Reactions of 2,3-bishydroxyimino-1,2,3,4-tetrahydro-quinoxalines and 2,3-bishydroxyimino-2,3-dihydro-4H-1,4-benzoxazines with ethyl chloroformate

Bishydroxyiminoquinoxalines 3a-b react with ethyl chloroformate 4 to afford the furazano[3,4-b]quinoxalines 5a-b . Bishydroxyiminobenzoxazines 6a-c on treatment with 4 are converted into the fused oxadiazolones 7a-c and 8a-c along with the bisethoxycarbonyloxyimino-derivatives 9a-c . From the reactions of 4 with the oxanilide dioximes 12a-c compounds 13a-c and 14a-b are obtained.     

The preparation of optically active α-amino 4H-[1,2,4]oxadiazol-5-ones from optically active α-amino acids

Optically active α-amino 4H-[1,2,4]oxadiazol-5-ones (oxadiazolones) were prepared from optically active α-amino acids in five synthetic steps. The oxadiazolone moiety serves as a bioisosteric replacement for the carboxylic acid. Incorporation of an α-amino oxadiazolone into a representative dipeptide mimic is described.     

Preparation and properties of some α-aza-amino-acid derivatives,their possible use in peptide synthesis

Some derivatives of azaglycine and azaphenylalanine are described. Esters of acetyl- and benzoyl-aza-amino-acids rapidly cyclise to stable oxadiazolones and it is concluded that similar derivatives would be unsuitable for aza-peptide synthesis. t-Butyloxycarbonyl-azaglycine azide was too unreactive for use in peptide synthesis. Benzoyl-azaglycylphenylalanine ethyl ester and acetyl-azaphenylalanylphenylalanine ethyl ester were prepared by coupling benzoyl hydrazide and N-acetyl-N'-benzylhydrazide respectively with 2,4-dinitrophenyloxycarbonyl-phenylalanine ethyl ester.     

Darstellung und Strukturen einiger N-(Tri-t-butoxysilyl)anilin-Derivate

Formation and Structures of N-(tri-t-butoxysilyl)aniline Compounds Para-substituted N-(tri-t-butoxysilyl)anilines (t-BuO)₃SiNRC₄H₄X-p, R = H, CH₃, with substituents of high electron affinity (X = CN, NO₂) were prepared by a one-pot reaction of tri-t-butoxychlorsilane, potassium t-butanolate and substituted anilines. Corresponding compounds with substituents of low electron affinity (X = OMe, H) preferably were prepared by metalation of anilines with sodium amide. Four crystal structures were determined. N-(tri-t-butoxysilyl)-p-nitro-aniline, N-methyl-(N-tri-t-butoxysilyl)-p-nitroaniline and N-(tri-t-butoxysilyl)-p-cyanoaniline crystallize at 298 K monoclinically, N-(tri-t-butoxysilyl)aniline crystallizes orthorhombically.     

Verdazyl radicals as substrates for organic synthesis: a synthesis of 3-methyl-5-aryl-1,3,4-oxadiazolones

The synthesis of oxadiazolones under hydrolytic conditions is described for a series of 3-methyl-5-aryl-1,3,4-oxadiazolone compounds. The unique starting materials for the hydrolysis reaction are obtained from efficient 1,3-dipolar cycloaddition reactions of styrene and azomethine imine dipoles derived from verdazyl radicals via a disproportionation reaction. A proposed mechanism for the formation of these biologically relevant oxadiazolones includes an opening of the tetrazinone ring followed by a 5-exo-trig ring closure. In support of the mechanism, in one case the ring-opened intermediate was isolated and subsequently treated with acid to give the relevant oxadiazolone.     

Synthesis of certain alkenyl purines and purine analogs

Synthesis of alkenyl derivatives of certain purines and purine analogs is described. Direct alkylation of the sodium salt of 6-chloropurine (1) either with 1-bromo-2-pentene or 4-bromo-2-methyl-2-butene in N,N-dimethylformamide furnished N-7, 4a and N-9, 3a , 3b alkenyl derivatives. Similar alkylation of 2-amino-6-chloropurine (2) provided the corresponding N-7, 4c-4e and N-9, 3c-3e alkenyl derivatives. Acid hydrolysis of these chloro derivatives 3a-3e, 4a,c-e furnished the corresponding alkenyl hypoxan-thines 6a, 6b and 7a or alkenyl guanines 6c-6e and 7c-7e. Treatment of 3a-3d with thiourea in absolute ethanol provided the corresponding 6-thio derivatives 5a-5d. Alkylation of the sodium salt of either purine-6-carboxamide (8) or 1,2,4-triazole-3-carboxamide (10) gave mainly one isomer 9a, 9b and 11a, 11b. The direct alkylation of pyrrolo[2,3-d]pyrimidin-4(3H)-one (12) gave N-3 alkenyl derivatives 13a, 13b , and the N-7 alkenyl derivatives 16a, 16b have been prepared starting from the 4-chloro derivative 14 . Synthesis of 2-amino-7-(2-penten-1-yl)pyrrolo[2,3-d]pyrimidin-4(3H)-one (19a) has been accomplished starting from 2-amino-4-methoxypyrrolo[2,3-d]pyrimidine (17) . These alkenyl derivatives were found to be devoid of anti-HCMV activity in vitro.     

Synthesis of some 4H,10H[1]benzoxepino[3,4-c]pyrazol-4-one derivatives

1H(or 2H)4H10H[1]Benzoxepino[3,4-c]pyrazol-4-ones were prepared from phenoxymethylpyrazolecarboxylic acids which in turn were synthesized from simple starting materials. Different pathways to allow the predominant formation of the N-1 or N-2 substituted derivatives are described. The isomeric 1 or 2-substituted structures were supported by ¹³C-nmr.     

POLY [N-(4-PYRIDINIUM DICHROMATE)-P-STYRENE SULPHONAMIDE] AS AN EFFICIENT REAGENT FOR OXIDATION OF ALCOHOLS

POLY [N-(4-PYRIDINIUM DICHROMATE)-P-STYRENE SULPHONAMIDE] is readily prepared. It is a stable, mild, and efficient oxidizing reagent that can be used for oxidation of different alcohols to their corresponding carbonyl compounds in approtic solvents. This polymer can be synthesized from the reaction between poly [N-(4-pyridyl)-p-styrene sulphonamide] and CrO ₃ in a minimum amount of water. The latter polymer was prepared by free radical polymerization of [N-(4-pyridyl)-p-styrene sulphonamide] by using azobis(isobutyronitrile) (AIBN) as an initiator. N-(4-pyridyl)-p-styrene sulphonamide was synthesized from commercial 4-vinyl benzene sulphonic acid sodium salt and 4-amino pyridine. POLY [N-(4-PYRIDINIUM DICHROMATE)-P-STYRENE SULPHONAMIDE] can oxidize both aliphatic and aromatic alcohols in good yields at a temperature of 38°C and in CH ₂ Cl ₂ as solvent. One advantage in using this reagent is the mild condition of the reaction system. The synthesized compounds including polymeric reagent and carbonyl compounds were identified by HNMR and IR spectroscopy.     

Synthesis and photochemical degradation of N-arylmethyl derivatives of the herbicide 3-amino-1,2,4-triazole

Reaction of an arylmethyl halide with 3-amino-1,2,4-triazole ( 1 ) allows the preparation of the three N-aryl-methyl derivatives of 1 bearing the substituent on the heterocyclic nitrogen atoms. In basic medium (methoxide anion in DMF or methanol, or in benzene by phase transfer catalysis), the isomers 3 and 5 substituted at N-1 and N-2 respectively are obtained, while the isomer 4 is isolated from neutral medium (DMF). The isomers 3 and 4 may be also prepared by cyclization of appropriate formylguanidinium derivatives. 3-Arylmethylamino-1,2,4-triazoles 2 may be obtained through reaction of 3-chloro-1,2,4-triazole ( 6 ) with arylmethylamines. Photolysis of the N-arylmethyl-3-amino-1,2,4-triazoles 2-5 in methanol or water-methanol mixture, induces homolytic and heterolytic cleavage of the arylmethyl-C-N bond giving rise to 3-amino-1,2,4-triazole ( 1 ). Thus, compounds 2-5 with arylmethyl groups able to absorb solar light may be considered as potential photoactivatable herbicides.     

2-Acylamino-3-chloroacrylonitriles,Promising Reagents for Heterocyclization

2-Acylamino-3-chloroacrylonitriles prepared by treating available N-(1,2,2-trichloroethyl)amides of carboxylic acids with sodium cyanide readily undergo cyclization in the presence of excess hydrazine hydrate. The cyclization products, 5-amino-4-acylaminopyrazoles, were applied to the synthesis of new imidazo[4,5-c]pyrazole and pyrazolo[1,5-a]pyrimidine derivatives.     

Synthèse et réactivité de dihydrotriazines et de dihydrotriazolotriazines

Generally, 4,5-dihydro-3triazinones have been prepared by a basic hydrolysis of 3-methylmercapto-4,5-dihydrotriazines. Of the serveral methylation methods, namely, diazomethane, methyliodide, dimethyl sulfate all in the presence of sodium methylate or silver carbonate, only methyl bromide in the presence of phase transfer catalyst was sucessful in producing all of the N-2 and/or N-4 methylate compounds. Two unequivocal syntheses of dihydrotriazolo[4,3-b]triazine are reported.     

New isomeric N-substituted hydrazones of 2-, 3-and 4-pyridinecarboxaldehydes

Eighteen compounds unknown in the literature, N-(E)-stilbenyloxyalkylcarbonyl- and N-(E)-stilbenyloxyalkylcarbonylaminoalkylcarbonyl-substituted hydrazones of 2-, 3- and 4-pyridinecarboxaldehydes have been prepared. The stereochemical behavior of these compounds in dimethyl-d₆ sulfoxide solution has been studied by ¹H-nmr technique. The E geometrical isomers and cisltrans amide conformers have been found for N-substituted-hydrazones 1–16 .     

A new synthesis of phthalimidines

A new synthesis of phthalimidines is described. 3-Acyloxy-2-aryl- and 2-acylamino-3-acyloxyphthalimidines were prepared by the reaction of 3-arylaminophthalides or o-formylbenzoic acid acylhydrazones with acetic or propionic anhydrides. Their reactions with O-, N-, S-, and C-nucleophiles were studied. The structure of 2-acetyl(cyanoacetyl)amino-3-acetoxyindolin-1-one was confirmed by X-ray diffraction analysis.     

Synthesis and properties of conformationally locked 1,3-bisalkyl-7-deazaxanthine 2′-deoxy-d-ribofuranosides

1,3-Dimethyl-7-deazaxanthine 2′-deoxyribofuranosides 1a and 6a and their N-3 isopropyl congeners 1b and 6b have been prepared employing the nucleobase anions 7a or 7b and 2-deoxy-3,5-di-O-(p-toluoyl)-α-D-erythropentofuranosyl chloride ( 8 ) upon glycosylation. The reaction was not stereoselective as found in case of other pyrrolo[2,3-d]pyrimidine nucleosides induced by the bulky N-3 substituent. Configuration of anomers was established by ¹H-nmr nOe difference spectroscopy. Those data also indicated that the conformation around the N-glycosylic bond was locked by the bulky N-3 substituent. Contrary to the purine nucleoside such as wyosine ( 2a ) the hydrolytic stability of the N-glycosylic bond of the pyrrolo[2,3-d]pyrimidine nucleosides was increased by N-3 alkylation. Moreover, it was shown by ¹⁵N-nmr spectroscopy that different to purine nucleosides the aglycon was not protonated in acidic medium. As a result the N-glycosylic bond hydrolysis did not follow an A-1 but an A-2 mechanism.     

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.     

Preparation and alkylation of 1,5-dihydro-3H-1,2,4-thiadiazolo[3,4-b]quinazolin-5-one 2,2-dioxides

1,5-Dihydro-3H-1,2,4-thiadiazolo[3,4-b]quinazolin-5-one 2,2-dioxides ( 3 ) are prepared by reaction of isatoic anhydrides with methyl N-(chloromethanesulfonyl)carbamimidothioate ( 6 ). The sodium salt of 3a , generated with sodium hydride in N,N-dimethylformamide, is alkylated excusively on N-10. An improved preparation of 6 is described, utilizing a two-phase sulfonylation.     

Synthesis of N-α-Fmoc-N-ε-Tetrabutyl Ester-EDTA-L-lysine: An Amino Acid Analog to Prepare Affinity Cleaving Peptides

Synthesis of an amino acid analog. N-α-Fmoc-N-ε-tetrabutyl ester EDTA-L-Lysine, suitable for incorporating a strong metal binding site at any internal sequence position in a peptide is described. To overcome the solubility and purification problems during the synthesis, we prepared esters of N-α-Fmoc-N-ε-Boc-L-Lysine. Since the t- butyl group on the amino acid is acid labile and Fmoc group at α-amino group is base sensitive, protection of N-α-Fmoc-N-ε-Boc-L-Lysine requires an ester that can be prepared and removed under neutral conditions. A scheme for selective protection and deprotection of lysine is reported.     

Synthesis and spectroscopic studies of novel mononuclear and binuclear ruthenium(III) complexes with bidentate and tridentate acyclic hydrazones

Nine novel acyclic hydrazone ligands, FINH?=?N-(furylidene)-N′-isonicotinoylhydrazine, FNH?=?N-(furylidene)-N′-nicotinoylhydrazine, PINH?=?N-(pyrienylidene)-N′-isonicotinoylhydrazine, PNH?=?N-(pyrienylidene)-N′-nicotinoylhydrazine, TINH?=?N-(thienylidene)-N′-isonicotinoylhydrazine, TNH?=?N-(thienylidene)-N′-nicotinoylhydrazine, FSH?=?N-(furylidene)-N′-salicyloylhydrazine, PSH?=?N-(pyrienylidene)-N′-salicyloylhydrazine and TSH?=?N-(thienylidene)-N′-salicyloylhydrazine, have been synthesized. Their corresponding mononuclear and binuclear ruthenium(III) complexes have been prepared by the reaction of the ligand with RuCl₃·3H₂O in 1?:?2 and 2?:?2 molar ratio and are characterized by elemental analyses, thermogravimetric analyses (TGA and DTG), IR, electronic, magnetic susceptibility and electrical conductance measurements. Electronic spectra and magnetic susceptibility measurements of the solid complexes (both mono- and binuclear) indicate an octahedral geometry around ruthenium(III). Particular emphasis is given to the binuclear complexes in which FSH, PSH and TSH behave as tridentate ligands and chloride bridges the Ru(III) ions. Conductance measurements show the mononuclear complexes are electrolytic and binuclear complexes are of non-electrolytic. The fungicidal activities of the ligands and metal complexes against Fusarium oxysporium and Aspergillus niger are described.     

Synthesis and polymerization of N-(p-vinylbenzyl)-3-carbamoyl-1,4-dihydropyridine and redox behavior of the oligomer

In order to prepare a soluble dihydropyridine-type redox polymer, N-(p-vinylbenzyl)-3-carbamoyl-1,4-dihydropyridine was synthesized and characterized by elemental analysis, infrared spectroscopy, and nuclear magnetic resonance spectroscopy. The polymerization of the vinyl monomer in N,N-dimethylformamide or chloroform was also studied. Only oligomers were obtained by radical polymerization. The reduction of various compounds by the oligomer thus prepared was examined in heterogeneous or homogeneous solution.     

Preparation and alkylation of regioisomeric tetrahydrophthalimide-substituted indolin-2(3H)-ones

A series of novel regioisomeric tetrahydrophthalimide-substituted indolin-2-ones has been prepared via the Sommelet-Hauser type cyclization of appropriately substituted anilines as potential herbicides. The resultant indolin-2-ones were then regioselectively alkylated at N-1 and C-3 to give 1,3,3-trisubstituted indolin-2-ones. The most active series was also prepared by the bis-nitration of m-fluorophenylacetic acid followed by reduction and cyclization to give 6-amino-5-fluoroindolin-2-one. Elaboration to the tetrahydrophthalimide-substituted indolin-2-one was followed by C- and N-alkylation to give the desired compounds.