First synthesis of 4-oxo-6-trifluoromethyl-4H-thiopyran-2-carboxylic acid and its derivatives

Treatment of 6-trifluoromethylcomanic acid with sodium hydrosulfide afforded for the first time 4-oxo-6-trifluoromethyl-4H-thiopyran-2-carboxylic acid (6-trifluoromethylthiocomanic acid). When heated or treated with H₂SO₄, this acid easily underwent decarboxylation leading to 2-trifluoromethyl-4H-thiopyran-4-one. Because of this, both ethyl and methyl 6-tri-fluoromethylthiocomanates were obtained in low yields (15–23%). Decarboxylation of 6-tri-(di)fluoromethylcomanic acids gave 2-tri(di)fluoromethyl-4H-pyran-4-ones in 77–80% yields.     

A convenient synthesis of 2-alkyl-3-fluoro-3-polyflouroalkyl-2-propenals

The synthesis and identification of 2-alkyl-3-fluoro-3-polyfluoroalkyl-2-propenals are described.     

新型树形化合物1,3,5-三-[7-(7-甲基-2,2-二-(2,2-二羟甲基-3-羟基丙氧基羰基)-6,8-二氧杂螺[3.5]-壬基)]苯的合成

以丙酮和甲酸乙酯为原料, 在醇钠的作用下合成了1,3,5-三乙酰基苯(1). 1与二溴新戊二醇在酸的作用下发生缩酮化反应, 制成1,3,5-三-(1-甲基-2,6-二氧杂-4,4-二溴甲基环己基)苯(2). 2与5,5-二甲基-4,6-二氧杂-1,3-环己二酮在乙醇钠的作用下合成了1,3,5-三-[7-(7-甲基-2,2-二-乙氧羰基-6,8-二氧杂螺[3.5]-壬基)]苯(3). 将3在氯仿中与季戊四醇进行酯交换反应得到产物1,3,5-三-[7-(7-甲基-2,2-二-(2,2-二羟甲基-3-羟基丙氧基羰基)-6,8-二氧杂螺[3.5]-壬基)]苯(4). 收率为47.7%. 标题化合物及中间产物使用IR, ¹H NMR和MS或元素分析进行了表征.     

Lithiation of Pyrrol-2-Acetic Acids. Synthesis of 2-Alkylpyrroles.

N-methylpyrrol-2-acetic acid and pyrrol-2-acetic acid were converted into di- and trianions on reaction with two equivalents of lithium diisopropylamide or three equivalents of t-butyllithium, respectively. Reaction of the anions with one equivalent of an alkyl bromide or iodide gave the corresponding mono-α-substituted acetic acids which on thermal decarboxylation gave pure 2-alkylpyrroles.     

One-pot synthesis of diverse 4-di(tri)fluoromethyl-3-cyanopyridine-2(1H)-thiones and their utilities in the cascade synthesis of annulated heterocycles

Diverse substituted 4-di(tri)fluoromethyl-3-cyanopyridine-2(1H)-thiones were synthesized via the Claisen condensation of alpha-methyl(methylene)ketones with di(tri)fluoroacetate, followed by the immediate Thorpe-Guareschi reaction of the preformed di(tri)fluoromethyl-1,3-diketones with cyanothioacetamide. The procedure allows facile synthesis of the di(tri)flouromethylated pyridine-2(1H)-thiones in 50-95% yields, without the need for isolation and purification of intermediates. Resultant 4-di(tri)fluoromethyl-3-cyanopyridine-2(1 H)-thiones were subsequently utilized in domino reactions to produce first various substituted thieno[2,3-b]pyridines and, then, thienopyridines polyannulated with pyridine, pyrimidine, benzodiazocine, diazepine, and pyran rings.     

Di- and tri(2-pyron-6-yl)arenes

Condensation of di- and triacetylarenes with 1,1,1,3-tetrachloro-3-alkoxypropanes or ,-dichloroacrolein in acidic media gave a number of (dichloropentadienyl)- and tris (dichloropentadienyl)-substituted aryl ketones, which, in the case of acetic acid in the presence of phosphoric acid, are converted to the corresponding di- and tri(2-pyron-6-yl)arenes. It was observed that nitric acid has an oxidation effect on 2-pyrones.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 897–901, July, 1977.     

Syntheses and spectral characteristics of 6-mono-, 3,6-di- and 3,5,6-trisubstituted-1,2,4-triazines

The reaction of acidhydrazides with α-substituted carbonyl compounds in the presence of metal acetates gives substituted 1,2,4-triazines. These cyclisations could be effected without any added acetate by refluxing in dimethyl formamide, pyridine/acetic acid or dimethyl sulfoxide Sixty five 3,5,6-tri-3,6-di and 6 monosubstituted-1,2,4-triazines (in 50–90% yields) with a wide variation in the C₃ substituent (alkyl, aryl or heteryl) and the C₆-substituent (aryl or heteryl) are reported. The mechanistic path followed in the formation of these compounds is discussed.     

Tuned Cd2+ Selectivity: Showcase of Electronic and Regio-Effect of π-Extended Di-2-Picolylamine-Substituted Quinoline-Based Tolans

π-Extended di-2-picolylamine (DPA)-substituted 8-hydroxyquinoline (8-HQ) tolans (2) were synthesized for testing electronic and regio-effects. The electron-poor CN-tolan (2b) showed clear selectivity for Cd²⁺ (>>Zn²⁺) over other metal ions via turn-on fluorescence, while the electron-rich MeO-tolan (2a) displayed no clear metal selectivity. Furthermore, considering that there was no significant energy difference between the Cd²⁺ complexes of 1 and 2b, the intended regio-effect (7- vs. 5-substituted effect) did not induce steric hindrance. Thus, the regio-effect is mainly electronic. Considering the above, 2a and 2b constitute a complete showcase in which electronic and regio-effects modulate the metal selectivity. The fluorescence titration of 2b (10 mM) with Cd²⁺ showed that the limit of detection (LOD) of the Cd²⁺-selective 2b was 158 nM in PBS (phosphate-buffered saline) (10 mM, pH 7.2) containing 50% MeOH.     

An effective synthesis of α-glycosides of -acetylneuraminic acid derivatives by use of 2-deoxy-2β-halo-3β-hydroxy-4,7,8,9-tetra- -acetyl- -acetylneuraminic acid methyl ester

Condensation of a new glycosyl donor, methyl 5-acetamido-4, 7,8,9-tetra- -acetyl-2,3-dibromo-2,3,5-trideoxy-β- -2-nonulopyranosonate with various acceptors such as methyl 2,3,4-tri- -benzyl-α- -glucopyranoside, cholesterol, methyl 2,4,6-tri- -bonzyl-α- -galactopyranoside, and nethyl 5-acetamido-4,7,9-tri- -acetyl-2,6-anhydro-3,5-dideoxy- -non-2-enopyranosonate gave only the corresponding β-glycosides. The 3α-bromo group of the glycoaides obtained above was reduced with tributylstannane to the corresponding glycosids, which were deprotected to give the free glycoaides in high yields.     

Synthesis of 6-substituted 3-cyano-5-nitropyridine-2(1H)-thiones

The reactions of 1-substituted 2-nitro-3-phenylaminoprop-2-en-1-ones with cyanothioacetamide afforded the corresponding 6-substituted 3-cyano-5-nitropyridine-2(1H)-thiones, which were used for the synthesis of 6-substituted 3-cyano-2-methylthio-5-nitropyridines and 7-substituted 4-hydroxy-8-nitropyrido[2",3":4,5]thieno[2,3-b]pyridin-2(1H)-ones.     

Maleic acid derivatives in the synthesis of 3-substituted 3,4-dihydroquinoxalin-2(1H)-ones

A process for preparing 3-substituted 3,4-dihydroquinoxalin-2(1H)-ones is proposed. It is based on the reaction of o-phenylenediamine with amides, di- and mono-esters of maleic acid as well as (E)-3-(5-phenyl-1,3,4-oxadiazol-2-yl)acrylic acid in the presence of N,N′-carbonyl-diimidazole.     

2-Trifluoroacetyl aminoindoles as useful intermediates for the preparation of 2-acylamino indoles

A three-step method was developed to convert N-1 unprotected 3-substituted indoles to 3-substituted 2-acylaminoindoles. Established indole chlorination chemistry was employed to generate stable 2-trifluoroacetylamino indoles, which were subsequently deprotected and selectively acylated.     

Glass and sub-glass transitions in methylphenyl and chlorophenyl polyitaconic acid esters

Two series of ring substituted poly(di-phenyl itaconate)s have been prepared and characterized. The 2-, 3-, and 4-methylphenyl and chlorophenyl derivatives were studied and the glass transition temperatures (Tg) of the 3-substituted polymers were found to be lower than those of the 2- or 4-substituted polymers in each series. Some suggestion of polar effects contributing to Tg was evident in the poly(di-(4-chlorophenyl)itaconate). Dynamic mechanical studies revealed prominent damping peaks in the glassy state of the poly(di(methylphenyl)itaconate)s which can be attributed to methyl group relaxation. The chloro-derivatives showed fewer features, although in the 4-chloro compound there is evidence of restricted ring oscillation in the glass.     

3-Fluoroalkyl (CF3, CHF2, CH2F) Cyclobutane-Derived Building Blocks for Medicinal Chemistry: Synthesis and Physicochemical Properties

Synthesis and physicochemical characterization of all possible cis- and trans-1,3-disubstituted cyclobutane-derived amines and carboxylic acids bearing mono-, di- and trifluoromethyl groups at the C-3 position is disclosed. Tetramethylammonium fluoride (TMAF)- or morpholinosulfur trifluoride (Morph-DAST)-mediated nucleophilic fluorination of appropriate cis- and trans-diastereomeric substrates was used as the key step for the preparation of CH₂F- and CHF₂-substituted derivatives. To obtain the corresponding cis- and trans-isomeric CF₃-substituted derivatives, resolution of known 3-(trifluoromethyl)cyclobutanecarboxylic acid (obtained as a mixture of diastereomers) was applied. The proposed procedures were suitable for the preparation of corresponding fluoroalkyl-substituted cyclobutane-derived amines and carboxylic acids on up to 50 g scale. All 12 building blocks obtained were characterized by measuring dissociation constants (pK_a) and lipophilicities (LogP, for model derivatives) to evaluate the effect of the fluoroalkyl substituents on their physicochemical properties relevant to further drug discovery applications.     

Preparation of twelve 1-methyl-2-formyl-5-substituted pyrroles and their hydrazones

Preparation of twelve 1-methyl-2-formyl-5-substituted pyrroles (2a-1), with five of them as new compounds, is described. Their derivatives, i.e., 1-methyl-2-formyl-5-substituted pyrrole phenyl hydrazones (3a-1) and 1-methyl-2-formyl-5-substituted pyrrole (4-nitrophenyl) hydrazones (4a-1) are all new compounds. They have also been prepared and further identified.     

5-取代吲哚-2-酮的合成

4-取代苯胺依次与水合氯醛及盐酸羟胺反应制得4-取代异亚硝基乙酰苯胺(2a～2e);2在浓硫酸作用下环合制得5-取代靛红(3a～3e);3通过改进的Wolff-Kishner-黄鸣龙反应合成了重要的药物中间体——5-取代吲哚-2-酮(5a～5e);5a通过硝化制得5-硝基吲哚-2-酮(5f);5f被还原制得5-氨基吲哚-2-酮(5g)。其结构经1H NMR和MS确证。     

2-氰基-3-取代氨基-3-(2-甲基苯基)丙烯酸乙酯的合成和杀菌活性

2-甲基苯甲酰氯与氰乙酸乙酯反应得到2-氰基-3-羟基-3-(2-甲基苯基)丙烯酸乙酯, 经氯化得到2-氰基-3-氯-3-(2-甲基苯基)丙烯酸乙酯, 再用三乙胺处理合成了11个2-氰基-3-取代氨基-3-(2-甲基苯基)丙烯酸乙酯类目标化合物. 生物活性研究表明这类新化合物具有良好的杀菌活性.     

Synthesis of 5-substituted 3-(2-oxopropyl)tetrahydrofuran-2-ones and heterocyclic compounds on their base

Alkylation of ethyl 2-oxotetrahydrofuran-3-carboxylates with 2,3-dichloroprop-1-ene and 3-bromoprop-1-yne gave new 3,5,5-tri- and 3,3,5,5-tetrasubstituted tetrahydrofuran-2-ones which were converted into the corresponding 3-(2-oxopropyl)tetrahydrofuran-2-ones. Reactions of the latter with semicarabazide, thiosemicarbazide, and phenylhydrazine were studied with a view to obtain new heterocyclic lactones.     

Rapid microwave assisted synthesis of 3-substituted 4-thioxo-oxazolidin-2-ones

The microwave assisted thionation of 3-substituted 4-imino-oxazolidin-2-ones with hydrogen sulfide in dichloromethane-pyridine afforded 3-substituted 4-thioxo-oxazolidin-2-ones.     

Anodic oxidation of sodium 2-mercaptobenztiazolate anion in the presence of 5-methyl-2-hexanol

The anodic oxidation of the sodium 2-mercaptobenztiazolate anion in alkaline solution yields a finely dispersed difficultly filterable form of di-(2-benztiazolyl)disulfide, an accelerant of the rubber sulfur vulcanization. A crucial problem in the establishing of the continuous di-(2-benztiazolyl)disulfide electrosynthesis is the choice of reaction mixture, which ensures easy filtration of the target product. It was found by using oscillographic voltammetry at platinum microelectrode that the sodium 2-mercaptobenztiazolate anion in aqueous alkaline solution in the presence of 5-methyl-2-hexanol is oxidized to a radical that undergoes dimerization, thus yielding easily filterable form of di-(2-benztiazolyl)disulfide. The obtained result is explained by assuming that the dimer formation occurs in the 5-methyl-2-hexanol adsorption layer at the electrode surface. A reaction scheme of the process is suggested.