New methods for the synthesis of heterocyclic quinones (review)

New methods for the synthesis of heterocyclic quinones are examined.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1155–1171, September, 1978.     

New heterocyclic syntheses from hydrazidoyl halides. Convenient syntheses of fused pyrimidines,pyridazines, and quinazolines

Aminocyanopyrazole derivatives and pyrazolo[2,3-a]quinazolones were obtained in good yields from hydrazidoyl halides and malononitrile. Pyrazolo[3,4-d]pyridazine and pyridazo[4′,5′: 1,2]pyrazolo[1,5-a]quinazoline derivatives were synthesized in quantitative yields by reaction of hydrazine hydrate with 2 and 16 , respectively. A novel ring system, a 3-substituted tetrahydro derivative of 7-oxo-6H,8H-pyridazo[3′,4′,5′-c'd']-pyrazolo[3,4-d]pyrimidine was prepared by reaction of 6 with dimethyl carbonate. Pyrazolo[3,4-d]pyrimidine-4,6-dithiones were obtained in good yields by reaction of 2 with carbon disulfide. The structures of the products were assigned and confirmed on the basis of their elemental analyses, spectral data, and alternate synthesis wherever possible. The structures of the parent fused heterocyclic systems discussed in this work are summarized in Scheme 1 .     

Regiospecific hydrogenation of quinolines and indoles in the heterocyclic ring

Quinolines, indoles, acridine, and carbazole were hydrogenated using a large variety of heterogeneous catalysts in hydrocarbon solvents in an effort to achieve selective hydrogenation of the heterocyclic ring. When quinolines were hydrogenated using supported platinum, palladium, rhodium, ruthenium, or nickel metal catalysts in the presence of hydrogen sulfide, carbon disulfide, or carbon monoxide, there was exclusive hydrogenation of the heterocyclic ring to give only 1,2,3,4-tetrahydroquinolines. Use of iridium, rhenium, molybdenum(VI) oxide, tungsten(VI) oxide, chromium(III) oxide, iron(III) oxide, cobalt(II) oxide-molybdenum(VI) oxide, or copper chromite catalysts also caused exclusive hydrogenation of the heterocyclic ring even without addition of sulfur Compounds or carbon monoxide. Hydrogenation of indoles using platinum, rhenium, or, in some cases, nickel catalysts (with or without sulfur Compounds) occurred exclusively in the heterocyclic ring to give indolines, but conversions were affected by indole-indoline equilibria.     

Convenient magnesiation of aromatic and heterocyclic rings bearing a hydroxy group in presence of LiCl

The reaction of various iodophenols with MeMgCl in presence of LiCl followed by the addition of i-PrMgCl provides the corresponding magnesiated magnesium phenolates as THF soluble reagents; this approach can be extended to heterocyclic compounds bearing a hydroxy group like pyridines and quinolines.     

Investigation of heterocyclic quinones XXV. Tautomeric and covalent hydration in the quinazolinequinone series

The tautomeric forms of 2-phenyl-4-hydroxy-8-piperidinoquinazoline-5,6-quinone were determined quantitatively by means of UV spectroscopy. It is shown that quinazolinequinones are not capable of covalent hydration.     

A versatile new synthesis of quinolines and related fused pyridines. Part III.

The action of dimethylformamide in phosphorus oxychloride on acylanilides gives 2-chloro-3-substituted quinolines, which may be dechlorinated to give 3-substituted quinolines in good yield. Similarly, N-nitrosodimethylamine in phosphorus oxychloride converts acylanilides into 2-chloro-3-substituted quinoxazolines.     

A versatile new synthesis of quinolines and related fused pyridines. Part II.

The conversion of acetanilides to 2-chloroquinoline-3-aldehydes by Vilsmeier reagent proceeds efficiently in POCl₃ solution at 75°. The intermediate, in which the acetyl group has been diformylated, may in some cases be isolated and separately cyclised.     

Partial hydrogenation of substituted pyridines and quinolines: a crucial role of the reaction conditions

Hydrogenation of pyridyl and quinolyl compounds 2-substituted with a carbonyl group (1a-c and 2b,c) using PtO₂ and 1 equiv. of HCl (conditions A) provides clean and total formation of the desired amino alcohol (hydrogenation of the heterocyclic ring and of the carbonyl) while under conditions B₁ and/or B₂ (concentrated HCl or pure CF₃CO₂H) the heterocyclic ring remains untouched and other aromatic parts are hydrogenated providing complex mixtures. When the heterocyclic ring is substituted by an alkyl group (quinaldine 3) conditions A provide mixtures while under conditions B₂ (pure CF₃CO₂H) the benzene ring is cleanly hydrogenated leading to a pure product.     

A versatile new synthesis of quinolines and related fused pyridines: Part 10. Routes to quinolines with fused azacycles

Three efficient routes to the title systems have been elaborated utilising 2-chloroquinoline-3-aldehyde acetals, 2-chloroquinoline-3-ketones or 2-aminoquinoline-3-aldehydes.     

tert-Amino effect in heterocyclic chemistry. Synthesis of hydrogenated spiro derivatives of quinolines

A new method was developed for the one-step synthesis of spiro derivatives of fused quinolines by the reactions of ortho-amino derivatives of benzaldehyde with Meldrum"s acid, cyclohexane-1,3-dione, or N,N"-disubstituted barbituric acids.     

Studies on heterocyclic enamines: New syntheses of 4H-pyranes,pyranopyrazoles and pyranopyrimidines

The behaviour of several 2-amino-3-cyano-4H-pyran derivatives toward a variety of nucleophilic reagents is reported.     

Pyrimido[5,4-b]quinolines. II. Reactions at the heterocyclic ring-carbon and nitrogen atoms

10-Chloro-7,8-dimethylpyrimido[5,4-b]quinolin-2,4(1H,3H)dione (I) was unreactive toward ammonia but it reacted with 2 molecules of n-butylamine, presumably via Dimroth-type ring-opening and closure, to give the N₃-butyl, N₁₀-butylamino derivative (IV). In similar reactions of 10-chloro-2,4-dimethoxy-7,8-dimethylpyrimido[5,4-b]quinoline (II) only the 4-meth-oxyl was displaced by either ammonia or n-butylamine. Alkyllithium reagents also displaced the 4-methoxyl as well as added to the 3,4 double bond of II to yield the corresponding gem-dialkyl substituted (C₄) derivatives; the C₁₀ chlorine remained unreactive. 2,4-Dimethoxy-7,8-di-methylpyrimido[5,4-b]quinoline-10-one (III) could be alkylated only in the form of the thallium salt. Treatment of the benzyl derivative of III with methylmagnesium bromide led only to the displacement of the 4-methoxyl by a methyl group.     

Studies on the syntheses of heterocyclic compounds. part CCLXXIX . Synthesis of O-isobutylcularidine

Although various methods of oxepine formation from phenoxybenzene dicarboxylic acids was attempted, only 11-hydroxy-4-isobutoxy-7,8-dimethoxydibenz[b,f]oxepin-l-ylaeetic acid lactone (XXX) was synthesized successfully. Compound XXX gave O-isobutylcularidine (XXXVlIb) in a few steps. Our synthetic O-isobutylcularidine was identical with that prepared from natural cularidine proving the structure for cularidine proposed by Manske. However, dealkylation of synthetic O-isobutylcularidine was unsuccessful.     

Studies on the syntheses of heterocyclic compounds. Part CCCXXX Synthesis of a homocularine type compound

An intramolecular Ullmann reaction of bromophenethylisoquinoline (X) was investigated in order to obtain the homocularine type compound (V), which could be one of the potential alkaloids belonging to 1-phenethylisoquinoline series. Methylation of the phenolic 8-hydroxyisoquinoline (XVIII), one of the position isomers which was separated by silica gel chromatography from a mixture of 6-hydroxy- (XVII) and 8-hydroxyisoquinoline (XVIII) prepared as usual, gave the starting material (X), which was cyclized by the Ullmann reaction in the presence of cupric oxide. The structure of our objective homocularine (V) was assigned from spectral data.