Reactions of 3,5-dibromo-1-(thiiran-2-ylmethyl)-1,2,4-triazole with NH-azoles

Reactions of 3,5-dibromo-1-(thiiran-2-ylmethyl)-1,2,4-triazole with 3,5-dimethylpyrazole, 1,3-dimethyl-3,7-dihydropurine-2,6-dione, 3,5-dibromo-1,2,4-triazole, 2,4,5-tribromoimidazole, and 2-chlorobenzimidazole lead to the formation of 5-azolylmethyl-2-bromo-5,6-dihydrothiazolo[3,2-b]-1,2,4-triazoles. In the case of 8-bromo-1,3-dimethyl-3,7-dihydropurine-2,6-dione the intermediate thiolate anion undergoes cyclization into 7-[(3,5-dibromo-1,2,4-triazol-1-yl)methyl]-1,3-dimethyl-6,7-dihydrothiazolo[2,3-f]purine-2,4(1H,3H)-dione. The structure of reaction products depends on the relative rate of substitution of leaving groups in the reagents.     

A one-step preparation of pyrido[3,4-d]pyrimidine ring system by reaction of 5-formyl-1,3,6-trimethyl-pyrimidine-2,4(1H,3H)-dione with primary amines

6,7-Dihydropyrido[3,4-d]pyrimidine-2,4(1H,3H)-diones were obtained in high yields from the reaction of 5-formyl-1,3,6-trimethylpyrimidine-2,4(1H,3H)-dione ( 1 ) and primary amines. For this pyridopyrimidine synthesis the following reaction pathway is proposed; the [1,5]-hydrogen shift of 1 gives a 5,6-dihydro-5,6-dimethylenepyrimidine-2,4(1H,3H)-dione intermediate. The cycloaddition reaction of the intermediate with aldimines from 1 and the primary amines affords 5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine-2,4(1H,3H)-diones, which are dehydrated to the final products.     

Reactions of triacetic acid lactone with carbonyl compounds. X-Ray structure determination of 3-acetoacetyl-2-chromenone and 3,6,9,12-tetramethyl-1H,6H,7H,12H-6,12-methanodipyrano[4,3-b:4,3-f]-dioxocin-1,7-dione

The structure of 3-acetoacetyl-2-chromenone has been definitely assigned to the product resulting from the reaction of 4-hydroxy-6-methyl-2-pyrone, 1 , with 2-hydroxybenzaldehyde. Also, the reaction of the pyrone 1 with pentane-2,4-dione in a 2:1 molar ratio gives 3,6,9,12-tetramethyl-1H,6H,7H,12H-6,12-methanodypirano[4,3-b:4,3-f]dioxocin-1,7-dione. X-Ray analyses of both products are presented.     

Aminomethylation of 6-methyl-1-(thietan-3-yl)pyrimidine-2,4(1H,3H)-dione

Mannich reactions of 6-methyl-1-(thietan-3-yl)pyrimidine-2,4(1H,3H)-dione with formaldehyde and morpholine, piperidine, N-methylpiperazine, and diethylamine gave the corresponding 5-aminomethylsubstituted pyrimidine derivatives. The title compound reacted with excess piperazine to form 3,5-bis-(piperazin-1-yl) derivative, while its reaction with an equimolar amount of piperazine afforded 5,5′-(piperazin-1,4-diylbismethylene)bis[6-methyl-1-(thietan-3-yl)pyrimidine-2,4(1H,3H)-dione].     

Stereoselective synthesis of cyclohexa-2,4-dien-1-ones and cyclohex-2-en-1-ones from phenols

A convenient synthetic method for the synthesis of substituted cyclohex-2-en-1-ones by the direct alkylation of phenols has been developed. Furthermore, enantiomerically enriched 2,6-dimethyl-6-(3-methylbut-2-enyl)-cyclohexa-2,4-dienone was prepared by the deprotonation of 2,6-dimethylphenol with a sparteine–lithium complex followed by alkylation with 1-chloro-3-methylbut-2-ene. 2,6-Dimethyl-6-(3-methyl-but-2-enyl)-cyclohex-2-enone was prepared from the corresponding cyclohexa-2,4-dien-1-one by selective hydrogenation of the 4,5-double bond. The method was extended to 2-methyl-naphthalen-1-ol and 1-methyl-naphthalen-2-ol resulting in 2-(R)-methyl-2-(3-methylbut-2-enyl)-2H-naphthalen-1-one and 1-(S)-methyl-1-(3-methylbut-2-enyl)-1H-naphthalen-2-one, respectively.     

Synthesis of cyclohexane derivatives including Br,Cl, N,O, and S at 1,2,4,5-positions: selectivity in addition reactions

Brominations of mono addition products of 1,4-cyclohexadiene with 2,4-dinitrobenzenesulfenyl chloride (RSCl) selectively gave 1R(S),2R(S),4R(S),5R(S)-4,5-dibromo-2-(2,4-dinitrophenylthio)cyclohexyl acetate and 1R(S),2R(S),4R(S),5R(S)-4,5-dibromo-2-chlorocyclohexyl)(2,4-dinitrophenylthio)sulfane. From series reactions 7-oxabicyclo[4.1.0]hept-3-ene with reagents, such as RSCl, NaN₃, and H₂SO₄/Ac₂O, six 1,2,4,5-tetrasubstituted cyclohexane derivatives including S, O, N, Cl, and Br were selectively obtained. Formations and structures of the products were discussed.     

Photochemical transformations of 3-alkyl-3-ferrocenylcyclopropenes

Photolysis of 3-ferrocenyl-3-methyl- and 3-ferrocenyl-3-isopropylcyclopropenes was studied. Sensitized irradiation (triplet excitation) afforded [2+2]-cycloaddition products, viz., tricyclohexane derivatives. Direct irradiation (singlet excitation) of methyl-substituted ferrocenylcyclopropene gave rise to 2-ferrocenylbut-1-en-3-yne and trans-2-ferrocenylbut-2-ene. The isopropyl analog was converted into 1-ferrocenyl-4,4-dimethylcyclobutene. The reaction of this cyclopropene with 2-ferrocenyl-3-methylbut-1-ene afforded 1,3-diferrocenyl-3-isopropyl-6,6-dimethylcyclohexene. The latter compound and 3,6-diferrocenyl-3,6-diisopropyltricyclo[3.1.0.0^2,4]hexane were studied by X-ray diffraction analysis. Possible reaction pathways are discussed.     

Pteridine. Teil LXXXI. Mechanismus der Photooxidation von 5,6-Dihydro-1,3-dimethyl-6-thioxopteridin-2,4(1H,3H)-dion

Mechanism of the Photooxidation of 5,6-Dihydro-1,3-dimethyl-6-thioxopteridine-2,4(1H,3H)-dione The mechanism of the photooxidation of 5,6-dihydro-1,3-dimethyl-6-thioxopteridine-2,4(1H,3H)-dione ( 9 ) has been investigated in dependence of the pH. Photooxidation of the anion species in weak alkaline solution takes place by singlet oxygen as well as the superoxide radical anion forming 1,2,3,4-tetrahydro-1,3-dimethyl-2,4-dioxopteridine-6-sulfinate ( 5 ) as the first detectable reaction product. In acidic medium, a more complex photooxidation process is observed leading, in a radical-chain mechanism, to 6,6′-dithiobis[1,3-dimethylpteridine-2,4(1H,3H)-dione] ( 6 ).     

Natural product chemistry. Part 158. Reactions of ethyl 4-hydroxy-1-methyl-3-quinolin-2(1H)-onecarboxylate with 1,4-dibromo-2-methyl-2-butene

Ethyl 4-hydroxy-1-methyl-3-quinolin-2(1H)-onecarboxylate ( 1 ) which is obtained conveniently by the condensation of N-methylisatoic anhydride with diethyl malonate [4], was reacted with 1,4-dibromo-2-methyl-butene ( 2 ) to give the main products 3 and 4 and the dimeric derivatives 5 and 6 .     

Electrocarboxylation of 1,4-dibromobut-2-ene in a CO2-DMF liquid mixture

The possibility of synthesizing dihydromuconic acid by cathodic carboxylation of 1,4-dibromobut-2-ene in the liquid CO₂-aprotic solvent system was investigated. The low yield of dihydromuconic acid in this reaction was explained by the competing reductive debromodimerization and oligomerization of 1,4-dibromobut-2-ene, which lead to the predominant formation of 1,8-dibromo-2,6-octadiene and polymeric products. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1637–1641, September, 1997.     

Cesium carbonate catalyzed efficient synthesis of quinazoline-2,4(1H,3H)-diones using carbon dioxide and 2-aminobenzonitriles

Abstract

An efficient protocol for the synthesis of quinazoline-2,4(1H,3H)-diones derivatives from 2-aminobenzonitriles with carbon dioxide using catalytic amount of cesium carbonate has been developed. 6,7-Dimethoxyquinazoline-2,4(1H,3H)-dione, which is one of the key intermediate for the synthesis of several drugs (Prazosin, Bunazosin and Doxazosin) was synthesized. The effect of different reaction parameters like influences of bases, solvent, temperature, CO₂ pressure and reaction time were investigated for the title reaction.     

New [f]-fused xanthines: Synthesis of 1,3-dipropyl-1H,3H-pyrazino,pyrido, pyrimido and pyrrolo[2, 1-f]purine-2,4-diones

Synthesis of 1,3-dipropyl-1H,3H-pyrazino, pyrido, pyrimido and pyrrolo[2,1-f]purine-2,4-diones, starting from 5,6-diamino-1,3-dipropylpyrimidine-2,4-dione 1 and 6-chloro-1,3-dipropylpyrimidine-2,4-dione 14 is described. A new synthetic approach to 1,3-dipropyl-1H,3H-pyrido(or pyrazino)[1′,2′-1,2]pyrimido[4,5-d]pyrimidine-2,4,5-triones 19 e, f, h has been also developed.     

Synthesis of thietanyl-substituted pyrimidine-2,4(1H,3H)-dions

Reactions of 6-methylpyrimidine-2,4(1H,3H)-dione or 5-hydroxy-6-methyl-pyrimidine-2,4(1H,3H)-dione with 2-chloromethylthiirane afforded the corresponding substituted 1-(thietan-3-yl)pyrimidine-2,4(1H,3H)-diones. The calculations in the framework of approximations PBE/3z, B3LYP/6-31G++(d,p) and MP2/6-31G++(d,p) showed that the alkylation occurred at the atom N¹ of the pyrimidine ring.     

Synthesis of novel 1,3-oxazino[6,5-b]indole-2,4-(3H,9H)-dione and 2H-1,3,5-oxadiazino[3,2-a]indole-2,4-(3H)-dione from oxindoles

Two novel tricyclic ring systems were designed as serine protease inhibitors and synthesized from oxindoles; the first series, 1,3-oxazino[6,5-b]indole-2,4-(3H,9H)-diones, were prepared from 2,3-dihydro-2-oxo-(1H)-indole-3-carboxamides and phosgene in tetrahydrofuran with triethylamine. The second, a 2H-1,3,5-oxadiazino[3,2-a]indole-2,4-(3H)-dione was made using a similar cyclization on 2,3-dihydro-2-oxo-N-phenyl-(1H)-indole-1-carboxamide.     

Synthesis of 5′-azido- and 5′-amino-2′,5′-dideoxynucleosides from quinazoline-2,4(1H,3H)-diones

Quinazoline-2,4(1H,3H)-diones 4 were silylated and condensed with methyl 5-azido-2,5-dideoxy-3-O-(4-methylbenzoyl)-α,β-D-erythro-pentofuranoside (3) using trimethylsilyl trifluoromethanesulfonate (TMS triflate) as the catalyst to afford the corresponding 5′-azidonucleosides 5 . 1-(5-Azido-2,5-dideoxy-α-D-erythro-pentofuranosyl)quinazoline-2,4(1H,3H)-diones 6 and the corresponding β anomers were obtained by treating 5 with sodium methoxide in methanol at room temperature. 6-Methyl-1-(5-amino-2,5-dideoxy-β-D-erythro-pentofuranosyl)quinazoline-2,4(1H,3H)-dione (8) was obtained by treatment of the corresponding azido derivative 7 with triphenylphosphine in pyridine, followed by hydrolysis with ammonium hydroxide.     

Rearrangement of 1,4-benzodiazepin-2,4-diones to 3,l-benzoxazin-4-ones

Treatment of 7-chloro-3,4-dihydro-1H-1,4-benzodiazepin-2,5-dione (Ia) with refluxing acetic anhydride in the presence of pyridine afforded 6-chloro-2-methyl-4H-3,1-benzoxazin-4-one (IIa). A plausible reaction path for this novel rearrangement reaction is described: Ia → 4-acetyl-7-chloro-3,4-dihydro-lH-1,4-benzodiazepin-2,5-dione → 7-chloro-1,4-diacetyl-3,4-dihydro-lH-1,4-benzodiazepin-2,4-dione → IIa. When 7-chloro-3,4-dihydro-4-methyl-lH-1,4-benzodiazepin-2,5-dione (Ib), 3,4-dihydro-4-methyl-1H-1,4-benzodiazepin-2,5-dione (Id) and 3,4-dihydro-1-methyl-1H-1,4-benzodiazepin-2,5-dione (Ie) were allowed to react with acetic anhydride under conditions similar to those used for the rearrangement reaction, only acetylation occurred.     

Synthesis and Photochemistry of 5,5-Dimethyl-1H-pyrrol-2(5H)-one and of Some N-Substituted Derivatives

In two steps, 5,5-dimethyl-1H-pyrrol-2(5H)-one ( 3a ) was prepared from 5,5-dimethylpyrrolidine-2,4-dione ( = dimethyltetramic acid; 4 ) in 71% overall yield (Scheme 1) and further converted to N-substituted derivatives 3b–f via acylation, alkylation, or methoxycarbonylation of its anion (Scheme 2). The substituents on the N-atom exert a strong influence on the photochemical reactivity ([2 + 2] photocycloaddition to 2,3-dimethylbut-2-ene, photocyclodimerisation, photoreduction) of these aza-enones 3 (Scheme 3). In general, N-alkyl compounds react much slower and with less efficiency than either the (N-unsubstituted) title compound 3a or its N-acetyl and N-(methoxycarbonyl) derivatives 3e and 3f , respectively. These compounds behave similarly to the corresponding lactone, 5,5-dimethyl-2(5H)-furanone, studied previously.     

Synthesis of 2-Benzylidene and 2-Hetarylmethyl Derivatives of 2H-1,4-Benzoxazin-3-(4H)-ones as Neuroprotecting Agents

A wide variety of the title compounds were synthesized by conventional and microwave methods in which the main step is a condensation of an aldehyde with a 1,4-benzoxazin-3-(4H)-one. In all cases, the Z diasteromers were the major products. Of particular importance is the synthesis of novel 2-(3,5-dibromo-4-hydroxy) and 2-(4-acetoxy-3,5-dibromobenzylidene derivatives of 2H-1,4-benzoxazin-3-(4H)-ones, four of which were shown in a previous publication to exhibit potent neuroprotecting properties. The yields of titled compounds ranged from 25 to 83%.     

Lanthanide reagent effects on 3-(2′,4′-dimethylphenyl)-1H,3H-quinazoline-2,4-dione

We report an analysis of the europium-shifted n.m.r. spectrum of 3-(2′,4′-dimethylphenyl)-1H,3H-quinazoline-2,4-dione and the resonance assignment of most of its protons.     

Natural product chemistry,Part 132: Synthesis and oxidative cyclisation of 1,3-dihydroxy-10-methyl-4-(3-methylbut-2-enyl)-9(10H)-acridinone (glycocitrine-II)

Summary Reaction of 1,3-dihydroxy-10-methyl-9(10H)-acridinone (1) and 1-bromo-3-methylbut-2-ene (mol. ratio 1:1) in tetrahydrofuran at 20°C in the presence of alumina gave prenylacidinones2 (glycocitrine-II) and8 and the diprenylacridinone9; with an excess of 1-bromo-3-methylbut-2-ene, the prenyldihydropyranoacridinones12 and13 were formed. Oxidation of glycocitrine-II (2) withm-chloroperbenzoic acid furnished the furanoacridinone5 and the pyranoacridinone6; dehydration of the latter compound gave noracronycine (10).(the late)