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 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 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 syntheses of analgesics. Part XXXVI. Synthesis of 1,2,3,4,5,6-ilexahydro-2,6-methano-6-phenyl-2 henzazocine [studies on the syntheses of heterocyclic compounds. Part D XI]

An attempt to obtain 2,3,4,5,6,7-hexahydro-lH2,7-methano-9-methoxy-3-rnethyl-7-phenyl-2,3-benzodiazonine (II) by the Pictet-Spengler reaction of 2,3,4,5,6,7-hexahydro-lH-4-(3-meth-oxyphenyl)-l-methyl-4-phenyl-1,2-diazepine (XI) prepared through several steps from 1-(3-methoxyphenyl)phenylaeetonitrile (IV) resulted instead, in the formation of 1,2,3,4,5,6-hexa-hydro-2,6-methano-8-methoxy-6-phenyl-2-benzazocine (XIV).     

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 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 analgesics. Part 50. Synthesis of optically active 2-[4-(1-oxo-2-isoindolinyl)phenyl]propanoic acid. [Studies on the syntheses of heterocyclic compounds. Part 742]

2-[4-(1-Oxo-2-isoindolinyl)phenyl]propanoic acid ( 1 ) having a potent analgesic and anti-inflammatory activity could be obtained by three methods, which were found to provide extremely useful ways for the synthesis of 1 from the industrial point of view. (E)- and (Z)-Isomers of 2-butenoic acid and oxiranecarboxylic acid derivatives as the intermedaites in the synthesis of 1 were separated and characterized. Furthermore, the optical resolution of (±)-2-[4-(1-oxo-2-isoindolinyl)phenyl]propanoic acid was successfully achieved using cinchonidine as a resolution reagent.     

Studies on the synthesis of analgesics. Part 51. Synthesis of 4-(1-oxo-2-isoindolinyl)phenyl derivatives. [Studies on the syntheses of heterocyclic compounds. Part 779]

In order to examine their effect on carrageenin-induced edema in rats, 4-(1-oxo-2-isoindolinyl)-phenyl derivatives were synthesized. 2-Hydroxy-3-[4-(1-oxo-2-isoindolinyl)phenyl]butyramide was found to be more effective than phenylbutazone.     

Studies on the syntheses of azole derivatives—V: The mass spectra of 1,2,4-triazoles and oxadiazoles (studies on the syntheses of heterocyclic compounds—CCCLXXIV)

The electron-impact induced fragmentation of twenty 3-alkyl-1-phenyl-Δ²-1,2,4-triazolin-5-ones, three 1-phenyl-1,2,4-triazolin-3,5-diones and ten 2-alkyl-4-phenyloxadiazolin-5-ones has been studied by conventional mass spectrometry. The major cleavages take place in the 1-phenyl-Δ²-1,2,4-triazolin-5-one nucleus, producing three major fragment ions. 4-Phenyloxadiazolin-5-ones exhibit a similar fragmentation pattern to 1-phenyl-Δ²-1,2,4-triazolin-5-ones. Furthermore, several additional fragmentation processes are observed in the case of specific 1,2,4-triasolines.     

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 synthesis of chemotherapeutics. I. Synthesis of 1-(2-tetrahydrofuryl)-5-fluorouracil [ftorafur] (studies on the syntheses of heterocyclic compounds. Part 703)

Synthesis of 1-(2-tetrahydrol'uryl)-5-fluorouracil [Ftorafur] ( 1 ) which is well known as an antitumor agent from 5-fluorouracil ( 2 ) with 2-alkoxytetrahydrofurans (4) is described. Among these reactions, the best yield was obtained by using 2-t-butoxytetrahydrofuran (4h).     

Studies on the syntheses of azole derivatives. Part I. Formation of 1-substituted-3-hydroxy-1H-indazole and I-substituted benzimidazolin-2-one derivatives by thermal reaction of N-substituted-N-arylcarbamoyl azides.

The formation of 1-substituted-3-hydroxy-1H-indazole and 1-substituted-benzimidazolin-2-one derivatives by thermal reaction of N-substituted-N-arylcarbamoyl azides was examined.     

Studies on the syntheses of heterocyclic compounds. Part DLXXXII . Synthesis of benzo[a] quinolizine derivatives and pyrrolo[2,1-a] isoquinoline derivatives by phenolic cyclization

Phenolic cyclization of 3-hydroxy phenethylamine with acylbutyric acid and acylpropionic acid afforded the lactam of the corresponding benzol[a] quinolizine and pyrrolo[2, 1-a]isoquinoline derivatives, which were reduced with lithium aluminum hydride to give the benzol[a]quinolizine and pyrrolo[2,1 -a] isoquinoline derivatives, respectively. The configurations of acetyl derivatives of these products were determined.     

Synthetic studies on chemotherapeutics. II. Synthesis of phenyl-substituted 1,4-dihydro-4-oxonicotinic acid derivatives. [Studies on the syntheses of heterocyclic compounds. Part 704]

The thermal cyclization of the arninomethylenemalonates (8) gave the 4-hydroxynicotinates ( 9 ), ethylation of which yieldedN-ethylated ( 11 ) and O-ethylated products ( 12 ). Hydrolysis of 9, 11 , and 12 led to the desired nicotinic acids (10, 4, and 13), respectively.     

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 XXXI. Synthesis of 1,2,3,4,5,6-Hexahydro-3-methyl-6-phenyl-2,6-melhano-2,3-benzo[g] diazocine [studies on the syntheses of heterocyclic compounds. Part CDLXXIX]

1,2,3,4,5,6 Hexahydro-8-methoxy-3-methyl-6-phenyl-2,6-methano-2,3-benzo[g]diazocine (IIa) was synthesized from 1-(3-methoxyphenyl)phenylaeetonitrile (III), readily available by the benzyne reaction of o-chloroanisole with phenylacetonitrile, through several steps. Treatment of IIa with 47% hydrobromic acid afforded 1,2,3,4,5,6-hexahydro-8-hydroxy-3-methyl-6-phenyl-2,6-methano-2,3-benzo[g]diazocine (IIb).     

Studies on heterocyclic compounds. VII. Syntheses of novel furo[2, 3-b]chromones

Furo[2, 3-b]chromone ( 1a ) was conveniently prepared by the PPE-promoted cyclization of 5-(2′-carboxy-phenoxy)furan-2-carboxylic acid ( 8 ) which was made from methyl salicylate and ethyl 5-nitrofuran-2-carboxyl-ate. Furo[2, 3-b]chromon-2-acrylic acid ( 13 ) was obtained by a similar cyclization. Direct acylation of 1a afforded 2-acetylfuro[2, 3-b]chromone ( 10 ). Several derivatives of furo[2, 3-b]chromone were found to display activity in the rat passive cutaneous anaphylaxis (PGA) test for antiallergic activity.     

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.     

Syntheses of benzomorphan and related compounds. Part 1. Synthesis of N-substituted-l,2,3,4,5,6-hexahydro-8-hydroxy-2,6-methano-6,11-dimethyl-3-benzazocine [studies on the syntheses of heterocyclic compounds. Part CCLXXXII ]

A modified synthesis of pentazocine, l,2,3,4,5,6-hexahydro-8-hydroxy-2,6-methano-6, H-dimethyl-3-(3-methyl-2-butenyl)-3-benzazocine (III), has been achieved and catalytic hydro-genation has been found to be effective for the debenzylation of quaternary ammonium salts.