Reaction of pyridothiouracil with hydrazonoyl halides and the antimicrobial activity of the products,pyrido[2,3-d][1,2,4]triazolo-[4,3-a]pyrimidin-5(1H)-one derivatives

New functionalized pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-5(1H)-one derivatives were synthesized via reaction of the hydrazonoyl halides with 7-(4-nitrophenyl)-5-phenyl-2,3-dihydro-2-thioxopyrido[2,3-d]pyrimidin-4(1H)-one or its 2-methylthio derivative. The biological activity of the products has been evaluated. The mechanism and the regioselectivity of the studied reactions have been discussed.     

Dechema corrosion handbook Vol. 3 Edited by D. Behrens,VCH Verlagsgesellschaft,Weinheim Frankfurt am Main, 1988. pp. ix + 282, price £286.00 (subscription price to series £238.00 per volume) ISBN 3-527-26654-2

4-Phenyl-5-aminopyrazole 2 obtained from phenylcyanoacetaldehyde 1 and hydrazine hydrate reacted with diethyl malonate to give 3-phenyl-5,7-dioxopyrazolo[1,5-a]pyrimidine 3 , used as the key compound in the synthesis of arylazo dyes. The key compound 3 was coupled with various aryldiazonium salts 4 to yield 3-phenyl-7-hydroxy-6-arylazopyrazolo[1,5-a]pyrimid-5-ones 5. The resulting arylazo dyes (5) were refluxed in phosphorus oxychloride to give 3-phenyl-5,7-dichloro-6-arylazo-pyrazolo[1,5-a]pyrimidines 6 , which subsequently reacted with refluxing morpholine and piperidine to yield 3-phenyl-5,7-bis(morpholino and piperidino)-6-aryiazopyrazolo[1,5-a]pyrimidines 7. The arylazo dyes 5 and 7 were applied to polyester fibres as disperse dyes and the arylazo dyes 6 were applied to polyamide fibres as disperse reactive dyes. The spectral and dyeing properties of the dyes were studied.     

Regioselective synthesis of new 5-methyl-5H-pyrimido[4′,5′:4,5][1,3]thiazino [3,2-a]perimidines

A convenient and efficient regioselective synthesis of new pyrimido[4′,5′:4,5] [1,3]thiazino[3,2-a]perimidines is described through intermolecular heterocyclization of 2,4-dichloro-5-(chloromethyl)-6-methylpyrimidine and 1H-perimidine-2(3H)-thione in short reaction times under mild conditions.     

Ring transformation and cyclization reactions of 1,1-dioxo-1,2-thiazines – syntheses of pyridines and benzo[c]thiazines with new substitution pattern

In presence of ammonia/ammonium acetate the 3,5-dimethyl-2-phenyl-1,1-dioxo-1,2-thiazine-4-carbaldehyde ( 1 ) reacts with ethyl cyanoacetate to the ethyl 2-cyano-4-[1-methyl-2-methylthio-2-(N-phenylsulfamoyl)vinyl)-hexa-2,4-dienoate] ( 3 ) and the Knoevenagel condensation product 4-(2-ethoxycarbonyl-2-cyanovinyl)-3,5-dimethyl-6-methylthio-1,1-dioxo-2-phenyl-2H-1,2-thiazine ( 2 a). The 4-(2,2-dicyanovinyl)-3,5-dimethyl-6-methylthio-1,1-dioxo-2-phenyl-2H-1,2-thiazine ( 2b ) is obtained from 1 and malononitril. The masked 1,5-dicarbonyl compound 2a undergoes ring transformation to the 3-cyano-1,6-dimethyl-5-[1-methylthio-2-(N-phenylsulfamoyl)vinyl]pyridin-2-one ( 5 ) with methylamine. With ethanolic ethoxide the condensation products 2a,b afford the 7-amino-6-ethoxycarbonyl-4-methylthio-2,2-dioxo-1-phenyl-benzo[c]1,2-thiazine ( 6a ), respectively the corresponding 6-cyano derivative 6b , while 3 cyclizises to furnish ethyl 2-amino-6-methyl-5-[1-methyl-2-methylthio-2-(N-phenyl-sulfamoyl)vinyl]nicotinate ( 4 ).     

Facile synthesis of novel 6-methyl-5-phenyl-2-sulfido-1,2,3,5-tetrahydro-4H[1,2] oxazolo[4′,5′:5,6]pyrano[2,3-d][1,3,2]diazaphosphinines

A number of 6-methyl-5-phenyl-2-sulfido-1,2,3,5-tetrahydro-4H[1,2]oxazolo[4′,5′: 5,6]pyrano[2,3-d][1,3,2]diazaphosphinines 4–11 were synthesized via an interaction of tetraphosphorus decasulfide and Lawesson’s reagent under different conditions with 6-amino-3-methyl-4-phenyl-4H-pyrano[3,2-d][1,2]oxazole-5-carbonitrile (3). The reaction mechanisms for these products were discussed. Structures of the newly synthesized products were established on the basis of elemental analysis and spectral data.     

Tautomerism and Reactions of 1H-1,2,4-Triazole-5-thiones with Hydrazonoyl Halides

The acid dissociation constants (K_a) of a series of 3,4-diaryl-1H-1,2,4-triazole-5-thiones ( 1 ) were determined and were found to correlated linearly with Hammett substituent constants; log K_a = 1.06 σ_x − 11.01. Such a result indicates that 1 exists essentially in one tautomeric form namely the thione form. Reactions of 1 with hydrazonoyl chlorides 2 gave the thiohydrazides 5 . Similiar reaction of 3-phenyl-1H(4H)- 1,2,4-triazole-5-thione 1g with 2a gave the thiohydrazide 5h which was converted into 1,3,5-triphenyl-1,2,4-triazolo[3,4-c]-1,2,4-triazole ( 9 ). The latter was also prepared from 3-phenyl-5-methylthio-4H-1,2,4-triazole ( 6 ) and 2a . The mechanism of the reaction of 1 with 2 is discussed.     

A tetrameric dialdehyde formed in the reaction of butyral dehyde and benzylamine: A possible intermediary component for protein cross-linking induced by lipid oxidation

We investigated the reaction of butyraldehyde and benzylamine and analyzed the products to identify the components that produce protein cross-linking in the reaction of butyraldehyde and proteins. When the mixtures of butyraldehyde and benzylamine were incubated at pH 7 and 37°C for 48 hr, many reaction products other than 2-ethyl-2-hexenal and Schiff bases of butyraldehyde and 2-ethyl-2-hexenal were produced. Fluorescent substance(s) were formed only in the presence of dissolved oxygen in the reaction mixture. Three new nonflourescent products—d,e andf—were isolated, and their structures are suggested to be 2,9-dibenzyl-4,6,8-triethyl-7-propyl-2,9-diazabicyclo[3,3,1] nona-3-ene (d), 1-phenyl-2-benzyl- 4,5,7-triethyl-6-propyl-1H,2H,3H,5H,6H,7H,8H-pyrido[1,2-clpyrimidine (e) and 1-phenyl-2-benzyl-4,5,7-triethyl-6-propyl-1H,2H,4aH,5H,6H,7H,8H-pyrido[1,2-c]pyrimidine (f). Formation of these compounds suggested that the protein, cross-linking with butyraldehyde is caused by the tretrameric dialdehyde formed by repeated aldol condensation and Michael reaction of butyraldehyde.     

Purification and characterization of a novel carbonyl reductase with high stereo-selectivity

A novel NADPH-dependent carbonyl reductase was separated from Candida parapsilosis CCTCC 203011. The enzyme gave a single band on sodium dodecyl sulfatepolyacrylamide gel electrophoresis (SDS-PAGE), which was purified through ammonium sulfate, Diethylamino Ethanol (DEAE) sepharose Fast flow (FF), phenyl-sepharose FF and blue sepharose FF chromatography from cell-free extract. The molecular mass of the enzyme was about 30 kDa. The optimum pH and temperature for reduction were 4.5°C and 35°C, respectively. The Cu²⁺ had strong restrictive effect on enzyme activity. In addition, the carbonyl reductase was an enzyme with high substrate specificity and stereo-selectivity, and showed high asymmetric reduction activity towards α-hydroxyacetophenone and ethyl 4-chloro acetoacetate. For the asymmetric reduction of α-hydroxyacetophenone and ethyl 4-chloro acetoacetate, (S)-1-phenyl-1,2-ethanediol and (R)-ethyl4-chloro-3-hydroxybutanoate were produced by the purified enzyme, with the 100% and 94.3% e.e. value, respectively. Therefore, the enzyme could be one of the effective biocatalysts for asymmetric synthesis of chiral alcohols. The amino acid sequences of one peptide from the purified enzyme were analyzed by LC-MASS-MASS, and the carbonyl reductase showed some identity to the hypothetical protein CaO19.10414 reported. __________ Translated from Journal of Chemical Industry and Engineering Progress, 2006, 25(9): 1,082–1,088 [译自: 化工进展]     

吡啶并吡唑类化合物与蛇毒蛋白的相互作用

运用荧光猝灭的原理在p H 7.6的生理条件下,眼镜蛇毒蛋白与系列6-氨基-4-芳基-5-氰基-3-甲基-1-苯基吡啶[2,3-c]并吡唑化合物之间的相互作用被研究,并且筛选出6-氨基-4-对羟基苯基-5-氰基-3-甲基-1-苯基吡啶[2,3-c]并吡唑（I）进行了详细研究。猝灭常数KSV、结合常数K以及结合位点n被获得。该实验证明眼镜蛇毒蛋白与I之间生成了新的化合物,而这一过程是静态猝灭的过程,并且它们之间存在着一定的结合。     

Synthesis of some new fused thiopyrano[2,3-d]thiazoles and their derivatives

A series of some new fused thiopyrano[2,3-d]thiazole derivatives have been synthesized by a stereo-selective hetero-Diels-Alder reaction of 5-(2,4-dihydroxy-benzylidene)-4-thioxo-thiazolidine derivatives 3a,b with acrylonitrile, ethyl acrylate, N-phenylmale-imide, ω-nitrostyrene and N-phenyl-1, 3, 4-triazole-2,5-dione. 5-Amino-9-hydroxy-dihydro-benzopyrano[3′,4′:4,5]thiopyrano[2,3-d]thiazol-6-one derivatives 14a,b have been synthesized by Michael addition of 3a,b with malononitrile. Structures and conceivable mechanisms are discussed.     

Thia- and selenaheterocycles by a four-component reaction using elemental sulfur and selenium

The course of the four-component reactions of (2-benzimidazolyl) acetonitrile, carbondisulfide, isothiocyanate, and sulfur and selenium, respectively, is quite different. Whereas in the case of sulfur a tetracyclic [1,3]thiazolo[4′,5′:4,5]pyrimido[1,6-a]benzimidazol-2(3H)-thione is formed, a zwitterionic 7-(benzimidazolium-2-yl)-[1,2]thiaselenolo[2,3-b][1,2,4]thiaselenazole-6-thiolate (an azaselenadithiapentalene) is the product in the case of selenium. The structures of the products have been established by X-ray crystallography, and reaction mechanisms for their formation are proposed.     

Heterocyclic compounds as releasers of the fright reaction in the giant danioDanio malabaricus (Jerdon) (Cyprinidae,Ostariophysi, Pisces)

Fifty-nine pteridine, purine, and pyrimidine derivatives were tested with schools of the giant danioDanio malabaricus (Jerdon). The fright reaction was elicited by three pteridine derivatives: 2,6-diamino-4-oxodihydropteridine, isoxanthopterin, and 6-acetonyliso-xanthopterin. A minor effect could not be excluded for three purine derivatives: I-5-MP, IDP, and ITP.     

New phenothiazine dyes and pigments

The synthesis of three new azaphenothiazine ring systems and an evaluation of their use as intermediates for new dyes and pigments is described. 2-Amino-5-bromopyrazine-3[4H]-thione (11) was prepared and converted to the novel 1,4,6,9-tetraazaphenothiazine ring system. The reaction of 4,5-diaminopyrimidine-6[1H]-thione (15) with 2,3-dichloropyrazines gave the isomeric 1,4,6,8-tetraazaphenothiazine ring system, another new heterocycle in this series. With 2,3-dichloroquinoxaline a previously unknown tetracyclic tetraazaphenothiazine ring system was isolated in satisfactory yields. The properties and reactions of these new heterocyclic systems are presented. Mixed nitric and sulphuric acids convert them to their 5-sulphoxides. Structural assignments were based on chemical evidence and their UV, IR, NMR and mass spectra. Mechanistic pathways to these compounds are also proposed.     

Synergic Effects of Ionic Liquid and Microwave Irradiation in Promoting Trifluoromethylpyrazole Synthesis

Abstract  

The synthesis of 5-trifluoromethyl-1-phenyl-1H-pyrazoles from the reactions of 4-alkoxy-1,1,1-trifluoro-3-alken-2-ones [CF₃C(O)CH=C(R¹)OR, where R = Me, Et; R¹ = H, Me, Bu, i-Bu, Ph, 4-MeC₆H₄, 4-FC₆H₄, 4-ClC₆H₄, 4-BrC₆H_4, 4-IC₆H_4, fur-2-yl] with phenyl hydrazine in the presence of ionic liquid [BMIM][BF₄] is reported. Synergic effects of ionic liquid and microwave irradiation in promoting pyrazole synthesis have been shown for the first time.     

Extreme sensitivity of grandisal to acids

Attempted purification of synthetic racemic grandisal1 by silica gel chromatography resulted in severe decomposition. The nature of this reaction was studied on silica gel and in an ether solution ofp-toluenesulfonic acid. The same products resulted from both reaction systems, although in different ratios. Five racemic, rearrangement products were isolated by preparative GC and identified as follows: (1RS, 3SR, 6RS)-1-methyl-5-methylenebicyclo[4.2.0]octan-3-ol (4); (1RS, 3RS, 6RS)-1-methyl-5-methylenebicyclo[4.2.0]octan-3-ol (5); (1RS,3RS,6RS)-1,5-dimethylbicyclo[4.2.0]oct-4-en-3-ol (6); (1RS,3SR,6RS)-1,5-dimethylbicyclo[4.2.0]oct-4-en-3-ol(7); and 3-methyl-7-methylenecyclooct-3-en-l-ol (8). The stereochemical assignments are based on our proposed mechanism, which also accounts for all products observed. The racemic bicyclic enone (3) was a by-product of grandisol (2) oxidation.     

Facile synthesis and characterization of novel bis(2-S-alkylpyridines) and bis(3-aminothieno[2,3-b]pyridines) incorporating 1,3-diarylpyrazole moiety

3-(4-Hydroxyphenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde (1) is condensed with acetophenone to afford the corresponding unsaturated carbonyl compound 4 whose potassium salt is reacted with 1,4-dibromobutane to afford the bis-unsaturated carbonyl compound 3. Both carbonyl compounds 3 and 4 are reacted with 2-cyanoethanethioamide, through Michael addition reaction followed by cyclocondensation, to prepare the starting materials bis(pyridine-2(1H)-thione) derivative 5 and pyridine-2(1H)-thione derivative 8. Two synthetic routes to synthesize the target materials 7 and 14 are described to get the most efficient method for preparation and maximum yield%. The first route came from the direct alkylation of the bis(pyridine-2(1H)-thione) derivative 5 using iodomethane (6a) and benzyl chloride (6b) to afford the corresponding bis(2-S-alkylpyridine) derivatives 7a,b. The reaction of 5 with halo-containing compounds 10a–d to synthesize the target materials bis(3-aminothieno[2,3-b]pyridine) derivatives 14a–d failed under various reaction conditions. The second route involves the reaction of pyridine-2(1H)-thione derivative 8 with 6a,b and 10a–d to afford the corresponding 2-S-alkylpyridine derivatives 9a,b and 3-aminothieno[2,3-b]pyridine derivatives 13a–d, through the formation of 2-S-alkylpyridine derivatives 12a–d followed by a Thrope-Ziegler reaction, whose potassium salts reacted with 1,4-dibromobutane to afford the corresponding target materials 7a,b and 14a–d, respectively. The structures of target molecules were elucidated using elemental analyses and spectral data.     

Studies on the Vilsmeier-haack reaction. Part XIII: Novel heterocyclo-substituted 4,4′-bi-pyrazolyl dithiocarbamate derivatives

5-Imino-3-methyl-l-phenyl-2-pyrazoline-4-dithiocarbamic acid (I) underwent simultaneous formylation and dimerization reactions with the Vilsmeier reagent giving 4-[5′-imino-3-(1″-formyl-2″-dimethylaminoethenyl)-3′-methyl-1′-phenyl-1′H-pyrazolo-4′-dithiocarbamyl-2,4-dihydro-3-imino-5-methyl-2-phenyl-1-pyrazoline]dithiocarbamate (II) which hydrolysed with sodium hydroxide to give 4-[3′-(1″-formyl-2″-hydroxyethenyl)-3′-methyl-1-phenyl-1′-H-pyrazolo-4′-dithiocarbamyl-1′-pyrazoline]dithiocarbamate-5,5′-dione (IV). Treatment of II and/or IV with morpholine, piperidine, piperazine, hydroxylamine, hydrazine hydrate or phenylhydrazine afforded the corresponding dipyrazolo-4,4′-dithiocarbamate derivatives with different heterocyclic systems at the 3-position. The structures of these compounds were confirmed by microanalysis data, IR and ¹H-NMR spectrometry. All synthesized compounds have been screened in vitro against Gram-positive and Gram-negative bacteria, and fungi.     

Synthesis and characterization of poly(1-sila-cis-pent-3-enes) substituted with pendant pyridinyl groups

Poly[1-methyl-1-[3′-(3″-pyridinyl)propyl]-1-sila-cis-pent-3-ene], poly[1-phenyl-1-[3′-(3″-pyridinyl)propyl)-1-sila-cis-pent-3-ene], and poly[1-phenyl-1-(4′-pyridinyl)-1-sila-cis-pent-3-ene] were synthesized by the anionic ring-opening polymerization of 1-methyl-1-[3′-(3″-pyridinyl)propyl]-1-silacyclopent-3-ene, 1-phenyl-1-[3′-(3″-pyridinyl)propyl]-1-silacyclopent-3-ene, and 1-phenyl-1-(4′-pyridinyl)-1-silacyclopent-3-ene, respectively. These are the first polycarbosilanes which contain heterocyclic pyridine units as side-chain substituents. These polymers were characterized by¹H,¹³C, and²⁹Si NMR as well as by IR and UV spectroscopy. The molecular weight distributions were determined by gel permeation chromatography, glass transition temperatures, by differential seanning calorimetry: (DSC) and thermal behavior, by thermogravimetric analysis. (TGA).     

Chemistry of fruit flies: Nature of glandular secretion and volatile emission ofBactrocera (bactrocera) cacuminatus (Héring)

The major component of the rectal glandular extract and volatile emission of maleBactrocera cacuminatus is racemic 1,7-dioxaspiro[5.5]undecane. l-Hydroxy-5-nonanone as its open chain form, together with 6-n-butyl-3,4-dihydro-2H-pyran are minor components. 1,7-Dioxaspiro[5.5]undecan-4-ol is present at a low level and is shown to be exclusively the diastereomer with an equatorial hydroxy group by comparison with synthesized samples of both epimers. Examination of the trifiuoroacetate by chiral gas chromatography has established the (4S,6S) stereochemistry (ca. 80% ee). The presence of 1,7-dioxaspiro[5.5]undecan-3-ol, or its isomerization product, 1,6-dioxaspiro[4.5]decan-2-ylmethanol, could not be confirmed. Trapping of the volatiles released by sexually mature male flies at dusk revealed that a number of the glandular components described above are released at mating time. Reexamination of the glandular secretion of sexually mature female olive flies (B. oleae) has failed to confirm the presence of any 1,7-dioxaspiro[5.5]undecanols, with the only volatile component (other than fatty acids) being 1,7-dioxaspiro[5.5]undecane.     

咪唑斯汀的生产工艺改进

首先以4-氟苄基氯和2-氯-1H-苯并咪唑为起始原料合成1-[（4-氟苯基）甲基]-2-氯-1H-苯并咪唑中间体;所得中间体进一步与甲胺哌啶反应得1-[1-（4-氟苄基）甲基-1H-苯并咪唑-2-基]-N-甲基-4-哌啶胺;最后,第二步产物进一步与2-甲硫基-4-嘧啶酮反应制得（2-[[1-[1-（4-氟苄基）-1H-苯并咪唑-2-基]-4-哌啶基]甲胺基]-4（1H）-嘧啶酮）（咪唑斯汀）,总生产收率达54%。