one-pot synthesis of substituted dibenzo[a,d]cycloheptenes involving the action of ClCH2OMe and TiCl4 on a variety of diphenylethanes,† which incorporates chloromethylation of a hydrocarbon followed by a Friedel– Crafts intramolecular cyclization reaction, is described.A large number of natural alkaloids which possess a dibenzo[ a,d]cycloheptene ring system, such as isopavine2 and thalisopavine,3 have shown potent and varied biological activity.4 In addition, there are many active antidepressant agents containing a tricyclic aromatic structure, the most well known being amitriptyline.5 The very potent antidepressant amitriptyline is generally prepared by several different routes5 from the basic structure dibenzocycloheptadienone, which is available in three steps from phthalic anhydride and phenylacetic acid.6 However, compounds with significant modifications in both aromatic rings are rare.7 Therefore, there is substantial interest in the facile construction of tricyclic aromatic hydrocarbons, dibenzo[a,d]cycloheptenes. Although the preparation of key intermediates for these compounds, dibenzo[a,d]cycloheptene derivatives, has been described by several workers, there are few reports of synthetic approaches to construct the above basic structures via Friedel–Crafts intramolecular cycloalkylation.7 The most familiar routes involve intramolecular Friedel–Crafts acylations, 8 Wittig reactions9 and pyrolysis of 7,12-dihydro-5H-dibenzo[ c, f ]thiocine 6,6-dioxide.10 Recently we reported11 the first success in the formation of a fluorene skeleton via Friedel–Crafts intramolecular benzylation during the action of ClCH2OMe and TiCl4 on the highly activated biphenyls, which are constructed such that the electrophilic substitution occurs ortho to the biphenyl linkage.This strategy is proposed to be employed for the preparation of dibenzo[a,d]cycloheptene derivatives.We describe here a highly efficient and mild one-pot procedure for the preparation of dibenzo[a,d]cycloheptenes from diphenylethanes by a direct chloromethylation reaction using chloromethyl methyl ether, which incorporates chloromethylation of a hydrocarbon followed by a Friedel–Crafts intramolecular cyclization. The attempted cyclobenzylation of 2,2p-bis(hydroxymethyl) diphenylethanes 13a under benzene refluxing for 2 h in the presence of 30 mass% of Nafion-H13 (a solid per- fluorinated sulfonic acid resin) led to the desired cyclobenzylation and gave a mixture of 10,11-dihydro-5H-dibenzo[ a,d]cycloheptene 5a and 1-benzyl-10,11-dihydro- 5H-dibenzo[a,d]cycloheptene 16a in 40 and 46% yields, respectively.A similar result was obtained in the reaction of the tert-butyl analogue 13b with benzene under the same conditions. Products 5 and 16 were isolated by simple column chromatography of the reaction residue. It seems reasonable to assume that the ipso-intramolecular cyclobenzylation by the cationic intermediate A occurs at the 2p-position of the other benzene ring to form intermediate B from which elimination of the hydroxymethyl group as a formaldehyde affords 10,11-dihydro-5H-dibenzo[a,d]cycloheptene 5.Interestingly, treatment of the bis(chloromethyl) derivatives 14a and 14b with benzene in the presence of TiCl4 exclusively afforded the 1-benzylated dibenzocycloheptenes 16a and 16b. The formation of the 10,11-dihydro-5H-di- *To receive any correspondence. †Throughout this paper, ‘diphenylethane’ refers to the 1,2-isomer.But But R R c R = Br d R = OMe 19 R But CH2CH2 R But b R = Br R = OMe ClCH2OMe TiCl4 0 °C for 0.5 h 11 18 But CH2CH2 But 2 Me But CH2CH2 Me But 17 Me OMe Me MeO Me Me 21 OMe OMe MeO MeO 25 But But ClH2C CH2Cl 19b But But Me Me 19a Me OMe Me MeO CH2Cl CH2Cl Me Me 26 OMe OMe MeO MeO 27 J.CHEM. RESEARCH (S), 1997 247 benzo[a,d]cycloheptenes 5a or 5b was not observed.This result seems to suggest that the ipso-attack at the hydroxymethyl group might be more favourable than that at the chloromethyl group. Thus, the presently developed intramolecular cyclobenzylation reaction of 2-chloromethyldiphenylethanes 14 to afford the dibenzo[a,d]cycloheptenes 16 should be useful for the preparation of various dibenzo[a,d]cycloheptene derivatives under chloromethylation conditions. In fact, when 4,4p-di-tert-butyldiphenylethane 2 was treated with 2.2 equiv. of ClCH2OMe in methylene dichloride in the presence of TiCl4 at 0°C for 0.5 h, a mixture of 3,7-di-tertbutyl- 10,11-dihydro-5H-dibenzo[a,d]cycloheptene 5b and the further chloromethylated compound, 3,7-di-tert-butyl- 1,9 - b i s ( c h l o r o m e t h y l ) - 10,11 - d i h y d r o - 5 H- d i b e n z o [a,d] - c y c l o - heptene 19b was obtained along with recovery of the starting compound. However, when 4,4p-di-tert-butyldiphenylethane 2 was treated with 7 equiv. of ClCH2OMe under the same reaction conditions, compound 19b was obtained as prisms in 97% yield.It was also found that treatment of 4,4p-di-tertbutyl- 2,2p-dimethyldiphenylethane 17 with TiCl4 in CH2Cl2 with ClCH2OMe under the same conditions as described above afforded 3,7 - di - tert - butyl - 1,9 - dimethyl - 10,11 - dihydro - 5H-dibenzo[a,d]cycloheptene 19a in 85% yield. An attempted reaction of 2,2p-dibromo-4,4p-di-tert-butyldiphenylethane 11b with ClCH2OMe under the same conditions as compound 17 to afford the corresponding 10,11-dihydro-5H-dibenzo[a,d]cycloheptene failed.Only the starting compound 11b was recovered in quantitative yield. The intramolecular cyclobenzylation reaction to form the cycloheptene skeleton can be attributed to the highly activated character of the aryl ring. It is notable that further chloromethylation at positions 2, 4, 6 and 8 of the dibenzo[ a,d]cycloheptene ring was found to be disturbed by the steric hindrance of the tert-butyl groups at positions 3 and 7. Unfortunately, in the case of 4,4p-di-tert-butyl-2,2p-dimethoxydiphenylethane 18, the desired dibenzo[a,d]cycloheptene 19d was not obtained.Only a large amount of resinous material and unidentified compounds were obtained. In order to study the present novel cyclobenzylation affording the dibenzo[a,d]cycloheptene skeleton in more detail, we attempted to prepare the methoxy-substituted diphenylethanes 21 and 25 and react these with ClCH2OMe under the same conditions as described above.Thus, when 21 and 25 were treated with ClCH2OMe in methylene dichloride in the presence of TiCl4 at 0 °C for 0.5 h, the desired dibenzo[ a,d]cycloheptenes 26 and 27 were obtained in 89 and 93% yields, respectively. Dibenzo[a,d]cycloheptene 27 is a precursor for isopavine. In conclusion, the method described herein employing chloromethylation of diphenylethanes offers a convenient, mild one-pot synthesis of substituted dibenzo[a,d]cycloheptenes. We are now developing this present method for the preparation of substituted dibenzo[a,d]cycloheptenes.These results will open up new preparative aspects for polycyclic aromatic hydrocarbon chemistry. Further studies on the Friedel–Crafts intramolecular cyclization reaction are now in progress. Techniques used: IR, 1H NMR, MS, gas chromatography, elemental analysis References: 18 Schemes: 7 Tables: 2 Received, 17th March 1997; Accepted, 15th April 1997 Paper E/7/01863K References cited in this synopsis 1 Part 6, T.Yamato, M. Fujimoto, Y. Nagano, A. Miyazawa and M. Tashiro, Org. Prep. Proced. Int., 1997, 29, 321. 2 S. F. Dyke, Rodd’s Chemistry of Carbon Compounds, ed. S. Coffey, Elsevier, New York, 1978, vol. 4H, p. 1. 3 S. M. Kupchan and A. Yoshitake, J. Org. Chem., 1969, 34, 1062. 4 (a) W. B. Lacefield, J. Med. Chem., 1971, 14, 82. 5 (a) R. D. Hoffsommer, D. Taub and N. L. Wendler, J. Org. Chem., 1962, 27, 4134. 6 A. C. Cope and S. W. Fenton, J. Am. Chem. Soc., 1951, 73, 1673. 7 (b) E. J. Michael and J. M. Steven, J. Am. Chem. Soc., 1981, 103, 1984. 8 (a) W. Treib and H. J. Klinkhammer, Chem. Ber., 1951, 84, 671. 9 H. J. Bestmann, R. Hartle and H. Haberlein, Liebigs Ann. Chem., 1968, 718, 33. 10 M. Tashiro and T. Yamato, Synthesis, 1978, 214. 11 (a) T. Yamato, K. Komine, N. Sakaue, T. Matsuda, Y. Nagano and M. Tashiro, J. Chem. Res. (S), 1993, 146; (b) T. Yamato, M. Komine and K. Matsuo, J. Chem. Res., 1977, (S) 82; (M) 0584. 13 (b) T. Yamato, J. Synth. Org. Chem. Jpn., 1995, 53, 487 and references cited therein. Table Chloromethylation of substituted diphenylethanes with ClCH2OMe in the presence of TiCl4 a Substrate Product Yield (%)b 97 85 89 93 aReaction temperature, 0 °C; reaction time, 30 min; ClCH2OMe: diphenylethanes, 7 mol molµ1; TiCl4:diphenylmethane, 6 mol molµ1. bIsolated yields are shown.

ISSN:0308-2342    

DOI:10.1039/a701863k

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

O R R¢O a R = Ph, R¢ = COPh b R = Me, R¢ = COPh c R = OEt, R¢ = COPh d R = OEt, R¢ = Me 1 Br R¢O O R¢O Br CHO i O R R¢O Br a R¢ = COPh b R¢ = Me 2 a R¢ = COPh b R¢ = Me 3 (38%) (34%) ii (55–78%) O OEt PhCO2 Br 1c O OEt PhCO2 5 (62%) Pd–C, H2 MeOH–C6H6 O PhCO2 Br 1a PhCO2 Br OCOPh Br O O 6a (Pyrex: yield 55%) (Quartz: yield 22%) hn 248 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 248–249 J. Chem. Research (M), 1997, 1736–1750 Synthesis and Photochemical Behaviour of 3-(Estran-16-yl)acrylates and 2-(Estran-16-yl)vinyl Ketones† Thies Thiemann,*a‡ Carolin Thiemann,a Shinya Sasaki,b Volkmar Vill,c Shuntaro Matakaa and Masashi Tashiro*a aInstitute of Advanced Material Study, Kyushu University, 6-1, Kasuga-koh-en, Kasuga-shi, Fukuoka 816, Japan bGraduate School of Engineering Sciences, Kyushu University, Kasuga-koh-en, Kasuga-shi, Fukuoka 816, Japan cInstitut f�ur Organische Chemie, Universit�at Hamburg, Martin-Luther-King Platz 6, D-20146 Hamburg, Germany C-16-substituted steroids having an unsaturation in the side chain have been synthesized by sequential Arnold–Vilsmeier and Wittig reactions, subsequent photochemical studies showing the formation of either a dimeric structure or the occurrence of E/Z-isomerization; for one example, treatment with H2 over Pd–C led to full reduction of the side-chain and ring D.Steroids play an important role in biological membranes.2 In close relationship to this role is their ability to show liquid crystalline (LC) behaviour.C-17-alkyl-substituted steroids, e.g.cholesterol, have found numerous applications in LC studies.4 However, C-16-alkyl-substituted analogues have not been as widely studied. In the course of our interest in the potential liquid crystalline behaviour of C-16-substituted steroids, we have prepared a number of estrone compounds 1a–d as precursors, containing an unsaturated side-chain at C-16. Introduction of the side chain at C-16 was achieved in a straightforward two-step preparation.Arnold–Vilsmeier reaction6 of 2 furnished the 17-bromo-16-formylestrone 3, Wittig reaction of which with stabilized phosphoranes 4 gave 1a–d. Benzoic acid was used as catalyst (Scheme 1). In an exemplary reduction, the 17-bromo-16,19-diene 1c was fully hydrogenated to 5 (Scheme 2). In the photoirradiation of 1a the dimeric compound 6a is formed (Scheme 3). *To receive any correspondence. †Dedicated to Professor Dr. Andr�e Campos Neves on the occasion of his 70th birthday.‡Present address: Universit�e Libre de Bruxelles, Facult�e des Sciences Appliqu�ees, Chimie G�enerale et Carbochimie, Av. F. D. Roosevelt 50, CP 165, B-1050 Bruxelles, Belgium. Scheme 1 Reagents: i, PBr3, DMF, CHCl3; ii, Ph3P�C(CO)R (4), PhCO2H, C6H6, 80 °C Scheme 2 Scheme 3J. CHEM. RESEARCH (S), 1997 249 Techniques used: 1H, 13C, IR and UV spectroscopy References: 22 Schemes: 4 Received, 2nd January 1997; Accepted, 14th April 1997 Paper E/7/00031F References cited in this synopsis 2 Cf. A. Makriyannis, D.-P. Yang and T. Mavromoustakos, The Molecular Features of Membrane Perturbation by Anaesthetic Steroids, in Steroids and Neuronal Activity, Ciba Foundation Symposium 153, Wiley, Chichester 1990, p. 172 and references cited therein. 4 (a) D. Demus, H. Demus and H. Zaschke, Fl�ussige Kristalle in Tabellen II, Deutscher Verlag f�ur Grundstoffindustrie, Leipzig, 1982; (b) H. Falk and P. Laggner, �O . Chem. Z., 1988, 9, 251. 6 (a) Z. Arnold and A. Holy, Collect. Czech. Chem. Co

ISSN:0308-2342    

DOI:10.1039/a700031f

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

R1 O R2 O N S N H2N H2N N N N S N R1 R2 N N R1 R2 NH2 NH2 + 4a–f 3a–f 2a–f 1 a R1 = R2 = H; b R1 = Me, R2 = H; c R1 = R2 = Me; d R1= Ph, R2 =H; e R1 = Ph, R2 = Me; f R1 = R2 = Ph 250 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 250–251† Studies on Pyrazines. Part 33.1 Synthesis of 2,3-Diaminopyrazines via [1,2,5]Thiadiazolo- [3,4-b]pyrazines† Nobuhiro Sato* and Hajime Mizuno Department of Chemistry, Yokohama City University, Yokohama 236, Japan The syntheses of [1,2,5]thiadiazolo[3,4-b]pyrazine (3) and its methyl and/or phenyl derivatives as well as their reduction to 2,3-diaminopyrazines 4 are described. The cleavage of fused pyrazines represents a useful method for the synthesis of substituted pyrazines.2 We have previously reported the synthesis of 2,3-diaminopyrazines via hydrogenolysis of furazano[3,4-b]pyrazines which were prepared by the condensation of 3,4-diaminofurazan with a-dicarbonyl compounds.3 Unfortunately, this methodology was limited to the synthesis of diaminopyrazines having at least one phenyl group, namely the diaminofurazan underwent condensation with neither glyoxal, methylglyoxal nor butane-2,3-dione.In contrast, 3,4-diamino-1,2,5-thiadiazole4 (1) was converted into a variety of [1,2,5]thiadiazolo[3,4- b]pyrazines 3 including the parent and dimethyl derivatives, 4–6 which would be expected to form similarly 2,3-diaminopyrazines 4 by reductive desulfurization. We report here the synthesis of the thiadiazolopyrazines 3 and their successful reduction to diaminopyrazines 4.The diaminothiazole 1 was conveniently prepared by the hydrolysis of [1,2,5]thiadiazolo[3,4-c][1,2,5]thiadiazole with ammonium hydroxide, in which the bicyclic compound was produced by the cyclization of oxamide dioxime with an excess of sulfur dichloride.6a Numerous thiadiazolopyrazines 3 have been synthesized mainly for use as agrochemicals, but since most of them are patented procedures, only a few preparations are available in the literature.Therefore, the synthesis of 3 from 1 and the 1,2-diketones 2 was investigated using a variety of solvents. Condensation of 1 with benzil 2f easily proceeded in refluxing acetic acid and after 4 h gave the thiadiazolopyrazine 3f in 85% yield. An almost equal yield of 3f was obtained using a mixture of acetic acid and ethanol (1:3 v/v)3 as the solvent for the same period, but trifluoroacetic acid was found to be less practical (81% yield) than the former acidic media.Treatment of 1 with phenylglyoxal hydrate in refluxing acetic acid for 4 h afforded 3d in excellent yield but treatment with 1-phenylpropane- 1,2-dione generated 3e in only 66% yield. Under identical conditions, however, the aliphatic diketones 2a–c gave modest yields (23–39%) of the corresponding products 3. When ethanol was used as the solvent instead of acetic acid, a better yield (60%) of 3c was obtained even after shortening the reaction time to 1 h.An obvious improvement in the yield to 90% was achieved by a dropwise addition of 2 equiv. of 2c into a boiling mixture of 1 in ethanol followed by refluxing. Similar treatment of 1 with 2e gave an excellent yield of 3e, and the synthesis of 3b was best effected by changing the solvent to methanol. This method, however, was found to be of little value for the preparation of 3f because of its low yield (24%). In comparison with the earlier synthetic procedure4 for the parent thiadiazolopyrazine 3a, the condensation was notably improved by running the reaction in ethanol at 55–60 °C, but a 42% yield of the desired product was barely realized after purification by sublimation.Incidentally, condensation of 1 with glyoxal–sodium bisulfite addition compound did not proceed at all. The results are summarized in Table 1. Reductive desulfurization is usually accomplished by treatment with Raney nickel or lithium aluminum hydride; use of the former to reduce diphenylthiadiazolopyrazine 3f only gave a 30% yield of the diaminopyrazine 4f and use of the latter led to no formation of 4 at all.Recently, treatment with tin powder in a mixture of concentrated hydrochloric acid and dioxane was shown to convert benzobis[1,2,5]thiadiazoles into tetraaminobenzenes.7 A modified procedure using tin(II) chloride in methanolic hydrochloric acid successfully transformed 3 into 4 in excellent yields. With the exception of 4a, the cleavage was optimized by treating with 5 equiv.of tin chloride at 60 °C (Table 2). Under the milder conditions of using hydrochloric acid at room temperature, the parent diaminopyrazine 4a was formed in 83% yield. We have previously8 carried out the reduction with tin chloride with complete conversion of azidopyrazines to aminopyrazines, in which case some 2,3-diaminopyrazines 3 were obtained from 2-amino-3-azidopyrazines. Compared with the existing synthetic routes via 2-amino-3-halopyrazines9,10 or 1,4-dihydropyrazine- 2,3-diones,11 the current method provides a most *To receive any correspondence (e-mail: nbsato@yokohama-cu.ac.jp). †This is a Short Paper as defined in the Instructions for Authors, Section 5.0 [see J.Chem. Research (S), 1997, Issue 1]; there is therefore no corresponding material in J. Chem. Research (M). Table 1 Synthesis of [1,2,5]thiadiazolo[3,4-b]pyrazines 3 Product 3 Solvent Methoda Yield (%) a bc def EtOH MeOH EtOH AcOH EtOH AcOH AAAB AB 42 77 90 90 85 85 aSee Experimental section.Table 2 Reduction to 2,3-diaminopyrazines 4 Product 4 t/h Yield (%) a bc def 1a 113 2.5 3 83 89 87 83 84 85 aAt room temperature (see Experimental section). Scheme 1J. CHEM. RESEARCH (S), 1997 251 convenient route to 2,3-diaminopyrazines 3 in terms of the accessibility of starting materials and the shorter reaction sequence. Experimental Melting points were determined using a B�uchi 535 apparatus and are uncorrected. 1H and 13C NMR spectra were obtained on a JEOL JNM EX270 instrument at 270 and 67.8 MHz, respectively, with solutions in CDCl3, unless otherwise stated, containing tetramethylsilane as internal standard. General Procedure for Condensation of 3,4-Diamino-1,2,5-thiadiazole 1 with 1,2-Diketones 2.·Method A. Glyoxal (2a) and methylglyoxal (2b) were used as 40% aqueous solutions. The 1,2-diketone solution (10 mmol for 2a–c, 6.0 mmol for 2e) was added via syringe to a boiling solution of 3,4-diamino-1,2,5-thiadiazole (1) (0.571 g, 5.0 mmol) in alcohol (10 cm3) over 10 min, and the resulting mixture was refluxed for 1 h.In the synthesis of 3a, the reaction temperature was kept at 55–60 °C during the reaction. After cooling, the reaction mixture was evaporated under vacuum, and the residue was purified by column chromatography (silica gel, 30 g) using ethyl acetate–hexane (1:7 to 1:1) as eluent, and then sublimed under reduced pressure.Analytical samples were obtained by recrystallization. Method B. A mixture of 3,4-diamino-1,2,5-thiadiazole (1) (0.233 g, 2.0 mmol) and the diketone (2.1 mmol) in acetic acid (4 cm3) was stirred and refluxed for 4 h. The reaction mixture was cooled and concentrated under vacuum. Water was added to the obtained residue, and the aqueous solution was extracted with chloroform (3Å15 cm3). The extract was washed with water, dried (MgSO4) and evaporated under vacuum. The residue was purified as described above. The yields of [1,2,5]thiadiazolo[3,4-b]pyrazines 3a–f are summarized in Table 1.The following compounds were obtained. [1,2,5]Thiadiazolo[3,4-b]pyrazine (3a), Method A, yellow needles, mp 166–168 °C (decomp.) (EtOH) [lit.,4 161–162 °C (decomp.)]; dH 9.05 (2 H, s); dC 149.2, 154.6. 5-Methyl[1,2,5] thiadiazolo[3,4-b]pyrazine (3b), Method A, tiny yellow needles, mp 167.5–168 °C (decomp.) (EtOH) (Found: C, 39.7; H, 2.6; N, 37.1. C5H4N4S requires C, 39.5; H, 2.65; N, 36.8%); dH 2.90 (3 H, s), 8.92 (1 H, s); dC 23.0, 150.9, 152.9, 154.1, 159.8. 5,6-Dimethyl- [1,2,5]thiadiazolo[3,4-b]pyrazine (3c), Method A, yellow needles, mp 125.5–126 °C (EtOH) (lit.,4 124–125 °C); dH 2.83 (6 H, s); dC 24.0, 153.2, 159.7. 5-Phenyl[1,2,5]thiadiazolo[3,4-b]pyrazine (3d), Method B, yellow needles,p 144.5–146 °C (EtOH) (lit.,5 115 °C) (Found: C, 56.0; H, 2.7; N, 26.3. C10H6N4S requires C, 56.1; 2.8; N, 26.15%); dH 7.59–7.65 (3 H, m), 8.28–8.33 (2 H, m), 9.56 (1 H, s); dC 128.4 (2 C), 129.5 (2 C), 131.9, 134.9, 148.5, 153.5, 154.5, 156.2. 5-Methyl-6-phenyl[1,2,5]thiadiazolo[3,4-b]pyrazine (3e), Method A, yellow needles, mp 120.5–121 °C (EtOH) (Found: C, 58.0; H, 3.5; N, 24.5. C11H8N4S requires C, 57.9; H, 3.5; N, 24.5%); dH 2.87 (3 H, s), 7.56–7.69 (5 H, m); dC 25.6, 128.7 (2 C), 129.0 (2 C), 130.1, 137.5, 153.15, 153.19, 159.1, 159.9. 5,6-Diphenyl[1,2,5]thiadiazolo[ 3,4-b]pyrazine (3f), Method B, tiny yellow needles, mp 182–182.5 °C (EtOH) (Found: C, 66.2; H, 3.4; N, 19.3.C16H10N4S requires C, 66.2; H, 3.5; N, 19.3%); dH 7.33–7.47 (6 H, m), 7.54–7.57 (4 H, m); dC 128.3 (2 C), 130.10, 130.14 (2 C), 137.7, 153.2, 158.7. General Procedure for the Reduction of [1,2,5]Thiadiazolo[3,4- b]pyrazines 3.·A mixture of [1,2,5]thiadiazolo[3,4-b]pyrazines 3 (1.0 mmol) and tin(II) chloride (1.13 g, 5.0 mmol) in 12 mol dmµ3 hydrochloric acid (6 cm3) and methanol (6 cm3) was stirred and heated at 60 °C (internal temperature).In the case of 3a, 1.5 mol dmµ3 hydrochloric acid was used instead of the concentrated acid, and the mixture was stirred at room temperature. The extent of the reaction was monitored by TLC and the reaction was completed in the time shown in Table 2. After being cooled to room temperature, the solution was basified with sodium carbonate at pH 8–9 and then evaporated to dryness under reduced pressure. The residue was extracted with hot ethyl acetate (4Å15 cm3), and the combined extracts were evaporated to dryness.Recrystallization of the residue gave the following 2,3-diaminopyrazines 4a–f (Table 2). 2,3-Diaminopyrazine (4a), light tan microprisms, mp 200 °C (MeOH) (lit.,8 207–209 °C); dH 4.23 (4 H, brs), 7.53 (2 H, s); dC [(CD3)2SO] 129.0, 143.9. 2,3-Diamino-5-methylpyrazine (4b), light tan needles, mp 176.5–177 °C (EtOAc) (lit.,8 176.5–178 °C); dH 2.29 (3 H, s), 4.05 and 4.21 (each 2 H, brs), 7.39 (1 H, s); dC 20.1, 130.8, 141.3, 141.5, 143.4. 2,3-Diamino-5,6-dimethylpyrazine (4c), yellow needles, mp 214–215 °C (C6H6) (lit.,10 212–216 °C); dH 2.26 (6 H, s), 4.05 (4 H, brs); dC 20.2, 138.3, 141.1. 2,3-Diamino-5-phenylpyrazine (4d), light tan needles, mp 172–173 °C (C6H6) (lit.,3 173 °C); dH 4.31 (4 H, brs), 7.34–7.46 (3 H, m), 7.84–7.86 (2 H, m), 7.99 (1 H, s); dC 125.8 (2 C), 127.9, 128.3, 128.7 (2 C), 129.5, 137.4, 142.8, 143.3. 2,3-Diamino-5-methyl-6-phenylpyrazine (4e), microcrystals, mp 168.5–169 °C (C6H6) (lit.,3 167–168 °C); dH 2.38 (3 H, s), 4.16 and 4.26 (each 2 H, brs), 7.34–7.50 (5 H, m); dC 21.2, 127.4, 128.1 (2 C), 129.0 (2 C), 138.2, 139.4, 140.9, 141.1, 142.2. 2,3-Diamino- 5,6-diphenylpyrazine (4f), light tan needles, mp 276–278 °C (MeOH) (lit.,8 288.5–290 °C); dH 4.35 (4 H, brs) and 7.22–7.33 (10 H, m); dC 127.3, 128.0 (2 C), 129.6 (2 C), 132.7, 139.3, 142.0. Received, 6th March 1997; Accepted, 13th March 1997 Paper E/7/01579H References 1 Part 32, see N. Sato and T. Matsuura, J.Chem. Soc., Perkin Trans. 1, 1996, 2345. 2 (a) G. B. Barlin, The Pyrazines, ed. A. Weissberger and E. C. Taylor, Interscience, New York, 1983, p. 35; (b) A. E. A. Porter, in Comprehensive Heterocyclic Chemistry, ed. A. R. Katritzky and C. W. Rees, Pergamon, Oxford, vol. 3, 1984, p. 157; (c) N. Sato, in Comprehensive Heterocyclic Chemistry, ed. A. R. Katritzky, C. W. Rees and E. F. V. Scriven, Pergamon, Oxford, 2nd edn., 1996, vol. 6, p. 233. 3 N. Sato and J. Adachi, J. Org. Chem., 1978, 43, 341. 4 A. P. Komin and M. Carmack, J. Heterocycl. Chem., 1976, 13, 13. 5 M. T. Clark and I. J. Gilmore, UK Pat., 2 122 492, 1984 (Chem. Abstr., 1984, 100, 204 992t). 6 (a) A. P. Komin, R. W. Street and M. Carmack, J. Org. Chem., 1975, 40, 2749; (b) P. Camilleri, B. Odell and P. O’Neill, J. Chem. Soc., Perkin Trans. 2, 1987, 1671. 7 (a) S. Mataga, H. Eguchi, K. Takahashi, T. Hatta and M. Tashiro, Bull. Chem. Soc. Jpn., 1989, 62, 3127; (b) S. Mataga, Y. Ikezaki, K. Takahashi, A. Torii and M. Tashiro, Heterocycles, 1992, 33, 791. 8 N. Sato, T. Matsuura and N. Miwa, Synthesis, 1994, 931. 9 F. G. McDonald and R. C. Ellington, J. Am. Chem. Soc., 1947, 69, 1034. 10 R. C. Ellingson and R. L. Henry, J. Am. Chem. Soc., 1948, 70, 1257. 11 J. Adachi and N. Sato, J. Org. Chem., 1972, 37, 221.

ISSN:0308-2342    

DOI:10.1039/a701579h

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

ArHal + e– ArH•– ArHal– • Ar• ( a) –Hal– 2 e–, H+ 2e–, H+ –Hal– ( b) –Hal– Rp Rm C O S Ro 1–6 ( cf. Table 1 for R o, Rm, R p) 252 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 252–253† EPR Studies on Carboxylic Esters. Part 14.1 Radical Anions of O-Phenyl Halobenzenecarbothioates†‡ J�urgen Voss,*a Thomas Behrens,a Manfred Krasmann,a Kai Osternacka and Lilia Prangovab aInstitut f�ur Organische Chemie der Universit�at Hamburg, Martin-Luther-King-Platz 6, D-20146 Hamburg, Germany bDepartment of Chemistry, University of Sofia, James-Baucher-Street 1, BG-1126 Sofia, Bulgaria Radical anions of O-phenyl halobenzenecarbothioates are generated by in situ electroreduction and shown to be mostly persistent by their EPR spectra; in certain cases, dependent on the nature and position of the halogen substituent, elimination of halide anions occurs. Radical anions of arenes with electron-withdrawing substituents such as nitro, carbonyl, alkoxycarbonyl (ester) or the corresponding thiocarbonyl groups are readily formed by chemical or electrochemical single electron transfer (SET). They are usually persistent species and their EPR spectra have been studied extensively.1,2 Radical anions of halobenzenes are, however, extremely labile if they exist at all.In general, according to Scheme 1, halide ions are eliminated simultaneously with (a) or immediately after (b) the SET process. Even in the latter case EPR detection of the primary radical anion ArHal.µ is hardly possible.As a result the radical anion ArH.µ of the protiodehalogenated arene is observed. This array of reactions has been studied by electrochemical and related experimental methods3 as well as by quantum chemical calculations.4 Whereas the stabilizing effect of a nitro substituent is strong enough to keep meta-chloro- and meta-bromo-nitrobenzene radical anions intact, immediate elimination of iodide occurs from meta-iodonitrobenzene.5 The radical anions of the chlorobenzaldehydes,6 chloroacetophenones, 7 chlorobenzonitriles8 and methyl chlorobenzoates, 4c on the other hand, are too short-lived even at low temperatures to be detectable by EPR spectroscopy.We therefore studied the radical anions of O-phenyl halobenzenecarbothioates 1–4 since the strong electron-withdrawing effect and the high polarizability of the thiocarbonyl group9 should give rise to a pronounced stabilization of the radical anions. Results and Discussion The radical anions 1.µ–6.µ were generated by in situ electroreduction in dry DMF as described previously.1,9,10 Intense and well resolved EPR spectra were recorded, Fig. 1. The experimental data, i.e. the proton and fluorine hfs coupling constants, are shown in Table 1. Inspection and consideration of the results allows a clear and consistent conclusion to be drawn. Obviously the stability of the thiono ester radical anions is controlled by the nature of the halogen substituent and its position in the benzene ring.All the isomeric fluoro 1 and chloro 2 derivatives are persistent. By comparison with the unsubstituted 5 and paratert- butyl 6 thiono benzoate it is possible to assign the 1H and also the 19F coupling constants. The latter are larger by a factor of ca. 2 as compared with the former if equivalent positions are considered. This effect is known from the literature. 2a Owing to the very small hfs coupling constants no splitting of the chlorine nuclei was observed.Therefore, one splitting is missing in 2a.µ, 2b.µ and 2c.µ and as a consequence the EPR spectrum of 2c.µ is nearly identical with that of 6.µ. Only the EPR spectrum of the meta-isomer 3b.µ can be observed in the bromothiono ester series 3. In this case the *To receive any correspondence. †This is a Short Paper as defined in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1997, Issue 1]; there is therefore no corresponding material in J.Chem. Research (M). ‡Dedicated to Professor Hans Sch�afer on the occasion of his 60th birthday. Scheme 1 Fig. 1 Experimental (left) and simulated (right) EPR spectra of the radical anions obtained from O-phenyl thiobenzoate (5), 2-fluorothiobenzoate (1a), 2-chlorothiobenzoate (2a) and 2-bromothiobenzoate (3a)J. CHEM. RESEARCH (S), 1997 253 3-position appears as a blind spot. As for the rest the coupling constants of 3b.µ and 5.µ are nearly identical. The radical anions of the ortho- 3a.µ and para-bromo thiono ester 3c.µ cannot be detected.The spectrum of 5.µ is instead observed. The same is true for the meta-iodo derivative 4. The protons needed for the protiodehalogenation obviously originate from traces of water or Hofmann elimination of the quaternary ammonium salt used as the supporting electrolyte. This result is not quite unexpected. It can be explained by the weakness of the carbon–bromine and carbon–iodine bonds as compared to the carbon–fluorine and carbon– chlorine bonds.It is, however, not in agreement with the enhanced reactivity of activated fluoroarenes in aromatic nucleophilic substitution (SNAr) reactions. In this case the attack of the nucleophile is the rate-determining step. It is controlled by the electron density at the respective carbon centre, which is the lowest if fluorine is the substituent. The leaving group ability is therefore irrelevant.11 With radical anions, on the contrary, the latter is the determining step since the ‘nucleophilic attack’, i.e. the SET process, is fast in any case.The regioselectivity observed in the bromo series 3.µ can be explained qualitatively by the spin densities, which are proportional to the proton hfs coupling constants. Accordingly, the elimination of bromide from the ortho- and paraposition is fast, whereas the meta-derivative 3b.µ is long-lived enough to be detected spectroscopically by EPR. It is noteworthy that the spin density distribution in the O-phenyl halobenzenecarbothioate radical anions 1.µ–3.µ is determined by the phenoxythiocarbonyl substituent and is hardly influenced by the halogen substituents.Experimental The O-phenyl arenecarbothioates 1–6 were prepared by thionation of the corresponding esters with Lawesson’s reagent in chlorobenzene as described in the literature.12 The radical anions were generated by in situ electroreduction at the appropriate reduction potentials.12 A solution containing 10µ3 mol lµ1 1–6 and 0.1 mol lµ1 of tetrapropylammonium bromide in dry DMF was used as the supporting electrolytic solvent and a silver wire was used as the internal reference electrode.The EPR spectra were recorded at room temperature on a Bruker 420 S spectrometer (X-band).1,9,10 Financial support from the Fonds der Chemischen Industrie is gratefully acknowledged. Lilia Prangova thanks the Deutscher Akademischer Austauschdienst and the University of Sofia, Bulgaria, for fellowships. Received, 3rd February 1997; Accepted, 17th March 1997 Paper E/7/00763I References 1 For Part 13, see J.Gassmann, H. G�unther, K. Osternack, A. Sawluck, K. Thimm and J. Voss, Magn. Reson. Chem., 1994, 32, 624. 2 (a) K. Scheffler and H. B. Stegmann, Elektronenspinresonanz, Springer, Berlin, 1970; (b) J. Voss and K. Schlapkohl, Tetrahedron, 1975, 31, 2982; (c) U. Debacher, W. Schm�user and J. Voss, J. Chem. Res., 1982, (S) 74; (M) 876. 3 (a) L. Eberson, Electron Transfer Reactions in Organic Chemistry, Springer, Berlin, 1987; (b) C. P. Andrieux, A. K. Gorande and J.-M. Sav�eant, J. Am. Chem. Soc., 1992, 114, 6892; (c) J.-M. Sav�eant, Tetrahedron, 1994, 50, 10 117. 4 (a) A. B. Pierini, J. S. Duca Jr. and M. T. Baumgartner, J. Mol. Struct., 1994, 311, 343; (b) A. B. Pierini and J. S. Duca Jr., J. Chem. Soc., Perkin Trans. 2, 1995, 1821; (c) J. Gassmann, PhD Thesis, University of Hamburg, 1995. 5 R. G. Compton, R.A. W. Dryfe, J. C. Eklund, S. D. Page, J. Hirst, L. Nei, G. W. J. Fleet, K. Y. Hsia, D. Bethell and L. J. Martingale, J. Chem. Soc., Perkin Trans. 2, Solar, N. Getoff, J. Holcman and K. Sehested, J. Phys. Chem., 1995, 99, 9425. 7 D. Behar and P. Neta, J. Am. Chem. Soc., 1981, 103, 280. 8 P. Neta and D. Behar, J. Am. Chem. Soc., 1981, 103, 103. 9 J. Voss and F.-R. Bruhn, Liebigs Ann. Chem., 1979, 1931. 10 R. Edler and J. Voss, Chem. Ber., 1989, 122, 187. 11 J. March, Advanced Organic Chemistry—Reactions, Mechanisms and Structure, Wiley, New York, 4th edn., 1992. 12 L. Prangova, K. Osternack and J. Voss, J. Chem. Res., 1995, (S) 234; (M) 1551. Table 1 Hfs coupling constants a in O-phenyl arenecarbothioate radical anions 1.µ–6.µ Substituents Coupling constants, mT Compound Ro Rm Rp a2 a3 a4 a5 a6 1a 1b 1c 2a 2b 2c 3a 3b 3c 456 F HH Cl HH Br HHHHH HF HH Cl HH Br HI HH HHF HH Cl HH Br HH But 0.670 0.363 0.396 — 0.363 0.380 0.367 0.375 0.367 0.125 0.250 0.129 0.125 — 0.122 — 0.117 0.122 0.520 0.580 1.025 0.483 0.592 — 0.479 0.483 — 0.125 0.104 0.129 0.125 0.107 0.122 0.108 0.117 0.122 0.425 0.320 0.396 0.358 0.242 0.380 0.367 0.375 0.367 EPR spectrum of 5.µ, cf. text EPR spectrum of 5.µ, cf. text EPR spectrum of 5.µ, cf. text

ISSN:0308-2342    

DOI:10.1039/a700763i

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

NH CN R2 R1 1a–h COCH2Cl R1 NH NC R2 2a–h N CN O R2 R1 3a–h i ii a b c d e f g h H 2-Cl 3-NO2 4-Cl 4-OMe 4-Me 4-Me 4-Cl H H H H H H 4-Br 4-Br 1–3 R1 R2 254 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 254–255† Novel Tri-n-butyltin Hydride–Azoisobutyronitrile-induced Intramolecular Ring-closure Reaction: a Convenient Synthesis of Substituted Azetidin-3-ones†,‡ Abhijit Roy Chowdhury, Versha V. Kumar, Raja Roy and A. P. Bhaduri* Division of Medicinal Chemistry, Central Drug Research Institute, Lucknow 226 001, India Tri-n-butyltin hydride–azoisobutyronitrile-mediated intramolecular ring-closure reactions yield 2-cyano-1,2-di(phenyl or substituted phenyl)azetidin-3-ones; 15N NMR studies support the assigned structures.Convenient methods for synthesising four-membered nitrogen- containing heterocycles are extremely limited.1–5 During the course of our studies on intramolecular ring-closure reactions induced by tri-n-butyltin hydride (TBTH)–azoisobutyronitrile (AIBN), novel intramolecular ring closures of a-anilino-a-(chloromethylcarbonyl)phenylacetonitriles leading to the formation of azetidin-3-one derivatives were observed.The details of this first report are presented here. Addition of HCN to the appropriate Schiff’s base6,7 yielded compounds 1a–h which reacted with chloroacetyl chloride in the presence of sodium hydrogen carbonate to yield the C-acylated products 2a–h instead of N-acetylated products. The C-acylation was confirmed on the basis of the disappearance of the methine proton and the presence of a D2Oexchangeable NH proton between dH 6.51 and 6.52 in the 1H NMR spectra.Reactions of 2a–h with TBTH in the presence of AIBN gave 2-cyano-1,2-di(phenyl or substituted phenyl)azetidin-3-ones 3a–h in excellent yields (72–77%) (Scheme 1). Attempted reactions of compounds 2a–h with TBTH alone did not yield 3a–h. The N·CH2 linkage in these four-membered heterocycles was established on the basis of 15N NMR studies carried out with 3d as the model compound.The nitrogen of the nitrile group appeared at dN 149.8 and the trisubstituted ring nitrogen showed up as a broad triplet at dN 127.2. The latter in a 15N inverse-gated experiment appeared as a singlet, indicating 2JNH long-range coupling with the methylene protons.8,9 Long-range HMBC (heteronuclear multiple bond correlation spectroscopy) experiments10 showed that the carbonyl carbon was coupled with the methylene protons.The presence of the methylene protons adjacent to the trisubstituted nitrogen was further reinforced by phase-sensitive ROESY (rotating-frame Overhauser effect spectroscopy) experiments11 in which the CH2 protons between dH 3.4 and 4.2 gave NOE cross-peaks with the ortho protons of the phenyl group attached to the N-1 position. The outcome of all the spectroscopic results, therefore, unambiguously proves the structure of the azetidinones as 3a–h. In conclusion, the present method provides a more convenient route to substituted azetidin-3-ones compared with existing ones.Studies are under way to elucidate the mechanism of this unusual ring-closure reaction. Experimental Melting points were determined on a hot-stage apparatus and are uncorrected. IR spectra were recorded on Beckmann Acculab- 10 or Perkin-Elmer 881 spectrophotometers. 1H NMR spectra, 15N NMR spectra and related 2D-NMR experiments were carried out on Bruker 400 FT NMR and Bruker Avance DRX 300 spectrometers.EI mass spectra were recorded on a JEOL JMS-D-300 spectrometer. Elemental analyses were carried out on a Carlo- Erba EA 1108 elemental analyser. Reactions were monitored by TLC on silica gel 60 (E. Merck) of 0.25 mm thickness. Column chromatography carried on Merck silica gel (70–230 mesh). a-Anilino-a-(chloromethylcarbonyl)phenylacetonitriles: General Procedure.·To a solution of 1a–h (2 mmol) in CHCl3 (25 ml) were added NaHCO3 (0.168 g, 3 mmol) and chloroacetyl chloride (0.239 ml, 2 mmol) in CHCl3 (10 ml) under stirring.The reaction mixture was allowed to stir for 8–10 h. Then, the reaction mixture was neutralised with saturated aqueous NaHCO3 followed by separation of the organic layer which was washed with brine (25 ml) and dried over anhydrous Na2SO4. Evaporation of the solvent led to a crude solid which was recrystallised in EtOH to afford products 2a–h. 2a: colourless crystals, mp 88 °C (from EtOH), 71% yield (Found: C, 67.58; H, 4.73; N, 9.91.C16H13ClN2O requires C, 67.49; H, 4.60; N, 9.80%); vmax (KBr)/cmµ1 1685 (C�O), 2252 (C�N), 3122 (NH); dH (400 MHz; CDCl3) 3.8 (2 H, s, CH2), 6.56 (1 H, br, NH, D2O exchangeable), 7.08 (1 H, m, ArH), 7.30 (4 H, m, ArH), 7.42 (4 H, d, J 9 Hz, ArH), 7.52 (1 H, m, ArH); m/z (EI-MS) 284 (M+, 2.4%), 248 (34.6). 2b: colourless crystals, mp 121 °C (from EtOH), 72.5% yield (Found: C, 60.46; H, 3.74; N, 8.72. C16H12Cl2N2O requires C, 60.20; H, 3.78; N, 8.77%); vmax (KBr)/ cmµ1 1670 (C�O), 2265 (C�N), 3085 (NH); dH (400 MHz, CDCl3) 3.83 (2 H, s, CH2), 6.51 (1 H, br, NH, D2O exchangeable), 7.06 (1 H, m, ArH), 7.14 (2 H, d, J 9 Hz, ArH), 7.31 (4 H, m, ArH), 7.43 (2 H, d, J 9 Hz, ArH); m/z (EI-MS) 320 (M+, 11.1%), 294 (34.3). 2c: yellow crystals, mp 107 °C (from EtOH), 70.5% yield (Found: C, 58.49; H, 3.75; N, 13.24. C16H12ClN3O3 requires C, 58.28; H, 3.66; N, 12.94); vmax (KBr)/cmµ1 1710 (C�O), 2252 (C�N), 3120 (NH); dH (400 MHz, CDCl3) 3.81 (2 H, s, CH2), 6.51 (1 H, br, NH, D2O exchangeable), 6.85 (1 H, s, ArH), 7.18 (4 H, s, ArH), 7.35 (1 H, m, ArH), 7.56 (2 H, d, J 9 Hz, ArH), 8.18 (1 H, s, ArH); m/z (EI-MS) 329 (M+, 4.9%), 253 (100.0). 2d: colourless crystals, mp 98 °C (from EtOH), 74.0% yield (Found: C, 60.52; H, 3.77; N, 8.60. C16H12Cl2N2O requires C, 60.20; H, 3.78; N, 8.77%); vmax (KBr)/cmµ1 1668 (C�O), 2251 (C�N), 3180 (NH); dH (400 MHz, CDCl3) 3.78 (2 H, s, CH2), 6.53 (1 H, br, NH, D2O exchangeable), 7.10 (4 H, s, ArH), 7.25 (2 H, d, J 9 Hz, ArH), 7.34 (2 H, d, J 9 Hz, ArH); m/z (EI-MS) 319 (M+, 2.3%), 283 (39.0). 2e: colourless crystals, mp 88 °C (from EtOH), 71.5% yield (Found: C, 64.72; *To receive any correspondence (e-mail: root%cdrilk@sirnetd. ernet.in). †This is a Short Paper as defined in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1997, Issue 1]; there is therefore no corresponding material in J. Chem. Research (M). ‡CDRI Communication No. 5549. Scheme 1 Reagents and conditions: i, ClCOCH2Cl, NaHCO3, CHCl3, room temp., 8–10 h; ii, TBTH, AIBN, anhydrous THF, 65 °C, 12–14 hJ. CHEM. RESEARCH (S), 1997 255 H, 4.93; N, 8.75. C17H15ClN2O2 requires C, 64.87; H, 4.80; N, 8.89%); vmax (KBr)/cmµ1 1666 (C�O), 2334 (C�N), 3016 (NH); dH (400 MHz, CDCl3) 3.82 (5 H, q, J 14 Hz, OCH3 and CH2), 6.48 (1 H, br, NH, D2O exchangeable), 7.26 (4 H, m, ArH), 7.33 (4 H, m, ArH), 7.40 (1 H, q, J 18 Hz, ArH); m/z (EI-MS) 314 (M+, 21.0%), 279 (30.1). 2f: colourless crystals, mp 92 °C (from EtOH), 74.5% yield (Found: C, 68.60; H, 5.18; N, 9.30.C17H15ClN2O requires C, 68.34; H, 5.06; N, 9.37%); vmax (KBr)/cmµ1 1670 (C�O), 2247 (C�N), 3120 (NH); dH (400 MHz, CDCl3) 2.35 (3 H, s, CH3), 3.78 (2 H, s, CH2), 6.48 (1 H, br, NH, D2O exchangeable), 6.95 (2 H, d, J 9 Hz, ArH), 7.09 (1 H, m, ArH), 7.18 (4 H, m, ArH), 7.24 (2 H, d, J 9 Hz, ArH); m/z (EI-MS) 298 (M+, 3.8%), 262 (32.9). 2g: colourless crystals, mp 129 °C (from EtOH), 70% yield (Found: C, 53.93; H, 3.83; N, 7.17.C17H14BrClN2O requires C, 54.06; H, 3.73; N, 7.41%); vmax (KBr)/cmµ1 1680 (C�O), 2258 (C�N), 3120 (NH); dH (400 MHz, CDCl3) 2.34 (3 H, s, CH3), 3.78 (2 H, s, CH2), 6.52 (1 H, br, NH, D2O exchangeable), 6.79 (2 H, d, J 9 Hz, ArH), 7.12 (2 H, m, ArH), 7.18 (2 H, d, J 9 Hz, ArH), 7.20 (2 H, d, J 9 Hz, ArH); m/z (EI-MS) 377 (M+, 16.3%), 343 (23.1). 2h: colourless crystals, mp 180 °C (from EtOH), 71% yield (Found: C, 48.51; H, 2.47; N, 7.18.C16H11BrCl2N2O requires C, 48.27; H, 2.78; N, 7.03%); vmax (KBr)/cmµ1 1666 (C�O), 2280 (C�N), 3322 (NH); dH (400 MHz, CDCl3) 3.75 (2 H, s, CH2), 6.52 (7.14 (1 H, m, ArH), 7.19 (2 H, d, J 9 Hz, ArH), 7.21 (2 H, d, J 9 Hz, ArH); m/z (EI-MS) 397 (M+, 12.1%), 249 (34.3). Azetidin-3-ones: Typical Procedure.·To a solution of 2a–h (2 mmol) in anhydrous THF (25 ml) was added a catalytic amount of AIBN and the reaction mixture was allowed to stir at 65 °C for 30 min under N2 atmosphere. Thereafter, the reaction mixture was cooled to room temperature (25 °C), followed by the addition of 0.87 ml (3.0 mmol) of TBTH in anhydrous THF and then refluxing at 65 °C for the next 12–14 h under a N2 atmosphere.The excess of solvent was distilled off in vacuo and the residue was extracted with EtOAc (3Å20 ml). Usual work-up of the organic layer furnished an oily residue which was purified by column chromatography.Elution with hexane–CHCl3 (75:25, v/v) furnished a crude solid which was recrystallised in MeOH–EtOAc to afford compounds 3a–h. 3a: colourless crystals, mp 79 °C (from MeOH–EtOAc), 77.2% yield (Found: 77.16; H, 4.97; N, 11.69. C16H12N2O requires C, 77.40; H, 4.87; N, 11.28%); vmax (KBr)/cmµ1 1770 (C�O), 2264 (C�N); dH (400 MHz, CDCl3) 3.35 (1 H, d, J 15 Hz, H of CH2), 3.92 (1 H, d, J 15 Hz, H of CH2), 7.13 (1 H, m, ArH), 7.34 (4 H, m, ArH), 7.48 (4 H, d, J 9 Hz, ArH), 7.58 (1 H, m, ArH); m/z (EI-MS) 248 (M+, 7.8%). 3b: colourless crystals, mp 122 °C (from MeOH– EtOAc), 72.5% yield (Found: C, 68.21; H, 3.57; N, 9.48. C16H11ClN2O requires C, 67.97; H, 3.92; N, 9.90%); vmax (KBr)/ cmµ1 1780 (C�O), 2265 (C�N; dH (400 MHz, CDCl3) 3.45 (1 H, d, J 15 Hz, H of CH2), 4.14 (1 H, d, J 15 Hz, H of CH2), 7.24 (1 H, m, ArH), 7.28 (1 H, d, J 9 Hz, ArH), 7.41 (4 H, m, ArH), 7.55 (2 H, d, J 9 Hz, ArH), 7.58 (1 H, d, J 9 Hz, ArH); m/z (EI-MS) 283 (M+, 19.5%), 214 (21.1). 3c: yellow crystals, mp 152 °C (from MeOH– EtOAc), 77.44% yield (Found: C, 65.82; H, 3.96; N, 14.71. C16H11N3O3 requires C, 65.52; H, 3.78; N, 14.32%); vmax (KBr)/cmµ1 1782 (C�O), 2270 (C�N); dH (400 MHz, CDCl3) 3.45 (1 H, d, J 15 Hz, H of CH2), 4.12 (1 H, d, J 15 Hz, H of CH2), 7.18 (1 H, m, ArH), 7.38 (4 H, s, ArH), 7.71 (1 H, m, ArH), 7.35 (1 H, d, J 9 Hz, ArH), 7.95 (1 H, d, J 9 Hz, ArH), 8.51 (1 H, s, ArH); m/z (EI-MS) 293 (M+, 35.5%). 3d: colourless crystals, mp 96 °C (from MeOH– EtOAc), 75.2% yield (Found: C, 67.78; H, 4.23; N, 9.76.C16H11ClN2O requires C, 67.97; H, 3.92; N, 9.90%); vmax (KBr)/ cmµ1 1768 (C�O), 2284 (C�N); dH (400 MHz, CDCl3) 3.38 (1 H, d, J 15 Hz, H of CH2), 3.02 (1 H, d, J 15 Hz, J 15 Hz, H of CH2), 7.16 (1 H, m, ArH), 7.34 (4 H, s, ArH), 7.45 (2 H, d, J 9 Hz, ArH), 7.53 (2 H, d, J 9 Hz, ArH); m/z (EI-MS) 282 (M+, 6.7%), 280 (15.1). 3e: colourless crystals, mp 86 °C (from MeOH–EtOAc), 74.56% yield (Found: C, 73.40; H, 4.99; N, 10.50.C17H14N2O2 requires C, 73.36; H, 5.07; N, 10.06%); vmax (KBr)/cmµ1 1780 (C�O), 2265 (C�N); dH (400 MHz, CDCl3) 3.32 (1 H, d, J 15 Hz, H of CH2), 3.75 (3 H, s, OCH3), 3.92 (1 H, d, J 15 Hz, H of CH2), 7.14 (1 H, s, ArH), 7.32 (4 H, s, ArH), 7.48 (2 H, d, J 9 Hz, ArH), 7.54 (2 H, d, J 9 Hz, ArH); m/z (EI-MS) 278 (M+, 5.1%), 210 (10.7). 3f: colourless crystals, mp 91 °C (from MeOH–EtOAc), 74.5% yield (Found: C, 77.90; H, 5.22; N, 10.52. C17H14N2O requires C, 77.84; H, 5.36; N, 10.67%); vmax (KBr)/cmµ1 1775 (C�O), 2262 (C�N); dH (400 MHz, CDCl3) 2.37 (3 H, s, CH3), 3.38 (1 H, d, J 15 Hz, H of CH2), 3.98 (1 H, d, J 15 Hz, H of CH2), 7.14 (1 H, m, ArH), 7.28 (4 H, q, J 9 Hz, ArH), 7.35 (2 H, d, J 9 Hz, ArH), 7.47 (2 H, d, J 9 Hz, ArH); m/z (EI-MS) 262 (M+, 16.9%), 144 (25.8). 3g: colourless crystals, mp 78 °C (from MeOH–EtOAc), 76.87% yield (Found: C, 59.84; H, 4.70; N, 9.80. C17H13BrN2O requires C, 59.84; H, 3.84; N, 8.20%); vmax (KBr)/ cmµ1 1765 (C�O), 2271 (C�N); dH (400 MHz, CDCl3) 3.38 (1 H, d, J 15 Hz, H of CH2), 3.82 (3 H, s, CH3), 3.91 (1 H, d, J 15 Hz, H of CH2), 6.98 (2 H, d, J 9 Hz, ArH), 7.21 (2 H, m, ArH), 7.38 (2 H, d, J 9 Hz, ArH), 7.40 (2 H, d, J 9 Hz, ArH); m/z (EI-MS) 341 (M+, 1.8%), 314 (14.1). 3h: yellow crystals, mp 81 °C (from MeOH– EtOAc), 74.84% yield (Found: C, 53.38; H, 3.09; N, 7.59.C16H10BrClN2O requires C, 53.14; H, 2.78; N, 7.74%); vmax (KBr)/ cmµ1 1772 (C�O), 2265 (C�N); dH (400 MHz, CDCl3) 3.38 (1 H, d, J 15 Hz, H of CH2), 3.81 (1 H, d, J 15 Hz, H of CH2), 6.95 (2 H, d, J 9 Hz, ArH), 7.23 (2 H, m, ArH), 7.43 (4 H, q, J 9 Hz, ArH); m/z (EI-MS) 361 (M+, 4.1%). Financial assistance (to A. R. C. and V. V. K.) from CSIR, New Delhi, is gratefully acknowledged. Received, 17th October 1997; Accepted, 14th March 1997 Paper E/6/07079E References 1 S. S. Chatterjee and A. Shoeb, Synthesis, 1973, 153. 2 S. S. Chatterjee, Tetrahedron Lett., 1972, 50, 5063. 3 A. Morimoto, T. Okutari and K. Masuda, Chem. Pharm. Bull., 1973, 21, 228. 4 H. Baumann and R. O. Duthaler, Helv. Chim. Acta, 1988, 71, 1035. 5 J. Podlech and D. Seebach, Helv. Chim. Acta, 1995, 78, 1238. 6 N. Singh and S. Mohna, J. Chem. Soc., Chem. Commun., 1969, 868. 7 J. S. Sandhu, S. D. Sethi and S. Mohan, J. Indian Chem. Soc., 1971, 48, 89. 8 K. L. Williamson and J. D. Roberts, J. Am. Chem. Soc., 1976, 98, 5082. 9 J. W. Paschel, D. E. Dorman, P. R. Srinivasan and R. L. Lichter, J. Org. Chem., 1978, 43, 2013. 10 A. Bax and M. F. Summers, J. Am. Chem. Soc., 1986, 108, 2093. 11 A. Bax and G. D. Davis,

ISSN:0308-2342    

DOI:10.1039/a607079e

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

CN CN CN CN MeS MeS 1 i, CS2–EtO– Na+ ii, MeI–MeOH N N N SMe NC H2N OH R O N N NC NH MeS Me R 3a R = H b R = Ph N N O H2N R 2a R = H b R = Ph N N O H2N R 7 4 NH2NH2 OH– N N N H2 N OH R 8 NH N H2N NH N N NC O MeS Me R 5 N N N OH HN Me R 6 N NH2NH2 Ph S N O O 1 + N S MeS CN OH 10 DMF–K2CO3 Ph O NH a R = H b R = Ph 2–8 9 NH2 256 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 256–257† Synthetic Strategies to Novel Condensed Methylsulfanylazoles: Reaction of Ketene Dithiocetals with Amino- and Oxo-azoles† Galal E.H. Elgemeie,*a Ahmed H. Elghandour,b Ali M. Elzanateb and Ahmed M. Husseinb aChemistry Department, Faculty of Science, Helwan University, Helwan, Cairo, Egypt bChemistry Department, Faculty of Science, Cairo University (Bani Suef Branch), Bani Suef, Egypt A novel synthesis of condensed methylsulfanylazoles via the treatment of [bis(methylsulfanyl)methylidene]malononitrile with amino- and oxo-azoles is reported and the synthetic potential of the method demonstrated.As a part of our programme directed towards the synthesis of sulfanylpurine, thioguanine and other antimetabolites,1–7 we report here a new one-pot synthesis of sulfanylpurine analogues by the reaction of ketene dithioacetals with aminoand oxo-substituted azoles. Thus, it was found that [bis(methylsulfanyl)methylidene] malononitrile 1 reacts with 3-methyl-2-pyrazolin- 5-ones 2a,b in 1,4-dioxane containing an equivalent amount of potassium hydroxide to give the corresponding 4-methylsulfanylpyrazolo[ 3,4-b]pyridines 5a,b in good yield.The formation of 5 from the reaction of 1 with 2 is assumed to proceed via the intermediate 4, which undergoes hydrolysis under basic conditions and recyclization to give the end products 5. Compounds 5 bearing latent functional substituents were found useful for the synthesis of fused derivatives. They reacted with hydrazine in refluxing ethanol containing catalytic amounts of piperidine to afford the corresponding dipyrazolo[3,4-b:4p,3p-d]pyridine derivatives 6.The behaviour of 3-amino-2-pyrazolin-5-ones 3a,b towards ketene dithioacetal 1 was also investigated. Thus, compounds 3 reacted with 1 to yield the corresponding 6-methylsulfanylpyrazolo[ 3,4-c]pyridines 7a,b in good yields. Formation of 7 was assumed to proceed via the addition of the active methylene in 3 to the a,b-unsaturated carbon atom in 1. The Michael adducts cyclized smoothly via MeSH elimination and addition of the most basic exocyclic ring nitrogen to the cyano group.Compounds 7 reacted with hydrazine hydrate in refluxing ethanol containing catalytic amounts of piperidine to afford the corresponding pentaaza-as-indacene analogues 8. The behaviour of ketene dithioacetal 1 towards other active methylene heterocycles was also investigated. Thus, compound 1 reacted with the 1,3-thiazol-4(5H)-one derivative 9 in refluxing N,N-dimethylformamide (DMF) containing the equivalent amount of potassium carbonate to yield the 7-methylsulfanylthiazolo[2,3-a]pyridine derivative 10.We also attempted the reaction of ketene dithioacetal 1 with cyclopentanone. When the reaction was conducted in the presence of potassium hydroxide in 1,4-dioxane followed by treatment with dilute HCl, the expected cycloalkane ringfused 4-methylsulfanyl-2(1H)-pyridine 12 was obtained. In contrast to the behaviour of 1 towards cyclopentanone in potassium hydroxide–1,4-dioxane, the ketene dithioacetal 1 reacted with dimedone under the same experimental condition to yield the cyclocondensed 2-pyran derivative 14 and not the expected 2(1H)-pyridone derivative.On the other hand, the dimedone anhydride derivative 15 was obtained by the reaction of 1 with dimedone in refluxing pyridine. The behaviour of compounds 12 and 14 towards hydrazine was investigated. Products resulting from substitution at the methylsulfanyl active site by the hydrazine followed by cyclization were obtained.Thus, from the reaction of hydrazine with 12 or 14, the cycloalkane-fused pyrazolo[3,4-b]pyridines 13 and 16 were obtained. The structures of all products were established on the basis of elemental analysis and spectral data. Experimental All melting points are uncorrected. The IR spectra were obtained (KBr disk) on a Perkin Elmer/1650 FTIR instrument, 1H NMR spectra were measured on a Varian 400 MHz spectrometer for solutions in (CD3)2SO using SiMe4 as internal standard. Mass spectra were recorded on a Ms-5988 spectrometer.Analytical data were obtained from the Microanalytical Data Center at Cairo University. 1-Substituted 3-Methyl-4-methylsulfanyl-6-oxo-6,7-dihydropyrazolo[ 3,4-b]pyridine-5-carbonitriles 5a,b. General Procedure.·To a solution of 2-pyrazolin-5-ones 2a,b (0.05 mol) and [bis(methylsulfanyl) methylidene]malononitrile 1 (0.05 mol) in 1,4-dioxane (80 ml), the appropriate amount of potassium hydroxide powder was added. The mixture was stirred for 20 h at room temperature and then poured into 300 ml cold water and neutralized with dil.HCl to isolate the solid product, which was filtered and recrystallized from the appropriate solvent. 5a: mp a300 °C from H2O, yield 68%; *To receive any correspondence. †This is a Short Paper as defined in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1997, Issue 1]; there is therefore no corresponding material in J.Chem. Research (M). Scheme 1O NC CN O O 15 O NH CN SMe O 14 O SMe CN NH 11 1 O O O KOH– 1,4-dioxane pyridine/heat NH O HN O 16 HN SMe CN O 12 HN O 13 N NH NH2 NH2NH2 NH2NH2 OH– N NH2 KOH– 1,4-dioxane J. CHEM. RESEARCH (S), 1997 257 vmax/cmµ1 (KBr) 3400–3141 (NH), 2225 (CN), 1679 (CO); dH [(CD3)2SO] 2.49 (s, 3 H, CH3), 2.55 (s, 3 H, SCH3), 7.53 (brs, 1 H, NH), 8.70 (brs, 1 H, NH); m/z 220 (Found: C, 49.4; H, 3.4; N, 25.7. C9H8N4SO requires C, 49.1; H, 3.6; N, 25.4%). 5b: mp 197 °C, from acetone, yield 70%; vmax/cmµ1 (KBr) 3426 (NH), 2215 (CN), 1640–1617 CO); m/z 296 (Found: C, 60.4; N, 3.8.N, 19.0. C15H12N4SO requires C, 60.8; H, 4.0; N, 18.9%). 6-Substituted 3-Amino-8-methyl-1,6-dihydrodipyrazolo[3,4-b:3p,4pd] pyridin-4-ols 6a,b. General Procedure.·A mixture of equivalent amounts of 5a,b (0.01 mol) and hydrazine hydrate was heated in ethanol (30 ml) containing a catalytic amount of piperidine for 3 h. The solid product formed on standing was isolated by filtration and recrystallized from the appropriate solvent. 6a: mp a300 °C, from EtOH, yield 66%; vmax/cmµ1 (KBr) 3550–3220 (OH, NH2, NH); dH [(CD3)2SO] 2.50 (s, 3 H, CH3), 4.40–6.00 (brs, 5 H, OH, 2NH, NH2); m/z 204 (Found: C, 47.2; H, 4.0; N, 41.0. C8H8N6O requires C, 47.0; H, 3.9; N, 41.2%). 6b: mp 160 °C, from EtOH, yield 71%; vmax/cmµ1 (KBr) 3400–3166 (OH, NH2, NH), 1702 (CO); m/z 280 (Found: C, 60.4; H, 4.4; N, 30.5. C14H12N6O requires C, 60.0; H, 4.3; N, 30.0%). 6-Amino-3-hydroxy-4-methylsulfanyl- 2H - pyrazolo[3,4 - b]pyridine- 5-carbonitrile 7a.·A solution of 3-amino-2-pyrazolin-5-one 3a (0.05 mol), 1 (0.05 mol) and potassium carbonate (0.06 mol) in DMF (30 ml) was heated under reflux for 3 h. The solution was then poured into iced water and neutralized with dil. HCl to isolate the product, which was filtered and recrystallized from DMF– EtOH. 7a: mp a300 °C, from DMF–EtOH, yield 81%; vmax/cmµ1 (KBr) 3600–3311, 3252 (OH, NH2, NH), 2261 (CN); m/z 221 (Found: C, 43.1; H, 3.4; N, 32.0.C8H7N5SO requires C, 43.4; H, 3.2; N, 31.7%). 6 - Amino- 3 - hydroxy-4-methylsulfanyl-2-phenylpyrazolo[3,4-b]pyridine- 5-carbonitrile 7b.·To a solution of equimolar amounts of 3-amino-1-phenyl-2-pyrazolin-5-one 3b and 1 (0.05 mol) in 1,4-dioxane (80 ml), potassium hydroxide powder (0.06 mol) was added. The mixture was stirred at room temperature for 20 h and then poured over iced water and neutralized with dil. HCl. The performed solid product was collected by suction filtration and recrystallized from ethanol. 7b: mp 260 °C, from EtOH, yield 79%; vmax/cmµ1 (KBr) 3450–3186 (OH, NH2), 2207; m/z 297 (Found: C, 56.2; H, 3.6; N, 23.2. C14H11N5SO requires C, 56.6; H, 3.7; N, 23.6%). 7 - S u b s t i t u t e d 3 , 4 - D i a m i n o - 1 , 7 - d i h y d r o d i p y r a z o l o[ 3 , 4 -b : 3p, 4 p- d ] - pyridin-8-ols 8a,b. General Procedure.·To a mixture of 7a,b (0.01 mol) and hydrazine hydrate (0.01 mol) in ethanol (30 ml), a catalytic amount of piperidine was added.The solution was heated for 3 h and the solid product isolated was recrystallized from DMF– EtOH. 8a: mp a300 °C, yield 70%; vmax/cmµ1 (KBr) 3600–3359 (OH, NH2, NH); m/z 205 (Found: C, 41.1; H, 3.5; N, 47.4. C7H7N7O requires C, 40.9; H, 3.4; N, 47.8%). 8b: mp a300 °C, yield 68%; vmax/cmµ1 (KBr) 3351–3280 (OH, NH2, NH); m/z 281 (Found: C, 55.3; H, 3.5; N, 34.4. C13H11N7O requires C, 55.5; H, 3.9; N, 34.9%). 8 - B e n z o y l - 3 - h y d r o x y - 5 - i m i n o - 7 - m e t h y l s u l f a n y l - 5 H - t h i a z o l o [ 2 , 3 - a ] -pyridine-6-carbonitrile 10.·A mixture of 2-benzoylmethyl-1,3- thiazol-4(5H)-one 9 (0.05 mol) and 1 (0.05 mol) was refluxed in DMF (50 ml) containing potassium carbonate (0.05 mol) for 3 h.The reaction mixture was then cooled, poured into iced water and neutralized with dil. HCl. The formed product was collected by filtration and recrystallized from DMF. 10: mp 260 °C, yield 78%; vmax/cmµ1 (KBr) 2205 (CN), 1685 (CO), 1650 (CO); dH [(CD3)2SO] 2.92 (s, 3 H, SCH3), 3.19 (s, 2 H, CH2), 7.14 (s, 1 H, NH), 7.48 (s, 1 H, CH), 7.52–8.00 (m, 5 H, Ph), 9.33 (s, br, 1 H, OH); m/z 341 (Found: C, 55.9; H, 3.0; N, 12.4.C16H11N3S2O2 requires C, 56.3; H, 3.2; N, 12.3%). 4 - M e t h y l s u l f a n y l - 2 - o x o - 1 , 2 , 6 , 7 - t e t r a h y d r o - 5 H - c y c l o p e n t a [ b ]p y r i - dine-3-carbonitrile 12.·A solution of the equivalent amounts of cyclopentanone and 1 (0.05 mol) was stirred at room temperature for 20 h.The solution was then poured into iced water and neutralized with dil. HCl to separate the product, which was filtered and recrystallized from ethanol. 12: mp 262 °C, yield 65%; vmax/cmµ1 (KBr) 3650, 3500, 3270 (NH), 2214 (CN), 1638 (CO); dH [(CD3)2SO] 2.67 (s, 3 H, SCH3), 2.70–2.81 (m, 6 H, 3CH2), 12.55 (brs, 1 H, NH); m/z 206 (Found: C, 46.0; H, 4.9; N, 3.2. C10H10N2SO requires C, 46.2; H, 4.8; N, 13.6%). 3 - A m i n o - 1 , 4 , 5 , 6 , 7 , 8 - h e x a h y d r o c y c l o p e n t a [ e ] p y r a z o l o [ 4 , 5 - c ]p y r i - din-4-one 13.·To a solution of 12 (0.01 mol) and hydrazine hydrate (0.01 mol) in ethanol (30 ml) a catalytic amount of piperidine was added. The solution was then refluxed for 6 h and the solid product obtained was filtered and recrystallized from DMF. 13: mp a300 °C, yield 55%; vmax/cmµ1 (KBr) 3441, 3355 (NH2, NH), 1635 (CO); dH [(CD3)2SO] 2.05 (m, 2 H, CH2), 2.62–2.70 (m, 4 H, 2CH2), 5.21 (brs, 2 H, NH2), 10.75 (brs, 1 H, NH), 11.77 (brs, 1 H, NH); m/z 190 (Found: C, 56.4; H, 5.0; N, 29.8.C9H10N4O requires C, 56.8; H, 5.3; N, 29.4%). 2 - I m i n o - 7 , 7 - d i m e t h y l- 4 - m e t h y l s u l f a n y l - 5 - o x o - 5 , 6 , 7 , 8 - t e t r a h y d r o - 2H-chromene-3-carbonitrile 14.·To a solution of dimedone (0.05 mol) and 1 (0.05 mol) in 1,4-dioxane (80 ml), the equivalent amount of potassium hydroxide was added. The solution was then heated under reflux for 2 h and, after being allowed to cool, poured into iced water.The solution was then neutralized with dil. HCl and the formed product was collected by suction filtration and recrystallized from ethanol. 14: mp a300 °C, yield 85%; vmax/cmµ1 (KBr) 3406–3257 (NH), 2205 (CN), 1687 (CO); dH [(CD3)2SO] 1.04 [s, 6 H, (CH3)2], 2.50 (s, 3 H, SCH3), 2.59 (s, 2 H, CH2), 2.63 (s, 2 H, CH2), 6.49 (brs, 1 H, NH); m/z 262 (Found: C, 59.2; H, 5.0; N, 10.5.C13H14N2SO2 requires C, 59.5; H, 5.3; N, 10.7%). ( 3 , 3 , 6 , 6 - T e t r a m e t h y l - 1 , 8 - d i o x o - 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 - o c t a h y d r o - 9 Hxanthen- 9-ylidene)malononitrile 15.·A solution of dimedone (0.01 mol) and 1 (0.01 mol) was heated under reflux in pyridine (30 ml) for 3 h. The solution was then poured into iced water and neutralized with dil. HCl to precipitate the solid product. The formed product was isolated by suction filtration and recrystallized from ethanol. 15: mp a300 °C, yield 85%; vmax/cmµ1 (KBr) 2227 (CN), 1673 (CO); dH [(CD3)2SO] 0.98–1.04 [s, 12 H, 2N(CH3)2], 2.51 (s, 4 H, 2CH2), 2.63 (s, 4 H, 2CH2); m/z 336 (Found: C, 71.0; H, 6.1; N, 8.0. C20H10N2O3 requires C, 71.4; H, 5.9; N, 8.3%). 3 - A m i n o - 7 , 7 - d i m e t h y l - 4 , 5 , 6 , 7 , 8 , 9 - h e x a h y d r o - 1 H - b e n z o [ e ] p y r a - zolo[4,5-c]pyridine-4,9-dione 16.·A solution of equivalent amounts of 14 and hydrazine hydrate (0.01 mol) in ethanol (20 ml) was refluxed for 4 h. The solution was then concentrated and set aside to precipitate the product, which was filtered off and recrystallized from DMF. 16: mp a300 °C, yield 65%; vmax/cmµ1 (KBr) 3747, 3470, 3229, 3175 (NH2, NH), 1681; dH [(CD3)2SO] 1.03 [s, 6 H, (CH3)2], 2.36 (s, 2 H, CH2), 2.69 (s, 2 H, CH2), 5.38 (brs, 2 H, NH2), 11.40 (brs, 1 H, NH), 12.00 (brs, 1 H, NH); m/z 246 (Found: C, 58.3; H, 5.4; N, 23.0. C12H14N4O2 requires C, 58.5; H, 5.7; N, 22.7%). Received, 6th January 1997; Accepted, 18th March 1997 Paper E/7/00128B References 1 G. E. H. Elgemeie and B. A. W. Hussain, Tetrahedron, 1994, 50, 199. 2 G. E. H. Elgemeie, A. M. Attia, D. S. Farag and S. M. Sherif, J. Chem. Soc., Perkin Trans. 1, 1994, 1285. 3 G. E. H. Elgemeie, S. E. El-Ezbawy, H. A. Ali and A. K. Mansour, Bull. Chem. Soc. Jpn., 1994, 67, 738. 4 G. E. H. Elgemeie and N. M. Fathy, Tetrahedron, 1995, 51, 3345. 5 G. E. H. Elgemeie, A. M. Attia and N. M. Fathy, Liebiegs Ann. Chem., 1994, 955. 6 G. E. H. Elgemeie and A. M. Attia, Carbohydr. Res., 1995, 268, 295. 7 G. E. H. Elgemeie, H. A. Ali and A. M. Elzanate, J. Chem. Res. (S), 1996, 340. Scheme 2

ISSN:0308-2342    

DOI:10.1039/a700128b

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

258 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 258–259† The Topography of Rhodium in Bimetallic Rhodium– Palladium Catalysts on a Silica Support† Paulo E. Araya,*a Eduardo E. Mir�ob and Laura Cornagliab aDepartamento de Ingenier�ýa Qu�ýmica, Universidad de Chile, Casilla 27877, Santiago, Chile bFacultad de Ingenier�ýa Qu�ýmica, Universidad Nacional de Litoral, 3000 Santa F�e, Argentina Benzene and hex-1-ene hydrogenation reactions are used to obtain information about the concentration and topography of the metals on the surface of bimetallic Rh–Pd/SiO2 catalysts.In a previous paper,1 the oxidation rates of CO with oxygen to produce CO2 were compared for a series of Pd–Rh/SiO2 catalysts prepared by different methods of impregnation. The Pd and Rh composition varied between 0% Rh–100% Pd and 100% Rh–0% Pd, maintaining a total metal load equal to 2% (w/w) with respect to the support. In brief, in the coimpregnation (CI) method the impregnation of both metals is done simultaneously, the support (Cabosil 5H) being treated with an aqueous solution of the inorganic salts of the two metals (PdCl2 and RhCl3).In the sequential impregnation (SI) method, the support is initially impregnated with Rh as described above and then dried and calcined at 500 °C. The Pd is then deposited in a separate second stage using an organic solution of bis(acetylacetonato) palladium in dichloromethane to avoid dissolving the deposited Rh.The CI method favours the formation of Pd and Rh alloys,2 while the SI method should lead to a random Pd deposit on the surface of the support impregnated with Rh,3 and should not form alloys to any significant extent. The mixed catalysts of the same composition, but prepared by the two different methods, showed important differences in their activity towards the oxidation of CO with oxygen. In general, the CO oxidizing activity of the catalysts prepared by the CI method is lower than that of those prepared by SI.The lower activity of the former can be attributed to various factors, such as the formation of alloys superficially enriched in the less active component (Pd), the existence of very small Rh clusters that are unable to oxidize CO, and/or the presence on the surface of isolated Rh atoms on which CO is adsorbed in the gem form, which is a low-activity species. Although a large quantity of CO adsorbed in the gem form could be observed in the less active catalysts, the available experimental data did not allow a clear separation to be made of the effects of the various factors mentioned above on the CO oxidation rate.This paper reports an attempt to obtain more information on the topography and concentration of Rh on the surface of some of these catalysts, in order to determine if, in addition to the presence of CO adsorbed in the gem form, the low activity of catalysts prepared by CI is due to a geometric factor (Rh cluster size on the surface) or to a superficial enrichment with Pd.To this end, hydrogenation experiments were carried out on hex-1-ene and benzene over some of the catalysts used in the oxidation of CO. According to Del Angel et al.,2 the reduction of hex-1-ene can occur easily on very small Rh clusters, and this reaction is not sensitive to the metal structure. The hydrogenation of benzene, however, requires at least one Rh cluster larger than 10 Å in diameter which can accommodate the benzene molecule.A comparison of the catalyst rates in these reactions would make it possible, therefore, to obtain valuable information on the topography and composition of Rh on the surface of these bimetallic catalysts. The surface of the catalysts was also analysed by the XPS technique on a Shimadzu 750 ESCA instrument using MoKa radiation. The bond energies were referred to Si 2p adopting the value of 103.8 eV in agreement with Gallaher et al.4 The atomic ratios were calculated using the Si 2p, Rh 3d and Pd 3d areas, the photoionization section given by Scofield,5 the mean free path reported by Seah and Dench6 and the instrument function supplied by Shimadzu.Experimental The hydrogenation experiments were carried out in a piston flow reactor operating under differential conditions. The reagents, hydrogen and organic compound, were fed into the reactor by bubbling the H2 through the hex-1-ene (at 0 °C) or the benzene (at 20 °C).The amount of catalyst used was about 0.001 g for the hydrogenation of hex-1-ene, and 0.030 g for that of benzene. The catalyst had been previously activated by allowing H2 to flow through it at 200 °C for 2 h. The temperature of the reactor was then lowered to that required for each experiment (0 °C for hex- 1-ene and 80 °C for benzene hydrogenation), and the direction of the H2 stream was reversed to make it go through the bubbler with the organic reagent. During this time the reactor remained isolated, and once the concentration of organic compound in the H2 stream became stabilized, the flow was directed to the reactor.The reagents and products were analysed by GC, using a thermal conductivity detector and a column (6 mÅ1/8 in ID) filled with 20% Carbowax on a Chromosorb support. Results and Discussion Bimetallic catalysts containing 0.66% Rh and 1.34% Pd were chosen for this work. The catalyst prepared by the CI method showed a CO oxidizing activity markedly lower than that of the catalyst prepared by SI.The oxidation rates of CO at 100 °C with these catalysts expressed as TOF Turn Over Frequency), i.e. in mol of CO2 produced per mol of exposed metal (Pd+Rh) on the surface per second, are shown in Table 1, which also shows the reduction rates of hex-1-ene and benzene found in this study. It is important to note that the activity of Rh in all the reactions considered was far greater than that of Pd, so it can be assumed that the changes in the activity of the catalyst may be attributed to the supported Rh phase.It is seen that, in the oxidation of CO and reduction of benzene reactions, the activity of the catalyst prepared by the CI method is considerably lower than that of the catalyst prepared by SI. However, in the hydrogenation of hex-1-ene both catalysts have similar activities. Table 2 shows the relationship between the activities of the two catalysts in the various reactions considered in this study.It can be seen *To receive any correspondence. †This is a Short Paper as defined in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1997, Issue 1]; there is therefore no corresponding material in J. Chem. Research (M). Table 1 Activities of catalysts for the various reactions TOF (sµ1) Catalyst CO oxidationa Hex-1-ene hydrogenation Benzene hydrogenation CI SI Monometallic 0.300Å10µ3 1.337Å10µ3 — 7.83 7.97 25.61 0.035 0.051 0.302 (0.66% Rh) aFrom ref. 1.J. CHEM. RESEARCH (S), 1997 259 that the ratio of the activities is almost unity for the hydrogenation of hex-1-ene. If it is accepted that the reaction is not sensitive to structure, this result suggests that the quantity of Rh on the surface of both catalysts is the same. Table 1 also reports the activity for the hydrogenation of hex-1-ene of a monometallic Rh catalyst with the same Rh content as the bimetallic catalysts (0.66% Rh). This catalyst was prepared by the wetness impregnation method using a RhCl3 solution as described in reference 1.If the TOFs of the bimetallic catalysts prepared using the CI and SI methods are calculated by the number of Rh atoms on the surface, considering the bulk composition, TOFs equal to 23.73 and 24.15 sµ1 are obtained for the CI and SI catalysts, respectively, in excellent agreement with the TOF of the monometallic catalyst, thus confirming the assumption that the surface composition is the same as the bulk composition, for both bimetallic catalysts.This conclusion is also supported by the results of the XPS characterization given in Table 3, which shows that the surface composition of both catalysts is almost the same, and it also similar to that of the bulk. Therefore, it is reasonable to suppose ferences in the activities of these catalysts in the oxidation of CO and the reduction of benzene cannot be attributed to differences in their surface composition.In the reduction of benzene, the lower activity of the catalyst prepared by CI as compared to that prepared by SI would be due to the existence of a greater number of Rh atoms forming a small-size cluster (smaller than 10 Å) on which the hydrogenation of benzene is hindered.2 In conclusion, it can be said that the low activity of the catalyst prepared by CI in the oxidation of CO is essentially due to the topography of Rh on the surface of the bimetallic catalyst, and not to a decrease in the concentration of this metal on the surface. We thank Fondecyt for the financial support of this work. Received, 16th December 1996; Accepted, 20th March 1996 Paper E/6/08411G References 1 P. Araya, J. P. Berrios and E. E. Wolf, Appl. Catal., 1992, 92, 17. 2 G. Del Angel, G. Cow and F. Figueras, J. Catal., 1985, 95, 167. 3 S. Oh and J. Carpenter, J. Catal., 1986, 98, 178. 4 G. Gallaher, J. G. Goodwin, Chen-Shi Huang and M. Hovalla, J. Catal., 1993, 140, 453. 5 J. H. Scofield, J. Electron Spectrosc. Relat. Phenom., 1976, 8, 129. 6 M. P. Seah and W. A. Dench, SIA, Surf. Interface Anal., 1979, 1, 2. Table 2 Relation between the activities of CI and SI catalysts Reaction Ratio TOF(CI)/TOF(SI) CO oxidation Hex-1-ene hydrogenation Benzene hydrogenation 0.22 0.98 0.70 Table 3 XPS characterization and chemisorption results of catalysts XPS (atomic ratio) Gas adsorbed (mol/mol metal)a Catalyst Rh/Si Pd/Si H/metal CO/metal CI SI Monometallic 0.0020 0.0023 · 0.0040 0.0042 · 0.37 0.30 0.42 0.46 0.27 · (0.66% Rh) aFrom Ref. 1.

ISSN:0308-2342    

DOI:10.1039/a608411g

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

NH NH2 CN Y S 3 OEt NH2 Cl– X + CN X 1 EtOH–HCl 0 °C CN NH2 S EtOH–MeCO2 –NH4 + NH NH2 H2N S 4 N NH2 H2N S 5 N NH2 H2N NHNH2 6 EtO–Na+ RI in the case of 5b NH2NH2 X R X EtO2C NH NH2 H2N S 7 X NNAr Ar N NCl– + a b c COPh CO2Et C(S)NH2 1,2,4 a b c Ph OH SH 3 X Y a b c d COPh CO2Et COPh CO2Et 5 X Me Me CH2COPh CH2COPh R a b c d COPh CO2Et C(S)NH2 COPh 7 X 4-MeC6H4 4-MeC6H4 4-MeC6H4 4-OMeC6H4 Ar 2 260 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 260–261† Novel Synthesis of Pyridine-2(1H)-thiones: Reaction of Imino Esters with Cyanothioacetamide† Galal E.H. Elgemeie,*a Ahmed H. Elghandour,b Hosny A. Alib and Ahmed A. Hussainb aChemistry Department, Faculty of Science, Helwan University, Helwan, Cairo, Egypt bChemistry Department, Faculty of Science, Cairo University (Bani Suef Branch), Bani Suef, Egypt A novel synthesis of pyridine-2(1H)-thiones via the reaction of imino esters with cyanothioacetamide is reported and the synthetic potential of the method is demonstrated.Imino esters are highly reactive compounds and are extensively utilized as reactants or reaction intermediates since their imino and ester functions are suitably situated to enable reactions with common bidentate reagents to form a variety of heterocyclic compounds.1,2 Moreover, the active hydrogen atom on C-2 of these compounds can also take part in a variety of condensation and substitution reactions. As part of a medicinal chemistry program in our laboratories, the syntheses of several substituted pyridine-2(1H)-thiones were required.The importance of the synthesized compounds as intermediates for the synthesis of the biologically active deazafolic acid and deazapyrimidine nucleoside ring systems prompted our interest in the synthesis and chemistry of this class of compounds.3–10 We now report the novel reaction of imino esters 2 with cyanothioacetamide. It was found that treating the cyano compounds 1a–c with hydrogen chloride in absolute ethanol at 0 °C gave the imino esters 2 in good yield.Compounds 2 reacted with cyanothioacetamide in refluxing ethanol containing ammonium acetate to yield 1:1 adducts, for which two possible structures, 3 and 4, were considered. The structure of 4 was established and confirmed on the basis of elemental analysis and spectral data. The IR spectrum of compound 4a showed the absence of a cyano group and the presence of a carbonyl group at 1650 cmµ1. The formation of 4 from the reaction of 2 with cyanothioacetamide is assumed to proceed via the initial Michael addition of the active methylene in 2 to the cyano group in cyanothioacetamide to yield intermediates, which cyclize via ethanol elimination to give the stable pyridine- 2(1H)-thione derivatives 4.Compounds 4 bearing latent functional substituents were found to be useful for the synthesis of pyridine derivatives. Thus, compounds 4 reacted with methyl iodide and phenacyl bromide in sodium ethoxide to afford the corresponding S-substituted derivatives 5.When compound 5b was treated with hydrazine, the 2-hydrazino derivative 6 was obtained. Compounds 4 were also coupled with aryldiazonium chlorides in ethanol containing sodium acetate to yield the corresponding hydrazones 7. The structures of 7 were established on basis of their elemental analysis and spectral data. Experimental All melting points are uncorrected. The IR spectra were obtained (KBr disk) on a Perkin Elmer/1650 FT-IR instrument. 1H NMR spectra were measured on a Varian 400 MHz spectrometer for solutions in (CD3)2SO using SiMe4 as internal standard. Mass spectra were recorded on a Varian MAT 112 spectrometer. Analytical data were obtained from the Microanalytical Data Center at Cairo University. Compounds 2a,b were prepared following the literature procedures.11 b-Imino-b-ethoxythioacetamide Hydrochloride 2c.·Hydrogen chloride gas was passed through a mixture of cyanothioacetamide (0.1 mol) and absolute ethanol (0.1 mol) in dry 1,4-dioxane for 3 h at 0 °C.The resultant precipitate was isolated by filtration and recrystallized from 1,4-dioxane–ethanol (2:1) to give 2c, mp 154 °C, yield 96%; vmax (KBr)/cmµ1 3590–3124 (NH2, NH). 5-Substituted 4,6-Diaminopyridine-2(1H)-thiones 4. General Procedure. ·A mixture of cyanothioacetamide (0.1 mol) and compounds 2a–c (0.1 mol) was treated with sodium acetate (0.15 mol) *To receive any correspondence.†This is a Short Paper as defined in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1997, Issue 1]; there is therefore no corresponding material in J. Chem. Research (M). Scheme 1J. CHEM. RESEARCH (S), 1997 261 and dry ethanol (100 ml) and then heated for 12 h. The solution was then poured into iced water and the resultant precipitate was collected and recrystallized from the appropriate solvent. 4a: mp 190 °C, yield 67%; vmax (KBr)/cmµ1 3637–3443, 3302 (NH2), 1650 (CO); dH [(CD3)2SO] 6.18 (brs, 2 H, NH2), 6.83 (s, 1 H, CH), 7.22–7.58 (m, 5 H, Ph), 7.62 (brs, 2 H, NH2), 13.86 (brs, 1 H, NH); m/z 245 (M+) (Found: C, 60.0; H, 4.8; N, 17.6.C12H11N3SO requires C, 58.8; H, 4.5; N, 17.1%). 4b: mp a300 °C, yield 53%; vmax (KBr)/cmµ1 3400–3132 (NH2, NH), 1747 (CO); m/z 213 (M+) (Found: C, 45.6; H, 5.0; N, 19.9. C8H11N3SO2 requires C, 45.1; H, 5.2; N, 19.7%). 4c: mp a300 °C, yield 53%; vmax (KBr)/cmµ1 3404–3200 (NH2, NH); m/z 200 (M+) (Found: C, 35.8; H, 4.3; N, 28.5.C6H8N4S2 requires C, 36.0; H, 4.0; N, 28.0%). 5-Substituted 4,6-Diamino-2-methylsulfanylpyridines 5a,b. General Procedure.·To a solution of sodium ethoxide [prepared by dissolving sodium metal (0.01 mol) in anhydrous ethanol (10 ml)], the equivalent amounts of 4a,b dissolved in 6 ml DMF were added. The reaction mixture was refluxed for 15 min, cooled, and then methyl iodide (0.012 mol) was added. The solution was stirred for 1 h at room temperature and allowed to stand overnight.The product was isolated by neutralizing the reaction mixture with dil. HCl and recrystallizing from the appropriate solvent. 5a: mp 165 °C, yield 62%; vmax (KBr)/cmµ1 3227, 3112 (NH2), 1707 (CO); m/z 259 (M+) (Found: C, 60.5; H, 4.8; N, 16.0. C13H13N3SO requires C, 60.2; H, 5.0; N, 16.2%). 5b: mp a300 °C, yield 79%; vmax (KBr)/cmµ1 3350–3186 (NH2), 1750–1730 (CO); m/z 227 (M+) (Found: C, 47.8; H, 5.4; N, 18.4. C9H13N3SO2 requires C, 47.5; H, 5.7; N, 18.4%). 5-Substituted 4,6-Diamino-2-phenacylsulfanylpyridines 5c,d. General Procedure.·To a solution of sodium ethoxide (0.01 mol), the equivalent amounts of 4a,b and phenacyl bromide were added. The mixture was then heated for 3 h and the product isolated by neutralization of the reaction mixture with dil. HCl and recrystallization from ethanol. 5c: mp 175 °C, yield 70%; vmax (KBr)/cmµ1 3650, 3334 (NH2), 1706, 1633 (2CO); dH [(CD3)2SO] 4.49 (s, 2 H, CH2), 6.77 (brs, 2 H, NH2), 6.92 (s, 1 H, CH), 7.18–7.76 (m, 10 H, 2Ph), 7.89 (brs, 2 H, NH2); m/z 363 (M+) (Found: C, 66.5; H, 4.5; N, 11.9.C20H17N3SO2 requires C, 66.1; H, 4.7; N, 11.6%). 5d: mp 221 °C, yield 56%; vmax (KBr)/cmµ1 3327 (NH2), 1795–1647 (2 CO); m/z 331 (M+) (Found: C, 57.7; H, 5.4; N, 12.8. C16H17N3SO3 requires C, 58.0; H, 5.1; N, 12.7%). Ethyl 4,6-Diamino-2-hydrazinopyridine-5-carboxylate 6.·An equivalent mixture of 5b and hydrazine hydrate (0.01 mol) was stirred in ethanol (20 ml) for 1 h.The product that separated on cooling was filtered and recrystallized from DMF–EtOH. 6: mp a300 °C, yield 54%; vmax (KBr)/cmµ1 3748, 3450–3175 (NH2, NH), 1735–1688 (CO); m/z 211 (M+) (Found: C, 45.0; H, 5.8; N, 33.5. C8H13N5O2 requires C, 45.5; H, 6.2; N, 33.17%. 5-Substituted 3-Arylazo-4,6-diaminopyridine-2(1H)-thiones 7a–d. General Procedure.·A solution of compounds 4 (0.01 mol) in ethanol containing sodium acetate (2.0 g) was cooled to 0 °C and then treated gradually with a cold solution of aryldiazonium chloride [prepared from arylamine (0.01 mol) and the appropriate quantities of HCl and NaNO2].The solid product formed was collected and recrystallized from the appropriate solvent. 7a: mp 210 °C, yield 80%; vmax (KBr)/cmµ1 3443, 3304, 3198 (NH2, NH), 1640–1620 (CO); dH [(CD3)2SO] 2.52 (s, 3 H, CH3), 7.13 (brs, 2 H, NH2), 7.20–7.50 (m, 9 H, Ph and C6H4), 7.97 (brs, 2 H, NH2), 9.60 (brs, 1 H, NH); m/z 363 (Found: C, 62.3; H, 4.5; N, 19.0.C19H17N5SO requires C, 62.8; H, 4.7; N, 19.3%). 7b: mp 280 °C, yield 75%; vmax (KBr)/cmµ1 3550–3367 (NH2, NH), 1677–1614 (CO); m/z 331 (M+) (Found: C, 54.8; H, 4.98; N, 21.4. C15H17N5SO2 requires C, 54.4; H, 5.14; N, 21.15%). 7c: mp a300 °C, yield 86%; vmax (KBr)/cmµ1 3400–3122 (NH2, NH); m/z 318 (M+) (Found: C, 49.2; H, 4.6; N, 27.0. C13H14N6S2 requires C, 49.0; H, 4.4; N, 26.4%). 7d: mp 222 °C, yield 67%; vmax (KBr)/cmµ1 3450, 3368–3275 (NH2, NH), 1680–1619 (CO); dH [(CD3)2SO] 3.88 (s, 3 H, OCH3), 7.06 (brs, 2 H, NH2), 7.11–7.55 (M, 9 H, Ph and C6H4), 7.78 (brs, 2 H, NH2), 9.99 (brs, 1 H, NH); m/z 379 (M+) (Found: C, 59.8; H, 4.7; N, 18.3.C19H17N5SO2 requires C, 60.2; H, 4.5; N, 18.5%). Received, 2nd December 1996; Accepted, 25th March 1997 Paper E/6/08114B References 1 R. Troschutz and T. Dennstedt, Arch. Pharm., 1994, 327, 85. 2 M. T. Cocco, C. Congiu, A. Maccioni and V. Onnis, J. Heterocycl. Chem., 1992, 29, 1631. 3 G. E. H. Elgemeie, A. M. Attia, D. S. Farag and S. M. Sherif, J. Chem. Soc., Perkin Trans. 1, 1994, 1285. 4 G. E. H. Elgemeie, S. E. El-Ezbawy, H. A. Ali and A. K. Mansour, Bull. Chem. Soc. Jpn., 19094, 67, 738. 5 G. E. H. Elgemeie and B. A. Hussain, Tetrahedron, 1994, 50, 199. 6 G. E. H. Elgemeie, A. M. Attia and N. M. Fathy, Leibigs Ann. Chem., 1994, 955. 7 G. E. H. Elgemeie and N. M. Fathy, Tetrahedron, 1995, 51, 3345. 8 G. E. H. Elgemeie, H. A. Ali and A. M. Elzanate, J. Chem. Res. (S), 1996, 340. 9 G. E. H. Elgemeie and A. M. Attia, Carbohydr. Res., 1995, 268, 295. 10 G. E. H. Elgemeie, A. M. El-zanate and A. K. Mansour, J. Chem. Soc., Perkin Trans. 1, 1992, 1037. 11 T. Emoto and A. Ozawa, Japan Kokai, 1977, 7 652 118 (Cl. C 07C67 122) (Chem. Abstr., 1977, 86, 16305 q).

ISSN:0308-2342    

DOI:10.1039/a608114b

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

Ph OSiMe3 1 Ph I+Ph O Ph CH2 + O 2 X = OBF2 or BF4 Ph R O O 4 3 (PhIO) n– BF3•Et2O or HBF4 R OSiMe3 R = Ph, substituted phenyl, etc X– (1) Ph O 5 CH2 CHCH2SiMe3 (PhIO) n–Me3SiOTf 4 (R = Ph) 1 SiMe3 I OSiMe3 Ph Me3SiOTf 1 –(Me3Si)2O Ph O I Ph –PhI 5 6 7 (PhIO) n– 262 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 262–263† a-Allylation of Carbonyl Compounds via Silyl Enol Ethers and Silyl Ketene Acetals using a Hypervalent Iodine Reagent† Robert M. Moriarty,* Widanagamage R.Epa and Om Prakash*‡ Chemistry Department, University of Illinois at Chicago, 845-West Taylor Street, Chicago, IL, 60607, USA Oxidation of allyltrimethylsilane with iodosobenzene and trimethylsilyl trifluoromethanesulfonate followed by treatment with trimethylsilyl enol ethers of ketones or trimethylsilyl ketene acetals of esters/lactones provides a new method for the a-allylation of the corresponding carbonyl compounds. There is considerable interest in the hypervalent iodine oxidation of a wide variety of organic compounds.1 One important goal achieved using this approach is the formation of carbon–carbon bonds.2 Oxidation of silyl enol ethers reported from our laboratory3 and other research groups4,5 has offered a useful way of accomplishing such a goal.We have reported that oxidation of silyl enol ethers with iodosobenzene in the presence of boron trifluoride–diethyl ether produces symmetrical 1,4-diones [e.g. 4, R=Ph in eqn. (1)].3 The method could not be used to synthesise unsymmetrical products.Zhdankin et al. modified this approach by generating in situ the hypervalent iodine intermediate, phenacyliodonium tetrafluoroborate (2, X=BF4), to synthesise cross-coupled products.4 Only the a-(trimethylsilyloxy) styrene was employed as a substrate. As an effort to introduce a new method for carbon–carbon cross coupling, we now report the a-allylation of carbonyl compounds via silyl enol ethers and silyl ketene acetals.Based on previous results that the iodine(III) intermediate 2, generated from the oxidation of a silyl enol ether, is equivalent to carbocation 3 and capable of forming a carbon– carbon bond with silyl enol ether itself or with external carbon nucleophiles thereby producing 4 [eqn. (1)], we first investigated the a-allylation by treating silyl enol ether 1 with iodosobenzene and trimethylsilyl trifluoromethanesulfonate followed by addition of allyltrimethylsilane. The reaction, however, gave the self coupling product butane-1,4-dione 4 (R=Ph) and the expected allylated ketone 5 was not obtained in any detectable amount (Scheme 1). Use of iodosobenzene and boron trifluoride–diethyl ether also gave 4.The above observations led us to change the strategy with the addition of allyltrimethylsilane followed by the addition of the trimethylsilyl enol ether. Thus, allyltrimethylsilane was added to a solution of (PhIO)n–Me3SiOTf in dichloromethane. The reaction was monitored by 1H NMR and the formation of allyliodine(III) intermediate 6 was indicated by the observation of a downfield shift of the methylene protons from d 1.8 to 5.0.Addition of silyl enol ether 1 afforded the a-allylated product 56 in 69% yield (Scheme 2). A similar approach was successfully used for the a-allylation of other silyl enol ethers (Table 1, entries 1–3). The method is regioselective as 8 gave only 9 in 76% yield (Table 1, entry 2). Furthermore, trimethylsilyl ketene acetals of esters and lactones can also be a-allylated using this approach (Table 1, entries 4–6).A plausible mechanism for this reaction involves the generation of the reactive IIII species PhI(OSiMe3)OTf7 from the reaction of iodosobenzene and trimethylsilyl trifluoromethanesulfonate. Allyltrimethylsilane then forms the initial intermediate 6 which then reacts with the silyl enol ether (e.g. 1) to give another intermediate 7. Finally, ligand coupling and reductive elimination of iodobenzene gives the a-allylated product (Scheme 2).Experimental Typical Procedure.·To an ice cooled suspension of iodosobenzene (528 mg, 2.4 mmol) in dry dichloromethane (75 ml) under nitrogen was added trimethylsilyl trifluoromethanesulfonate (0.48 ml, 566 mg, 2.4 mmol). To the resulting yellow solution was added allyltrimethylsilane (0.38 ml, 274 mg, 2.4 mmol) which turned the solution colourless. The cooling bath was then removed and the *To receive any correspondence.†This is a Short Paper as defined in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1997, Issue 1]; there is therefore no corresponding material in J. Chem. Research (M). ‡On leave of absence from Kurukshetra University, Kurukshetra, 132119, India. Scheme 1 Scheme 2OSiMe3 OSiMe3 OSiMe3 8 Ph OEt OSiMe3 O OSiMe3 O OSiMe3 O O O 9 O O O O CO2Et J. CHEM. RESEARCH (S), 1997 263 trimethylsilyl enol ether of acetophenone (1) (384 mg, 2.0 mmol) was added.After stirring overnight at room temperature, the reaction mixture, now violet, was washed with water (2Å25 ml) and saturated aqueous sodium hydrogen carbonate (25 ml). Drying of the organic phase (MgSO4) followed by removal of solvent in vacuo yielded the crude product as a slightly coloured liquid. Purification by flash chromatography on silica gel with ethyl acetate–hexane as eluent gave 208 mg (69%) of 1-phenylpent-4-en-1-one (5) as a colourless oil,6 IR (neat) v/cmµ1 1660, 1705; dH (CDCl3, 200 MHz) 2.5 (m, 2 H), 3.1 (t, 2 H), 5.1 (m, 2 H), 5.9 (m, 1 H), 7.5–8.0 (m, 5 H); dC (100 MHz) 28.1 (C3), 37.7 (C2), 115.3 (C5), 128, 128.5, 133 (aromatic), 136.9 (aromatic or C4), 137.3 (aromatic or C4), 199.43 (C1).Following the above procedure, other silyl enol ethers and silyl ketene crystals were converted into the corresponding a-allylcarbonyl compounds (Table 1). We thank the National Science Foundation (Grant No. 9520157) for financial support.Received, 21st February 1997; Accepted, 1st April 1997 Paper E/7/01224A References 1 A. Varvoglis, The Organic Chemistry of Polycoordinated Iodine, VCH, New York, 1992; Hypervalent Iodine in Organic Synthesis, Academic Press, 1996; P. J. Stang and V. V. Zhdankin, Chem. Rev., 1996, 96, 1123; G. F. Koser, The Chemistry of Halides, Pseudohalides and Azides, Suppl. D2, ed. S. Patai and Z. Rappoport, Wiley, Chichester, 1995, ch. 21, p. 1173; O. Prakash, N.Rani, M. P. Tanwar and R. M. Moriarty, Contemp. Org. Synth., 1995, 2, 121; O. Prakash, N. Rani and P. K. Sharma, Synlett, 1994, 221; R. M. Moriarty, R. K. Vaid and G. F. Koser, Synlett, 1990, 365; R. M. Moriarty and O. Prakash, Acc. Chem. Res., 1986, 19, 244. 2 R. M. Moriarty and R. K. Vaid, Synthesis, 1990, 431. 3 R. M. Moriarty, O. Prakash, M. P. Duncan, J. Chem. Soc., Perkin Trans. 1, 1987, 559; Synth. Commun., 1985, 15, 789. 4 V. V. Zhdankin, M. Mullikin, R. Tykwinski, R.Cable, B. Berguland, N. S. Zefirov and A. S. Koz’min, J. Org. Chem., 1989, 54, 2605; N. S. Zefirov, N. S. Samoniya, T. G. Kutateladze and V. V. Zhdankin, J. Org. Chem. USSR (Engl. Transl.), 1991, 27, 220. 5 K. Chen and G. F. Koser, J. Org. Chem., 1991, 56, 5764. 6 E. N. Marvell and H. C. T. Li, J. Am. Chem. Soc., 1978, 100, 883. 7 R. M. Moriarty, R. W. Epa, R. Penmasta and A. Awasthi, Tetrahedron Lett., 1989, 30, 667. 8 J. Tsuji, I. Minami, I. Shimiju and H. Kataoka, Chem. Lett., 1984, 1133. 9 H. O. House, D. T. Manning, D. Mellilo, L. F. Lee, O. R. Haynes and B. E. Wikes, J. Org. Chem., 1976, 41, 855. 10 N. A. Bumagin, A. N. Kasatkin and I. P. Beletskaya, Dokl. Acad. Nauk. SSSR, 1982, 266, 862. 11 A. I. Meyers, Y. Yamamoto, E. D. Mihelich and R. A. Bell, J. Org. Chem., 1980, 45, 2792. 12 A. Patra and S. K. Misra, Magn. Reson. Chem., 1991, 29, 749. Table 1 a-Allylation of carbonyl compounds Entry Substrate Producta Yield (%) (Lit.) 1 2 3 4 5 6 52 65 61 70 40 75 (8) (9) (8) (10) (11) (12) aSpectral data (IR, 1H NMR and MS) of all products were in agreement with those previously reported or required.

ISSN:0308-2342    

DOI:10.1039/a701224a

出版商:RSC    

年代:1997

数据来源: RSC