Reaction of 2-dimethylaminomethylene-1,3-diones with dinucleophiles. VI. Synthesis of ethyl or methyl 1,5-disubstituted 1H-pyrazole-4-carboxylates

Reaction of ethyl or methyl 3-oxoalkanoates with N,N-dimethylformamide dimethyl acetal gave, generally in excellent yields, a series of ethyl or methyl 2-dimethylaminomethylene-3-oxoalkanoates II which reacted with phenylhydrazine to afford the esters of 5-substituted 1-phenyl-1H-pyrazole-4-carboxylic acids III in high yields. Esters III were hydrolyzed to the relative 5-substituted 1-phenyl-1H-pyrazole-4-carboxylic acids which were converted by heating to 5-substituted 1-phenyl-1H-pyrazoles in excellent yields. Reaction of II with methylhydrazine afforded in general a mixture of 3- and 5-substituted ethyl 1-methyl-1H-pyrazole-4-carboxylates with the exception of IIg , which gave in high yield methyl 5-benzyl-1-methyl-1H-pyrazole-4-carboxylate, which was hydrolyzed to the relative pyrazolecarboxylic acid. This afforded by heating 5-benzyl-1-methyl-1H-pyrazole in quantitative yield.     

Reaction of 2-dimethylaminomethylene-1,3-diones with dinucleophiles. VIII. Synthesis of ethyl and methyl 2,4-disubstituted 5-pyrimidinecarboxylates

Reaction of ethyl or methyl 2-dimethylaminomethylene-3-oxoalkanoates with N-C-N dinucleophiles such as guanidine, acetamidine or benzamidine afforded in high yields the relative esters of 4-substituted 2-amino-, 2-methyl- or 2-phenyl-5-pyrimidinecarboxylic acids, respectively. These esters were hydrolyzed to the corresponding carboxylic acids, which were converted by heating to 4-substituted 2-pyrimidinamines, 2-methyl or 2-phenylpyrimidines, respectively, generally in excellent yields. The 4-unsubstituted ethyl 2-amino-, 2-methyl- and 2-phenyl-5-pyrimidinecarboxylates were obtained in moderate yields by reaction of the above dinucleophiles with ethyl 2,2-diformylacetate. These esters were hydrolyzed and the corresponding acids (with the exception of the 2-methyl derivative) were decarboxylated to give 2-pyrimidinamine and 2-phenylpyrimidine in satisfactory yields.     

Reaction of 2-dimethylaminomethylene-1,3-diones with dinucleophiles. I. Synthesis of 1,5-disubstituted 4-acylpyrazoles

Reaction of open-chain and cyclic sym-1,3-diones with N,N-dimethylformamide dimethyl acetal gave, generally in high yield, a series of sym-2-dimethylaminomethylene-1,3-diones which reacted with phenylhydrazine and methylhydrazine to afford, generally in satisfactory yield, a number of 1,5-disubstituted 4-acylpyrazoles. The applications and limits of this new pyrazole synthesis are presented and discussed.     

Reaction of 2-dimethylaminomethylene-1,3-diones with dinucleophiles. III. Synthesis of 5-acylpyrimidines and 7,8-dihydroquinazolin-5(6H)-ones

The reaction of open-chain and cyclohexane sym-2-dimethylaminomethylene-1,3-diones with amidines and guanidine in refluxing ethanol gave, generally in good yields, a series of 5-acylpyrimidines and 7,8-dihydroquinazolin-5(6H)-ones, respectively. With formamidine (and in part acetamidine), 2-formylimino-1,3-diones were formed in general, as sole products or mixtures with the corresponding pyrimidines or dihydroquinazolinones.     

Reaction of 2-dimethylaminomethylene-1,3-diones with dinucleophiles. II. Synthesis of 5-(alkyl)(phenyl)-4-acylisoxazoles and 6,7-dihydro-1,2-benzisoxazol-4(5H)-ones

The reaction of open-chain and cyclohexane sym-2-dimethylaminomethylene-1,3-diones with hydroxylamine hydrochloride in refluxing methanol gave in good to moderate yields a series of 5-(alkyl)(phenyl)-4-acylisoxazoles and 6,7-dihydro-1,2-benzisoxazol-4(5H)-ones, respectively. As 3-unsubstituted isoxazoles, all these compounds easily isomerized with sodium methoxide to the corresponding 2-cyano-1,3-diones in high yields.     

Synthesis of 5-[bromo(aryl)methyl]-2,2-dimethyl-1,3-oxazolidin-4-ones

A Darzens condensation of α-chloroacetamide with aromatic aldehydes furnished a series of 3-aryl-2,3-epoxypropionamides, which were further converted to 5-[bromo(aryl)methyl]-2,2-dimethyl-1,3-oxazolidin-2-ones.     

Reaction of 2-dimethylaminomethylene-1,3-diones with dinucleophiles. V. Synthesis of 5-acyl-1,2-dihydro-2-oxo-3-pyridinecarbonitriles and 1,2,5,6,7,8-hexahydro-2,5-dioxo-3-quinolinecarboxamides

The reaction of open-chain sym-2-dimethylaminomethylene-1,3-diones Ia-d with sodium cyanoacetamide gave, generally in good yields, 6-substituted 5-acyl-1,2-dihydro-2-oxo-3-pyridinecarbonitriles IIa-d, whereas cyclohexane sym-2-dimethylaminomethylene-1,3-diones Ie-h afforded in general a mixture of 1,2,5,6,7,8-hexahydro-2,5-dioxo-3-quinolinecarbonitriles and 5,6,7,8-tetrahydro-2,5-dioxo-2H-1-benzopyran-3-carboxamides, the latter being isolated in two cases. The reaction of Ie-h with cyanoacetamide in refluxing anhydrous ethanol gave 1,2,5,6,7,8-hexahydro-2,5-dioxo-3-quinolinecarboxamides IIIe-h in excellent yields, whereas Ia-d did not react with the exception of Ia which afforded in good yield 3-pyridinecarboxamide IlIa. Other 3-pyridine-carboxamides were obtained by partial hydrolysis of nitriles IIb,d. 3-Pyridine and 3-quinoline carboxamides were hydrolyzed in satisfactory yields with hydrochloric acid to the corresponding carboxylic acids, which were decarboxylated in good yields to 5-acyl-2(1H)-pyridinones and 7,8-dihydro-2,5(1H,6H)-quinolinediones, respectively, by reflux in quinoline containing a catalytic amount of copper powder.     

2,2-Dimethyl-5-(5-r-2-furfurylidene)-1,3-dioxane-4,6-diones

2,2-Dimethyl-5-(5-methyl-2-furfurylidene)-1,3-dioxane-4,6-dione crystals were subjected to an x-ray diffraction study. The unit cell of the crystal contains two symmetrically independent A and B molecules that exist in the x-cis conformation, which is stabilized by conjugation between the heteroring and, possibly, an intramolecular hydrogen bond.See [1] for Communication 1.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1453–1456, November, 1988.     

Synthesis of 5-Aryl-2,2-dimethyl-4-oxaspiro[5,5]undecane-1,3-diones by Reformatsky Reaction

Alkyl 3-(1-bromocyclohexyl)-2,2-dimethyl-3-oxopropanoates react with zinc and aromatic aldehydes to yield 5-aryl-2,2-dimethyl-4-oxaspiro[5,5]undecane-1,3-diones.     

An improved synthesis of (4S,5S)-2,2-dimethyl-4-phenyl-1,3-dioxan-5-amine

The title compound is prepared in 78% yield using an improved one-pot procedure which does not require final purification.     

5-叔丁基-5-(1'-羟基-2'-甲基丙基)-2,2-二甲基-1,3-二氧六环的合成研究

为得到3,4-二取代双环硫化磷酸酯的中间体5-叔丁基-5-(1'-羟基-2'-甲基丙基)-2,2-二甲基-1,3-二氧六环, 通过5-叔丁基-5-甲酰基-2,2-二甲基-1,3-二氧六环与异丙基溴化镁反应没有得到目标化合物, 而得到了还原产物, 改用异丙基锂代替异丙基溴化镁反应后得到目标化合物, 通过超声波辅助反应, 大幅度提高了反应收率.     

2,2-dimethyl-5-(5-r-furfurylidene)-1,3-dioxane4,6 diones 7. Synthesis,structure, and properties of 2,2dimethyl-5-(3-furfuryldiene and 3-thienylidene)-1,3dioxane-4,6-diones

The corresponding 3 furfurylidene(thienylidene)-dioxanediones were obtained by the reaction of 2,5-R,Rfuran(thiophen)-3-carbaldehydes with Meldrum's acid. It was shown by x-ray crystallographic analysis that they have the s-trans disposition at the C₍₂₎=C₍₃₎ bond of the five-membered heterocycle and an exocyclic multiple bond. The character of the conjunction in their molecules was considered in the light of data of x-ray crystallographic analysis, electronic spectra, and NMR. The corresponding 3-furfuryl(thienyl)]dioxanediones were obtained by the selective ionic hydrogenation of the exocyclic double bond.For part 6 see [1]Kuban State Technological University, Krasnodar 350072. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 899–905, July, 1995. Original article submitted October 25, 1994; revision submitted June 5, 1995.     

A synthesis of 1-substituted 5-[2-(acylamino)ethyl]-1H-pyrazole-4-carboxamides

A seven-step synthesis of 1-substituted 5-(2-acylaminoethyl)-1H-pyrazole-4-carboxamides 20 as the pyrazole analogues of histamine was developed. The synthesis starts with a three-step preparation of N(1)-substituted methyl 5-(2-tert-butoxycarbonylaminoethyl)-1H-pyrazole-4-carboxylates 7 from commercially available Boc-β-alanine (1). Subsequent four-step transformation of the key-intermediates 7 into the final products 20 was performed following two complementary reaction sequences comprising acidolytic removal of the Boc group, hydrolysis of the COOMe group, amidations of the COOH group, and acylations of the NH₂ group. The structures of pyrazole derivatives were determined by spectroscopic methods and by X-ray diffraction.     

Facile syntheses of 2,2-dimethyl-6-(2-oxoalkyl)-1,3-dioxin-4-ones and the corresponding 6-substituted 4-hydroxy-2-pyrones

A variety of 2,2-dimethyl-6-(2-oxoalkyl)-1,3-dioxin-4-ones 5a-l and the corresponding 6-substituted 4-hydroxy-2-pyrones 3a-l were prepared in high yields under mild reaction conditions by the reaction of 2,2,6-trimethyl-1,3-dioxin-4-one 4 with 1-acylbenzotriazoles 9 in the presence of LDA followed by thermal cyclization of 5a-l to 3a-l. Synthesis of novel 6-(1-benzoylalkyl)-2,2-dimethyl-1,3-dioxin-4-ones 12a-c was achieved by alkylation of dioxinone 5a and their subsequent cyclization gave 5-alkyl-4-hydroxy-2-pyrones 13a-c.     

2,2-Dimethyl-5-(5-r-2-furfurylidene)-1,3-dioxan-4,6-diones. 1. Synthesis,properties, and structure

5-R-Furanaldehydes react with Meldrum's acid under Knoevenagel reaction conditions. The reaction products have s-cis conformation. The pK _a values of the electroneutral Lewis acids synthesized were determined.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1325–1329, October, 1986.     

Preparative synthesis of 2,2-dimethyl-5-(trifluoroacetyl)-1,3-dioxane-4,6-dione (2-trifluoroacetyl Meldrum's acid) and 2,2-dimethyl-6-(trifluoromethyl)-4H-1,3-dioxin-4-one and their synthetic usefulness as (trifluoroacetyl)ketene precursors

A simple and reliable method for the preparation of 2,2-dimethyl-5-(trifluoroacetyl)-1,3-dioxane-4,6-dione and 2,2-dimethyl-6-(trifluoromethyl)-4H-1,3-dioxin-4-one on a multigram scale was developed. These (trifluoroacetyl)ketene precursors were used in the hetero-Diels-Alder reaction with dialkylcyanamides and 1-ethoxyprop-1-yne, as well as in some reactions with nucleophiles.     

Reaction of 2-aryl(methyl)-4-cyano-5-hydrazino-1,3-oxazoles with aryl Isothiocyanates

Accessible 2-aryl(methyl)-4-cyano-5-hydrazino-1,3-oxazoles add to aryl isothiocyanates. The resulting products undergo recyclization to form new 1,3,4-thiadiazole derivatives bearing an acylamino group on C² and an (acylamino)(cyano)methyl group on C⁵. The structure of the new compounds was proved by their IR and ¹H NMR spectra, as well as by conversion in other 1,3,4-thiadiazole derivatives.