Reaction of 3-azidoisoxazoles with active methylene compounds

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1,4-Benzodioxin-2(3H)-one and some of its derivatives

The methods of synthesis of 1,4-benzodioxin-2(3H)-one have been reexamined. Frequently quoted in the literature the method of Ghosh has been found to give impure (2-hydroxyphenoxy)acetic acid rather than the lactone. Using various methods some simple derivatives of the title lactone substituted in the benzene ring have been prepared and characterized. The bromination of the lactone with NBS gives predominantly 7-bromo-1,4-benzodioxin-2(3H)-one under electrophilic conditions, while 6-bromo-1,4-benzodioxin-2(3H)-one is obtained as a major isomer under photolytic conditions.     

Synthesis of benzofuran-2-one derivatives by copper(I)-promoted coupling reactions of o-bromophenol with active methylene compounds

Treatment of o-bromophenoxide anion with sodium salts of active methylene compounds in the presence of copper(I) bromide in dioxane afforded benzofuran-2-one derivatives. The phenoxide group of o- and p-bromophenol activates the coupling reaction.     

Reaction of tetrachloropyrazine with active methylene compounds

When tetrachloropyrazine was allowed to react with the anions formed from diethyl malonate and malonitrile, the normal alkylation took place. When the anions from ethyl acetoacetate and N,N-diethylacetoacetamide were used, alkylation was followed by enolization and ring formation to give furo [2,3-b] pyrazines. The structure proof and reaction of the furo [2,3-b] pyrazines are discussed.     

Reaction of thiopyrylium ion with active methylene compounds

The reaction of 2,4,6-triphenylthiopyrylium ion with several active methylene compounds in the presence of base has been found to yield 2,4,6-triphenylbenzene derivatives. In the case of the reaction of 2,4,6-triphenylthiopyrylium fluoroborate with nitromethane, an alkali treatment gave 2,4,6-triphenylnitrobenzene, and an acid treatment afforded 2,4,6-triphenylbenzene, respectively. From these results, the reaction behaviour of the thiopyrylium ion has been discussed.     

Benzoxazol-2 (3H)-one and 1,3,4-oxadiazol-2(3H) -one derivatives from substituted enaminones and ketoenamines

Enaminones and ketoenamines bearing a hydrazine type substituent undergo side chain thermal cyclization, the former into benzoxazol-2 (3H)-one derivatives and the latter into 1, 3, 4-oxadiazol-2 (3H)-one derivatives. Factors affecting such reactions are discussed.     

Reaction of α-keto hydrazonyl bromide with carbanions of some active methylene compounds

Treatment of 1-phenyl-2-bromo-2-arylhydrazonoethanone (VII) with sodium etiolates of 2,4-pentanedione, 1-phenyl-1,3-butanedione, dibenzoylmethane, ethyl benzoylacetate, acetoaceta-nilide, and of benzoylacetanilide in ethanol afforded the substituted pyrazoles, VIII-XIII, respectively. The results show that VII, unlike 1-phenyl-2-bromo-2-hydroximinoethanone (V), is not easily deprotonated by carbanions; and that its reactions with β-diketones, β-keto esters, and β-keto amides follow one and the same mechanism. The structures of the products (VIII-XIII) were inferred from their elemental analyses and spectral data.     

New synthesis of 4,5-dihydro-1,2,4-triazin-3(2H)-one derivatives through cyclic transformation of 1,3,4-oxadiazol-2(3H)-one derivatives

Some 5-aryl(or benzyl)-2-oxo-1,3,4-oxadiazole-3(2H)-acetones or acetophenones 2 were easily prepared. These compounds reacted with hydrazine derivatives to give 4,5-dihydro-1,2,4-triazin-3(2H)-one derivatives 3 , 4 and 6 in good yields. With phenylhydrazine, the intermediate hydrazones 5 were obtained. Their conversion into triazinones necessitated the presence of sodium ethylate.     

Reaction of 1-alkylthioisoquinolinium salts with active methylene compounds

2-Alkyl-1-alkylthioisoquinolinium salts were readily prepared from 2-alkyl-1(2H)-isoquinolones via 2-alkyl1(2H)-thioisoquinolones in two steps. Under mild conditions, the reaction of 2-alkyl-1-alkylthioisoquinolinium salts with active methylene compounds in the presence of sodium hydride afforded 2-alkyl-1-(substituted methylene)iso-quinolines in good yields. Pyrrolo[2,1-a]isoquinolines were synthesized by the cyclization of 2-benzyl-1-(substituted methylene)isoquinolines using acetic anhydride.     

4-Hydroxy-2-quinolones. 112. Reaction of 2-ethoxycarbonylmethyl-4H-3,1-benzoxazin-4-one with active methylene compounds

The reaction of 2-ethoxycarbonylmethyl-4H-3,1-benzoxazin-4-one with malononitrile in dry pyridine leads to 1-hydroxy-3,6-dioxo-4,6-dihydro-3H-pyrimido[1,2-a]quinoline-5-carbonitrile. Acetoacetic and cyanoacetic esters under analogous conditions form anilides of 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid while diethyl malonate gives N,N′-di-2-carboxyanilides of malonic acid. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 75–79, January, 2007.     

Synthesis of 2(3H)-benzofuranone derivatives by copper (i)-promoted substitution reactions of active methylene carbanions

Activation of soft carbanions by copper(I) in the sub-stitution reaction toward aryl halides and allyl halides was demonstrated. Derivatives of 2(3H)-benzofuranones (2, 14 -18) were prepared in a one-pot procedure by the reaction of copper(I) diethyl malonate with sodium o-bromophenoxide. 2-Hydroxybenzofuran (4) and its 2-amino derivative (5) were obtained by using copper(I) salts of ethyl acetoacetate and ethyl cyanoacetate. The reaction of sodium p-bromophenoxides with copper(I) diethyl malonate yielded p-1,1,2,2-tetracaeboethoxyethylphenols (7, 8). 3-Carboethoxy-3-β-methallyl-2-benzofuranone (14) was converted into spiro[2-benzofuranone-3,3'-(5',5'-dimethyl)-γ-butyrolactone] (22) under acidic conditions. The latter compound was further decarboxylated to give spiro [2-benzofuranone-3,1'-(2',2'-dimethyl)cyclopropane] (23) by the treatment with sodium ethoxide.     

Synthesis and antiproliferative evaluation of some novel quinazolin-4(3H)-one derivatives

A series of novel quinazolinone derivatives was designed and synthesized. The antiproliferative activities were evaluated in vitro using MTT assay against hepatocellular carcinoma (HepG-2) and mammary gland breast cancer (MCF-7). The preliminary bioassay results demonstrated that tested compounds exhibited antiproliferation with various degrees. Triazole moiety enhanced the activity against the two cell lines when incorporating with quinazolinone moiety in a single molecular framework. Acetohydrazide-quinazolinone derivative showed strong activity against the two cancer cells comparable to that of doxorubicin. Biological evaluation indicated that all the tested compounds possessed antiproliferative activity with certain degrees.     

Synthesis and anticonvulsant activity of some quinazolin-4-(3H)-one derivatives

A number of 3-substituted-2-(substituted-phenoxymethyl) quinazolin-4(3H)-one derivatives 4a,b, 5a-c, 6, 7a-f, 8a-e and 9a,b have been synthesized. Their structures have been elucidated on the basis of elemental analyses and spectroscopic studies (IR, 1H-NMR, MS). A preliminary evaluation of the anticonvulsant activity of the prepared compounds has indicated that compounds 4b, 7b-f, 8a and 9b exhibit significant anticonvulsant activity, while compounds 6, 8b and 8d show mild to moderate activity.     

Synthesis of 3-methylquinazolin-4(3H)-one derivatives

Oxidation of 3-methyl-2-sulfanylquinazolin-4(3H)-one with chlorine dioxide under different conditions gave 2,2??-disulfanediylbis[3-methylquinazolin-4(3H)-one], 3-methyl-4-oxo-3,4-dihydroquinazoline-2-sulfonic acid, 3-methylquinazoline-2,4(1H,3H)-dione, 6-chloro-3-methylquinazoline-2,4(1H,3H)-dione, and N,N-diethyl-3-methyl-4-oxo-3,4-dihydroquinazoline-2-sulfonamide.     

Acylaminoacetyl derivatives of active methylene compounds. 4

Meldrum's acid has been found to be effectively acylated using the imidazolides of N-protected glycines, X-NHCH₂COOH (X = -COPh, -COMe, -Z, -Boc, -COOMe and -COOEt). The corresponding C-acylation compounds were isolated in high yields and were readily converted to the N-protected tetramic acids. It was shown by pmr spectroscopy that these acids exist as the enol tautomers in DMSO-d₆ solution, whereas in deuteriochloroform solution both the enol and keto tautomers can be observed.     

Reaction of 2,3,3-trimethyl-3H-indole salts with acrylamide. Synthesis of 1,2,3,4,10,10a-hexahydropyrimido[1,2-a]indol-2-one derivatives

Methyl derivatives of pyrimido[1,2-a]indol-2-one were obtained by the reaction of 2,3,3-trimethyl-3H-indole salts with acrylamide in a proton-containing solvent. The products were condensed with aromatic aldehydes. The interconversion of pyrimido[1,2-a]indol-2-ones and 1-(2-carbamoylethyl)-3H-indolium salts under the influence of acids and bases was studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1056–1059, August, 1986.     

Reaction of 2, 6-dimethylthiapyrone with compounds containing active methyl or methylene groups

The reaction of 2, 6-dimethylthiapyrone with compounds containing active methyl or methylene groups is investigated. Position 4 in the thiapyrone ring is found to react. If the components with active methylene groups are malonodinitrile or cyclic diketomethylene compounds, the methylene groups in the resultant 2, 6-dimethylthiapyrane compounds are still reactive towards electrophilic reagents, a property which is utilized for synthesis of nonionic polymethylene dyes containing thiapyrane rings.