Rearrangement of some chlorosubstituted 3-amino-3,4-dihydro-1-hydroxycarbostyrils in hydrogen halide acids

The general conditions and results of rearrangement studies of the 5-, 6-, 7-, and 8-chloro-substituted 3-amino-3,4-dihydro-1-hydroxycarbostyrils in concentrated hydrochloric and hydro-bromic acids to the corresponding dihalosubstituted 3-amino-3,4-dihydrocarbostyrils have been described. The 5-, 7- and 8-chlorocarbostyrilhydroxamic acids undergo nucleophilic displacement by either chloride or bromide ion preferentially at the 6-position to form the respective 5,6-, 6,7- and 6,8-dihalolactams. However, with the 3-amino-6-chloro-3,4-dihydro-1-hydroxycarbo-styril where the 6-position is blocked, nucleophilic displacement by halide ions occurs at the 8-position to afford the 6,8-dihalolactams. The 6,8-dichloro- and 6,8-dibromolactams were also prepared by alternative halogenation procedures for purposes of comparison with the rearrangement products.     

Synthesis of 3-substituted-3,4-dihydro-2(1H)-pyridinones from nitriles

A number of the title compounds have been prepared through a three step reaction sequence based on the cyclization of Δ-acetal amides.     

Synthesis and properties of 3-chloro- and 3,7-dichloro-3,4-dihydro-1-hydroxycarbostyrils and related heterocyclic compounds

3-Chloro- and 3,7-dichloro-3,4-dihydro-1-hydroxycarbostyrils were synthesized by the catalytic hydrogenation of the α-chloro- and α,4-dichloro-β-(o-nitrophenyl)propionic acids in strong acidic solution over platinum-on-carbon sulfided catalyst. However, the catalytic hydrogenation of α-bromo-β-(o-nitrophenyl)propionic acid yielded 3,4-dihydro-1-hydroxycarbostyril under the same experimental conditions. The 3-chloro-3,4-dihydro-1-hydroxycarbostyril and the α-chloro-β-(o-nitrophenyl)propionic acid underwent facile dehydrochlorination in mild alkaline solution to give 1-hydroxycarbostyril and o-nitrocinnamic acid, respectively. Selective reduction of 3-chloro-3,4-dihydro-1-hydroxycarbostyril and 1-hydroxycarbostyril to the corresponding lactams, 3-chloro-3,4-dihydrocarbostyril and carbostyril, was effected by catalytic hydrogenation in hydrochloric acid over platinum black catalyst. The structures of the substituted carbostyril derivatives were correlated with their proton nmr spectra.     

Reaction of pyromeconic acid with β-diazopropionic ester. Synthesis and attempted cyclization of β-(4H-pyran-4-on-3-yloxy)propionic acid

A procedure which utilizes a special sublimate condenser for preparation of pyromeconic acid (I) by decarboxylation of either meconic or comenic acid is reported. O-Alkylation of pyromeconic acid with ethyl β-diazopropionate ex situ yields ethyl β-(4H-pyran-4-on-3-yloxy)-propionate (II), acidic hydrolysis of which affords the free acid III. The acid III is refractory to ring-closure to a chromanone analog IV under a wide range of acidic conditions. O-Allylation of 1 gives 3-allyloxy-4H-pyran-4-one (V) as a low-melting crystalline solid.     

Synthesis of some 7-α-carboxyethyl-1,3-dihydro-(2H)-1,4-benzodiazepin-2-ones

1,4-Benzodiazepin-2-ones possessing an α-carboxyethyl group in 7-position (21-25) were prepared from a key compound, 2-amino-5-α-carboxyethylbenzophenone (8) or from its O-benzyl derivative 14 , using methods developed previously. An optimized route to 8 starting from 2-nitro-5-chlorobenzophenone ( 1 ), as well as some unsuccessful attempts are described. Compound 8 was deaminated into racemic α-(3-benzoyl)-phenylpropionic acid ( 9 ), a well-known antiinflammatory agent.     

Synthesis of(E)7-[[2-[4-(m-trifluoromethylphenoxy)-3α and 3β-hydroxy-1-butenyl]-5-oxo-1 -pyrrolidinyl]]heptanoic acids

The synthesis of an 8-aza-PGE₁ analog, (E)-7-[[2-[4-(m-trifluoromethylphenoxy)-3α and 3β-hydroxy-1-butenyl]-5-oxo-pyrrolidinyl]]heptanoic acids is reported.     

Amine-induced rearrangements of 2-bromo-1-(1H-indol-3-yl)-2-methyl-1-propanones: A new route to α-substituted indole-3-acetamides, β-substituted tryptamines, α-substituted indole-3-acetic acids and indole β-aminoketones

The reaction of 2-bromo-1-(1H-indol-3-yl)-2-methyl-1-propanone ( 1 ) and 2-bromo-1-(1-methyl-1H-indol-3-yl)-2-methyl-1-propanone ( 2 ) with primary amines proceeds in good yields to produce rearranged amides by a proposed pseudo-Favorskii mechanism. These amides in turn can either be reduced to produce β-substituted tryptamines or hydrolyzed to produce substituted indole-3-acetic acids. When the reaction is carried out using bulky primary or secondary amines, β-aminoketones are produced by elimination of hydrogen bromide followed by Michael addition. When hindered secondary amines or tertiary amines are used, elimination to the α,β-unsaturated ketones occurs.     

Synthesis of 2-(5′-substituted isoxazol-3′-yl)-4-oxo-3-thiazolidinylalkanoic acids

A series of 2-substituted 4-oxo-3-thiazolidinylalkanoic acids bearing an isoxazole nucleus in the 2-position have been prepared. None of the compounds synthesised showed antibacterial activity in vitro.     

The synthesis of some 1-(β-diethylaminoethyl)-2-(p-ethoxybenzyl)-5-substituted benzimidazoles

The syntheses of several 5-substituted benzimidazoles structurally related to the highly active analgesic 1-(β-diethylaminoethyl)-2-(p-ethoxybenzyl)-5-nitrobenzimidazole are presented.     

Mass spectra of some 1-(6′-substituted-4′-methyl-2′-quinolyl)-3-methylpyrazol-5-ols and their 4-substituted analogues

Electron impact induced fragmentation of some 1-(6′-substituted-4′-metbyI-2′-quinolyI)-3-methylpyrazoI-5-ols follows a route where the pyrazole moiety is preferentially cleaved with successive losses of two moieties of 41 u. High-resolution measurements have established that the first loss is due to the ?₂HO moiety, which necessitates an intramolecular hydrogen transfer followed by ring fission. The resultant ion loses CH₃CN in a subsequent step. The origin of many fragment ions was traced with the use of B/E linked-scan spectra.     

Synthesis of 1h-2,3,4,5-tetrahydro- 1,5 -benzodiazepin-2-ones by reductive cyclization of 3- (o-nitrophenylamino)propionic acids

A new synthesis of 1H-2,3,4,5-tetrahydro-1,5-benzodiazepin-2-ones (I) by the reductive cyclization of o-nitro derivatives of N-phenyl--alanine is described. It is more convenient to use the amide of acrylic acid rather than acrylic acid itself, its nitrile, or ester for the synthesis of I from the appropriate o-phenylenediamines.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 987–991, July, 1971.     

The synthesis of 1-substituted-2-(β-dimethylaminoethyl)benzimidazoles

2-(β-Dimethylaminoethyl)benzimidazoles have been prepared by the reduction of the corresponding 2-benzimidazole-N,N-dimethylacetamides. Condensation of ethyl cyanoacetate with N-benzyl or phenyl-o-phenylenediamines led to N-cyanoacetyl-N'-substituted-o-phenylenediamines, the structure of which were assigned from u.v. and n.m.r. data. An improved synthesis of benzimidazole - 2 - acetic acid derivatives, from substituted ethyl acetimidates and o-phenylenediamines, is described. Dimerisation of 1-phenyl-benzimidazole occurs in the presence of phenyllithium.