Allenic Nitriles Research Articles

Synthesis of biologically active heterocyclic compounds from allenic and acetylenic nitriles and related compounds

Abstract Cyclic and polycyclic compounds containing moieties such as imidazole, pyrazole, isoxazole, thiazoline, oxazine, indole, benzothiazole and benzoxazole benzimidazole are prized molecules because of the various pharmaceutical properties that they display. This led Prof. Landor and co-workers to engage in the synthesis of several of them such as alkylimidazolenes, oxazolines, thiazolines, pyrimidopyrimidines, pyridylpyrazoles, benzoxazines, quinolines, pyrimidobenzimidazoles and pyrimidobenzothiazolones. This review covers the synthesis of biologically active heterocyclic compounds by the Michael addition and the double Michael addition of various amines and diamines on allenic nitriles, acetylenic nitriles, hydroxyacetylenic nitriles, acetylenic acids and acetylenic aldehydes. The heterocycles were obtained in one step reaction and in most cases, did not give side products. A brief discussion on the biological activities of some heterocycles is also provided.

ChemInform Abstract: A Novel Synthesis of Allenic Nitriles from Ynones via Cyano Phosphates.

ChemInform Abstract: A Novel Synthesis of Allenic Nitriles from Ynones via Cyano Phosphates.

Heterocycles of biological importance. Part 5. The formation of novel biologically active pyrimido[1,2-a]benzimidazoles from allenic nitriles and aminobenzimidazoles

The reaction of allenic nitriles with 2-aminobenzimidazoles gives 2-aminopyrimido[1,2-a]benzimidazoles 5 in very good yields. The pharmacological screening of compound 5a, 5d and 5i shows that they possess slight antibiotic and antiarrythmic properties.

A New Synthesis of Allenic Nitriles from Ynones via Cyano Phosphates.

A New Synthesis of Allenic Nitriles from Ynones via Cyano Phosphates.

ChemInform Abstract: Allenes. Part 50. Pyrimido(1,2‐a)pyrimidines and Pyrimido(1,6‐a)pyrimidines and Their Hydrolysis Products from Allenic Nitriles and Phenylpropynenitrile.

AbstractReaction of the aminopyrimidines (I) or (VII) with the allenic nitriles (II) or (VIII) yields initially the title compounds (III) or (IX).

Allenes. Part 50. Pyrimido[1,2-a]pyrimidines and pyrimido[1,6-a]pyrimidines and their hydrolysis products from allenic nitrites and phenylpropynenitrile

2-Aminopyrimidine and 2-amino-4-methylpyrimidine react with allenic nitriles to give, initially, 2-imino-4-alkylpyrimido[1,2-a]pyrimidines (2) which rapidly add water and cleave to 3-(4-amino-6-alkyl-2-pyrimidylamino)aldehydes (6). 2-Amino-4,6-dimethylpyrimidine similarly gives the corresponding ketones (5; R3= R4= Me). 2-Imino-4-alkylpyrimido[1,6-a] pyrimidines (11) areformed as intermediates from 4-amino-2,6-dimethylpyrimidine and allenic nitriles and are hydrolysed to amides (12).

Allenes. Part 49. 4-Amino-2-(1-hydroxyalkyl)quinolines from phenylhydroxylamine and allenic nitrites

Allenic nitriles, when heated with phenylhydroxylamine in ethanol for 24 h, form the intermediate 2-alkylidene-4-amino-1,2-dihydro-1-hydroxyquinolines (4) which rearrange spontaneously by a 1,3-hydroxy shift to 4-amino-2-(1-hydroxyalkyl)quinolines. The 1-hydroxyquinoline intermediate (4) does not isomerise to 2-alkyl-4-aminoquinoline 1-oxide by a 1,4-proton shift as shown by an independent synthesis of the latter. Phenylpropynenitrile with phenylhydroxylamine gave 8% of 4-amino-2-(2-hydroxyphenyl)quinoline (15).

ChemInform Abstract: Allenes. Part 48. A New General Method for the Synthesis of Dihydro‐4H‐1,4‐thiazines.

AbstractThe allenic nitriles (I) react with thio compounds, e.g. (II) and (IV), to give thiazines such as (III) and (VI).

ChemInform Abstract: Allenes. Part 46. Synthesis of 1,2‐Dihydro‐4H‐3,1‐benzoxazines, 4H‐3,1‐Benzoxazines, and 3‐Cyanoquinolines from Allenic and Acetylenic Nitriles.

AbstractThe aminobenzyl alcohol (I) reacts with the allenic nitriles (II) to yield mixtures of the enaminic nitriles (III) and the dihydrobenzoxazines (IV); the latter result from cyclization of the former (with the exception of (IIIb) all compounds are isolated separately).

Allenes. Part 48. A new general method for the synthesis of dihydro-4H-1,4-thiazines

The base-catalysed reaction between allenic nitriles and aminoethanethiol, cystamine, cysteine, cysteine methyl ester, cystine or cystine dimethyl ester in refluxing ethanol, with passage of oxygen through the reaction mixture, gives 80–90% yieldsof3-alkyl-5,6-dihydro-4H-1,4-thiazine-2-carbonitriles and chiral 5-carboxy and 5-methoxycarbonyl analogues. Detailed investigation and spectroscopic studies have elucidated the seven-step mechanism of this one-pot reaction. Under similar conditions, 2-aminothiophenol failed to give the corresponding 1,4-benzothiazines. Alkaline hydrogen peroxide oxidised the dihydrothiazine to the S-oxide quantitatively.

Allenes. Part 47. Pyrido[1,2-a]pyrimidines and their hydrolysis products from allenic and acetylenic nitriles

The reactions between 2-aminopyridine, C-substituted 2-aminopyridines, and allenic nitriles or phenylpropynenitrile give, initially, 2-amino-2H-pyrido[1,2-a]pyrimidines which are moderately stable under acidic conditions but undergo addition of water with extreme ease under basic conditions to form 4-hydroxypyrido[1,2-a]pyrimidines. These undergo ring cleavage when refluxed in ethanol to pyridyl ketones (5).

Allenes. Part 46. Synthesis of 1,2-dihydro-4H-3,1 -benzoxazines, 4H-3,1-benzoxazines, and 3-cyanoquinolines from allenic and acetylenic nitriles

Allenic nitriles or phenylpropynenitrile react in refluxing ethanol with o-aminobenzyl alcohol to give first enaminic nitriles (2) which slowly cyclise to dihydro-4H-3,1-benzoxazines (3). The latter eliminate acetonitrile on heating to give 4H-3,I -benzoxazines (4) whereas the enaminic nitriles under the same conditions give mainly 2-alkyl-3-cyanoquinolines (5). Mechanistic considerations and spectroscopic details are discussed.

Allence. Part 43. A novel synthesis of pyrimidines of potential pharmaceutical interest from allenic nitriles

The reactions of 4,4-dialkylbuta-2,3-dienenitriles and 3-phenylpropynenitrile with guanidine and acetamide have been investigated; a number of 6-alkyl-2,4-diaminopyrimidines and 6-alkyl-2-methyl-4-aminopyrimidines as well as 2,4-diamino-6-phenylpyrimidine and 4-amino-2-methyl-6-phenyl-pyrimidine have been synthesised.

Allenes. Part 42. Nucleophilic addition of hydroxylamine to allenic and acetylenic nitriles; synthesis of 3-alkyl-5-amino, 5-amino-3-phenyl-, and 3-amino-5-phenyl-isoxazoles

Hydroxylamine adds to allenic nitriles to give 3-alkyl-5-aminoisoxazoles in excellent yield. Hydroxyacetylenic nitriles similarly give 5-amino-3-(1-hydroxyalkyl)isoxazoles. Phenylpropynenitrile under varying conditions of temperature and solvent yields mainly 5-amino-3-phenylisoxazole with varying amounts of 3-amino-5-phenylisoxazole as a by-product.

Allenes. Part 40. 2:1 Bis-adducts from allenic nitriles and phenylpropynenitriles with difunctional nucleophiles and their conversion into heterocycles

Two equivalents of allenic nitrile or phenylpropynenitrile add to 1,2- and 1,3-diamines, 2-aminoethanethiol, ethanedithiol, and 4-aminopyridine to give 2:1 adducts of structures (2), (4), and (5). Ring closure and elimination of one equivalent each of allenic nitrile (or phenylpropynenitrile) and acetonitrile gave the imidazolines (29), the thiazolines (30), and the tetrahydropyrimidines (31). Mass spectral fission patterns are discussed.

Allenes. Part 39. The synthesis of 3-alkyl-5-aminopyrazoles and 3H-indoles from allenic or acetylenic nitriles

Hydrazine adds to allenic or acetylenic nitriles to give 3-alkyl-substituted 5-aminopyrazoles in excellent yields. Conjugated and unconjugated enaminic nitriles may be isolated from the Michael addition of phenylhydrazine to allenic nitriles and ring-closed to give 3-alkyl-5-amino-N-phenylpyrazoles and 3H-indoles.

Allenes. Part 38. Imidazolines, benzimidazoles, and hexahydrobenzimidazoles from 1,2-diamines and allenic or acetylenic nitriles

The double Michael addition of 1,2-diamine to allenic or acetylenic nitriles has been shown to give imidazolines, benzimidazoles, or hexahydrobenzimidazoles in excellent yields via conjugated enaminic nitriles.

N-phenylpyrazoles and 3H-indoles from allenic nitriles. A novel fischer-indole reaction.

N-phenylpyrazoles and 3H-indoles from allenic nitriles. A novel fischer-indole reaction.

Oxazolines, thiazolines, oxazoles, thiazoles and pyrazoles from allenic and acetylenic nitriles

Oxazolines, thiazolines, oxazoles, thiazoles and pyrazoles from allenic and acetylenic nitriles

Synthesis and reactions of allenic amides : Allenes-XXXI

Allenic amides are prepared from allenic nitriles using alkaline hydrogen peroxide and by a Ritter reaction with t-butyl alcohol, when N-t-butylamides are obtained. Strong nucleophiles attack the central carbon of the allene system to give α,β-unsaturated addition products.