Naphth[1,2-d]oxazole intermediates in the preparation of 3-hydroxy-4-(1-alkyl-3-methyl-5-hydroxy-4-pyrazolyl)-azo-1-naphthalenesulfonamide dyes

Acylation of 4-amino-3-hydroxy-1-naphthalenesulfonic acid ( 3 ) with benzoyl chloride in pyridine gave pyridinium 3-hydroxy-4-(N-benzoylamino)-1-naphthalenesulfonate ( 12 ) which was converted by thionyl chloride followed by diethylamine into N,N-diethyl-2-phenylnaphth[1,2-d]oxazole-5-sulfonamide ( 14 ). The naphthoxazole moiety was hydrolyzed with potassium hydroxide and the resulting N,N-diethyl-4-amino-3-hydroxy-1-naphthalenesulfonamide ( 11 ) coupled with 1-alkyl-3-methyl-5-pyrazolones. The 2-phenylnaphth[1,2-d]oxazole intermediates and various by-products were investigated.     

Synthesis and prototropic tautomerism of 1-n-alkyl-3-methyl-4-nitroso-5-pyrazolones

Nitrosation at C-4 of 1-n-alkyl-3-methyl-5-pyrazolones is achieved in about 50% yield with sodium nitrite in hydrochloric acid medium. A tautomeric equilibrium in solution with a proton moving from the OH at C-5 to N-2 in the nitrosated pyrazolones is proposed.     

Synthesis and spectral analysis of (±)-cis-N-[1-(2-hydroxy-2-phenyl-ethyl)-3-methyl-4-piperidyl]-N-phenylpropanamide and (±)-cis-N-[1-(2-hydroxy-1-phenylethyl)-3-methyl-4-piperidyl]-N-phenylpropanamide

Treatment of (±)-cis-N-(3-methyl-4-piperidyl)-N-phenylpropanamide (2) with styrene oxide (1) yielded a mixture of (±)-cis-N-[1-(2-hydroxy-2-phenylethyl)-3-methyl-4-piperidyl]-N-phenylpropanamide (3) and (±)-cis-N-[1-(2-hydroxy-1-phenylethyl)-3-methyl-4-piperidyl]-N-phenylpropanamide (4) . The structure of compound 3 was confirmed by an unambiguous synthesis via (±)-cis-N-[1-(2-oxo-2-phenylethyl)-3-methyl-4-piperidyl]-N-phenylpropanamide (6) . The proton and carbon-13 resonances of compounds 3 and 4 were assigned with the aid of two-dimensional heteronuclear correlation experiments.     

The chemistry of 2H-3,1-benzoxazine-2,4(1H)-dione (isatoic anhydride). 10. Reactions with ester enolates. Synthesis of 4-hydroxy-1-methyl-3-prenyl-2(1H)-quinolinones,Crucial intermediates in the synthesis of quinoline alkaloids

N-Methylisatoic anhydride reacts with the lithium enolates of esters to produce β-ketoesters 4 in nearly quantitative yield. Thermal cyclization of these relatively unstable intermediates afford the corresponding 3-substituted-4-hydroxy-1-methyl-2(1H)-quinolinones (5) in good yields. The reaction of the lithium enolate of 5-methyl-4-hexenoic acid ethyl ester ( 14 ) with various nuclear substituted isatoic anhydrides gives 4-hydroxyl-methyl-3-prenyl-2(1H)-quinolinones 8, 9 , and 18 which are highly desirable intermediates in the synthesis of a variety of quinoline alkaloids. Treatment of 18 with DDQ furnishes oricine in 73% yield.     

Regioselective Synthesis of Heterocycles from 3-Cyclohex-2-enyl-4-hydroxy-1-methylquinolin-2-(1H)-one

3-Cyclohex-2-enyl-4-hydroxy-1-methylquinolin-2(1H)-one (5) reacts with pyridine hydrotribromide in CH₂Cl₂ at 0–5°C for 0.75h to give a furo fused heterocycle 6 in 96% yield. Product 6 on treatment with KOH-EtOH eliminates HBr to give compound 8 which on treatement with Pd-C in refluxing diphenyl ether for 0.5h furnishes benzofuro[3,2-c]quinolone 9 in 90% yield. Substrate 5 on sequential treatment with Ac₂O-AcONa and Br₂/AcOH followed by KOH-EtOH, however produces bicyclic product 7 in excllent overall yield. Substrate 5 reacts with 1 equivalent of m-chloroperbenzoic acid in refluxing benzene to furnish bicyclic heterocycle 12 in 80% yield and with cold conc. H₂SO₄ at 0–5°C for 2h generates the bicyclic heterocycle 14 in 90% yield.     

Structure and chemistry of 4-hydroxy-6-methyl-2-pyridone

The structure of 4-hydroxy-6-methyl-2-pyridone formed by the reaction of 6-methyl-2H-pyran-2,4(3H)-dione and ammonia is characterized. A method is discussed for the structure determination of pyridone type compounds. Reaction of 4-hydroxy-6-methyl-2-pyridone with an equivalent amount of benzenesulfonyl chloride gives 4-benzenesulfonyloxy-6-methyl-2-pyridone. With two equivalent amounts of benzenesulfonyl chloride, 2,4-dibenzenesulfonyloxy-6-picoline is formed. 4-Hydroxy-6-methyl-2-pyridone is preferentially attacked by electrophiles at the 3 position.     

Synthesis of N-substituted 3-hydroxy-2-methyl-4-pyridones and -pyridonimines

Carbohydrates with 1,4 glycosidic bonds like maltose, lactose, dextrin or starch react with primary amines as well as amino acids or proteins to give i.e. 3-hydroxy-2-methyl-4-pyridones 5 and 3-hydroxy-2-methyl-4-pyridonimines 7. A generally applicable synthesis of compounds of this type is described. The pyridones 5 and pyridonimines 7 are strongly complexing agents. Molybdenum-derivatives, for instance, are suitable as fairly stable oxidation catalysts.     

Synthesis of pyridazino[4,5-b]indole derivatives from 2-(3-carboxy-1-methylindole)acetic acid anhydride

2-(3-Carboxy-1-methylindole)acetic acid anhydride ( 1 ) reacts with aryldiazonium salts to give 85–95% of the corresponding α-hydrazono anhydrides 2 . Treating 2 with boiling hydrazine hydrate in xylene, the respective 2-aryl-4-carbohydrazido-5-methyl-1-oxo-1,2-dihydro-5H/-pyridazino[4,5-b]indoles 3 were obtained (47–67%), and these compounds characterized as the respective benzylidene derivatives 4 . Compounds 2 react with amines (aniline, morpholine, piperidine) to give the respective 2-(3-carboxy-1-methylindole)aceta-mide 5 or the respective 2-aryl-4-carboxamido-5-methyl-5H-pyridazino[4,5-b]indole 6 , the product obtained depending on the structure of the aryl substituent. Boiling 2b (aryl = 4-chlorophenyl) with 5% sodium hydroxide gave (80%) 2-(3-carboxy-1-methylindole)acetic acid ( 7 ). Hydrolysis of 2b gave a mixture of 7 and 2-(3-carboxy-1-methylindolyl)-2-(4-chlorophenylhydrazono)acetic acid ( 8 ).     

The reactions of 4-dicyanomethylene-2-phenyl-4H-1-benzopyran and some benzologs with nucleophiles

4-Dicyanomethylene-2-phenyl-4H-1-benzopyran (1) reacts with primary amines under mild conditions to give 4-imino-3-alkyl-5-alkylimino-2-phenyl-3,4-dihydro-5H-[1]benzopyrano[3,4-c]-pyridine derivatives which, in turn, are hydrolyzed with acid to 4-imino-3-alkyl-2-phenyl-3,4-dihydro-5H-[1]benzopyrano[3,4-c]pyridin-5-ones. When more vigorous conditions are employed for the reactions of 1 with primary amines, Dimroth rearrangements take place and the products are derivatives of 4-alkyl- (or aryl)amino-5-alkyl- (or aryl)imino-2-phenyl-5H-[1]benzopyrano-[3,4-c]pyridine. The latter compounds are hydrolyzed by acid to the corresponding 5-pyridone derivatives. The reaction of 1 with piperidine gives 2-phenyl-4-piperidyl-5H-[1]benzopyrano-[3,4-c]pyridin-5-one. Sodium methoxide reacts with 1 to give 3-cyano-2-methoxy-4-(2-hydroxyphenyl)-6-phenylpyridine. Two benzologs of 1 have been allowed to react with primary and secondary amines and the products are analogous to those obtained from 1 .     

Synthesis of aldehyde and carboxylic acid derivatives from 2-hydroxymethyl-3-hydroxy-4H-pyran-4-one (α-hydroxymaltol)

α-Hydroxymaltol (2-hydroxymethyl-3-hydroxy-4H-pyran-4-one) ( 1 ) has been converted to the 3-O-methyl ether 2 and 3-O-p-nitrobenzyl ether 4 by standard methods. The ethers 2 and 4 have been oxidized by barium manganate to the corresponding aldehydes, 3 and 5 , in 91 and 77% yields respectively. Long-term reaction of 5 with hydrogen bromide in acetic acid gives 3-hydroxy-4H-pyran-4-one-2-carboxaldehyde ( 6 ). The aldehyde 3 is readily oxidized by short-term reaction with silver oxide to the corresponding acid 7 .     

Alkyl nitrate nitration of active methylene compounds. Nitration of 1-methyl4-piperidone, 1-methyl-2-pyrrolidinone and 1,3-dimethyl-2-pyrrolidinone

The reaction of 1-methyl-4-piperidone ( 1 ) with amyl nitrate in the potassium tert-butoxidetetrahydrofuran system gave dipotassium 5-methyl-2-oxo-1,3-piperidinedinitronate ( 4 ) in 78% yield. Similar treatment of 1-methyl-2-pyrrolidinone ( 2 ) afforded potassium 3-methyl-2-oxopyrrolidinenitronate ( 7 ) in 85% yield. In contrast, the nitration of 1,3-dimethyl-2-pyrrolidinone ( 3 ) led to opening of the lactam ring with the formation of amyl 2-aza-2-methyl-5-nitrohexanoate ( 10 ) in 40% yield. Acidification of disalt 4 did not cause ring opening but gave the dipolar ion of 1-methyl-3-nitro 4-hydroxy-5-aci-nitro-Δ³-tetrahydropyridinium (6).     

Cyanoacetylene and Its Derivatives. 30. Reactions of 2,3-Dimercaptoquinoxaline with 3-Phenyl-2-propynonitrile and 4-Alkyl-4-hydroxy-2-alkynonitriles

The reaction of 2,3-dimercaptoquinoxaline with 3-phenyl-2-propynonitrile (~10 mass % KOH, 20-25°C, 5 h, dioxane) gave the S,S-diadduct (as with unsubstituted acetylene). 2,3-Dimercaptoquinoxaline reacted with 4-alkyl-4-hydroxy-2-alkynonitriles to give 2-cyanomethyl-2-(1-hydroxy-1-alkyl)-1,3-dioxolano[4,5-b]quinoxalines or 3-cyanomethylene-8-imino-2,2,6,6-tetramethyl-1,7-dioxa-4-thiaspiro[4.4]nonane.     

Photochemical reactivity of α,β-unsaturated δ-lactams: Synthesis of seco-steroids. Photochemical reactions. XIII [1]

The UV. irradiation of 17 β-hydroxy-2-aza-4-androsten-3-one (1) , N-methyl-17 β-hydroxy-2-aza-4-androsten-3-one (3) , 17 β-hydroxy-4-aza-5 β-androst-1-en-3-one (2) and N-methyl-17 β-hydroxy-4-aza-5 β-androst-1-en-3-one (4) , gives rise to 1,10-seco (from 1 and 3 ) and 5, 10-seco (from 2 and 4 ) steroids.     

Formation of pyrrole derivatives through aminolysis of 2-azetidinone derivatives

A mixture of 3-(α,β-epoxyisopropyl)-1-phenyl-2-azetidinone and benzylamine was heated in a sealed tube at 120–130° yielding 4-anilinomethyl-1-benzyl-3-hydroxy-3-methyl-2-pyrrolidinone as a mixture of diastereoisomers. By this method, 4-anilinomethyl-3-hydroxy-3-methyl-1-phenyl-2-pyrrolidinone and 4-anilinomethyl-3-hydroxy-3-methyl-1-(3,4-dimethoxyphenethyl)-2-pyrrolidinone were obtained by using aniline and 3,4-dimethoxyphenethylamine, respectively, instead of benzylamine. The reaction of 4-formyl-1-phenyl-2-azetidinone with 3,4-dimethoxyphenethylamine afforded 4-anilino-1-(3,4-dimethoxyphenethyl)-2,3-dihydro-2-oxopyrrole. In a similar fashion, the 1-n-butyl and 1-isobutyl analogues were obtained by the use of n-butylamine and isobutylamine, respectively, instead of 3,4-dimethoxyphenethylamine.     

Ring transformation of 6-methyl-3,4-dihydro-2H-1,3-oxazine-2,4-diones

Ring transformation of 6-methyl-3,4-dihydro-2H-1,3-oxazine-2,4-dione (Ia) and its N-sub-stituted derivatives, such as 3-methyl (Ib), 3-ethyl (Ic), and 3-benzyl (Id) derivatives is described. Reaction of Ia with hydrazine hydrate gave 1-amino-6-methyluracil (II), while Id reacted with hydrazine hydrate to give 3-hydroxy-5-methylpyrazole (III). Reaction of Ia,b,d with ethyl acetoacetate in ethanol in the presence of sodium ethoxide afforded ethyl 3-acetyl-6-hydroxy-4-methyl-2(1H) pyridone-5-carboxylate derivatives (IVa,b,d). On the other hand, reaction of Ib,c,d with ethyl acetoacetate in tetrahydrofuran in the presence of sodium hydride did not give IV, but gave 3-acetyl-1-alkyl-5-(N-alkylcarbamoyl)-6-hydroxy4-methyl-2(1H) pyridone (VIb,c,d). Mechanisms for the formation of compounds IV and VI are discussed.     

Transformations of 2-(3-Hydroxy-3-methyl-1-butynyl)adamantan-2-ol >Catalyzed by Acids

Reaction of 2-(3-hydroxy-3-methyl-1-butynyl)adamantan-2-ol with acetonitrile under Ritter reaction conditions is accompanied by isomerization and partial hydration where the water addition to the triple bond occurs nonselectively. As a result of reaction carried out in the presence of 8 equiv of sulfuric acid a mixture was obtained of N ²-[4-(1-acetylamino-2-adamantyl)-2-methyl-3-butyn-2-yl]acetamide, N ³-[1-(1-acetylamino-2-adamantyl)-3-methyl-2-oxo-3-butyl]-acetamide, and N ³-[1-(1-acetylamino-2-adamantyl)-3-methyl-1-oxo-3-butyl]acetamide in ~10:3:2 ratio. In the presence of 2 equiv of the acid the mixture obtained consisted of N ²-[4-(1-acetylamino-2-adamantyl)-2-methyl-3-butyn-2-yl]acetamide, N ³-[1-(1-acetylamino-2-adamantyl)-3-methyl-2-oxo-3-butyl]acetamide, and 1-(1-acetylamino-2-adamantyl)-3-methyl-2-buten-1-one in the same ratio. In Rupe reaction conditions we obtained instead of the expected ,-unsaturated ketones a mixture of 1-(1-hydroxy-2-adamantyl)-3-hydroxy-3-methylbutan-1-one and 1-(1-hydroxy-2-adamantyl)-3-hydroxy-3-methylbutan-2-one in a 5:3 ratio.     

Reactions of 5-aryl-4-acyl-1-(4-hydroxyphenyl)-3-hydroxy-3-pyrrolin-2-ones with arylamines

The reaction of 5-(4-chlorophenyl)-4-benzoyl-1-(4-hydroxyphenyl)-3-hydroxy-3-pyrrolin-2-one with aromatic amines affords the corresponding 3-arylamino derivatives, and the reactions of 5-aryl-4-acetyl-1-(4-hydroxyphenyl)-3-hydroxy-3-pyrrolin-2-ones with p-toluidine yield 5-aryl-4-(1-p-tolylamino)ethylene-1-(4-hydroxyphenyl)pyrrolidin-2,3-diones.     

Synthesis of some 3-EthoxycarbonyI-5-hydroxy-4-oxo-2-pyrroline derivatives from 3(2H)furanones

A number of 3-ethoxycarbonyl-5-hydroxy-2-methyl-5-or-1,5-substituted 4-oxo-2-pyrrolines have been prepared, respectively, by the action of ammonium hydroxide or primary aliphatic amines on 2-arylidene or 2-N-acetyl-N-arylaminomethylene-4-ethoxycarbonyl-5-methyl-3(2H)furanones. The structures of these prepared compounds have been determined by spectroscopic data and chemical means.     

Synthesis of azolo[a]pyridines from 5-(bromomethyl)hept-4-en-3-one and 5-bromopent-3-en-2-one derivatives

Alkyl derivatives of 1H-imidazo[1,2-a]pyridin-4-ium, 5H-pyrido[1,2-a]benzimidazol-10-ium, 1H-[1,2,4]-triazolo[4,3-a]pyridin-4-ium, and 3-methylthiazolo[3,2-a]pyridin-4-ium bromides were obtained in two stages from (4Z)-5-(bromomethyl)-2,2,6,6-tetramethylhept-4-en-3-one, 5-bromo-4-methylpent-3-en-2-one, or (3E)-5-bromopent-3-en-2-one by alkylation of 1-alkyl-1H-imidazoles, 1-alkyl-1H-benz-imidazoles, 1-methyl-1H-1,2,4-triazole, and 4-methylthiazole and subsequent cyclization of the quaternary azolium salts in the presence of bases.     

Synthesen von Heterocyclen, 101. Mitt.: Zur Chemie des 6-Chlor-4-hydroxy-2-oxopyran-3-carbonsäurechlorids

Zusammenfassung 6-Chlor-4-hydroxy-2-oxopyran-3-carbonsäurechlorid (1) reagiert mit N,N'-Di-p-tolyl-carbodiimid zum 7-Chlor-4,5-dioxo-3-p-tolyl-2-p-tolylimino-3,4-dihydro-2H,5H-pyrano[3,4-e][1,3]oxazin (3). Benzoxazol gibt mit1 in analoger Reaktion über6 die Verbindung7.

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6-Chloro-4-hydroxy-2-oxo-pyran-3-carboxylic acid chloride (1) reacts with N,N'-di-p-tolyl-carbodiimide yielding 7-chloro-4,5-dioxo-3-p-tolyl-2-p-tolylimino-3,4-dihydro-2H,5H-pyrano-[3,4-e] [1,3]oxazin (3). In an analogous reaction1 interacts with benzoxazol via6 to yield compound7.