Studies on the syntheses of azole derivatives. Part IX. Formation of 2,4-disubstituted δ2 -1,3,4-oxadiazolin-5-one and 4-substituted 1,2,4-triazolidin-3,5-dione derivatives by thermal reaetion of N-aryl-N-benzylearbamoyl azides

The structure of the novel produets, 2,4-ltis-(N-benzy1-4-nitroanilino)-Δ²-1,3,4-oxadiazolin-5-one (VII), 2-benzy1-1-(N-benzy1-4-chloroanilino)-4-(4-chlorophenyl)-1,2,4-triazolidin-3,5-dione (XIVa), and 2-benzy1-1-(N-benzylanilino)-4-pheny1-1,2,4-triazolidin-3,5-dione (XIVb), obtained upon thermal reaction of N-bcnzyl-N-(4-nitrophenyl)carbamoyl azide (la), N-benzyl-N-(4-chloro-phenyl)carbamoyl azide (Ib) and N-benzyl-N-phcnylcarbamoyl azide (le), respectively, were determined.     

Studies on the syntheses of azole derivatives. Part VIII. Photolysis of N-aryl-N-benzylearbamoyl azides [studies on the syntheses of heterocyclic compounds. Part CDXV

Photolysis of N-benzyl-N-phenylearbamoylazide (IVc) afforded 1-benzy 1-2-benzimidazolinone (Ic), 2-benzimidazolinone (IIe), 4-benzy 1-2-benzimidazolinone (IIe), and 5-benzy1-2-benzimidazo-linone (IIf)- The same reaction of N-benzyl-N-(4-chlorophenyl) carbamoyl azide (IVd) gave 3-benzyl-1-(phenylhydrazocarbonyl)-2-benzimidazolinone (VIb) besides the above four products. In the case of N-benzyl-4-(4-butoxyphenyl)carbamoyl azide (IVe), 1-benzy1-5-butoxy-2-benz-imidazolinone (1e), 5-butoxy-2-benzimidazolinone (IId), 5-benzy1-2-benzimidazolinone (IIf), and 4-benzy1-6-butoxy-2-benzimidazolinone (IIg).     

Studies on the syntheses of azole derivatives. Part VII. Syntheses of 1 -phenyl-Δ2-1,2,4-triazolin-5-one derivatives [studies on the syntheses of heteroeyclic compounds. CD XI]

Bromination of 3-methyl-1-phenyl-Δ²-1,2,3-lriazolin-5-one (II) and its 4-phenyl derivative III afforded the corresponding I-(p-Bromophenyl) derivatives IV and V, respectively. (Chlorination of the 4-phenyl derivative III gave I-(P-chlorophenyl) derivative VI. In addition, 3-N-subsuituted-carhamoyl-1,2,4-triazolin-5-ones(XII, XIII, and XIV) were synthesized by the Schotten-Baumann reaction of 3-carboxy-1-phenyl-Δ²-1,2,4-triazolin-5-one (XI) with various amines.     

Studies on the syntheses of azole derivatives. Part II . Syntheses of N-(1- or 2-Substituted)indazolones via Diazotization

Syntheses of 2,5-disubstituted-indazolones (Ixa–g) and 3-hydroxy-1-substituted-1H-indazoles (XIVa,b) were achieved by diazotization of 2-benzoylaniline (VIa–g) and N-benzoylhydrazine (XIIa–c), respectively.     

Studies on the syntheses of azole derivatives. Part III. Syntheses of 1-Phenyl-Δ2-1,2,4-triazolin-5-one and 4-Phenyl-Δ2-1,3,4-oxadiazolin-5-one Derivatives by Fusion of 1-Phenyl-2-acylhydrazine with Urea

Fusion of 1-phenyl-2-acylhydrazine (III) with urea gave Δ²-1,2,4-triazolin-5-one and Δ²-1,3,4-oxadiazolin-5-one derivatives together with various by-products. Furthermore, various derivatives were synthesized for the purpose of examination in a pharmacological screening test.     

Studies on the syntheses of azole derivatives. Part IV. Novel Syntheses of 1-Benzylbenzimidazolines by Photolysis of N-Aryl-N-benzylcarbamoyl Azides [Studies on the Syntheses of Heterocyclic Compounds. Part CCCLXXVIII

Photolysis of N-benzyl-N-(4-substituted-phenyl)carbamoyl azides (Ia and Ib) afforded N-benzylidene-N′-benzylhydrazines (XIIa and XIIb) and the debenzylated benzimidazolines (XIIIa and XIIIb).     

Studies on the reaction of 3-substituted-4-hydroxy-2H-1,2-benzothiazine 1,1-dioxides with aryl isocyanates and the synthesis of corresponding derivatives

The reaction of 3-substituted-4-hydroxy-2H-1,2-benzothiazine 1,1-dioxides with aryl isocyanate under different equivalents of strong base NaH was studied.Seventeen of new derivatives were obtained whose structures were characterized by 1H NMR,IR,MS,elementary analysis and FeCl3 test.     

Studies on the syntheses of heterocyclic compounds. Part DCLV.. Two stereoisomers of 1-benzyl-5-hydroxy-6-(4-methoxybenzyl)-4,5-dimethylpiperidin-2-one

The stereochemistry of two diastereoisomers of 1-benzyl-5-hydroxy-6-(4-methoxybenzyl)-4,5-dimethylpiperidin-2-one (IV), which is an intermediate for synthesis of pentazocine (I), was elucidated.     

Catalyst-free synthesis of 3-substituted-3-hydroxy-2-oxindoles by reaction of isatin and cyclic enaminone in water

An easy protocol for the synthesis of enaminone attached 3-substituted-3-hydroxy-2-oxindoles has been demonstrated by reaction of isatin and cyclic enaminone in water. The developed catalyst-free reaction has the advantage of being atom-economical, eco-friendly, and benign reaction conditions. The broader substrate scope, experimentally simple procedures, and easy purification of products with high yield further make this method attractive and useful.     

A simple and efficient one-step synthesis of 3-substituted-4-hydroxyquinolin-2-one derivatives

A new simple and efficient one-step procedure for the preparation of 3-substituted-4-hydroxyquinolin-2-one derivatives was developed. Product isolation is simple, isolated yields are good to excellent and this method tolerates a variety of substitution patterns.     

Studies on the syntheses of heterocyclic compounds. Part DLXXXI . Syntheses of 3-carboxy-1,2,3,4-tetrahydroisoquinoline derivatives by phenolic cyclization

3-Carboxy-1,1-dimethylisoquinoline and 3-carboxy-1-spirocycloalkano-and 1-spiroheterocyclo-alkanoisoquinoline derivatives were synthesized by phenolic cyclization reaction using m-tyrosine and several carbonyl compounds.     

Studies on the syntheses of analgesics. Part XXXII. An alternative synthesis of 1,2,3,4,5,6-Hexahydro-8-hydroxy-6,11-dimethyl-3-(3-methyl-2-butenyl)-2,6-methano-3-benzazoeine [Studies on the syntheses of heterocyclic compounds. Part CDLXXX]

Bischler-Napieralski reaction of the amides (VIII and IX), derived from the 3-methyl-3-pentenylamine (III) with the phenylacetic acid derivatives (V ～ VII), gave the 5,6-dihydropyridines (XII and XIII), which were reduced, followed by N-benzylation, to afford the 1,2,5,6-tetrahydropyridines (XIX ～ XXI). Grewe-type cyclization of these compounds gave 3-benzyl-3-benzazocine (II), which was already converted into pentazocine (Ic). Moreover, the 1,2,5,6-tetrahydropyridines (XIX ～ XXI) were also obtained from the 2-benzylidene-1,2,5,6-tetrahydropyridine (XVII ～ XVIII) from the N-benzylamine (IV) of III via the amides (X and XI).     

Studies on the syntheses of heterocyclic compounds. Part CCCXXIX. Syntheses of i-spiroisoquinoline derivatives by phenolic cyclization

Phenolic cyclization of 2-(3-hydroxyphenyl)-2-methylethylamine (XIIIa) and 2-(3-hydroxyphenyl)phenethylamine (XIIIb) with various carbonyl compounds afforded eight types of corresponding 1-spirocycloalkano- and 1-spiroheterocycloalkano-1,2,3,4-tetrahydroisoquinoline derivatives (1-VIII) and 1,1-disubstituted-1, 2,3,4-tetrahydroisoquinoline derivative (IX). The acetyl derivatives of VI and IX and the benzoyl derivatives of III and V were also prepared. In addition, a synthetic method for obtaining the starting phenethylamines was examined.     

Studies on the syntheses of heterocyclic compounds. Part CDXCVII. Total syntheses of (±)-cryptaustoline and (±)-thaliporphine by the benzyne reaction

The indisputable benzyne reaction of 1-(5-bromo-3,4-dimethoxybenzyl)-1,2,3,4-tetrahydro-7-hydroxy-6-metlioxy-2-methylisoquinoline (II) with sodium amide in liquid ammonia afforded the following compounds, (±)-cryptaustoline iodide (VI), (±)-thaliporphine (VIII), 1 -(3,4-dimeth-oxybenzyl)- (III), and 1 -(2-amino-4,5-dimethoxybenzyl)-l,2,3,4-tetrahydro-7-hydroxy-6-meth-oxy-2-methylisoquinoline (IV).     

Formation of new 4-isocyanobut-2-enenitriles by thermal ring cleavage of 3-pyridyl azides

A new thermal ring cleavage of 3-pyridyl nitrenes for the formation of 4-isocyanobut-2-enenitrile products is reported. Thermolysis of 4-(thien-3-yl)-3-pyridyl azide 1 and 3-azido-4-(1-TIPS-1H-pyrrol-3-yl)pyridine 5 afforded two new isonitrile-nitrile products by ring cleavage; 4-isocyano-2-(thiophen-3-yl)but-2-enenitrile (3, 27%) and 4-isocyano-2-(1-TIPS-1H-pyrrol-3-yl)but-2-enenitrile (7, 20%), in addition to our previously reported pyrido[3,4-b]thienopyrrole (2, 29%) and pyrido[3,4-b]pyrrolo[3,2-d]pyrrole (6, 71%) products. Minor amounts of 2-(thien-3-yl)-1H-pyrrole-3-carbonitrile (4, 6%), formed by ring contraction, were also isolated after thermolysis of azide 1. Isonitriles 3 and 7 underwent degradation into amine 3b and formamide 7a by acidic hydrolysis. The nature and chemistry of compounds 3, 4 and 7 were investigated.     

Studies on chemotherapeutics I. Synthesis of 5-substituted-4-oxo-1,4-dihydro-3-pyridinecarboxylic acid derivatives

Ethyl 5-substituted-4-oxo-1,4-dihydro-3-pyridinecarboxylates were synthetized by reacting 1,3,5-triazine with 4-substituted ethyl acetoacetate derivatives in ethanol, in the presence of sodium ethoxide. The l-alkyl-5-substituted-4-oxo-1,4-dihydro-3-pyridinecarboxylic acids required for the antimicrobial studies were prepared by N-alkylation (with triethyl phosphate or alkyl halides) and alkaline hydrolysis of the pyridone esters.     

Mannich and eschweiler-clarke reaction of 1-benzyl-1,2,3,4-tetrahydroisoquinolines. Studies on the syntheses of heterocyclic compounds. Part CCCXVIII

Modified Mannich reactions of a number of 1-benzyl-1,2,3,4-tetrahydroisoquinolines (Ia-Ie) were attempted to afford the corresponding protoberberine derivatives (IIa-IIe) in good yield. Treatment of both If and Ig with formalin under a variety of Mannich or Eschweiler-Clarke conditions did not give the expected protoberberine derivatives IIf and IIg, but afforded the N-methyl derivatives (VIIa) and (VIIb), respectively.