Studies on the Carbon Zip Reaction of 2-Oxocycloalkane-1-carbonitriles

As a part of continuing interest in the zip reaction, we present the results on a carbon ring-enlargement reaction of activated ketones with a CN group as a charge stabilizer. Two series of (1-cyano-2-oxocy-cloalkyl)alkanoates were prepared from 8- and 12-membered cyano-ketones 1 and 2 , respectively, namely the propanoates 3 and 4 , the butanoates 6 , 8 and 9 as well as the pentanoates 12 and 15 . While treatment with t-BuOK of the former two homologous esters resulted in both ring enlargement and competitive transesterification, the pentanoates 12 and 15 afforded mostly the diastereoisomeric mixtures of bicyclic alcohols 20a – c and 31a , b , respectively, which remained intact on further exposure to base. It was shown that – apart from the base used (t-BuOK) vs. Li(i-Pr)₂N – the distribution of products was greatly influenced by the ring size of substrates. This is further illustrated by treatment of ketones 34 and 35 with t-BuOK. While the former rearranged smoothly to diketone 36 , no reaction at all took place with the latter. The behavior of the substrates is discussed in terms of steric and energetic reasons.     

Synthesis of 1-vinylpyrrole-2-carbonitriles

A new highly synthetically potent series of bifunctional pyrroles, 1-vinylpyrrole-2-carbonitriles, were synthesized from readily available 1-vinylpyrrole-2-carbaldehyde oximes by two methods: (1) reaction with acetylene (KOH/DMSO, 70 °C, 10 min, yields 58-67%) and (2) reaction with acetic anhydride (90-100 °C, 5 h, yields 83-93%). Starting from 2-phenyl-1-vinylpyrrole, the one-pot synthesis of the corresponding 1-vinyl-2-carbonitrile was accomplished directly by successive treatment with a DMF/(COCl)₂ complex, NH₂OH·HCl/NaOAc, and acetic anhydride (yield 58%).     

Synthesis and reactions oe 2-chlorohexafluorocyclopentene- and 2-chlorooctafluorocyclohexene-1-carbonitriles

2-Chlorohexafluorocyclopentene- and 2-chlorooctafluorocyclohexene-1-carbonitriles were synthesized. Products of substitution of the chlorine atoms by a phenylamino group and the fluorine atoms in the position by a phenylimino group were obtained by reaction of the products with aniline. The reactions with amidines of trifluoro- and trichloroacetic acids, as well as with 2-aminopyridine, lead to pyrimidine derivatives with condensed perfluorinated five- and six-membered rings.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1407–1409, October, 1982.     

Thermolysis of 1-phthalimidoaziridine-2-carbonitriles in the presence of dipolarophiles

Thermolysis of trans-3-phenyl-1-phthalimidoaziridine-2-carbonitrile and trans-1-phthalimidoaziridine-2,3-dicarbonitrile in the presence of several dipolarophiles involves 1,3-dipolar cycloaddition to intermediate azomethine ylides and leads to 1-phthalimidopyrrolidine derivatives with good yields and high stereoselectivity. Thermally induced opening of the three-membered ring in trans-2,3-disubstituted 1-phthalimidoaziridines occurs in conrotatory mode to produce the corresponding cis-azomethine ylides in keeping with the orbital symmetry conservation rules. The relative configuration of substituents in the dipolarophiles is retained, which implies concerted mechanism of the addition.     

Detosylation of 3-amino-1-tosylindole-2-carbonitriles using DBU and thiophenol

Attempted detosylation of the 3-amino-1-(p-tosylamino)indole-2-carbonitriles 4a-c using either K₂CO₃ in EtOH or DBU in PhH at reflux gives unexpectedly the 3-(N-p-tosylamino)indole-2-carbonitriles 5a-c, respectively in high yields. Nevertheless, treatment of 1-(p-tosylamino)indoles 4a-c with thiophenol and DBU in PhH at reflux gives the detosylated 3-aminoindole-2-carbonitriles 5a-c. Reaction mechanisms supporting the tosyl migration (4→5) and the reductive detosylation (4→2) are proposed. All new compounds are fully characterised.     

Synthesis of New Highly Functionalized 1H-Indole-2-carbonitriles via Cross-Coupling Reactions

An approach for the preparation of polysubstituted indole-2-carbonitriles through a cross-coupling reaction of compounds 1-(but-2-ynyl)-1H-indole-2-carbonitriles and 1-benzyl-3-iodo-1H-indole-2-carbonitriles is described. The reactivity of indole derivatives with iodine at position 3 was studied using cross-coupling reactions. The Sonogashira, Suzuki–Miyaura, Stille and Heck cross-couplings afforded a variety of di-, tri- and tetra-substituted indole-2-carbonitriles.     

2－烷基环戊－2－烯酮衍生物的合成及抗炎活性研究

２－烷基环戊－２－烯酮衍生物的合成及抗炎活性研究齐传民计志忠，李玉兰，王彪（北京农业大学应用化学系，北京，１０００９４）（沈阳药科大学）关键词环戊烯酮衍生物，β－氨基甲基酮，Ｍａｎｎｉｃｈ反应，缩合反应，抗炎活性目前，许会抗炎药物是芳香酸类比合物，它...     

New synthesis of 3-amino-1H-benzo[f]chromene-2-carbonitriles

3-Amino-1H-benzo[f]chromene-2-carbonitriles were synthesized by non-catalytic reaction from Mannich bases of the naphthalene series and malononitrile. Reactive 1-benzylidene(or methylidene)naphthalen-2(1H)-ones were presumed as intermediate products.     

Synthesis and [2+4]cycloadditions of two 1-aza-1,3-butadiene-1-carbonitriles

3-Methyl- and 3-ethyl-1-aza-1,3-butadiene-1-carbonitriles were synthesized by reaction of the corresponding 3-alkylacroleins with bis(trimethylsilyl)-carbodiimide using titanium tetrachloride as catalyst. They were highly reactive and difficult to purify rigorously. Attempted anionic polymerizations gave only oligomers of molecular weight ∼500 Da. These 3-alkyl-azadienecarbonitriles cycloadded to the electron-rich olefins iso-butyl vinyl ether and p-methoxystyrene to give [2+4] cycloadducts with moderate yields.     

酸促进2-乙烯基苯胺与重氮的[5+1]环化合成2-芳基喹啉

利用廉价易得的2-乙烯基苯胺与重氮化合物在三氟乙酸催化下发生[5+1]环化反应, 以中等至良好的产率合成了24种2-芳基喹啉衍生物. 该方法无需金属催化剂, 官能团兼容性好, 反应成本低, 不仅拓展了重氮化合物参与的新型有机反应, 同时也为2-芳基取代喹啉的合成提供了高效、 经济且简洁的新方法.     

Photocycloaddition of 2-Oxopyran-3-carbonitriles to 2,3-Dimethylbut-2-ene

On acetone-sensitized irradiation in the presence of 2,3-dimethylbut-2-ene, α-cyano-α,β-unsaturated δ-lactone 5 is converted both to cyclopentapyrans resulting from stepwise addition of the alkene to the olefinic C(β)- and the nitrile C-atom of triplet excited 5 , and cyclobutapyranes, i.e., [2+2] cycloadducts. Similarly, direct irradiation of 1-benzopyran-3-carbonitrile 6 in the presence of the same alkene affords cyclobutabenzopyran 13 and cyclopentabenzopyran 14 , the latter resulting from an upper excited triplet state of 6 .     

Synthesis of 2-amino-5-nitro-4H-pyran-3-carbonitriles

Reaction of 2-carbomethoxy-ω-nitroacetophenone with arylmethylenemalononitriles gives the previously unknown 2-amino-4-aryl-5-nitro-6-(2-carbomethoxyphenyl)-4H-pyran-3-carbonitriles. N. D. Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 117913. E-mail: muskat@cacr.ioc.ac.ru. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1661–1663, December, 1998.     

π-Extended Pleiadienes by [5+2] Annulation of 1-Boraphenalenes and ortho-Dihaloarenes

Palladium-catalyzed [5+2] annulation of 1-boraphenalenes with ortho-dihaloarenes afforded negatively curved π-extended pleiadienes. Two benzo[1,2-i:4,5-i’]dipleiadienes (BDPs) featuring a seven-six-seven-membered ring arrangement were synthesized and investigated. Their crystal structure revealed a unique packing arrangement and theoretical calculations were employed to shed light onto the dynamic behavior of the BDP moiety and its aromaticity. Further, a naphthalene-fused pleiadiene was stitched together by oxidative cyclodehydrogenation to yield an additional five-membered ring. This formal azulene moiety led to distinct changes in optical and redox properties and increased perturbation of the aromatic system.     

Cross-Conjugated Cyclopentenone Prostaglandins. Recent Advances

Russian Journal of Organic Chemistry - The review covers the literature on the total synthesis of cross-conjugated cyclopentenone prostaglandins (PGs), published from 2000 until present. In view of...     

Synthesis of 2-methylthioindolizine-3-carbonitriles using nitro ketene dithioacetal

The reaction of 1-cyanomethylpyridinium chloride or bromide, 1a-i , with 1,1-bis(methylthio)-2-nitroethylene ( 2 ) in the presence of triethylamine as a base in ethanol gave the corresponding 2-methylthioindolizine-3-carbonitrile 3 and 2-methyl-thio-1-nitroindolizine-3-carbonitrile 4 in good yields, respectively. Compounds 3a,f were key intermediates for the synthesis of cycl[3.2.2]azine derivatives.     

The conversion of 2-cyano cyanothioformanilides into 3-aminoindole-2-carbonitriles using triphenylphosphine

2-Cyano cyanothioformanilide 3a reacts with triphenylphosphine in the presence of water to give 2-(cyanomethyleneamino)benzonitrile 4a, 2-(cyanomethylamino)benzonitrile 5, 3-aminoindole-2-carbonitrile 2a and (2-cyanoindol-3-yl)iminotriphenylphosphorane 6a. In the presence of p-toluenesulfonic acid in MeOH the reaction between 2-cyano cyanothioformanilide 3a and triphenylphosphine (2 equiv) gives 3-aminoindole-2-carbonitrile 2a in 90% yield. Under the same conditions 2-(cyanomethyleneamino)benzonitrile 4a gives anthranilonitrile 8a, 3-aminoindole-2-carbonitrile 2a and N-(2-cyanophenyl)formamide 9. In addition, substituted 2-cyano cyanothioformanilides 3b-f react with triphenylphosphine and p-toluenesulfonic acid in MeOH to give 3-aminoindole-2-carbonitriles 2b-f in 63-75% yields. Under analogous conditions 2-cyano-4,5-dimethoxyphenyl cyanothioformanilide 2g gives only 4,5-dimethoxyanthranilonitrile 8g and 4,6,7-trimethoxyquinazoline-2-carbonitrile 14g, but in refluxing dry PhMe in the absence of p-toluenesulfonic acid 2-cyano-4,5-dimethoxyphenyl cyanothioformanilide 3g, (2-cyano-5,6-dimethoxyindol-3-yl)iminotriphenylphosphorane 6g and 2-(cyanomethyleneamino)-4,5-dimethoxybenzonitrile 4g are obtained. The structure of 2-(cyanomethyleneamino)-4,5-dimethoxybenzonitrile 4g is supported unambiguously via independent synthesis and comparison to the isomeric 6,7-dimethoxyquinazoline-2-carbonitrile 15. All new compounds are fully characterised and a tentative mechanism for the transformation of 2-cyano cyanothioformanilides to indoles is proposed.     

One-Pot Green Synthesis of 2-Oxo-2H-chromene-3-carbonitriles Using Dual-Frequency Ultrasonication

Russian Journal of Organic Chemistry - A green synthesis of 2-oxo-2H-chromene-3-carbonitriles has been carried out in one step by reacting 2-hydroxybenzaldehydes or 2-hydroxyacetophenones with...