Hydrogenation of derivatives of 2-oxo-4-(2-thienyl)butenoic acid at palladium and nickel catalysts

The hydrogenation of sodium and ethyl 2-oxo-4-(2-thienyl)butenoate at Raney nickel and palladium black was investigated. With Raney nickel the reaction products were the corresponding derivatives of 2-oxo-4-(2-thienyl)butyric acid and 2-hydroxy-4-(2-thienyl)butyric acid and the products from bimolecular condensation. If palladium black is used, the reaction can be directed toward the selective formation of the corresponding derivative of 2-oxo-4-(2-thienyl)butyric acid. The hydrogenation of the salts is more selective than that of the esters. During the hydrogenation of ethyl 2-oxo-4-(2-thienyl)butenoate at palladium black in solution in anhydrous ethanol the ethyl esters of 2-oxo-4-(2-thienyl)butyric and 2-oxo-4-(2-tetrahydrothienyl)butyric acids and the corresponding ketals are formed. The mechanism of the hydrogenation of 4-substituted 2-oxobutenoic acids is discussed. Latvian Institute of Organic Synthesis, Riga, Latvia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1329–1334, October, 1998.     

Nitration of 2- and 4-[2-(2-furyl)vinyl]thiazole derivatives

Nitration of 4-methyl-2-[2-(nitro-2-furyl)vinyl]thiazole with a mixture of concentrated nitric and sulfuric acids leads to 4-methyl-5-nitro-2-[2-(3,5-dinitro-2-furyl)vinyl]thiazole. Under the same conditions 2-methyl- and 2-acetamido-4-[1-R-2-(5-nitro-2-furyl)vinyl]thiazoles (R=CH₃, Cl) are nitrated in the 3 position of the furan ring, 2-amino-4-[1-chloro-2-(5-nitro-2-furyl)vinyl]thiazole is nitrated in the 5 position of the thiazole ring and 2-acetamido-5-nitro-4-[2-(2-furyl)vinyl]thiazole undergoes profound changes. Under the influence of a mixture of of nitric acid and acetic anhydride the latter compound is converted quantitatively to the 5-nitro derivative (with respect to the furan ring), whereas 4-[2-(5-nitro-2-furyl)vinyl]thiazole derivatives do not undergo reaction.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 314–317, March, 1977.     

Synthesis of Nitriles of δδ-Oxocarboxylic and γγ-Nitrocarboxylic Acids

A cyanoethylation of 2-acetyl-5-R-furans, 1-nitro-2(5-R-2-furyl)ethanes, and 2-nitro-1-(2-furyl)propane was investigated. The optimum conditions were determined for preparation of monocyanoethylated products: nitriles of 5-oxo-5-(5-R-2-furyl)pentanoic and 4-nitro-5-(5-R-2-furyl)pentanoic acids. The cyanoethylation of furyl-containing nitroethanes with excess acrylonitrile provided bisadducts, dinitriles of 4-nitro-4-(5-R-furfuryl)heptanedionic acids.     

Highly enantioselective sequential hydrogenation of ethyl 2-oxo-4-arylbut-3-enoate to ethyl 2-hydroxy-4-arylbutyrate

The hydrogenation of (E)-ethyl 2-oxo-4-arylbut-3-enoate with [NH2Me2](+)[{RuCl [(S)-SunPhos]}2(mu-Cl3)] gave ethyl 2-hydroxy-4-arylbutyrate with 94-96% ee. Further investigation has proved that the hydrogenation proceeded via a sequential hydrogenation of CO and CC bonds, which is sensitive to the reaction temperature. Hydrolysis of ethyl 2-hydroxy-4-phenylbutyrate (ee 93%) provided the 2-hydroxy-4-phenylbutyric acid with 81% yield at 99% ee after a single recrystallization from 1,2-dichloroethylene.     

A Facile Synthesis of Functionalized 1,2,6,7-Tetrahydroimidazo[1,5-c]pyrimidine-3,5-diones

A Pd-mediated hydrogenation of ethyl 6-azidomethyl-1,2,3,4-tetrahydro-4-R-2-oxo-5-pyrimidinecarboxylates leads to the corresponding ethyl 6-aminomethyl1,2,3,4-tetrahydro-4-R-2-oxo-5-pyrimidinecarboxylates. The latter react with bis(trichloromethyl)carbonate, yielding the title ethyl 1,2,3,5,6,7-hexahydro-7-R-3,5-dioxoimidazo[1,5-c]pyrimidine-8-carboxylates.

Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.     

Asymmetric Reductive Alkylation of Alanylproline by the Ethyl Esters of 4-Substituted 2-Oxobutenoic Acids

A method was developed for the synthesis of N-[1-(S)-(ethoxycarbonyl)-3-phenylpropyl]alanylproline (enalapril) by reductive alkylation of alanylproline with ethyl 2-oxo-4-phenylbutenoate under the conditions of hydrogenation in the presence of palladium black and 1.6% Pd/C. The yield of enalapril amounted to 65%. With the ethyl ester of the -oxo acid the diastereoselectivity of formation of the S,S,S-diastereomer was higher than with the saturated synthon. It is assumed that with ethyl 2-oxo-4-phenylbutenoate as synthon a conformationally restricted surface complex is formed between the unsaturated synthon and the active centers of the catalyst. During reductive alkylation of alanylproline by ethyl 2-oxo-4-(2-thienyl)butenoate poisoning of the catalyst occurs.     

Effect of the β-substituent with respect to the azido group on the reactivity of methyl (2E)-3-[5-(azidomethyl)-2,2-diethyl-1,3-dioxolan-4-yl]-2-methylprop-2-enoate

Unlike methyl (2E)-3-[5-(azidomethyl)-2,2-diethyl-1,3-dioxolan-4-yl]-2—methylprop-2-enoate which is stable on storage, its acyclic derivative, methyl (2E,4S,5S)-6-azido-5-hydroxy-2-methyl-4-(pent-3-yloxy) hex-2-enoate at 20°C undergoes unusual decomposition with formation of exo-methylidenepyrrolidine. Analogous transformation was also observed in the epoxide ring opening in methyl (2E)-2-methyl-4-[(S)-oxiran-2-yl]-4-(pent-3-yloxy)but-2-enoate and in the substitution reaction of ethyl 5,6-bis(methanesulfonyloxy)-2-methyl-4-(pent-3-yloxy)hex-2-enoate with azide ion. Opening of the oxirane ring in the former by the action of azide ion was accompanied by formation of oxazetidine derivative as a minor product. The major intramolecular cyclization products, 4-hydroxy- and 4-mehtanesulfonyloxypyrrolidines were converted into stable pyrrole derivatives via elimination of the leaving groups. The hydrogenation of methyl and ethyl (2E)-3-[5-(azidomethyl)-2,2-diethyl-1,3-dioxolan-4-yl]-2-methylprop-2-enoates over palladium catalyst afforded the expected reduction products.     

Synthesis of heterocycles based on arylation products of unsaturated compounds: XVII. Arylation of 2-acetylfuran and synthesis of 3-R-6-(5-aryl-2-furyl)-7<Emphasis Type="Italic">H</Emphasis>-[1,2,4]triazolo[3,4-<Emphasis Type="Italic">b</Emphasis>][1,3,4]thiadiazines

Reaction of 2-acetylfuran with arenediazonium chlorides under Meerwein reaction conditions led to the formation of 5-aryl-2-acetylfurans. The bromination of these compounds gave 2-bromo-1-(5-aryl-2-furyl)-ethanones that reacted with 4-amino-4H-5-R-1,2,4-triazole-3-thiols to form 3-R-6-(5-aryl-2-furyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines.     

Synthesis of Some New Benzopyranopyrimidin-2-Thiol Derivatives

Reaction of 2-mercapto-4-hydroxy-5H-[1]-benzopyrano-[4,3- d ]-pyrimidin-5-one ( 3 ) with phenyl isothiocyanate and methyl acrylate yielded the corresponding 2-(substituted)thio-4-hydroxy-5H-[1]-benzopyrano-[4,3- d ]-pyrimidin-5-ones ( 4 , 5 ). Hydrolysis and hydrazinolysis of 5 gave acid derivative 6 , and hydrazone 7 . Treatment of hydrazone 7 with ethyl acetoacetate, diethyl malonate, and phenyl isothiocyanate yielded the corresponding 2-(substituted)thio-4-hydroxy-5H-[1]-benzopyrano- [4,3- d ]-pyrimidin-5-ones ( 8 , 9 , and 11 ). Cyclization of 11 with 2 N NaOH led to 12 .     

Synthesis, Reactions, and Anti-arrhythmic activity of Substituted Heterocyclic Systems Using 5-Chloroanisic Acid as Starting Material

Summary. A series of substituted heterocyclic systems were prepared from N1-[4-(4-fluorocinnamoyl)phenyl]-5-chloro-2-methoxybenzamide, which was prepared from the corresponding 5-chloroanisic acid (2-methoxy-4-chlorobenzoic acid) as starting material. Treating of the cinnamoyl derivative with hydrazine hydrate in dioxane afforded a pyrazoline, which was reacted with morpholine and paraformaldehyde to give the N-substituted pyrazoline. Acylation of pyrazoline with acetyl chloride in dioxane afforded the N-acetyl analogue. Also, the cinamoyl derivative was reacted with methylhydrazine, phenylhydrazine, or ethyl cyanoacetate to yield the corresponding N-methyl-, N-phenylpyrazoline, pyrane, and pyridone derivatives. Condensation of the cinnamoyl derivative with cyanothioacetamide gave the pyridinethione derivative, which was treated with ethyl chloroacetate affording the ethyl carboxylate derivative. Also, it was reacted with malononitrile or ethyl acetoacetae to give the cyano amino analougues and ethyl carboxylate, which was reacted with methylhydrazine to give the (indazolyl)phenyl derivative. On the other hand, reaction of cinnamoyl derivative with acetyl acetone afforded the cyclohexenyl derivative, which was reacted with hydrazine hydrate to give the [methylindazolyl]phenyl derivative. Condensation of the cinnamoyl derivative with guanidine hydrochloride or thiourea afforded the aminopyrimidine derivative and thioxopyrimidine. The latter was condensed with chloroacetic acid to yield a thiazolopyrimidine, which was condensed with 2-thiophenealdehyde to yield the arylmethylene derivative, however, it was also prepared directly from thiopyrimidine by the action of chloroacetic acid, 2-thiophenealdehyde, and anhydrous sodium acetate. The pharmacological screening showed that many of these compounds have good anti-arrhythmic activity and low toxicity.     

Hydrogen-mediated aldol reductive coupling of vinyl ketones catalyzed by rhodium: high syn-selectivity through the effect of tri-2-furylphosphine

[reaction: see text]. Catalytic hydrogenation of methyl vinyl ketone (MVK) and ethyl vinyl ketone (EVK) in the presence of diverse aldehydes at ambient temperature and pressure using tri-2-furylphosphine-ligated rhodium catalysts enables formation of aldol products with high levels of syn-diastereoselectivity. A progressive increase in diastereoselectivity is observed upon sequential replacement of phenyl residues for 2-furyl residues (Ph3P, FurPh2P, Fur2PhP, Fur3P). Hydrogen-labile functional groups, including alkynes, alkenes, benzylic ethers, and nitroarenes, remain intact under the coupling conditions.     

Benzodiazines

The ionization constants of 2-R-4-quinazolones (where R=H, CH₃, phenyl, N-pyrrolidinyl, or -pyridyl), and of 4-R-2-quinazolones (where R=H, phenyl, and N-pyrrolidinyl), have been measured. The polarographic reduction potentials of the corresponding 2-R-4-chloroquinazolines and 4-R-2-chloroquinazolines have been determined. A satisfactory relation between the E_1/2 of 2-R-4-chloroquinazolines and the pKa for the removal of a proton from 2-R-4-quinazolones has been found.For part XII, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, Vol. 6, No. 5, pp. 687–690, May, 1970.     

Synthesis of phenylacetylene containing 1,2,3-triazole group

Bromination of (E)-1-[4-(2-carboxy-vinyl)phenyl]-[1,2,3]triazole-4-carboxylic acid ethyl ester, which was synthesized in 90% yield by a Huisgen-type [3 + 2]-cycloaddition reaction between 3-(4-azidophenyl) acrylic acid and ethyl propiolate, in CHCl₃ followed by a debrominative decarboxylation reaction with Et₃N in DMF under microwave irradiation condition afforded stereoselective (Z)-1-(4-(2-bromovinyl)phenyl)-1,2,3-triazole-4-carboxylic acid ethyl ester in 94% yield. Treatment of (Z)-1-(4-(2-bromovinyl)phenyl)-1,2,3-triazole-4-carboxylic acid ethyl ester with EtONa in DMF afforded 1-(4-ethynylphenyl)-1,2,3-triazole-4-carboxylic acid ethyl ester in a yield of 90%.     

The reaction of alkyl 4-hydroxy-2-alkynoates and 4-hydroxy-2-alkyn-1-ones with palladium tributylammonium formate and with tributylamine: Preparation of 1,4-dicarbonyl compounds

Ethyl 4-oxo-2-alkenoates and 1,4-dioxo-2-alkenes are easily prepared by treating ethyl 4-hydroxy-2-alkynoates and 4-hydroxy-2-alkyn-1-ones with n-tributylamine. Treatment of ethyl 4-hydroxy-2-alkynoates and 4-hydroxy-2-alkyn-1-ones with palladium-tributylammonium formate produces ethyl 4-oxo-alkanoates and 1,4-alkandiones in good to high yield through a novel one-pot isomerization/hydrogenation reaction.     

Reaction of 5-oxo-2-phenyl-4,4-bis(trifluoromethyl)-4,5-dihydro-1,3,2-benzodioxaphosphepine with chloral. The synthesis and spatial structure of 5-carbaphosphatrane containing a four-membered ring

Phosphorylation of 2-hydroxyphenyl 2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl ketone with dichloro(phenyl)phosphine gave 5-oxo-2-phenyl-4,4-bis(trifluoromethyl)-4,5-di-hydro-1,3,2-benzodioxaphosphepine. Heating of the latter initiated an intramolecular interaction of the P atom with the carbonyl group. Hydrolysis of the intermediate product yielded 3-hydroxy-2-oxo-2-phenyl-3-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]-2,3-di-hydro-1,2λ⁵-benzo[d]oxaphosphole. The reaction was highly stereoselective (P_RC_S/P_SC_R). The reaction of the starting phosphepine with chloral proceeded highly stereoselectively (P_RC_SC_S/P_SC_RC_R) to give a 5-carbaphosphatrane derivative containing a four-membered ring, namely, 1-phenyl-3-trichloromethyl-10,10-bis(trifluoromethyl)-6,7-benzo-2,4,8,9-tetraoxa-1λ⁵-phosphatricyclo[3.3.2.0¹,⁵]decene. The trigonal bipyramid of the 5-carbaphosphatrane derivative is made up of the equatorial O atoms and the apical C atoms.     

The preparation of 2,6-diaminopyrazine, 2,6-diazidopyrazine and some of their derivatives

A much improved synthesis of the heretofore difficultly obtainable 2,6-diaminopyrazine (4) was afforded by the low-pressure catalytic hydrogenation (palladium on carbon) of 2,6-diazido-pyrazine (2) ; reaction of 2,6-dichloropyrazine (1) and sodium azide gave 2 in 84% yield. The outcome of the reduction was found to be solvent dependent: 1,2-dimethoxyethane containing aqueous ammonia gave 4 in 83% yield; 1,2-dimethoxyethane alone gave 5-aminotetrazolo[1,5-a]-pyrazine (3) in 26% yield. Additional alternative syntheses of 3 and 4 are described. A number of acyl and azo derivatives of 4 were prepared. Reactions of 2 with dimethyl acetylenedicarboxylate and ethyl acetate (base catalyzed) leading to vic-triazole derivatives are also described.     

New method for the annelation of a pyridine ring on derivatives of imidazole and benzimidazole

The interaction of (Z)-1,3-diaryl-4-bromo-2-buten-1-ones with 1-substituted (benz)imidazoles in benzene gave (Z)-1-R-3-(2,4-diaryl-4-oxo-2-butenyl)-1H-imidazolium bromides and (Z)-1-R-3-(2,4-diaryl-4-oxo-2-butenyl)-1H-benzimidazolium bromides which readily cyclize in the presence of base to form derivatives of 7,9-diarylpyrido[1,2-a]benzimidazole and 6,8-diarylpyrimidazo[1,2-a]pyridine. The effects of the nature of substituents in the benzene ring of the diarylbutenones and the substituent at N(1) in the (benz)imidazoles on the alkylation and cyclization reactions has been studied. The optimum conditions for the synthesis of the 5-R-4-hydroxy-2,4-diphenyl-4,5-dihydro-1H-pyrido[1,2-a]benz-imidazol-10-ium, 5-R-2,4-diaryl-4-hydroxy-4,5-dihydro-3H-pyrido[1,2-a]benzimidazol-10-ium, and 5-R-2,4-diaryl-5H-pyrido[1,2-a]benzimidazol-10-ium have been found.     

Synthesis and hydrazinolysis of β-(1,3,4-oxadiazol-2-yl)pyridines

Cyclization of the hydrazide of 5-ethoxycarbonyl-2,6-dimethylpyridine-3-carboxylic acid by acylation with aromatic or aliphatic acid chlorides with subsequent boiling in POCl₃ or heating in orthoformic acid gave the corresponding ethyl 2,6-dimethyl-5-(5-R-1,3,4-oxadiazol-2-yl)pyridine-3-carboxylate. The cyclization of the reaction products with hydrazine hydrate has been studied. Cyclization of the dihydrazide of 2,6-dimethyl-3,5-pyridinedicarboxylic acid under analogous conditions gave only 3,5-bis-(5-R-1,3,4-oxadiazol-2-yl)-2,6-dimethylpyridines, containing R = 2-FC₆H₄, H.     

Pyrroles from ketoximes and acetylene. 41. Some reactions of 1-vinyl-2-(2-furyl)- and-(2-thienyl)pyrroles

We have studied the reaction of 1-vinyl-2-(2-furyl)- and -(2-thienyl)pyrroles with trifluoroacetic anhydride, with hydrogen in the presence of catalysts (Raney nickel, palladium black, palladous chloride), with propargyl alcohol in electrophilic conditions [catalysis by perfluorobutyric acid in the system azoisobutyrodinitrile (AIBN)-CCl₄), and with alkane thiols with AIBN initiation. The products are novel substituted hetarylpyrroles.See [1] for Communication 40.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 337–342, March, 1991.     

Hydrogenation of the Sodium Salt of 2-Oxo-4-(3-pyridyl)butenoic Acid on Palladium Black

We have studied the hydrogenation of the sodium salt of 2-oxo-4-(3-pyridyl)butenoic acid on palladium black in the temperature range 20-70°C in aqueous-alcohol medium. The products of the reaction are the sodium salts of 2-oxo-4-(3-pyridyl)butanoic acid and 2-hydroxy-4-(3-pyridyl)butanoic acid together with hydrogenolysis products. The reaction occurs via a series-parallel mechanism.