Synthesis and properties of 1-Benzothiopyrano[2,3-d]-pyrimidine-2,4-(3H)diones (10-thia-5-deazaflavins)

Treatment of 6-arylthiouracils with the Vilsmeier reagent (dimethylformamide-phosphorus oxychloride) gave the corresponding 6-arylthio-5-formyluracils, which could alternatively be prepared by the condensation of 6-chloro-5-formyluracils with thiophenols. Dehydrative cyclization of the above 5-formyluracils with polyphosphoric acid gave 1-benzothiopyrano[2,3-d]pyrimidine-2,4-(3H)diones (10-thia-5-deazaflavins). These 10-thia-5-deazaflavins oxidized alcohols to give the corresponding carbonyl compounds with the aid of strong base, and they were hydrogenated to 1,5-dihydro-10-thia-5-deazaflavins. Treatment of 10-thia-5-deazaflavins with concentrated aqueous potassium hydroxide led to the exclusive formation of 1,5-dihydro-10-thia-5-deazaflavins and 1,5-dihydro-10-thia-5-deazaflavin-5-ones via intermolecular oxidation-reduction (disproportionation) between initially formed 1,5-dihydro-5-hydroxy-10-thia-5-deazaflavins and unchanged 10-thia-5-deazaflavins.     

Synthesis of a novel 8-thia-1,4-diazacycl[3.3.2] azine

A unique covalently hydrated cyclazine adduct, 2-imino-6a-hydroxy-4,5,6,6a-tetrahydro-7H-8-thia-J, 4-diazacycl[3.3.2]azin-5-one hydrochloride was prepared by reacting ethyl 4-chloro-acetoacetate with 4,6-diamino-2-thiopyrimidine in neutral alcohol. Neutralization gave 2-imino-5,6a-dihydroxy-6,6a-dihydro-7H-8-thia-1,4-diazacycl[3.3.2]azine which decomposed to 4,6-diamino-2-acetonylthiopyrimidine upon heating in water. Warming the hydrated hydrochloride in concentrated hydrochloric acid caused dehydration to yield 2-imino-5-hydroxy-6H-8-thia-1,4-diazacycl[3.3.2]azine hydrochloride. Partial isomerization (20%) to 2-imino-5-hydroxy-7H-8-thia-1,4-diazacycl[3.3.2]azine hydrochloride occurred during recrystallization from aqueous acidic methanol. The free base, 2-imino-5-hydroxy-7H-8-thia-1,4-diazacycl[3.3.2]azine was obtained after neutralizing either of the tautomeric hydrochlorides. Treating the free base with trifluoroacetic acid produced a mixture of the trifluoroacetate salts of the two tautomeric bases. Isomerization of one trifluoroacetate salt into the other in trifluoroacetic acid was observed by pmr at room temperature. Both 2-amino-5-hydroxy-7-nitroso-8-thia-1,4-diazacycl[3.3.2]azine and 2-amino-5-hydroxy-6-nitroso-8-thia-1,4-diazacycl[3.3.2]azine were isolated after nitrosation of the hydrochloride mixture.     

Synthesis via pummerer intermediates. IV. Synthesis of 1-(4-hydroxy-2-oxo-2H-1-benzopyran-3-yl)pyridinium hydroxide inner salt derivatives and 3-(2H)benzofuranones by the action of phosgene in pyridine on 2-hydroxy-1-[(methylsulfinyl)acetyl]benzene derivatives

The treatment of ketosulfoxide 1 with phosgene in pyridine gave a mixture of 1-(4-hydroxy-8-methoxy-2-oxo-2H-1-benzopyran-3-yl)pyridinium hydroxide inner salt ( 4 ) and 7-methoxy-2-(methylthio)-3-(2H)benzofuranone ( 7 ). Ketosulfoxides 8 and 11 behaved similarly. The inner salt structure assigned to compounds 4, 10 , and 13 was confirmed by the unambiguous synthesis of 10 and 13 from hydroxycoumarins 15 and 18 .     

Benzofused tricycles based on 2-quinoxalinol

This paper describes our recent efforts to synthesize novel compound scaffolds integrating 2-quinoxalinol with privileged structures of 1,3-dihydro-benzoimidazol-2-one, 1,3-dihydro-benzoimidazole-2-thione, 3-hydroxy-1H-quinoxalin-2-one, 2H-benzo[1,4]oxazin-3-ol, 2H-benzo[1,4]thiazin-3-ol, and 1,3,4,5-tetrahydro-benzo[1,4]diazepin-2-one, respectively. Eight novel benzofused tricycles and their substituent diversity points were developed. These include pyrazino[2,3-g]quinoxaline-2,8-diol (I), 3-hydroxy-6,8,9,10-tetrahydro-1,4,6,10-tetraaza-cyclohepta[b]naphthalen-7-one (II), 6-hydroxy-4H-1-oxa-4,5,8-triaza-anthracen-3-one (III), 6-hydroxy-4H-1-thia-4,5,8-triaza-anthracen-3-one (IV), 6-hydroxy-1,1-dioxo-1,4-dihydro-2H-1lambda(6)-thia-4,5,8-triaza-anthracen-3-one (V), 6-hydroxy-1,3-dihydro-imidazo[4,5-g]quinoxalin-2-one (VI), 6-hydroxy-1,3-dihydro-imidazo[4,5-g]quinoxaline-2-thione (VII), and 7-hydroxy-1,4-dihydro-pyrazino[2,3-g]quinoxaline-2,3-dione (VIII). This strategy of integrating two benzofused privileged structures into one molecule may provide a greater chance for the discovery of novel lead compounds.     

Preparation and properties of polymers from aryl cyclic sulfonium zwitterions

A new class of zwitterionic monomers were prepared in which the positive and negative sites are cyclic sulfonium and phenolate. Thermal polymerization occurs by phenolic anionic attack upon the aliphatic carbon α to the sulfonium sulfur. Polymerization proceeds with ring opening and net loss of charge to form nonionic polymers. The monomeric zwitterions are generally hydrated, crystalline solids that are soluble in water or alcohol. Chlorination of the aromatic portion of the molecule yields nonhydrated species. The polymerizations of 1-(4-hydroxy-3-methylphenyl)tetrahydrothiophenium hydroxide inner salt (dihydrate) and 1-(3,5-dichloro-4-hydroxyphenyl)tetrahydrothiophenium hydroxide inner salt were studied. The latter monomer gave a polymer with M?_n of 46,000 when a nucleophile was present as an initiator. The physical properties of this polymer were determined. Cyclization appears to be the main mechanism of termination in the polymerization of zwitterions.     

Amidrazones. 8. Synthesis of 1,2,4-oxdiazoles by thermolysis of N3-acylamidrazone ylides

N³-Acylamidrazone ylides 3 were synthesized by the reaction of 2-(iminophenylmethyl)-1,1,1-trimethylhydrazinium hydroxide, inner salt ( 2a ) or 2-(1-iminoethyl)-1,1,1-trimethylhydrazinium hydroxide, inner salt ( 2b ) with acyl chlorides or acetic anhydride. Thermolysis of 3 gave 3,5-disubstituted oxadiazoles 4 and trimethylamine.     

Zwitterionic polymerization of 1-[4-[(4-hydroxy-1-naphthyl)thio]butyl]quinuclidinium hydroxide inner salt

The zwitterion, 1-[4-[(4-hydroxy-1-naphthyl)thio]butyl]quinuclidinium hydroxide inner salt, was synthesized from tetrahydro-1-(4-hydroxy-1-naphthyl)thiophenium hydrochloride and quinuclidine and characterized by NMR and IR spectroscopy. Polymerization of the zwitterion was studied over the temperature range 175–225°C. The polymer was identified as poly(1,4-piperidinediylethyleneoxy-1,4-naphthylenethiotetramethylene) based on NMR and IR spectroscopy. The polymer was found to contain 3-butenylthio and 4-hydroxy-1-naphthyl end groups. Based on the signal area of the olefinic end group, the polymer M⌅_n varied between 8500 and 13,000. The highest molecular weight was achieved at the lowest temperature, indicating that termination became more favored at higher temperature. A mechanism is proposed to describe the polymerization. © 1996 John Wiley & Sons, Inc.     

Condensation of 4-benzamido-3-oxothiophan with acrolein. synthesis of 1-benzamido-4-hydroxy-6-thiabicyclo[3.2.1]-octan-8-one and 6-benzoyl-7-hydroxy-2-thia-6-azaspiro[4.4]-nonan-4-one

It is shown that acrolein adds to the 4 position (rather than to the 2 position) of 4-benzamido-3-oxothiophan under the influence of catalysts with basic character; the aldehyde group of the intermediate compound reacts with the amino group (if the reaction is carried out in chloroform) to give 6-benzoyl-7-hydroxy-2-thia-6-azaspiro[4.4]nonan-4-one or (if the reaction is carried out in a mixture of alcohol and chloroform) 1-benzamido-4-hydroxy-6-thiabicyclo-[3.2.1]octan-8-one as a result of intramolecular aldol condensation.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1620–1624, December, 1978.     

Synthesis and crystal structure of a covalently hydrated 8-thia-1,4-diazacycl[3.3.2]azine

Condensation of ethyl 4-chloroacetoacetate with 4-amino-6-hydroxy-2-pyrimidinethiol produced ethyl 3-hydroxy-5-amino-7-oxothiazolino[3,2-a]pyrimidin-3-acetate ( 7a ) on crystallization. Subsequent ring closure of 7a produced the tricyclic 6a-hydroxy-5,6,6a,7-tetrahydro-8-thia-1,4-diazacycl[3.3.2]azin-2,5-dione ( 8 ). The structure of 8 was confirmed by crystal x-ray diffraction analysis.     

Design and synthesis of novel tricycles based on 4H-benzo[1,4]thiazin-3-one and 1,1-dioxo-1,4-dihydro-2H-1lambda6-benzo[1,4]thiazin-3-one

This paper reports our recent efforts to develop novel tricycles based on 4H-benzo[1,4]thiazin-3-one ( 2) and 1,1-dioxo-1,4-dihydro-2H-1lambda(6)-benzo[1,4]thiazin-3-one (3) using 1,5-difluoro-2,4-dinitrobenzene (1). All of these tricycles integrate two privileged structures into one skeleton, including 3,8-dihydro-5-thia-1,3,8-triaza-cyclopenta[b]naphthalene-7-one (4, 10, 12), 5,5-dioxo-3,5,6,8-tetrahydro-5lambda(6)-thia-1,3,8-triaza-cyclopenta[b]naphthalene-7-one (5, 11), 3,8-dihydro-5-thia-1,2,3,8-tetraaza-cyclopenta[b]naphthalene-7-one (6), 5,5-dioxo-3,5,6,8-tetrahydro-5lambda(6)-thia-1,2,3,8-tetraaza-cyclopenta[b]naphthalene-7-one (7), 3,8-dihydro-1H-5-thia-1,3,8-triaza-cyclopenta[b]naphthalene-2,7-dione (8), and 5,5-dioxo-3,5,6,8-tetrahydro-1H-5lambda(6)-thia-1,3,8-triaza-cyclopenta[b]naphthalene-2,7-dione (9). A typical library of scaffold 5 was synthesized in a parallel solution-phase manner and analyzed by HPLC-UV-MS or HPLC-UV-ELSD method.     

Amidrazones V. thermolysis of N1-benzyl-substituted amidrazone ylides

Thermolysis of 1,1-dimethyl-1-benzyl-2-(iminophenylmethyl)hydrazinium hydroxide inner salt gave dimethylamine, 2,4,6-triphenyl-s-triazine and 2,4,6-triphenyl-1,2-dihydro-s-triazine.     

Synthese von 2-Thia-6-aza-adamantan und Derivaten

The synthesis of 2-thia-6-aza-adamantane ( 19 ) and several of its derivatives was achieved starting from 9-azabicyclo[3.3.1]nona-2,6-diene ( 9 ) which was prepared from cis, cis-cycloocta-1, 5-diene ( 1 ). Transannular addition of sulfur dichloride to its N-benzenesulfonyl and N-formyl derivatives 10 and 11 yielded the tricyclic dichlorides 12 and 13 , respectively; the 2-thia-6-aza-adamantanes 14–19 were synthesized from 13 .     

Thiylation of diallyl sulfide by hydrogen sulfide in the alkali metal hydroxide-DMSO system

Preparative methods have been developed for the synthesis of 3,7-dimethyl-1,2,5-trithiacycloheptane and 4-thia-1-heptene-6-thiol from diallyl sulfide and hydrogen sulfide in a system containing an alkali metal hydroxide and DMSO.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 483–484, April, 1989.     

Synthesis of 10-thia-5-deazafolic acid and 2-desamino-2-oxo-10-thia-5-deazafolic acid

The folate analogue, 10-thia-5-deazafolic acid, was obtained via a multistep synthetic sequence beginning with the known intermediate, 2,4-diaminopyrido[2,3-d]pyrirnidine-6-carboxaldehyde. Reduction of this aldehyde with sodium borohydride gave 2,4-diamino-6-(hydroxymethyl)pyrido[2,3-d]pyrimidine, which when heated in base gave 2-amino-3,4-dihydro-6-(hydroxymethyl)-4-oxopyrido[2,3-d]pyrimidine. Treatment of the latter compound with phosphorus tribromide in tetrahydrofuran afforded 2-amino-6-(bromomethyl)-3,4-dihydro-4-oxopyrido[2,3-d]pyrimidine, thus constituting the first successful synthesis of this elusive intermediate. The aforementioned bromomethyl compound reacted smoothly with the sodium salt of ethyl 4-mercaptobenzoate, and the resulting ester was saponified to give 10-thia-5-deazapteroic acid. Conventional peptide bond coupling to di-tert-butyl L-glutamate followed by treatment with trifluoroacetic acid afforded the target compound in respectable yield. Attempts to prepare its 5,6,7,8-tetrahydro derivative by catalytic hydrogenation were unsuccessful.     

A novel approach to the synthesis of 6-amino-7-hydroxy-flavone

A novel approach to the synthesis of 6-amino-7-hydroxyflavone (1) is described. Reaction in acetone of 2',4'-dihydroxy-5'-nitroacetophenone and benzoyl chloride in the presence of potassium carbonate affords 3-benzoyl-7-hydroxy-6-nitroflavone, which is cleaved in 5% ethanolic potassium hydroxide to give 1-(2,4-dihydroxy-5-nitrophenyl)-3- phenyl-1,3-propanedione. The 1,3-diketone thus formed is then transformed into 7-hydroxy- 6-nitroflavone, followed by reduction to afford the title compound.     

Structure and reactions of a thiazolino[3,2-a]pyrimidine carbinolamine

Ethyl 4-chloroacetoacetate condenses with 4-amino-6-hydroxy-2-pyrimidinethiol to yield ethyl 3-hydroxy-5-oxo-7-aminothiazolino[3,2-a]pyrimidin-3-acetate ( 3 ), and not ethyl 3-hydroxy-5-amino-7-oxothiazolino[3,2-a]-pyrimidin-3-acetate, as previously reported. This compound reacts with ammonia to produce ethyl 4-(6′-amino-4′-oxo-2′-pyrimidinethiol)-3-aminocrotonate ( 8 ), the open chain structure of which accounts for the cyclization of 3 to the poly-cyclic lactam, 6a-hydroxy-5,6,6a,7-tetrahydro-8-thia-1,4-diazacycl[3.3.2]azine-2,5-dione, rather than the sterically more favorable lactone, when 3 was treated with triethylamine. Some other reactions of 3 are described, and the structures of 3 and 8 were comfirmed by single crystal X-ray diffraction analysis.     

硫杂冠醚的合成

冠醚化合物对金属离子的络合不仅具有较高的稳定性,而且更重要的是具有良好的选择性。当冠醚环中的氧原子部分或全部被氮或硫原子取代后,它们对碱金属、碱土金属的亲和性能降低,而对过渡金属离子的亲和能力相应提高。硫杂冠醚对亲硫的贵金属、重金属离子具有更强的络合能力和更高的选择性。1974     

Dithiaindenes: Synthesis of 6-thia-7H-benzo [b] thiophene (1,6-dithiaindene) and 1,3-dimethyl-5-thia-4H-benzo [c] thiopene (1,3-dimethyl-2,5-dithiaindene) and attempted synthesis of 5-thia-4H-benzo [b] thiophene (1,5-dithiaindene)

Synthesis of the heteroaromatic systems 6-thia-7H-benzo [b] thiophene (3) and 1,3-dimethyl-5-thia-4H-benzo [c] thiopbene (5) have been achieved by reduction and dehydration of 1,6-dithiaindan-4-one (4) and 1,3-dimethyl-2,5-dithiaindan-7-one (8) respectively. A similar attempt to synthesise 5-thia-4H-benzo [b] thiophene (4) by dehydration of 7-hydroxy-1,5-dithiaindane (16) resulted in the formation of 7,7′-bis (1,5-dithiaindanyl) ether.     

Hydroxide-promoted redox reactions in water of α-Phenyl-4-nitro-benzenemethanol, α-(p-Nitrophenyl)-4-pyridinemethanol,and α-(p-Nitrophenyl)-4-Pyridinemethanol N-Oxide steric inhibition of resonance

α-Phenyl-4-nitrobenzenemethanol ( 3 ) reacted with 1 M sodium hydroxide to yield 4, 4′-dibenzoyl-azoybenzene ( 5 ) (51%), 4-hydroxy-4′-benzoylazobenzene ( 6 ) and benzoic acid (12% each), and smaller amounts of 4-aminobenzophenone and 4-nitrobenzophenone. Both α-phenyl-2-nitrobenzenemethanol ( 9 ) and 3, 5-dimethyl-4-nitrobenzenemethanol ( 10a ) did not react with 1 M sodium hydroxide, presumably due to steric hindrance. α-(p-Nitrophenyl)-4-pyridinemethanol ( 14 ) and its N-oxide 11 with 1 M sodium hydroxide yielded 4,4′-diaroylazoxybenzenes 15a and 12a , respectively, 4,4′-diaroylazobenzenes 15b and 12b , respectively, as well as 4-hydroxy-4′-aroylazobenzenes 16 and 13 , respectively. The relative reaction rates were 11 > 14 > 3 . Studies with 11 showed that the nitro group is involved in the redox reaction in preference to the N-oxide group.     

Synthesis of 1-phenylseleno-1-vinyl and 1-methylseleno-1-vinyl cyclopropanes by formal dehydration of β-hydroxycyclopropyl selenides

Unknown 1-phenylseleno-1-vinyl and 1-methylseleno-1-vinyl cyclopropanes are readily available from β-hydroxycyclopropyl selenides using (carboxysulfamoyl.) triethylammonium hydroxide inner salt methyl ester. Limitations of the method are presented.