Synthetic Approach to 6-Benzoyl-2H-[1,2,4]triazine-3,5-dione and 6-Benzyl-5-thioxo-3,4-dihydro-2H-[1,2,4]triazin-3-one and Studies on Their Transformation to Fused[1,2,4]triazine Systems

Reaction of phenylpyruvic acid with semicarbazide afforded 6-benzyl-2H-[1,2,4]triazine-3,5-dione ( 1 ) which upon oxidation with potassium dichromate furnished 6-benzoyl-2H-[1,2,4]triazine-3,5-dione ( 2 ) in good yield. Constructing pyrazolo[3,4-e][1,2,4]triazine system ( 4 ) was achieved by reacting 2 with arylhydrazines in ethanolic solution. However treatment of 2 with the less reactive heteroarylhydrazines gave only the corresponding hydrazones ( 3 ). Attempt for constructing 1,2,4,5,10-pentaaza-dibenzo[a,d]cyclohept-3-one ( 7 ) from 2 was failed and (benzoimidazol-2-yl) [1,2,4] triazine derivative ( 6 ) was the only product. Reaction of 1 with phosphorus pentasulphide afforded compounds 8 and 9 . Compound 8 was transformed to the hydrazino compound 14 , which led to the construction of triazolo[4,3-d] [1,2,4]triazine system. Thus compounds 15 and 16 were obtained by reacting 14 with carbon disulfide or acetic anhydride respectively. Attempt to couple 8 with chloroacetic acid failed, while it's known isomer 10 led to the formation of thiazolo [2,3-c] [1,2,4]triazine derivative ( 13 ). Simple theoretical calculation using AM1 and PM3 semiempirical Hamitonian provided rational ways to correlate the reactivity with structure proposed.     

1,3-Disubstitutedpyrazole-4-caboxaldehyde in Heterocyclic Synthesis: A Novel Synthesis of Pyridine-2(1H)-thione and Fused Nitrogen and/or Sulfur Heterocyclic Derivatives

Pyridine-2(1H)-thione 5 was synthesized from the reaction of 3-[3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-yl]-1-phenylpropenone (3) and cynothioacetamide (4). Compound 5 reacted with halogented compounds 6a–e to give 2-S-alkylpyridine derivatives 7a–e, which could be in turn cyclized into the corresponding thieno[2,3-b]-pyridine derivatives 8a–e. Compound 8a reacted with hydrazine hydrate to give 9. The latter compound reacted with acetic anhydride (10a), formic acid (10b), acetic acid, ethyl acetoacetate, and pentane-2,4-dione to give the corresponding pyrido[3′,2′:4,5]thieno-[3,2-d]pyrimidine 13a,b, pyrazolo[3′,4′:4,5]thieno[3,2-d]pyridine 14 and thieno[2,3-b]-pyridine derivatives 18 and 20, respectively. Alternatively, 8c reacted with 10a,b and nitrous acid to afford the corresponding pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine 24a,b and pyrido[3′,2′:4,5]thieno[3,2-d][1,2,3]triazine 26 derivatives, respectively. Finally compound 5 reacted with methyl iodide to give 2-methylthiopyridine derivative 27, which could be reacted with hydrazine hydrate to yield the corresponding pyrazolo[3,4-b]-pyridine derivative 29.     

Reactions of 2-Cyano-2-nitrosomethylbenzthiazole: One-Pot Synthesis of New Polyfunctional Pyrazine Derivatives

2-Cyano-2-nitrosomethylbenzthiazole reacts with some active methylene and nucleophile derivatives to yield new fused and isolated polyfunctional pyrazine, -[1,2,4]triazine, -[1,4,5]benzoxadiazepin, -[1,4,5]benzothiadiazepine, [1,4,5]benzotriazepine, -triazole and -triazolo[3,2-c]triazine derivatives in one-pot reaction. The structures were based on IR, MS, and 1 H NMR spectra and elemental data.     

Halogen effect on tandem [4+2] cycloaddition/aromatization sequence of allenyl 2-halo-3-vinylcyclohex-2-enyl ether

Steric and enthalpic effects of substituents on diene moieties play a crucial role in intramolecular cycloaddition reactions. Allenyl 2-halogenated-3-vinylcyclohex-2-enyl ethers underwent a tandem [4+2] cycloaddition/aromatization reaction to afford the corresponding tetrahydro-3H-naphtho[1,8-bc]furan compound in high yield.     

Reaction of ene-bis(phosphinylallenes): [2+2] versus [4+2] cycloaddition

Reaction of ene-bis(phosphinylallenes), derived from ene-bis(propargyl alcohols) and chlorodiphenylphosphine, was investigated. Benzene-bridged bis(phosphinylallenes) exclusively gave intramolecular [2+2] cycloadducts in the presence of dimethyl fumarate in sharp contrast to the reaction of benzene-bridged bis(sulfinylallenes), which gave the corresponding [4+2] cycloadducts. On the other hand, substituted ethylene- or five-membered heterocycle-bridged bis(phosphinylallenes) provided [4+2] cycloadducts. Reaction of benzene-bridged diallene bearing both a sulfinyl group and a phosphinyl group on the two allenyl groups was also described.     

Rearrangements of the [2+2]-cycloadducts of DDQ and 2-ethynylpyrroles

The [2+2]-cycloadducts of DDQ and 2-ethynylpyrroles, upon ethanolysis (reflux, 15 min or room temperature, 24 h), rearrange from bicyclo[4.2.0]octadienediones to bicyclo[3.2.0]heptadienone- and cyclobutenyl-dihydrofuranone moieties in 55-83% yields, the former rearrangement being the major direction. Benzoquinone ring cleavage is regioselective to afford mostly bicyclo[3.2.0]heptadienone-pyrrole ensembles (85-90% selectivity) in 39-78% yields. The only exception is when the starting compounds contain an ethoxycarbonyl substituent and the pyrrole counterpart is a 4,5,6,7-tetrahydroindole fragment. In this case, the ratio of the rearrangement products is 1:1.2 in a total yield of 83%. An important feature of the dihydrofuranone pathway rearrangement is its 100% diastereoselectivity.     

2-Ethanethioamide in Heterocyclic Synthesis: Synthesis and Characterization of Several New Pyridine and Fused Azolo- and Azinopyridine Derivatives

Pyridine-2(1H)-thione derivatives 3a,b were synthesized from the reaction of 1-(phenyl-sulfanyl)acetone (1) and cinnnamonitrile derivatives 2a,b. Compounds 3a,b reacted with different halogenated reagents 7a–f to give 2-S-alkylpyridine derivatives 8a–l, which could be, in turn, cyclized into the corresponding thieno[2,3-b]pyridine derivatives 9a–l. Compounds 9d,j reacted with acetic anhydride, formic acid, carbon disulfide, phenyl isothiocyanate, and nitrous acid to yield the corresponding pyrido[3′,2′:4,5]thieno[2,3-d]pyrimidine 12a,b, 15a,b, 17a,b, 20a,b, and pyrido[3′,2′:4,5]thieno[2,3-d][1,2,3]triazinone derivatives 22a,b, respectively.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Synthesis of (R)-quinuclidine-2-carboxylic acid in enantiomerically pure form

Enantiomerically pure (R)-quinuclidine-2-carboxylic acid has been prepared by following two related 7 step synthetic routes in 16% and 19% overall yield, respectively, from a 1,2,4-trisubstituted piperidine that is easily prepared from inexpensive d-mannitol.     

Phase Transfer Catalyzed Synthesis and Antibacterial Activity of Water-soluble S-Triazolo[3,4-b][1,3,4]thiadiazoles Containing Piperazine Group

6/3-（4-Chlorophenyl）-s-triazolo[3, 4-b][1, 3, 4]thiadiazoles （2,a-e） and （Sa-e） were synthesized respectively by intermolecular cyclization of 5-aryl / 4-chlorophenyl-4-amino-3- mercapto-1, 2, 4-triazoles （la-e） and （4） with 4-chlorobenzoic acid / aryl acids, which were condensed with piperazine under phase transfer catalyst TBAB to yield the corresponding free bases of monopiperazine derivatives and followed to form water-soluble salts （3a-e） and （6a-e） with hydrochloric acid in good yields. The in vitro biological results showed that piperazine group conjugated with the above fused heterocycles played an important role in antibacterial activity. The structures of novel compounds were confirmed by IR, ＇H NMR, MS and elemental analysis.     

A Facile One‐Pot Synthesis of Functionalized 1,5‐Dihydro‐2H‐[1]benzopyrano[2,3‐b]pyridin‐5‐ones

The highly reactive 1 : 1 intermediate generated in the reaction between dialkyl acetylenedicarboxylate (=but‐2‐ynedioic acid dialkyl ester) 4 and triphenylphosphine was trapped by 2‐amino‐4‐oxo‐4H‐1‐benzopyran‐3‐carboxaldehydes 5 to yield highly functionalized dialkyl‐1,5‐dihydro‐5‐oxo‐1‐phenyl‐2H‐[1]benzopyrano[2,3‐b]pyridine‐2,3‐dicarboxylates in high yield.     

One-Pot Synthesis of Hydroxybenzo[d]-oxazole-2-aliphatic Acid Derivatives by Meerwein's Reagent

A general one-pot synthesis of hydroxylbenzo[d]oxazole-2-aliphatic acid esters and hydroxylbenzo[d]oxazole-2-amino acid esters was successfully achieved in good yield by using Meerwein's reagent.     

Synthesis of (S)-2-amino-7-methoxytetralin and isoindolo[1,2-a]isoquinolinone derivatives from l-aspartic acid

This paper describes a new total synthesis for (S)-2-amino-7-methoxytetralin, (S)-7-MeO-AT, from l-aspartic acid in an overall yield of 10% over nine steps. The major loss was ascribed to a key intramolecular Friedel–Crafts cyclization step, which afforded up to 36% yield. Attempts to perform a Friedel–Crafts cyclization of an intermediate phthalimide protected amino alcohol 13 did not give the desired protected (S)-7-MeO-AT. On the other hand, two new isoindolo[1,2-a]isoquinolinone derivatives 14 and 15, were isolated in 21 and 11% yield, respectively. The yield of 15 was improved to 70%.     

A one-pot four-component synthesis of N-arylidene-2-aryl-imidazo[1,2-a]azin-3-amines

N-Arylidene-2-aryl-imidazo[1,2-a]azin-3-amines were synthesized via a one-pot, four-component condensation reaction using a 2-aminoazine, toluene-4-sulfonylmethyl isocyanide (TsCH₂NC), and two equivalents of readily available aromatic aldehydes. The reaction was performed in diethyl ether as the solvent, with p-toluenesulfonic acid (p-TSA) as the catalyst at reflux temperature.     

Novel Synthesis of 2-(2-(3-Hydroxy-5-oxo-4-phenylthiophen-2(5H)-ylidene)-2-phenylacetamido)propanoic Acid Analogues and Their Anti-Inflammatory Properties

This article describes the reaction of 3,6-diphenyl-thieno[3,2-b]furan-2,5-dione 1 with different amino acids 2a–j in glacial acetic acid which afforded the 2-(2-(3-hydroxy-5-oxo-4-phenylthiophen-2(5H)-ylidene)-2-phenylacetamido)propanoic acid analogues 3a–j and also describes the reaction of 3,6-diphenyl-thieno[3,2-b]thiophene-2,5-dione 4 with different amino acids 5a–e in acidic medium to give 2-(2-(3-mercapto-5-oxo-4-phenylthiophen-2(5H)-ylidene)-2-phenylacetamido)propanoic acid analogues 6a–e. All the compounds have been screened for their anti-inflammatory activity against the carrageenan induced rat paw edema in albino rats. In the primary screening, some of the compounds exhibited appreciable activity.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Catalytic enantioselective [2+2]-cycloaddition reaction of 2-methoxycarbonyl-2-cyclopenten-1-one by chiral copper catalyst

A new catalytic system for enantioselective [2+2]-cycloaddition reaction of 2-methoxycarbonyl-2-cyclopenten-1-one with thioacetylene derivatives is described. The use of a catalytic amount (20-30 mol%) of copper(II) salt with chiral bis-pyridine ligand was found to be effective in promoting the [2+2]-cycloaddition reaction, furnishing the corresponding bicyclic compound in good yield and good enantioselectivity.     

含氮手性杯[4]芳烃对羧酸的手性识别

Chiral nitrogen-containing calix[4]arene was easily synthesized by the reaction of 25,27-di（2-bromoethoxy）- 26,28-dihydroxy-5,11,17,23-tetrakis（t-butyl）calix[4]arene with S-（-）-1-phenylethylamine in excellent yield, and showed good ability to recognize the enantiomers of mandelic acid and 2,3-dibenzoyltartaric acid. This finding has potential application to assay and separation of enantiomers of the carboxylic acids.     

Synthesis and unusual [2+2]-cycloaddition reactions of ethyl 4-chloro-2-oxobut-3-ynoate with unactivated alkenes

The highly activated acetylenes, ethyl 4-chloro-2-oxobut-3-ynoate and ethyl 4-bromo-2-oxobut-3-ynoate, were prepared from readily available bis(trimethylstannyl)acetylene in two steps with high overall yield. An unusual ability of the former to furnish [2+2]-cycloadducts with 1,1-disubstituted alkenes in the absence of irradiation and catalysts was discovered. The cycloaddition of ethyl 4-chloro-2-oxobut-3-ynoate to the 1,2-disubstituted alkenes was shown to be effectively catalyzed with stannic chloride.     

水中"一锅法"合成2-氨基-3-氰基-4-芳基-7,7-二甲基-5-氧代-4H-5,6,7,8-四氢苯并[b]吡喃

报道了以十二烷基苯磺酸(DBSA)为催化剂,芳醛、丙二腈和5,5-二甲基-1,3-环己二酮为原料于水中一步生成2-氨基-3-氰基-4-芳基-7,7-二甲基-5-氧代-4H-5,6,7,8-四氢苯并[b]吡喃.该方法具有产率高、操作简便、对环境友好、催化剂可重复使用等优点.     

微波法合成2-羟乙基苯并[d]异噻唑-3(2H)-酮

以苯并异噻唑-3(2H)-酮(BIT)及氯乙醇为原料微波法合成了2-羟乙基苯并[d]异噻唑-3(2H)酮。考察了氢氧化钠量,氯乙醇用量,反应时间,反应温度对反应的影响,经正交实验设计得到了最佳反应条件,最佳反应条件下收率为83.3%。结果表明,与传统工艺相比,微波技术合成2-羟乙基苯并[d]异噻唑-3(2H)-酮的方法具有操作方便、收率高等特点,具有一定的应用价值。     

Studies on the Chemistry of Thienoannelated O , N - and S , N -Containing Heterocycles, 28 [1]. Synthesis of Imidazo[1,5- d ]thieno[2,3- b ][1,4]thiazine Derivatives as GABA -Receptor Ligands

Summary.  GABA-receptor-ligands are still very interesting in drug-development. Usually benzodiazepines are used in the treatment but they have serious side-effects. Thus, a recently synthesized quioxaline derivative which showed reduced side-effects in an animal model was used as a model-substance. The cyclus was modified to optimize the pharmacological profile. Accordingly, a series of imidazo-thieno-thiazines was synthesized starting from 5-acetyl-2-chloro-3-nitrothiophene to yield 6-ethyl-2,3-dihydro-1H-thieno[2,3-b][1,4]thiazine-2-one. Reaction with potassium tert-butoxide and diethylchlorophosphate gave an intermediate, which resulted in the desired ring system after adding the corresponding isocyanides and potassium tert-butoxide. Corresponding author. E-mail: thomas.erker@univie.ac.at Received August 6, 2002; accepted August 13, 2002