Synthesis of 9-(2-fluorobenzyl)-6-methylamino-9H-purine

Synthesis of 9-(2-fluorobenzyl)-6-methylamino-9H-purine ( 1 ) from nine different precursors is reported. Compound 1 was prepared by methylamination of 6-chloro-9-(2-fluorobenzyl)-9H-purine ( 4 ), by alkylation of 6-methylaminepurine ( 5 ) or form 9-(2-fluorobenzyl)-1-methyladeninium iodide ( 8 ) via the Dimroth rearrangement. Selective 2-step methylation of 6-aminopurine 6 was accomplished by hydride reduction of 6-formamidopurine 9 , 6-dimethylaminomethyleneaminopurine 10 or 6-phenylthiomethyl purine 11 to give 1. Compound 1 was also prepared by dethiation or reductive dechlorination of 2-methylthiopurine 16 or 8-chloropurine 19 , respectively, or by hydrolysis of 6-N-methylformamidopurine 12 , which was prepared from 6-dimethylaminopurine 13 by selective oxidation.     

Synthesis of nucleoside analogs of 1,4-oxathiane, 1,4-dithiane,and 1,4-dioxane

The two regioisomers 6-chloro-9-(1, 4-oxathian-3-yl)-9H-purine ( 5 ) and 6-chloro-9-(1,4-oxathian-2-yl)-9H-purine ( 6 ) were obtained when 3-acetoxy-1,4-oxathiane ( 3 ) was subjected to the acid-catalyzed fusion procedure; compound 3 was prepared by a Pummerer reaction with 1,4-oxathiane 4-oxide ( 2 ). The nucleoside analog 6 could he converted into the adenine derivative 7 and 9-(1,4-oxathian-2-yl)-9H-purine-6(1H)thione ( 8 ). The following nucleoside analogs have also been synthesized: 6-chloro-9-(1,4-dithian-2-yl)-9H-purine ( 13 ), 9-(1,4-dithian-2-yl)adenine ( 14 ), 9-(1,4-dithian-2-yl)-9H-purine-6(1H)thione ( 15 ), and 6-chloro-9-(1,4-dioxan-2-yl)-9H-purine ( 18 ).     

Synthesis of α-(aminomethylene)-9-(methoxymethyl)-9H-purine-6-acetic acid derivatives

α-(Aminomethylene)-9-(methoxymethyl)-9H-purine-6-acetamide and the ethyl acetate, 3 and 8 , have been synthesized by catalytic hydrogenation of 6-cyanomethylene-9-methoxymethylpurine derivatives 2 and 7 which were obtained by the substitution of 6-chloro-9-(methoxymethyl)purine ( 1 ) with α-cyanoacetamide and ethyl cyanoacetate, respectively. Substitution of 3 and 8 with amines gave the corresponding N-substituted α-(aminomethylene)-9-(methoxymethyl)-9H-purine-6-acetamide and the ethyl acetate 4 and 10 . Reaction of 3 with piperidine gave 9-(methoxymethyl)-9H-purine-6-acetamide ( 5 ).     

Synthesis of 2-(2′,3′-dihydroxypropyl)-5-amino-2H-1,2,4-thiadiazol-3-one and 3-(2′,3′-dihydroxypropyl)-5-amino-3H-1,3,4-thiadiazol-2-one

The synthesis of two new acyclic nucleoside analogs, 2-(2′,3′-dihydroxypropyl)-5-amino-2H-1,2,4-thiadiazol-3-one (1) and 3-(2′,3′-dihydroxypropyl)-5-amino-3H-1,3,4-thiadiazol-2-one (2), is reported. The first compound, 1, was obtained by reaction of 3-chloro-1,2-propanediol with the sodium salt of 5-amino-2H-1,2,4-thiadiazol-3-one (3) in anhydrous dimethylformamide. Similarly, 5-amino-3H-1,3,4-thiadiazol-2-one (4) reacted with 3-chloro-1,2-propanediol to give 2. The thiadiazole 4 was prepared by condensation-cyclization of hydrazothiodicarbonamide (9).     

Synthesis of 1, 5- and 1, 7-dichloro-9H-thioxanthen-9-ones

1, 5-Dichloro-9H-thioxanthen-9-one ( 2 ) was prepared by cyclization of 2-chloro-6-[(2-chlorophenyl)thio]-benzoic acid ( 10 ) obtained from 2-chloro-6-iodobenzoic acid ( 9 ) and 2-chlorobenzenethiol. Similarly, 1, 7-di-chloro-9H-thioxanthen-9-one ( 6 ) was prepared from 9 via 2-chloro-6-[(4-chlorophenyl)thio]benzoic acid ( 11 ). Compound 6 was also obtained by condensation of 2-chloro-6-mercaptobenzoic acid ( 12 ) with chlorobenzene in the presence of sulfuric acid.     

Synthesis and antimalarial effects of 5,6-dichloro-2-[(4-||4-(diethylamino)-i-methylbutyl] amino||-6-methyl-2-pyrirnidinyl)amino] benzimidazole and related benzimidazoles and lH-imidazo[4,5-b] pyridines

A group of fifty-five 2-[(4-11[(dialkylamino)alkyI]amino11-6-methyl-2-pyrimidinyl)amino]-benzimidazoles (VII) was synthesized in 3-88% yield by the condensation of the requisite 2-[(2-benzimidazolyl)amino]-4-chloro-6-methylpyrimidine (VI) with the appropriate polyamine in ethanol-hydrochloric acid or neat with excess amine containing potassium iodide. The 2-[(2-benzimidazolyl)amino]-6-methyl-4-pyrirnidinol precursors (V), obtained in 11-51% yield by cyclization of 2-(cyanoamino)-4-hydroxy-6-methylpyrimidine with a suitably substituted o-phenylenediamine, were chlorinated with phosphorus oxychloride to give the intermediate 2-[(2-benzimidazolyl)amino]-4-chloro-6-rnethylpyrimidines (VI) (27-99%). Oxidation of 5,6-dichloro-2-[(4-11[4-(diethylamino)-l-methylbutyl] amino 11-6-methyl-2-pyrimidinyl) amino ]benzimidazole ( 29 ) with m-chloroperbenzoic acid gave the distal N⁴'-oxide ( 31 ) (19%). Fusion of 2,3-uiaminopyridine with 2-(cyanoamino)-4-hydroxy-6-methylpyrimidine provided 2-[(4-hydroxy-6-tnethyl-2-pyrimidinyl)amino]-lH-imitlazo[4,5-b]pyrimidine (VIII) (30%), which upon chlori-nation with phosphorus oxychloride (63%) followed by amination with i N, N-diethylethylene-diamine afforded 2-(4-11[2-(diethylamino)ethyl] amino 11-6-methyl-2-pyrimidinyl)-lH-imidazo [4,5-b]pyridine (X) (8%). Thirty-eight of the novel 2-[(4-amino-6-methyl-2-pyrimidinyl)amino]-benzimidazoles possessed “curative” activity against Plasmodium berghei at single subcutaneous doses ranging from 20.640 mg./kg. Orally, thirty-one compounds exhibited suppressive activity against P. berghei comparable with or superior to the reference drugs 1-(p-chlorophenyl)-3-(4-11[2-(diethylarnino)ethyl]amino 11-6-methyl-2-pyrimidinyl)guanidine (I) and quinine hydrochloride, while twelve of them were 5 to 28 times as potent as I and quinine hydrochloride. Eight compounds also displayed strong suppressive activity against P. gallinaceum in chicks. 5,6-Dichloro-2-[(4-112-(diethylamino)ethyl]amino11-6-methyl-2-pyrimidinyl] benzimidazole (18) showed marked activity against a cycloguanil-resistant line of P. berghei, and the most promising member of the series, namely 5,6-dichloro-2-[(4-11[4-(diethylamino)-l-methylbutyl]amino11-6-methyl-2-pyrimidinyl)amino]benzimidazole ( 29 ) (Q = 28), was designated for preclinical toxico-logical studies and clinical trial. Structure-activity relationships are discussed.     

7-(2-fluorobenzyl)-4-(substituted)-7-H-imidazo[4,5-d −1,2,3-triazines and −7H-pyrazolo[3,4-d]-1,2,3-triazines. Synthesis and anticonvulsant activity

The imidazo[4,5-d]-1,2,3-triazine and pyrazolo[3,4-d]-1,2,3-triazine analogues of the potent anticonvul-sant purine, BW 78U79 (9-(2-fluorobenzyl)-6-methylamino-9H-purine, 1 ), were synthesized and tested for anticonvulsant activity. The imidazo[4,5-d]-1,2,3-triazines 11–13 were prepared in four steps from 5-aminoimidazole-4-carboxamide (2) and the pyrazolo[3,4-d]-1,2,3-triazines 18–21 were synthesized starting with 5-amino-1-(2-fluorobenzyl)pyrazole-4-carbonitrile (14) . The intermediate 1,2,3-triazin-4-ones 6 and 16 were converted to the 4-substituted targets via the 4-(4-dimethylaminopyridinium) salts 10 and 17 . Imidazotriazine 11 had potent anticonvulsant activity against maximal electroshock-induced seizures, but its propensity to cause emesis precluded further development.     

6-Substituted-9-(3-formamidobenzyl)-9H-purines. Benzodiazepine receptor binding activity

A series of 6-substituted-9-(3-formamidobenzyl)purines were synthesized and studied for benzodiazepine receptor (BZR) binding activity. Most of the target compounds were prepared by reaction of 6-chloro-9-(3-formamidobenzyl)-9H-purine ( 17 ) with the appropriate amine, alcohol or other nucleophilic reagent. Alternatively, the 6-cyclopropylaminopurine 5 was synthesized via the nitrobenzyl precursor 22 , and the 6-alkyl-thiopurines 14 and 15 were prepared by alkylation of the appropriate purine with 3-formamidobenzyl bromide. Purines with a variety of 6-substituents retained potent BZR binding properties, although certain bulky 6-substituents led to compounds with diminished activity. None of the compounds exhibited significant activity on a modified Geller-Seifter Conflict schedule.     

Synthesis of 2-(β-D-ribofuranosyl)pyrimidines,A new class of C-nucleosides

A new C-glycosyl precursor for C-nucleoside synthesis, 2,5-anhydroallonamidine hydrochloride ( 4 ) was prepared and utilized in a Traube type synthesis to prepare 2-(β-D-ribofuranosyl)pyrimidines, a new class of C-nucleosides. The anomeric configuration of 4 was confirmed by single-crystal X-ray analysis. Reaction of 4 with ethyl acetoacetate gave 6-methyl-2-(β-D-ribofuranosyl)pyrimidin-4-(1H)-one ( 5 ). Reaction of 4 with diethyl sodio oxaloacetate gave 2-(β-D-ribofuranosyl)pyrimidin-6(1H)-oxo-4-carboxylic acid ( 6 ). Esterification of 6 with ethanolic hydrogen-chloride gave the corresponding ester 7 which when treated with ethanolic ammonia gave 2-(β-D-ribofuranosyl)pyrimidin-6(1H)-oxo-4-carboxamide ( 8 ). Condensation of 2,5-anhydroallonamidine hydrochloride ( 4 ) with ethyl 4-(dimethylamino)-2-oxo-3-butenoate ( 9 ), gave ethyl 2-(β-D-ribofuranosyl)pyrimidine-4-carboxylate ( 10 ). Treatment of 10 with ethanolic ammonia gave 2-(β-D-ribofuranosyl)pyrimidine-4-carboxamide ( 11 ). Single-crystal X-ray analysis confirmed the β-anomeric configuration of 11. Acetylation of 11 followed by treatment with phosphorus pentasulfide and subsequent deprotection with sodium methoxide gave 2-(β-D-ribofuranosyl)pyrimidine-4-thiocarboxamide ( 14 ). Dehydration of the acetylated amide 12 with phosphorous oxychloride provided 2-(β-D-ribofuranosyl)pyrimidine-4-carbonitrile ( 15 ). Treatment of 15 with sodium ethoxide gave ethyl 2-(β-D-ribofuranosyl)pyrimidine-4-carboximidate ( 16 ), which was converted to 2-(β-D-ribofuranosyl)pyrimidine-4-carboxamidine hydrochloride ( 17 ) by treatment with ethanolic ammonia and ammonium chloride. Treatment of 16 with hydroxylamine yielded 2-(β-D-ribofuranosyl)pyrimidine-4-N-hydroxycarboxamidine ( 18 ). Treatment of 2-(β-D-ribofuranosyl)pyrimidine-4-carboxamide ( 11 ) with phosphorus oxychloride gave the corresponding 5′-phosphate, 19 , Coupling of 19 with AMP using the carbonyldiimidazole activation procedure gave the corresponding NAD analog, 2-(β-D-ribofuranosyl)pyrimidine-4-carboxamide-(5′ ? 5′)-adenosine pyrophosphate ( 20 ).     

Über die Einwirkung von Ammoniak auf 5-Chlor-2-(N-methyl-jodmethansulfonamido)-benzophenon

Zusammenfassung 5-Chlor-2-(N-methyl-jodmethansulfonamido)-benzophenon (6 b) reagiert mit flüss. NH₃ zu 6-Chlor-4-hydroxy-1-methyl-4-phenyl-3,4-dihydro-1H-2,1-benzothiazin-2,2-dioxid (7), mit NH₃ in absol. Alkohol zu 6-Chlor-4-hydroxy-3-jod-1-methyl-4-phenyl-3,4-dihydro-1H-2,1-benzothiazin-2,2-dioxid (9). Der Mechanismus dieser Reaktionen wird diskutiert.

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The reaction of ammonia with 5-Chloro-2-(N-methyl-iodo-methanesulfonamido)-benzophenone

The reaction of 5-chloro-2-(N-methyl-jodomethanesulfon-amido)-benzophenone (6b) with liquid or absol. alcoholic ammonia leads to 6-chloro-4-hydroxy-1-methyl-4-phenyl-3,4-dihydro-1H-2,1-benzothiazine-2,2-dioxid (7) and 6-chloro-4-hydroxy-3-jodo-1-methyl-4-phenyl-3,4-dihydro-1H-2,1-benzothiazine-2,2-dioxid (9) resp. The mechanism of these reactions is discussed.

     

Synthesis of New Nucleosides by coupling of chloropurines with 2- and 3-deoxy derivatives of N-methyl-D-ribofuranuronamide

The synthesis of new deoxyribose nucleosides by coupling chloropurines with modified D -ribose derivatives is reported. The methyl 2-deoxy-N-methyl-3-O-(p-toluoyl)-α-D -ribofuranosiduronamide (α-D - 8 ) and the corresponding anomer β-D - 8 were synthesized starting from the commercially available 2-deoxy-D -ribose ( 1 ) (Scheme 1). Reaction of α-D - 8 with the silylated derivative of 2,6-dichloro-9H-purine ( 9 ) afforded regioselectively the N⁹-(2′-deoxyribonucleoside) 10 as anomeric mixture (Scheme 2), whereas β-D - 8 did not react. Glycosylation of 9 or of 6-chloro-9H-purine ( 17 ) with 1,2-di-O-acetyl-3-deoxy-N-methyl-β-D -ribofuranuronamide ( 13 ) yielded only the protected β-D -anomers 14 and 18 , respectively (Scheme 3). Subsequent deacetylation and dechlorination afforded the desired nucleosides β-D - 11 , β-D - 12,15 , and 16 . The 3′-deoxy-2-chloroadenosine derivative 15 showed the highest affinity and selectivity for adenotin binding site vs. A₁ and A_2A adenosine receptor subtypes.     

Synthesis of 2-(4H-1,2,6-thiadiazin-4-ylidene)malononitriles

The base-free TiCl₄-mediated condensation of 3,5-disubstituted-4H-1,2,6-thiadiazin-4-ones 8 with malononitrile affords 20 difficult to access (3,5-disubstituted-4H-1,2,6-thiadiazin-4-ylidene)malononitriles 7. The reaction tolerates 3,5-diaryl, diphenoxy, dimethoxy and diphenylthio substituted thiadiazinones, but not diamino, monohydroxy or dihalo substituents. Nevertheless, asymmetrically substituted 3-halo-5-phenyl- and 3-chloro-5-methoxy-4H-1,2,6-thiadiazin-4-ones convert into the corresponding ylidenemalononitriles in good yield. Furthermore, the condensation works well with ethyl cyanoacetate and diethyl malonate, but not with Meldrum's acid, dimedone or nitromethane. Finally, 2-(3-chloro-5-phenyl-4H-1,2,6-thiadiazin-4-ylidene)malononitrile (7q) reacts with aniline to give 4,7-diphenyl-6-(phenylimino)-6,7-dihydropyrrolo[2,3-c][1,2,6]thiadiazine-5-carbonitrile (12) in moderate yield demonstrating the potential use of these ylidenes to prepare novel 6–5 fused 4H-1,2,6-thiadiazines.     

Synthesis of 2′-deoxyribofuranosyl indole nucleosides related to the antibiotics SF-2140 and neosidomycin

The 2′-deoxyribofuranose analog of the naturally occurring antibiotics SF-2140 and neosidomycin were prepared by the direct glycosylation of the sodium salts of the appropriate indole derivatives, with 1-chloro-2- deoxy-3,5-di-O-p-toluoyl-α-D-erythropentofuranose ( 5 ). Thus, treatment of the sodium salt of 4-methoxy-1H- indol-3-ylacetonitrile ( 4a ) with 5 provided the blocked nucleoside, 4-methoxy-1-(2-deoxy-3,5-di-O-p-toluoyl-β- D-erythropentofuranosyl)-1H-indol-3-ylacetonitrile ( 6a ), which was treated with sodium methoxide to yield the SF-2140 analog, 4-methoxy-1-(2-deoxy-β-D-erythropentofuranosyl)-1H-indol-3- ylacetonitrile ( 7a ). The neosidomycin analog ( 8 ) was prepared by treatment of the sodium salt of 1H-indol-3-ylacetonitrile ( 4b ) with 5 to obtain the blocked intermediate 1-(2-deoxy-3,5-di-O-p-toluoyl-β-D-erythropentofuranosyl) ?1H-indol-3-ylace-tonitrile ( 6b ) followed by sodium methoxide treatment to give 1-(2-deoxy-β-D-erythropentofuranosyl)-1H- indol-3-ylacetonitrile ( 7b ) and finally conversion of the nitrile function of 7b to provide 1-(2-deoxy-β-D- erythropentofuranosyl)-1H-indol-3-ylacetamide ( 8 ). In a similar manner, indole ( 9a ) and several other substituted indoles including 1H-indole-4-carbonitrile ( 9b ), 4-nitro-1H-indole ( 9c ), 4-chloro-1H-indole-2-carboxamide ( 9d ) and 4-chloro-1H-indole-2-carbonitrile ( 9e ) were each glycosylated and deprotected to provide 1-(2-deoxy-β-D-erythropentofuranosyl)-1H-indole ( 11a ), 1-(2-deoxy-β-D-erythropentofuranosyl)-1H-indole-4- carbonitrile ( 11b ), 4-nitro-1-(2-deoxy-β-D-erythropentofuranosyl)-1H-indole ( 11c ), 4-chloro-1-(2-deoxy-β-D- erythropentofuranosyl)-1H-indole-2-carboxamide ( 11d ) and 4-chloro-1-(2-deoxy-β-D-erythropentofuranosyl)- 1H-indole-2-carbonitrile ( 11e ), respectively. The 2′-deoxyadenosine analog in the indole ring system was prepared for the first time by reduction of the nitro group of 11c using palladium on carbon thus providing 4-amino-1-(2-deoxy-β-D-erythropentofuranosyl)- 1H-indole ( 16 , 1,3,7-trideaza-2′-deoxyadenosine).     

Synthesis of 1-substituted-2,3,4,9-tetrahydro-(2-oxopropyl)-1H-pyrido [3,4-b] indoles and their base-catalyzed rearrangements to N- [2-[2-(1-alkyl-3-oxobutenyl)-1H-indol-3-yl] ethyl]acetamides

The condensation of 1H-indole-3-ethanamides, 1 , with 2,4-pentanediones, 2 , gave enamines 3 . Acid catalyzed ring closure of 3 gave 1-(1-substituted-2,3,4,9-tetrahydro- (2-oxopropyl) -1H-pyrido [3,4-b] indoles 4 . Subsequent N-acetylation yielded 5 which sequentially produced 2,3-disubstituted indoles 6 and 7 resulting from C? N bond cleavage after treatment with sodium alkoxide in ethanol. Controlled catalytic hydrogenation of the latter gave saturated derivatives 8 and 9 .     

Nucleosides. Part LI The 2-(4-nitrophenyl)ethoxycarbonyl (npeoc) and 2-(2,4-dinitrophenyl)ethoxycarbonyl (dnpeoc) groups for protection of hydroxy functions in ribonucleosides and 2′ -deoxyribonucleosides

The Common 2′ -deoxypyrimidine and -purine nucleosides, thymidine ( 4 ), O⁴-[2-(4-nitrophenyl)ethyl]-thymidine ( 17 ), 2′-deoxy-N⁴-[2-(4-nitrophenyl)ethoxycarbonyl]cytidine ( 26 ), 2′-deoxy-N⁶-[2-(4-nitrophenyl)-ethoxycarbonyl]adenosine- 39 , and 2′-deoxy-N²-[2-(4-nitrophenyl)(ethoxycarbonyl]-O⁶-[2–4-nitrophenyl)ethyl]-guanosine ( 52 ) were further protected by the 2-(4-nitrophenyl)ethoxycarbonyl (npeoc) and the 2-(2,4-dinitrophenyl)ethoxycarbonyl (dnpeoc) group at the OH functions of the sugar moiety to form new partially and fully blocked intermediates for nucleoside and nucleotide syntheses. The corresponding 5′-O-monomethoxytrityl derivatives 5 , 18 , 30 , 40 , and 56 were also used as starting material to synthesize some other intermediates which were not obtained by direct acylations. In the ribonucleoside series, the 5′ -O-monomethoxytrityl derivatives 14 , 36 , 49 , and 63 reacted with 2-(4-nitrophenyl) ethyl chloroformate ( 1 ) to the corresponding 2′,3′-bis-carbonates 15 , 37 , 50 , and 64 which were either detriylated to 16 , 38 , 51 , and 65 , respectively, or converted by 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) treatment to the 2′,3′-cyclic carbonates 66 – 69 . The newly synthesized compounds were characterized by elemental analyses and UV and ¹H-NMR spectra.     

Synthesis of the Ethyl Esters of 4-(3-Pyridyl)- and 4-(4-Pyridyl)-2-oxobutenoic Acids

We have developed a method for the synthesis of ethyl 4-(3-pyridyl)- and 4-(4-pyridyl)-2-oxobutenoates by condensation of 3-pyridinecarbaldehyde and 4-pyridinecarbaldehyde monohydrate respectively with ethyl pyruvate, esterifiction of the target acids, and hydrolysis of the corresponding ethyl ester ketals in the presence of FeCl₃·6H₂O.     

Ethyl 3,3-diamino-2-(2-p-tolylpyrimidin-4-yl)acrylate,a new representative of hetarylketene aminals

A new representative of hetarylketene aminals, ethyl 3,3-diamino-2-(2-p-tolylpyrimidin-4-yl)acrylate, was synthesized by the reaction ofp-toluamidine with the condensation product of dimethylformamide dimethyl acetal and the difluoroboron chelate of acetyl(ethoxycarbonyl)ketene (N-benzoyl)aminal. This synthesis is an example of pyrimidine ring assembly using the methodology based on transformations of chelate complexes.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1638–1640, September, 1994.This research was partially supported by the International Science Foundation (Grant No. M5QOOO).     

Synthesis and some transformations of 6(8)-substituted 4-hydrazino-2-methylquinolines

6(8)-Substituted 4-hydrazino-2-methylquinolines were synthesized by reaction of the corresponding 4-chloro-2-methylquinolines with hydrazine hydrate. Reactions of the title compounds with ethyl acetoacetate and acetone gave 2,4-dimethyl-1H-pyrrolo[3,2-c]quinolines and 4-(5-ethoxy-3-methyl-1H-pyrazol-1-yl)-2-methylquinolines.     

Photoisomerization of 2H,6H-Thiin-3-ones to 2-(Alk-1-enyl)thietan-3-ones

Reaction of 3-bromo-3-methylbutan-2-one ( 1 ) with mercapto-esters 2 affords 5-oxo-3-thiahexanoates 3 which cyclize to thiane-3,5-diones 4 . Conversion of these dicarbonyl compounds to their ethyl enol ethers 5–7 followed by reduction with LiAlH₄ gives 2H,6H-thiin-3-ones 8–10 . On irradiation (350 nm) in either MeCN, benzene, or i-PrOH, these newly synthesized heterocycles isomerize efficiently to 2-(alk-l-enyl)thietan-3-ones 11–13 . The rearrangement seems to proceed from an excited singlet state, as it is not quenched by naphthalene, and also occurs with the same efficiency in the presence of added alkene. A (9-S-3) sulfuranyl-alkyl biradical formed by bonding of C(α) of the enone C?C bond on sulfur is discussed as possible intermediate.     

Synthesis of 1-(2-hydroxyphenyl)-2,4-imidazolidinedione derivatives through cyclic transformations of ethyl 2-oxo-3(2H)-benzoxazoleacetate derivatives

A series of ethyl 2-oxo-3(2H)-benzoxazoleacetate derivatives 2 have been synthesized. By reaction with ammonia, primary amines or hydrazine, these compounds 2 were transformed into 1-(2-hydroxyphenyl)-2,4-imidazolidinedione derivatives 4, 5 and 6 , respectively. Some of these new hydantoins 4 , treated with phosphorus oxychloride, gave 3H-2-oxoimidazo[2,1-b]benzoxazole derivatives 9 . Ethyl 2-oxo-3(2H)-benzoxazolepropionate ( 10 ) was prepared by a Michaël reaction of ethyl acrylate with 2-benzoxazolone ( 1a ). With 10 , no cyclic transformation was observed in the presence of ammonia or alkylamine.