Synthesis and single-crystal X-ray diffraction analysis of 2-sulfamoyladenosine (6-amino-9-β-D-ribofuranosylpurine-2-sulfonamide)

2-Amino-9-β-D-ribofuranosylpurine-2-sulfonamide (2-sulfamoyladenosine, 4 ), a congener of sulfonosine ( 3 ), was synthesized by four different routes. Acid catalyzed fusion of 6-chloropurine-2-sulfonyl fluoride ( 5 ) with 1,2,3,5-tetra-O-acetyl-β-D-ribofuranose ( 8 ) gave a good yield of 6-chloro-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)purine-2-sulfonyl fluoride ( 9 ). Ammonolysis of 9 furnished 4 . Lewis acid catalyzed glycosylation of the trimethylsilyl derivative of either 6-chloropurine-2-sulfonamide ( 6 ) or 6-aminopurine-2-sulfonamide ( 7 ) with 8 gave the corresponding N9-glycosylated products, 10 and 11 , respectively, which on ammonolysis gave 4 . Amination of 2-thioadenosine ( 12 ) with chloramine solution gave the sulfenamide derivative 13 , which on subsequent oxidation with m-chloroperoxybenzoic acid furnished an alternate route to 4 . The structure of 4 was established by single-crystal X-ray diffraction studies. 2-Sulfamoyladenosine ( 4 ) is devoid of significant inhibitory activity against L1210 leukemia in mice.     

Synthesis of [1,5-A]Pyrimidinone Ring Derivatives

Cyclodehydrogenation of the benzalhydrazino derivatives 5 and 6 gave 6-cyano-7-(4-methoxyphenyl)- 2-phenyl-5-oxo-1,2,4-triazolo[1,5-a]pyrimidine (8) and 6-cyano-7-(4-methoxyphenyl)-4-methyl-2-phenyl- 5-oxo-1,2,4-triazolo[1,5-a]pyrimidine (9) respectively. Melhylation, acetylation and benzylation of 8 gave the corresponding N-methyl, acetyl and benzyl derivatives 10-12 . Methylation of 5 with dimethylsulfate gave 2-benzalhydrazino-5-cyano-3-methyl-6-(4-methoxyphenyl)-3,4-dihydropyrimidin-4-one (6) , of which the reaction with acetic anhydride in pyridine afforded the N-acetylbenzalhydrazino derivative 15 . The latter was also prepared from acetylation of 5 followed by medthylation with iodomethane. Acetylation of 5 with boiling acetic anhydride afforded the diacetyl derivative 16 , whereas its benzylation gave the mono-N-benzyl derivative 14 .     

Studies on imidazole derivatives and related compounds. I. Synthesis of novel antineoplastic derivatives of 4-carbamoylimidazolium-5-olate

Acylation of 4-carbamoylimidazolium-5-olate ( 2 ) with a variety of acid chlorides produced 4(5)-carbamoyl-1H-imidazol-5-(4)yl acid carboxylates ( 3a-j ). Treatment of esters 3a,c with sodium hydroxide gave imides, 4a,c . Methylation of 3a and 2 with diazomethane gave the N-3 methyl derivative ( 6 ) and a mixture of the N-3, O-dimethyl derivative ( 9 ), the N-1, N-3-dimethyl derivative ( 10 ) and the O-methyl derivative ( 11 ), respectively. 5-Carbamoyl-1-methylimidazolium-4-olate ( 7 ) and its 4-carbamoyl isomer ( 16 ) were prepared from 2-aminopropanediamides 8 and 15 , respectively. Treatment of the imidazolium compound ( 10 ) with aqueous potassium hydroxide gave the recyclized product, 1-methyl-5-methylcarbamoylimidazolium 4-olate ( 18 ). Methyl derivatives 6, 7 , and 9 except 16 demonstrated the complete lack of antitumor activity against Lewis lung carcinoma or sarcoma 180 in mice.     

Synthesis of 2-aza analog of rosoxacin

Diazotization of 2-nitro-4-(4-pyridinyl)aniline ( 4 ) in hydrobromic acid gave the corresponding bromo derivative 5 which was treated with cuprous cyanide to give the benzonitrile derivative 6 which in turn was converted to 2-nitroacetophenone derivative 9 . Reduction of 9 followed by diazotization of the resulting amine 10 gave 7-(4-pyridinyl)cinnolin-4(1H)-one ( 11 ) which was subsequently converted to 1 -ethyl-1,4-dihydro-4-oxo-7-(4-pyridinyl)cinnoline-3-carboxylic acid ( 14 ) in three steps.     

Furopyridines. V. A simple synthesis of furo[2,3-c]pyridine and its 2-and 3-methyl derivatives

A simple synthesis of furo[2,3-c]pyridine and its 2- and 3-methyl derivatives from ethyl 3-hydroxyisonicotinate ( 2 ) is described. The hydroxy ester 2 was O-alkylated with ethyl bromoacetate or ethyl 2-bromopropionate to give the diester 3a or 3b . Cyclization of compound 3a afforded ethyl 3-hydroxyfuro [2,3-c]pyridine-2-carboxylate ( 4 ) which was hydrolyzed and decarboxylated to give furo[2,3-c]pyridin-3(2H)-one ( 5a ). Cyclization of 3b gave the 2-methyl derivative 5b . Reduction of 5a and 5b with sodium borohydride yielded the corresponding hydroxy derivative 6a and 6b , respectively, which were dehydrated with phosphoric acid to give furo[2,3-c]pyridine ( 7a ) and its 2-methyl derivative 7b . 4-Acetylpyridin-3-ol ( 8 ) was O-alkylated with ethyl bromoacetate to give ethyl 2-(4-acetyl-3-pyridyloxy) acetate ( 9 ). Saponification of compound 9 , and the subsequent intramolecular Perkin reaction gave 3-methylfuro[2,3-c]pyridine ( 10 ). Cyclization of 9 with sodium ethoxide gave 3-methylfuro[2,3-c]pyridine-2-carboxylic acid, which in turn was decarboxylated to give compound 10 .     

1,3-Dipolar cycloadditions of diazoalkanes to pyridazine derivatives. Thermal 1,5-sigmatropic rearrangement of methyl groups in 3,3-dimethyl-3H-pyrazolo[3,4-d]pyridazine derivatives

Thermal 1,5-sigmatropic rearrangements of one of the methyl group attached at position 3 of 3,3-dimethyl-3H-pyrazolo[3,4-d]pyridazin-4(5H)-ones 1–3 taking place either in a clock-wise or anti-clockwise direction gave N₂-methylated products 4–6 and C_3a-methylated products 7– 9 . The -7(6)-one derivative 10 and -4,7(5H,6H)-dione derivative 12 gave only N₂-methylated products 11 and 13 respectively, and 1,2-dihydro derivative 14 produced after elimination of methane, 15 .     

Furopyridines. XVII . Cyanation,chlorination and nitration of furo[3,2-b]pyridine N-oxide

The N-oxide 2 of furo[3,2-b]pyridine ( 1 ) was cyanated by the Reissert-Henze reaction with potassium cyanide and benzoyl chloride to give 5-cyano derivative 3 , which was converted to the carboxamide 4 , carboxylic acid 5 , ethyl ester 6 and ethyl imidate 8 . Chlorination of 2 with phosphorus oxychloride yielded 2-9a , 3- 9b , 5- 9c and 7-chloro derivative 9d . Reaction of 9d with sodium methoxide, pyrrolidine, N,N-dimethylformamide and ethyl cyanoacetate afforded 7-methoxy- 10 , 7-(1-pyrrolidyl)- 11 and 7-dimethylaminofuro[3,2-b]pyridine ( 14 ) and 7-(1-cyano-1-ethoxy-carbonyl)methylene-4,7-dihydrofuro[3,2-b]pyridine ( 12 ). Nitration of 2 with a mixture of fuming nitric acid and sulfuric acid gave 2-nitrofuro[3,2-b]pyridine N-oxide ( 15 ).     

Synthesis of 3-(β-D-ribofuranosyl)pyrazolo[3,2-i]-purine derivatives and their cytotoxic activities

9-Amino-3-(β-D-ribofuranosyl)pyrazolo[3,2-i|purine ( 6 ) has been prepared from a fully protected 3-(β-D-ribofuranosyl)pyrazolo[3,2-i]purine ( 2 ) and the 9-bromo substituted derivative 3 by nitration, followed by reduction. Reaction of 9-bromo-3-(β-D-ribofuranosyl)pyrazolo[3,2-i)purine ( 1b ) with alkali gave the (pyrazol-3-yl)imidazole derivative, followed by diazocyclization with sodium nitrate to give 9-bromo-3-(β-D-ribofuran-osyl)imidazolo[4,5-d]pyrazolo[2,3-c][1,2,3]triazine ( 10 ) after deacetylation. Compounds 6 and 10 exhibited cytotoxic activity against leukemia cells.     

Furopyridines. VI. Preparation and reactions of 2- and 3-substituted furo[2,3-b]pyridines

This paper describes the synthesis and chemical properties of some 2- and 3-substituted furo[2,3-b]pyridines. Reaction of ethyl 2-chloronicotinate 1 with sodium ethoxycarbonylmethoxide or 1-ethoxycarbonyl-1-ethoxide gave β-keto ester 2 or ketone 5 , respectively. Ketonic hydrolysis of 2 afforded ketone 3, from which furo[2,3-b]pyridine 4 was obtained by the method of Sliwa. While, 2-methyl derivative 7 was prepared from 5 by reduction, O-acetylation and the subsequent pyrolysis. Reaction of ketone 3 with methyllithium gave tertiary alcohol 8 which was O-acetylated and pyrolyzed to give 3-methyl derivative 9 . Formylation of 4 , via lithio intermediate, with DMF yielded 2-formyl derivative 10 , from which 7 , was obtained by Wolff-Kishner reduction. Dehydration of the oxime 11 of 10 gave 2-cyano derivative 12 , which was hydrolyzed to give 2-carboxylic acid 13 . Reaction of 3-bromo compound 14 with copper(I) cyanide gave 3-cyano derivative 15 . Alkaline hydrolysis of 15 afforded compound 16 and 17 , while acidic hydrolysis gave carboxamide 18 . Reduction of 15 with DIBAL-H afforded 3-formyl derivative 19 . Wolff-Kishner reduction of 19 gave no reduction product 9 but hydrazone 20 . Reduction of tosylhydrazone 21 with sodium borohydride in methanol afforded 3-methoxymethylfuro[2,3-b]pyridine 22 .     

A Novel,Degraded Polyketidic Lactone,Leptosphaerolide, and Its Likely Diketone Precursor,Leptosphaerodione. Isolation from Cultures of the Marine Ascomycete Leptosphaeria oraemaris (LINDER)

Acetone extraction of cultures of the marine ascomycete Leptosphaeria oraemaris (LINDER) on cornmeal disk gave the novel polyketide derivative leptosphaerolide ( = (+)-7-[(1E)-l,3-dimethylpent-1-enyl]-10-hydroxy-3-methoxybenzo[1,2-b:5,4-c′]dipyran-2(9H)-one; (4+)-8) besides the o-dihydroquinone 3-[(1E)-1,3-dimethylpent-1-euyl]-8,10-dihydroxy-7-methoxy-8-(2-oxopropyl)-1H-naphtho[2,3-c]pyran-9(8H)-one ( 1 ) as a 10:9 mixture of epimers. retro-Aldol reaction of 1 gave leptosphaerodione ( = (?)-3-[(1E)-1,3-dimethylpent-1-enyl]-10-hydroxy-7-methoxy-1H-naphtho[2,3-c]pyran-8,9(8H)-dione; (?)-6) which was also present in small amounts in the extracts and which gave 1 on reaction with acetone. It is thus likely that 1 is an artefact of the extraction by acetone. Biogenetically (+)-8 might derive from (?)-6 via an unusual oxidation with loss of CO₂.     

Ringschlussreaktionen mit 2-(β-Styryl)benzylaminen 5-Phenyl-1H-2-benzazepine. 23. Mitteilung über siebengliedrige Heterocyclen

Cyclization reactions with 2-(β-styryl)benzylamines 5-Phenyl-1H-2-benzazepines Cyclization of the urea derivative 3 with POCl₃ to give 2-(4-methyl-1-piperazinyl)-4-phenylquinoline ( 4 ) was carried out in analogy to the quinoline synthesis of Foulds & Robinson. This reaction was used for the preparation of 2-benzazepines. The trisubstituted ureas 6 and 8 , derived from the 2-(β-styryl)-benzylamines 5 , were cyclized with POCl₃ to yield the 3-amino-5-phenyl-1H-2-benzazepines 7 and 9 , respectively. Similarly, cyclization of the corresponding acetyl-derivatives 10 gave the 3-methyl-5-phenyl-1H-2-benzazepines 12 . On the other hand, the disubstituted urea 15 , cyclized under the same conditions to the 1-methyl-1-phenylisoindoline derivative 16 , and 2-(β-styryl)benzylamine ( 5a ) on treatment with phosgene gave the isoindoline 17 in an analogous manner.     

Furopyridines. II. Bromination and nitration of furo[2,3-b]-, furo[3,2-b]-, furo[2,3-c]- and furo[3,2-c]pyridine

In order to reveal the reactivities of furopyridines, we undertook bromination and nitration of four furopyridines ( 1, 2, 3 and 4 ) whose chemical properties had been almost unknown. Bromination of 1, 2, 3 and 4 gave the corresponding trans-2,3-dibromo-2,3-dihydro derivatives 6, 8, 10 and 12 , respectively, which were converted to 3-bromofuropyridines 7, 9, 11 and 13 by treatment with sodium hydroxide in aqueous methanol. Nitration of 1 with a mixture of fuming nitric acid and sulfuric acid afforded a mixture of addition products 14a, 14b and 14c and 2-nitro derivative 15 . Both 14a and 14b were easily converted to 15 by treatment with sodium bicarbonate. Compound 2 was nitrated to give a mixture of cis- and trans-2-nitro-3-hydroxy-2,3-dihydro derivative 16a and 16b and 2-nitro derivative 17 . The cis isomer 16a was transformed to the trans isomer 16b by refluxing on silica gel in ethyl acetate. Compound 16b was dehydrated with acetic anhydride to give 17 . Nitration of 3 gave a nitrolic acid derivative 20 . Nitration of 4 gave a mixture of 2-nitro derivative 22 and 3-(trinitromethyl)pyridin-4-ol ( 23 ). The structures of 20 and 23 were established by single crystal X-ray analysis. The differences of behavior observed in these reactions are discussed in connection with the results of the determination of pKa values and the relative reactivities of deuteriodeprotonation of these furopyridines.     

Design and Synthesis of Aminoglycoside Antibiotics to Selectively Target 16S Ribosomal RNA Position 1408

The glucopyranosyl moiety (ring I) of paromomycin was modified in a search for novel aminoglycoside antibiotics. The key intermediates were the 4′,6′‐O‐benzylidenated N‐Boc derivative 3 and the azido analogue 18 . The bromobenzoates 4 and 19 were prepared by treating the benzylidene acetals 3 and 18 , respectively, with N‐bromosuccinimide (NBS), and the diol 8 was obtained by hydrogenolysis of 3. The C(6′)‐deoxy derivative 5 was obtained from 4 by treatment with Bu₃SnH. Selective fluorodehydroxylation of 8 gave the fluoro derivative 9. The pseudotrisaccharide 13 was obtained by reductive fragmentaion of the iodo compound 12 obtained from the bromobenzoate 4 . The 3′,6′‐anhydro derivative 20 was obtained upon deacetylation of 19. Standard deprotection gave the C(6′)‐deoxy compound 7 , the fluoro compound 11 , the pseudotrisaccharide 15 , and the 3′,6′‐anhydro‐paromomycin 22 . As compared to paromomycin, the C(6′)‐deoxy and fluorodeoxy derivatives 7 and 11 showed a lower activity against both wild type 1408A and 1408G mutant ribosomes. A lower activity was also found for the 3′,6′‐anhydro derivative 22 and for the pseudotrisaccharide 15 .     

Directed regiospecificity of 1,3-dipolar cycloaddition of 2-diazopropane to 4- and 5-substituted pyridazin-3(2H)-ones

6-Methoxy-2-methylpyridazin-3(2H)-one ( 1 ) gave with 2-diazopropane ( 8 ) a mixture of 3H-pyrazolo[3,4-d]-pyridazin-4(5H)-one derivative 12 , as the main product, and -7(6H)-one derivative 10 , as the minor product. On the other hand, 4-substituted pyridazin-3(2H)-ones 2, 3 , and 4 gave 3H-pyrazolo[3,4-d]pyridazin-7(6H)-one 10 , exclusively, while 5-substituted pyridazin-3(2H)-ones 5, 6 , and 7 produced only the isomeric 3H-pyrazolo[3,4-H]pyridazin-4(5H)-one 12 . The 5-phenylsulfonyl derivative 13 gave with 8 by elimination of a molecule of nitrogen, followed by rearrangement, 1,2-diazepine derivative 15 and with an excess of 8 3H-pyrazolo[3,4-d][1,2]diazepine derivative 16. 1 ,2-Dimethylpyridazine-3,6-(1H,2H)-dione and its derivatives 18 and 19 produced 3H-pyrazolo[3,4-d]pyridazine-4,7(5H,6H)-dione derivative 23 , while from 17 and 1-diazoindane ( 24 ) the spiro compound 27 was obtained. The 1,2-dihydro and 3a,7a-dihydro intermediates 21 and 25 were isolated.     

Synthesis of certain 3-alkoxy-1-β-D-ribofuranosylpyrazolo[3,4-d]pyrimidines structurally related to adenosine,inosine and guanosine

Several 3-alkoxysubstituted pyrazolo[3,4-d]pyrimidine ribonucleosides structurally related to adenosine, inosine and guanosine have been prepared by the direct glycosylation of preformed aglycon precursor containing a 3-alkoxy substituent. Ring closure of 5(3)-amino-3(5)-ethoxypyrazole-4-carboxamide ( 6b ) with either formamide or potassium ethyl xanthate gave 3-ethoxyallopurinol ( 7b ) and 3-ethoxy-6-thioxopyrazolo[3,4-d]-pyrimidin-4(5H,7H)-one ( 10 ), respectively. Methylation of 10 gave the corresponding 6-methylthio derivative 15 . Similar ring annulation of 5(3)-methoxypyrazole-4-carboxamide ( 6a ) with formamide afforded 3-methoxyallopurinol ( 7a ). Treatment of 5(3)-amino-3(5)-methoxypyrazole-4-carbonitrile ( 5a ) with formamidine acetate furnished 4-amino-3-methoxypyrazolo[3,4-d]pyrimidine ( 4 ). High-temperature glycosylation of 7b with 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose in the presence of boron trifluoride etherate gave a 2:1 mixture of N-1 and N-2 glycosyl blocked nucleosides 11b and 13b . Deprotection of 11b and 13b with sodium methoxide gave 3-ethoxy-1-β-D-ribofuranosylpyrazolo[3,4-d]pyrimidin-4(5H)-one ( 12b ) and the corresponding N-2 glycosyl isomer 14b , respectively. Similar glycosylation of either 4 or 7a , and subsequent debenzoylation gave exclusively 4-amino-3-methoxy-1-β-D-ribofuranosylpyrazolo[3,4-d]pyrimidine ( 9 ) and 3-methoxy-1-β-D-ribofuranosylpyrazolo[3,4-d]pyrimidin-4-(5H)-one ( 12a ), respectively. The structural assignment of 12a was made on the basis of single-crystal X-ray analysis. Application of this general glycosylation procedure to 15 gave the corresponding N-1 glycosyl derivative 16 as the sole product, which on debenzoylation afforded 3-ethoxy-6-(methylthio)-1-(3-D-ribofuranosylpyrazolo[3,4-d]pyrimidin-4(5H)-one ( 17 ). Oxidation of 16 and subsequent ammonolysis furnished the guanosine analog 6-arnino-3-ethoxy-1-β-D-ribofuranosylpyrazolo[3,4-d]-pyrimidin-4(5H)-one ( 19 ). Similarly, starting from 3-methoxy-4,6-bis(methylthio)pyrazolo[3,4-d]pyrimidine ( 20 ), 6-amino-3-methoxy-1-β-D-ribofuranosylpyrazolo[3,4-d]pyrimidin-4(5H)-one ( 23 ) was prepared.     

248. Methylation reactions of 30-oxa-(14)-cytochalasanes

For synthetic studies the protection of the hydroxyl groups of phomin (cytochalasin B) ((7S,22R,26R)-7,26-dihydroxy-22-methyl-30-oxa-[14]cytochalasa-6(18), 19^t 27^t-trien-1,29-dion) ( 1 ), the dodecahydro-derivative 2 , and the dihydro-derivative 4 by methylation was investigated. Treatment of 1 with CH₃I/Ag₂O gave the iminoether 6 . The reaction of 4 with CH₂N₂/BF₃ led to the di-O-methyl derivative 8 and to the N-methyl-di-O-methyl derivative 9 , whereas 2 was transformed to the N-methyl-di-O-methyl compound 10 and to the iminoether 11 . NaBH4 reduction of 3 yielded not only 4 but also the epimeric dihydro derivative 5 .     

Synthesis,characterization, and biological activities of some novel thienylpyrido[3′,2′:4,5]thieno[3,2-d]pyrimidines and related heterocycles

3-Cyano-5-ethoxycarbonyl-6-methyl-4-(2′-thienyl)-pyridine-2(1H)-thione ( 1 ) is synthesized and reacted with chloroacetamide or chloroacetonitrile to give 3-amino-5-ethoxycarbonyl-6-methyl-4(2′-thienyl)-thieno[2,3-b]pyridine-2-carboxamide 3a or its 2-carbonitrile analog 3b , respectively. Cyclocondensation of 3a with triethylorthoformate produced the corresponding pyridothienopyrimidineone 4 , which on heating with phosphorus oxychloride gave 4-chloropyrimidine derivative 5 . Compound 5 was used as key intermediate for synthesizing compounds 6 , 9 , 10 , 11 , and 12 upon treatment with some nucleophilic reagents such as thiourea, 5-phenyl-s-triazole-3(1H)-thione, piperidine, morpholine, or hydrazine hydrate, respectively. Reaction of pyridothienopyrimidinethione 6 with N-(4-tolyl)-2-chloroacetamide or ethyl bromoacetate afforded the corresponding S-substituted methylsulfanylpyrimidines 7 or 8 . The condensation of 3b with triethylorthoformate gave azomethine derivative 13 , which was reacted with hydrazine hydrate to give ethyl 3-amino-3,4-dihydro-4-imino-7-methyl-9-(2′-thienyl)pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine-8-carboxylate ( 14 ). Compounds 12 and 14 were used as precursors for synthesizing other new thienylpyridothienopyrimidines as well as isomeric thienyl-s-triazolopyridothieno- pyrimidines. All synthesized compounds were characterized by elemental and spectral analyses such as IR, ¹H NMR, and ¹³C NMR. In addition, majority of synthesized compounds were tested for their antifungal activity against five strains of fungi. Moreover, compounds 3a , 5 , 6 , 8 , and 22 were screened for their anticancer activity against HEPG-2 and MCF-7 cell lines.     

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

α-(Aminornethylene)-9H-purine-6-acetamide ( 3a ) and the corresponding ethyl acetate 9 have been synthesized by catalytic hydrogenation of 6-cyanomethylenepurine derivatives 2 and 7 which were obtained by the substitution of 6-chloropurine derivatives with α-cyanoacetamide and ethyl cyanoacetate, respectively. Substitution of α-(aminomethylene)-9-(tetrahydrofuran)-9H-purine-6-acetamide ( 3b ) with amines gave the corresponding N-alkyl- and N-arylamines 5 , which were treated with acid to give N-substituted α-(aminomethylene)-9H-purine-6-acetamides 6 . Substitution of 9 with amines gave the corresponding N-alkyl- and N-aryl substituted amines 10 .     

Novel polycyclic heterocycles. X. Synthesis of 3-amino derivatives derived from 1,2-dihydro-l 1 (trifluoromethyl)-3H,7H-quino [8,1-cd][ 1,5]benzoxazepin-3-one

The reactions of the tetracyclic ketone, 1,2-dihydro-11-(trifluoromethyl)-3H,7H-quino[8,1-cd] [1,5]benzoxazepin-3-one ( 1 ) with pyrrolidine, piperazine, N-methylpiperazine, and dimethyl-amine gave the enamines 2, 13, 11 , and 4 . These were reduced with sodium borohydride to the corresponding 3-amino derivatives 3, 14, 12 , and 5 . The 3-(2-hydroxyethylpiperazino) derivative ( 8 ) was obtained from the 3-chloro compound ( 7 ); 7 was prepared from the carbinol ( 6 ). The 3-NH₂ derivative ( 10 ) was obtained by reduction of the oxime ( 9 ). In 3, 5, 6, 7, 8, 10, 12 , and 14 , the -OCH₂ protons were non-equivalent, since in the pmr spectrum of each of these compounds there was seen a symmetrical, perturbed AB quartet, with a common JAB of 12 cps, that must be attributed to geminal interproton coupling. This phenomenon had not previously been observed with 1, 9 , or the enamines, since in their pmr spectra, the -OCH₂ protons had invariably been seen as singlets.     

Synthesis of Some New Heterocycles Derived from Phenylacetyl Isothiocyanate

Phenylacetyl isothiocyanate (1) was reacted with benzoyl hydrazine (2a) in acetonitrile to give thiosemicarbazide derivative 3 which was cyclized by polyphosphoric acid to give 1,2,4-triazoline-5-thione derivative 4. Treatment of 1 with thiosemicarbazide (2b) yielded another 1,2,4-triazoline-5-thione derivative 5. Similar treatment of 1 with phenyl hydrazine (2c) in acetonitrile gave a differently substituted 1,2,4-triazoline-5-thione derivative 6 in one pot-reaction. On the other hand, when the reaction was carried out in acetone, a mixture of 6 and thiadiazolidine derivative 7 was obtained. However, reaction of 1 with hydrazine hydrate (2d) gave hydrazine derivative 8. Reaction of isothiocyanate 1 with anthranilic acid (9) gave benzo[d][1,3,6]oxazin-1-one derivative 10. Treatment of 1 with 2-aminothiophenol (11a), 2-aminophenol (11b) or o-phenylenediamine (11c) produced benzothiazole derivative 12a, benzoxazole derivative 12b and benzimidazole derivative 12c, respectively. The structures of all the products were confirmed by micro-analytical and spectral data.