José L. Soto

The reaction of malononitrile with chalcone: a controversial chemical process

Abstract Given the significant discrepancies in the several reported results on the reaction of chalcone (1,3-diphenyl-2-propne-1-one) (1) with malononitrile (2), a careful reinvestigation was carried out. Depending upon the reaction conditions either the open-chain Michael adduct (4), an alkoxypyridine (5), an aminoisophthalonitrile (6) or a cyclohexanol (7) is obtained. However, no 4H-pyran could be isolated from this reaction.

A convenient,one step synthesis of pyrano[2,3-b]pyridines

Abstract A novel,one step synthesis of pyrano[2,3-b]pyri-dines from malononitrile and unsaturated ketones is reported. The reaction mechanism is discussed and takes place through an intermediate monocyclic 4H-pyran.Several derivatives with different substitution patterns are prepared.

Synthesis of methyl 4-aryl-6-methyl-4,7-dihydro-1H-pyrazolo-[3,4-b]pyridine-5-carboxylates from methyl 4-aryl-6-methyl-2-oxo-1,2,3,4-tetrahydropyridine-5-carboxylates

Novel methyl 4,7-dihydro-1H-pyrazolo[3,4-b]pyridine-5-carboxylates 3a–e have been prepared in a two step procedure from the readily available 2-oxo-1,2,3,4-tetrahydropyridine-5-carboxylates 1a–e by treatment with the Vilsmeier–Haack reagent. Further treatment of the novel o-chloroformyl substituted methyl 1,4-dihydropyridine-5-carboxylates 2a–e with hydrazine affords the corresponding methyl pyrazolo[3,4-b]pyridine-5-carboxylates in good yields. Semiempirical calculations reveal a favoured geometry with a boat conformation in the dihydropyridine system and a planar pyrazole ring.

Ring transformation of isoxazoles into furan and pyran derivatives

A ring transformation of isoxazole into 3,5-dicyano-4H-pyran-2-amines (4) and N-arylidenefuran-2-amines (7) is reported. It involves a ring opening of the isoxazole ring in the presence of an aromatic aldehyde, leading to 2-arylidene-3-oxopropanenitrile (2), followed by nucleophilic attack by either cyanide or propanedinitrile and then heterocyclization. The reaction can also be applied to 5-substituted isoxazoles.

A convenient preparation of [1,2,4]triazolo[1,5-a]pyridines from acetohydrazide derivatives. Synthetic and mechanistic aspects

A novel synthesis of triazolo[1,5-a]pyridines (4) from 2′-acetyl-2-cyanoacetohydrazide (2) and arylidenemalononitriles (3) is described. The synthesis can be carried out either in one step or via 1-acetamidopyridones (5). Alternatively, acetylation of 1-aminopyridones (7) also gives triazolo[1,5-a]pyridines (4). Reaction of (2) with (3) in the presence of piperidine leads to the piperidinium salt of the triazolo[1,5-a]pyridine (6), which can be neutralized to give (4).

Synthesis of 2,4-dioxo-, 2-oxo-4-thioxo-, 4-oxo-, and 4-thioxo-pyrimidine-5-carbonitriles

Methyl N-methoxycarbonylimidates (1)–(4) cyclized readily with 2-cyanoacetamide (5) or 2-cyanoethanethioamide (6) to 2,4-dioxopyrimidine-5-carbonitriles (7)–(10) or 2-oxo-4-thioxopyrimidine-5-carbonitriles (11) and (12). In analogous reactions with alkyl N-acylimidates (15)–(19) 4-oxo-pyrimidine-5-carbonitriles (20)–(23) or 4-thioxopyrimidine-5-carbonitrile (24) were obtained. Representatives of 4-thioxopyrimidine-5-carbonitriles (11), (24) were methylated to 4-methylthio-pyrimidine-5-carbonitriles (13) and (25) or cyclized with methyl chloroacetate to give methyl thieno[2,3-d]pyrimidine-6-carboxylates (14) and (26)

On the reaction of chalcone with ethyl cyanoacetate

Abstract The recently reported condensation of chalcone with ethyl cyanoacetate is discussed and a cyclohexanol structure is proposed for the reaction product.

Synthesis of isomeric 5-(phenylsulphonyl)pyrimidines

The reaction of alkyl N-cyanoimidates (1a–d) with (phenylsulphonyl)acetonitrile (2) and sodium meth-oxide afforded intermediate salts (3a–d), which were characterized as their conjugate acids (10b,c). Acidic hydrolysis of salts (3a–d) yielded 3-[(aminocarbonyl)amino]propenenitriles (4a–d), which cyclized to pyrimidin-2-ones (5a–d) upon dissolution in 2M-sodium hydroxide. These, in turn, were methylated to pyrimidin-4-amines (6a,c,d). The isomeric pyrimidin-4-ones (8a–d) were prepared unambiguously from the imidates (1a–d) and 2-(phenylsulphonyl)acetamide (7) and were methylated to pyrimidin-2-amines (9a–d). Hydrogen chloride induced a selective cyclization of the dicarbonitriles (10b,c) to 2-chloro-(11) or 4-chloro-pyrimidine (12). Several representatives of pyrimidinamines (6) and (9) were obtained alternatively by selective cyclizations of the salts (3).

Reaction of N-substituted acetohydrazides with 2-substituted cinnamonitriles. Competitive cyclizations to pyrazolo[3,4-b]pyridinones and [1,2,4]triazolo[1,5-a]pyridinones

A novel synthesis of pyrazolo[3,4-b]pyridinones 9 from 2′-acyl-2-cyanoacetohydrazide 5 and arylidenecyanoacetates 6 is described. In the reaction, an alternative cyclization leading to [1,2,4]triazolo[1,5-a]pyridinones takes place. Compounds 9 were isolated from the reaction mixture as the corresponding piperidinium salts due to the high stability of the heterocyclic anion. Acidification with dilute hydrochloric acid yielded the neutral pyrazolo[3, 4-b]pyridinone. Depending on the reaction conditions, the corresponding intermediate dihydropyridinone 12 and pyrazolo derivatives 16 were also obtained.

N-amino-2-pyridones from acetohydrazide derivatives

The synthesis of a variety of N-amino-2-pyridones from ethoxycarbonyl acetohydrazide (1) is described. α-Benzoylcinnamonitriles (2) react with (1), in two different ways, giving rise to two kinds of N-aminopyridones (4) and (5) depending upon the cyclization taking place at the carbonyl or cyano group. Reaction of (1) with ethyl α-cyanocinnamates (10) involves cyclization at the cyano group affording the diaminopyridones (11). In contrast, ethyl malonamate (18) reacts with (10) at the ester group, leading to piperidinediones (20). Aromatic rings obtained by oxidation of some of the above compounds are also reported.