Synthesis of 3-substituted 2-oxo-1,4-thiazines and evaluation of their protective effect against endotoxin shock in mouse.

5-Methyl-2,3-dioxo-2H,4H-1,4-thiazine (7) was obtained by the oxidation of 5-methyl-2H-1,4-thiazin-3(4H)-one (5) with m-chloroperbenzoic acid in MeOH, followed by acid hydrolysis of the resulting 2,2-dimethoxy-1,4-thiazine (6). 3-Chloro-2-oxo-1,4-thiazine (10), which was obtained from 7 by heating with phosphorous oxychloride, reacted with various nucleophiles to give 3-substituted 2-oxo-1,4-thiazines (11a--y). Some of these 2-oxo-1,4-thiazines, 11a--b, e, o and r--s, showed a protective effect against endotoxin shock in D-galactosamine-sensitized mice.     

The use of the wittig reaction in the modification of purine nucleosides

The Pfitzner-Moffatt oxidation of 6-chloro-9-(2,3-O-isopropylidene-β-D-ribofuranosyl)purine, 9-(2,3-O-isopropylidene-β-D-ribofuranosyl)-6-(methylthio)purine, and 2′,3′-O-isopropylideneadenosine gave the corresponding 5′-aldehydes (3, 13, and 4), which were allowed to react with a number of Wittig ylids. The resulting olefins, primarily trans, were reduced either catalytically or with diimide before removal of the 2′,3′-O-isopropylidene groups to give the desired 5′-substituted purine ribonucleosides.     

Synthesis of 6-substituted 1-alkoxy-5-alkyluracils

Synthesis of 6-substituted 1-alkoxy-5-alkyluracils 2a-c have been achieved from readily accessible 2-alkyl-3,3-di(methylthio)acryloyl chlorides 4a,b in high overall yields. Treatment of 4a,b with silver cyanate followed by reaction of the resulting isocyanates 5a,b with an appropriate alkoxyamine afforded N-alkoxy-N′-[2-alkyl-3,3-di(methylthio)acryloyl]ureas 6a,b in 85–88% yields. Cyclization of 6a,b in acetic acid containing methanesulfonic acid followed by oxidation with 3-chloroperoxybenzoic acid gave high yields of 1-alkoxy-5-alkyl-6-(methylsulfonyl)uracils 9a,b. Nucleophillic addition-elimination reaction of 9a,b with sodium azide, phenylthiol, or phenylselenol produced 6-azido-1-butoxythymine ( 2a , 98%), 5-ethyl-1-(2-phenoxyethoxy)-6-(phenylthio)uracil ( 2b , 95%), or 5-ethyl-1-(2-phenoxyethoxy)-6-(phenylselenenyl)uracil ( 2c , 91%).     

Synthesis of 5,6,7,8-tetrahydro-5-oxopyrido[2,3-d]pyrimidine-6-carbonitriles and -6-carboxylic acid esters

Dieckmann ring closure reactions of 4-[(2-cyanoethyl)substituted amino]-2-phenyl-5-pyrimidinecarboxylates (Ha-f) afforded several 5,6,7,8-tetrahydro-5-oxo-2-phenylpyrido[2,3-d]pyrimidine-6- carbonitriles (IIIa-f). The open-chain intermediates (IIa-f) were prepared by dechloroamination of 5-carbethoxy-4-chloro-2-phenylpyrimidine (1a) with several 3-substituted amino- propionitriles. Alkylation of the sodium salt of 5,6,7,8-tetrahydro-8-methyl-5-oxo-2-phenyl-pyrido[2,3-d]pyrimidine-6- carbonitrile (IIIa) with methyl iodide in DMF resulted in methylation at C-6 to afford IV. Tosylation of IIIa in pyridine gave the corresponding tosyl ester (V) of the enolic form. Oxidative dehydrogenation at the 6,7-position resulted when IIIa reacted with thionyl chloride, affording 5,8-dihydro-8-methyl-5-oxo-2-phenylpyrido[2,3-d]pyrimidine-6- carbonitrile (VII). Dechloroamination of la or 5-carbethoxy-4-chloro-2-methylthiopyrimidine (Ib) with ethyl 3-ethylaminopropionate followed by Dieckmann cyclization of the resulting open-chain intermediates gave the corresponding ethyl 5,6,7,8-tetrahydro-5-oxopyrido[2,3-d]pyrimidine-6-carboxylates IX'a and IX'b, respectively. These exist predominately in the enol form and undergo alkylation and oxidation reactions similar to IIIa.     

Studien zur Chemie von thienoanellierten O,N- und S,N-haltigen Heterocyclen, 10. Mitt.: Synthese von 2- substituierten Thieno-Diltiazemderivaten

Summary The syntheses of 2-acetyl-, 2-benzyl-, and 2-ethyl-thieno-diltiazem derivatives are described starting from the corresponding 5-substituted 3-nitro-2-thiophenthiolvia reaction with racemic methyltrans-3-(4-methoxyphenyl)-glycidate under different conditions (solvent, catalyst, temperature) to obtain purethreo orerythro products. The nitro groups of these products were reduced and the resulting amino esters cyclized. The thieno[2,3-b][1,4]thiazepin-5(4H)-ones were N-alkylated and acetylated in position 3. The desired 2-substituted 4-(2-dimethylaminoethyl)-4,5,6,7-tetrahydro-7-(4-methoxyphenyl)-5-oxothieno[2,3-b][1,4]thiazepin-6-yl acetates were isolated in good yields.

     

Anodic preparation of [Re2Cp2(CO)6]2+: a dimeric dication that provides the powerful one-electron oxidant [ReCp(CO)3]+

The half-sandwich piano-stool compounds Re(eta5-C5R5)(CO)3 (1, R = H; or 2, R = Me) are oxidized to the corresponding 17-electron Re(II) cations at glassy carbon anodes in CH2Cl2/[NBu4][B(C6F5)4]. Despite the very strongly positive E1/2 values of the couples (1.16 V for 1/1+ and 0.91 V for 2/2+ vs ferrocene/ferrocenium), the radical cations are persistent in this medium and exist in equilibrium with the corresponding dimeric dications, which may be cathodically reduced back to the neutral starting material. DFT calculations show that the dimer of 1+ achieves its stability through formation of a single long (almost 3.3 A) Re-Re bond made possible when the HOMO in 1 is rehybridized away from the metal in the one-electron oxidation process. The pure salts [1][B(C6F5)4]2 and [2][B(C6F5)4]2 were isolated by preparative anodic electrochemistry. The former may be used for storage of the very strong one-electron oxidant 1+, which was used to prepare a number of oxidation products as their [B(C6F5)4]- salts.     

Synthesis of Azo-Sulfa Drugs Based on 2-Pyridinone and 2-Pyridinethione

Some new azo sulfa drugs 3-cyano-4,6-diphenyl-1-[4-(N-substituted)sulfamyl]phenylazo-2-pyridinone dyes (1-6) and 3-cyano-4,6-diphenyl-1-[4-(N-substituted)sulfamyl]phenylazo-2-pyridinethione dyes (1′-6′) were synthesized by coupling of 4-(N-substituted)sulfamylbenzene diazonium salts with 3-cyano-4,6-diphenyl-2-pyridinone and/or with 3-cyano-4,6-diphenyl-2-pyridin-ethione. The corresponding iron (1a-6a, 1′a-6′a), copper (1b-6b, 1′b-6′b) and mercury (1c-6c, 1′c-6′c) chelates wvere also prepared. All synthesized compounds were screened in vitro for antibacterial and antifungal activities.     

Reaction of 2- and 4-vinylpyridines with phenacylpyridinium ylids

The reaction of 2- and 4-vinylpyridines with 3-substituted phenacylpyridinium ylids takes place regioselectively with the formation of only 6-substituted 1-pyridyl-3-aroylindolizines. The reaction of the same ylids with dimethyl acetylenedicarboxylate gives a mixture of isomeric 6- and 8-substituted 1,2-dicarbomethoxy-3-aroylindolizines. In the analogous reaction of 2-bromo-1-phenacyl-pyridinium ylid, in addition to the corresponding 5-bromoindolizine, the product of its spontaneous cyclization, viz., 4,5-dicarbomethoxy-6-oxo-(6H)-10c-azaacephenanthrylene, was isolated.Deceased.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 651–656, May, 1980.     

Synthesis of pyrimidino[4,5-b][1,5]benzodiazepin-2-ones and pyrimidino[1,6-a]benzimidazol-1-ones from 4-ethoxycarbonylamino-1H-1,5-benzodiazpine-3-carbonitrile via 4-(2-aminoanilino)pyrimidin-2(1H)-one-5-carbonitriles

Reactions of 4-ethoxycarbonylamino-1H-1,5-benzodiazepine-3-carbonitrile (2) with aliphatic primary amines gave 1-substituted 4-(2-aminoanilino)pyrimidin-2(1H)-one-5-carbonitriles 3. Analogous reactions of 2 with aromatic primary amines afforded 2-(2′-anilino-1′-cyanovinyl)benzimidazoles 5 and 6. Upon treatment with triethylamine, 3 underwent intramolecular cyclization to give 3-substituted 5-aminopyrimidino[4,5-b]-[1,5]benzodiazepin-2(3H,11H)-ones 8 . Heating of 3 with p-toluenesulfonic acid in ethanol gave 2-substituted pyrimidino[1,6-a]benzimidazol-1(2H)one-4-carbonitriles 9 . Reactions of 2 with hydrazines were also described. Mechanistic pathways are proposed to account for the products.     

Heterocyclic compounds from 2-(alkoxycarbonylcyanomethylene)-1,3-dioxolanes

2-(Alkoxycarbonylcyanomethylene)-1,3-dioxolanes reacted with hydrazines and hydroxylamine to yield 1-substituted 4-alkoxycarbonyl-5-amino-3-(2′-hydroxyethoxy)pyrazoles and 4-alkoxycarbonyl-5-amino-3-(2′-hydroxyethoxy)isoxazoles respectively. With guanidine and benzamidine 2-substituted (R = NH₂, C₆H₅) 5-cyano-6-(2′-hydroxyethoxy)pyrimidin-4-ones were obtained. Reaction of 2-(cyanomethoxycarbonylmethylene)-1,3-dioxolane with 1,3-diaminopropane afforded 2-(cyanomethoxycarbonylmethylene)-1,3-hexahydro-pyrimidine whereas treatment of the same compound with 4,5-dimethyl-1,2-phenylenediamine gave 2-(cyanomethoxycarbonylmethylene)-5,6-benzimidazoline. The structures of pyrazoles and pyrimidones were assigned on the basis of ¹H-{¹H} and ¹³C-{¹H}-nOe experiments.     

Five-Membered 2,3-Dioxo Heterocycles: XLVI. Reaction of 5-Aryl-4-quinoxalinyl-2,3-dihydrofuran-2,3-diones with Aldehydes and Ketones. Molecular and Crystalline Structure of 5-(3-p-Tolylquinoxalin-2-yl)-4H-1,3-dioxine- 2-spiro-2'-adamantan-4-one

Aroyl(quinoxalinyl)ketenes generated by thermolysis of 5-aryl-4-(3-arylquinoxalin-2-yl)-2,3-di-hydrofuran-2,3-diones act as dienes in [4 + 2]-cycloaddition at the carbonyl group of aldehydes and ketones to afford 2-substituted 6-aryl-5-(3-arylquinoxalin-2-yl)-4H-1,3-dioxin-4-ones. The structure of 5-(3-p-tolylquino-xalin-2-yl)-4H-1,3-dioxine-2-spiro-2'-adamantan-4-one was proved by X-ray analysis.     

Thiophene-thiophene versus phenyl-phenyl coupling in 2-(Diphenylamino)-Thiophenes: an ESR-UV/Vis/NIR spectroelectrochemical study.

The oxidation of several 2-diphenylamino-substituted thiophenes and N,N'-bis(2-diphenylamino-5-thienyl)-substituted phenylene-1,4-diamines with different substitution patterns in the 5-position of their thiophene moieties was studied by cyclovoltammetric and spectroelectrochemical measurements (ESR, UV/Vis/NIR). These measurements revealed both the structure of the oxidation products obtained and that of their cationic intermediates, as well as the pathway of their formation and follow-up reactions. Thus, the formation of the radical cations in the first electrochemical oxidation step of the target molecules was demonstrated. Depending on the substitution pattern, these radical cations give rise to several consecutive processes to a different extent. Thus radical dimers, dehydrodimers with a 2,2-bithiophene, 3,3'-bithiophene, or benzidine structure, as well as radical monocationic and dicationic products can be formed. For N,N'-bis(2-diphenylamino-5-thienyl)-substituted phenylene-1,4-diamines rather stable radical cations and dications were primarily formed and unambiguously identified. These species were transformed into 2,2'-bithiophene dimers and oligomers when the 5-position of the thiophene moiety was unsubstituted. By in situ spectroelectrochemistry the influence of the substituents on the type of coupling reactions can be demonstrated and followed in detail.     

Transformation of 4-(1-dimethylaminoethylidene)-2-phenyl-5(4H)-oxazolone into methyl 2-benzoylamino-3-oxobutanoate. The synthesis of 1-substituted 4-benzoylamino-3-methyl-5(2H)-pyrazolones

Methyl 2-benzoylamino-3-oxobutanoate ( 3 ) was prepared from hippuric acid (1) which was converted with N,N-dimethylacetamide and phosphorus oxychloride into 4-(1-dimethylaminoethylidene)-2-phenyl-5(4H)-oxazolone ( 2 ) followed by hydrolysis with hydrochloric acid in methanol. Compound 3 was treated with hydrazines 4 to give 4-benzoylamino-3-methyl-1H-pyrazol-5(2H)-one ( 6a ) and its 1-substituted derivatives 6b-j . The corresponding hydrazones 5f, i, j were isolated as intermediates.     

Synthesis and isomeric conversions of several 2-substituted 1,4-dihydro-4-oxo-3-quinolinecarboxylic acid derivatives

Ethyl ester derivatives of 6- and 8-substituted 2-methyl-1,4-dihydro-4-oxo-3-quinolinecarboxylic acids have been synthesized by treatment of the diethyl ester of acetylmalonic acid with 2- or 4-substituted anilines. Condensation of these newly synthesized quinolinecarboxylic acid derivatives with 4-nitrobenzaldehyde resulted in the formation of 6- and 8-substituted 2-[2-(4-nitrophenyl)-vinyl]-1, 4-dihydro-4-oxo-3-quinolinecarboxylic acids and ethyl esters of 6- and 8-substituted 2-[2-(4-nitrophenyl)vinyl]-4-acetoxy-3-quinolinecarboxylic acids. The tautomeric and conformational transformations of these newly synthesized compounds have also been investigated, using IR, NMR, and UV spectroscopy.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 931–938, July, 1988.     

Supramolecular motifs and solvatomorphism within the compounds [M(bpy)3]2[NbO(C2O4)(3)]Cl.nH2O (M = Fe2+, Co2+, Ni2+, Cu2+ and Zn2+; n = 11, 12). Syntheses, structures and magnetic properties

Solvatomorphism has been found between two series of complexes of the composition [M(bpy)3]2[NbO(C2O4)3]Cl.nH2O [M = Fe2+ (1, 2), Co2+ (3, 4), Ni2+ (5, 6), Cu2+ (7) and Zn2+ (8, 9); bpy = 2,2'-bipyridine)], crystallizing in the monoclinic space group P2 1/c [3, 5, 8 (n = 11)] or in the orthorhombic space group P21 21 21 [2, 4, 6, 7 (n = 12)]. All the structures contain two symmetry independent [M(bpy)3]2+ cations, one [NbO(C2O4)3]3- anion, one Cl(-) anion, and crystal water molecules. The cations possess a trigonally distorted octahedral geometry, with an additional tetragonal distortion in 7. Analysis of crystal packing reveals a specific type of supramolecular contact comprising four bipyridine ligands from two neighbouring [M(bpy)3]2+ cations--quadruple aryl embrace (QAE) contact. The contact is realized by the alignment of two molecular two-fold rotation axes, preserving the parallel orientation of the molecular three-fold rotation axes. The resulting two-dimensional honeycomb lattices of [M(bpy)3]2+ cations are placed between the hydrogen bonding layers made of [NbO(C2O4)3]3- and Cl(-) anions and the majority of the crystal water molecules. The temperature-dependent magnetic susceptibility measurements (1.8-300 K) show a significant orbital angular momentum contribution for 3 and 4 (high-spin Co2+), the influence of zero-field splitting for 5 and 6(Ni2+) and a substantially paramagnetic Curie behaviour for the Cu2+ compound (7).     

Synthesis and biological evaluation of some novel-3-(5-substituted benzimidazol-2-yl)-5-arylisoxazolines

<正>The synthesis of a new series of 3-(5-substituted benzimidazol-2-yl)-5-arylisoxazolines(6a-h) was achieved in excellent yields by the condensation of 1-(1H-benzimidazol-2-yl)-3-(substituted phenyl)prop-2-en-1-ones(5a-h) with hydroxylamine at room temperature.These 1-(1H-benzimidazol-2-yl)-3-(substituted phenyl)prop-2-en-1-ones(5a-h) were obtained by the condensation of 2-acetyl benzimidazoles(4a-d) with different aromatic aldehydes,which in turn were obtained by the oxidation of 2-(α-hydroxy) ethyl benzimidazoles(3a-d) prepared by the reaction of o-phenylenediamines(1a-d) withα-hydroxy propionic acid 2. The synthesized compounds were characterized by their IR,~1H NMR and MS analyses.These compounds were screened for their antibacterial and antifungal activity by standard methods and found some of them active.     

Novel Approaches to Synthesis of 4-Alkyl-6-amino-5-cyano-3-methyl(propyl, phenyl)-2H,4H-pyrano[2,3-c]pyrazoles

We have obtained 4-alkyl-6-amino-5-cyano-3-methyl(propyl, phenyl)-2H,4H-pyrano[2,3-c]pyrazoles by reaction of 4-alkylmethylene-3-substituted 5-pyrazolones with malononitrile or cyanothioacetamide. We have used X-ray diffraction to study the structure of 6-amino-5-cyano-4-isopropyl(hexyl)-3-phenyl-2H,4H-pyrano[2,3-c]pyrazoles.     

ADDUCTS FROM 2, 3-DIARYL-5-PHENYLMETHYLENE-4-OXO-1, 3-THIAZOLIDINE-1-OXIDES

Abstract

5-Phenylrnethylene-2, 3-diaryl-4-oxo-1,3-thiazolidine-1-oxides 2 which synthesised via peracetic acid oxidation of the respective 1, 3-thiazolidines 1 reacted with benzylamine and Grignard reagents to afford the respective 5-α-substituted benzyl-2, 3-diaryl-4-oxo-1,3-thiazolidine-l-oxides 3 and 4. Structures of 3 and 4 were based on analytical and spectral evidence.     

5-Diazo-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydroindazoles in [3+2] cycloaddition reactions

The [3+2] cycloaddition reactions of a series of 1,3-substituted 5-diazo-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydroindazoles with maleic anhydride and dimethyl acetylenedicarboxylate gave 1′,3′-substituted 3-spiro[4,6-dioxo-4,6,3a,6a-tetrahydro-3H-furo[3,4-c]pyrazole]-5′-[6′,6′-dimethyl-4′-oxo-4′,5′,6′,7′-tetrahydroindazoles] and 1′,3′-substituted 3-spiro[4,5-di(methoxycarbonyl)-3H-pyrazole]-5′-[6′,6′-dimethyl-4′-oxo-4′,5′,6′,7′-tetrahydroindazoles] respectively. When heated the former eliminate nitrogen and are transformed into 1′,3′-substituted 6-spiro[2,4-dioxo-3-oxabicyclo[3.1.0]hexane]-5′-[6′,6′-dimethyl-4′-oxo-4′,5′,6′,7′-tetrahydroindazoles]. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1784–1791, December, 2007.     

Facile syntheses of 2,2-dimethyl-6-(2-oxoalkyl)-1,3-dioxin-4-ones and the corresponding 6-substituted 4-hydroxy-2-pyrones

A variety of 2,2-dimethyl-6-(2-oxoalkyl)-1,3-dioxin-4-ones 5a-l and the corresponding 6-substituted 4-hydroxy-2-pyrones 3a-l were prepared in high yields under mild reaction conditions by the reaction of 2,2,6-trimethyl-1,3-dioxin-4-one 4 with 1-acylbenzotriazoles 9 in the presence of LDA followed by thermal cyclization of 5a-l to 3a-l. Synthesis of novel 6-(1-benzoylalkyl)-2,2-dimethyl-1,3-dioxin-4-ones 12a-c was achieved by alkylation of dioxinone 5a and their subsequent cyclization gave 5-alkyl-4-hydroxy-2-pyrones 13a-c.