Simple syntheses of benzothiazol‐2‐ylazoles

Syntheses of the title ring systems are described starting with benzothiazol‐2‐ylacetohydrazide (1). Thus, 1 was reacted with carbon disulfide to afford the 2‐methyl heteroaryl derivative 2, which on reaction with hydrazine hydrate yielded the corresponding triazole compound 3. Also, 1 can undergo a reaction with an isothiocyanate to give the N‐thiocarbonyl adduct 4 that can then be cyclized to produce a 2‐methyl heteroaryl analog 5 or 6. Compounds 8 or 9 could be obtained by the reaction of 1 with an aryl aldehyde followed by malononitrile or via its self‐cyclization, respectively. © 1999 John Wiley & Sons, Inc. Heteroatom Chem 10: 177–182, 1999     

Efficient access to 2-aryl-3-substituted benzo[b]thiophenes

[reaction: see text] Benzo[b]thiophene derivatives are important in part because of their use as selective estrogen receptor modulators. They are usually synthesized by intramolecular cyclization. Here, we propose a method for the synthesis of 2-arylbenzo[b]thiophenes with heteroatoms at the 3-positions directly from the benzo[b]thiophene core by using an aromatic nucleophilic substitution reaction and Heck-type coupling. This methodology provides 2-aryl-3-amino or phenoxybenzo[b]thiophenes in about 35% overall yield in 5 steps.     

焦化汽油中硫化物类型分布的气相色谱-硫化学发光检测方法

建立了焦化汽油中硫化物类型分布的气相色谱-硫化学发光检测分析方法。考察了色谱条件对焦化汽油中各种硫化物分离的影响,定性了某焦化汽油中的74个硫化物。以硫化氢、乙硫醇、正丙硫醇、噻吩、2-甲基噻吩、2-乙基噻吩、2-丙基噻吩、碳四噻吩(tR=40.28 min)、苯并噻吩、甲基苯并噻吩(tR=58.13 min)的保留时间为尺度,计算了焦化汽油中各种硫化物的保留指数,并可推广到其他类型的汽油馏分中各种硫化物保留指数的计算,为仅能提供硫化物信息的仪器提供了可靠的定性依据。焦化汽油中几种主要硫化物(异丙硫醇、正丙硫醇、正丁硫醇、2-甲基噻吩、3-甲基噻吩、2,4-二甲基噻吩、2,3,4-三甲基噻吩)含量测定值的相对标准偏差均小于5%。当信噪比为3时,测得硫的检测限为0.05 mg/L。研究发现:同其他类型的汽油相比,焦化汽油的硫含量较高且所含硫醇比例明显偏高,2-甲基噻吩和3-甲基噻吩的含量差别较大。该法可为加氢脱硫催化剂和工艺的研究提供数据。     

Synthesis of 3,4-Biheterylthieno[2,3-b]-thiophenes. Part I: Synthesis of 3,4-Bi(1′,3′,4′-thiadiazolyl-, s-triazolyl-,1′,3′,4′-thiadiazinyl-, 1′,3′,4′-triazinyl-, thiazolyl-, 1′,3′-thiazinyl- and primidinyl)-thieno[2,3-b]thiophenes

3,4-Diamino-2,5-dicarbethoxythieno[2,3-b]thiophene ( 1 ) was allowed to react with NaNO 2 and active methylenes to afford the corresponding azo compounds 2a-c . Hydrazonyl chloride 2a was treated with carbon disulfide, phenyl isothiocyanate, benzonitrile, benzyl cyanide, malononitrile, benzalaniline, ethyl mercaptoacetate, and ethyl glycinate to give 1,3,4-thiadiazolyl-, s-triazolyl-, 1,3,4-thiadiazinyl-, 1,3,4-triazinylthieno[2,3-b]thiophenes 3-6 respectively. The reaction of 2b,c with urea, thiourea, and guanidine afforded pyrimidinyl- and thiazinylazothieno [2,3-b]thiophenes 7-10 respectively. Bithiazolylthieno[2,3-b]thiophenes 11 and 13 were synthesized by treating compound 1 with CS 2 along with halo compounds. The addition of S,S-, N,S-, and N,O-acetals to the Schiff base 14 afforded compounds 15-17 respectively.     

Reactivity of 3‐(benzothiazol‐2‐yl)‐3‐oxopropanenitrile: A facile synthesis of novel polysubstituted thiophenes

The reaction of 3‐(benzothiazol‐2‐yl)‐3‐oxopropanenitrile 1 with active methylene reagents 2a–d and sulfur afforded polysubstituted thiophenes 3a–c . The synthetic potential of the β‐enaminonitrile moiety in 3a was explored. The reaction of 3a with active methylene reagents 2a–e afforded thieno[2,3‐b]pyridine derivatives 6–8. Refluxing of 3a with acetic anhydride alone, with acetic anhydride/pyridine mixture, or with carbon disulfide in pyridine afforded the acetamido 9, thieno[2,3‐d]pyrimidine 10, and pyrimidinedithiol 11 derivatives, respectively. The pyrimidinedithiol 11 was alkylated smoothly with methyl iodide to give the bis(methylthio) derivative 12. Also, compound 3a reacted with trichloroacetonitrile to give the thieno[2,3‐d]pyrimidine derivative 14. Compound 3a reacted with triethyl orthoformate or formamide to give the ethoxymethylideneamino 15 and thieno[2,3‐d]pyridine 16, respectively. Compound 15 reacted with hydrazine to afford thieno[2,3‐d]pyridine 17, which reacted with various reagents such as chloroacetyl chloride, ethyl cyanoacetate, diethyl oxalate, or chloroethylformate to give 1,2,4‐triazolo[1,5:1,6]pyrimidino‐[4,5‐b]thiophene derivatives 18a–c and 19, respectively. © 2000 John Wiley & Sons, Inc. Heteroatom Chem 11:94–101, 2000     

Nitration of 5-formyl-substituted 2-cyclopropylfurans and 2-methylfurans and the corresponding thiophenes

In the nitration of 5-formyl-substituted 2-cyclopropylfurans and the corresponding thiophenes, in addition to the formation of the corresponding 3-nitro derivative the replacement of the formyl group by a nitro group takes place. For a thiophene derivative the latter direction of the reaction is observed to a substantially smaller degree. Under nitration conditions, 5-formylsylvane is converted only into 5-nitrosylvane, while the corresponding formylmethylthiophene is nitrated exclusively in position 3. The difference observed in the behavior on nitration of the furans and thiophenes studied is explained by the different degrees of participation of the heteroatom in the delocalization of the charges in the heterocyclic ipso-ions formed as intermediates.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 455–460, April, 1980.     

Synthesis of Benzo[c]thiophene Analogs Containing Benzimidazole,Benzothiazole, and Oxazole

Iodine-mediated cyclization of benzo[c]thiophene aldehyde with 1,2-diphenylamine/2-aminophenylthiol led to the formation of benzimidazole/benzothiazole-incorporated benzo[c]thiophenes. Similarly, reaction of benzo[c]thiophene aldehyde with p-toluenesulfonylmethyl isocyanide (TOSMIC) reagent in the presence of K₂CO₃ as a base furnished oxazole-containing benzo[c]thiophene analogs.     

Synthesis of new 1,2,4-oxadiazolidin-5-ylthiophenes and thienopyrimidine derivatives by aza-Wittig reaction using a thienyl carbodiimide

Azidation of aminothiophene derivative 1 afforded the corresponding azido derivative 2.The latter reacted with triphenylphosphine to afford iminophosphorane derivatives 3.Reacting 3 with phenylisocyanate gave the highly reactive carbodiimide intermediate 4,which was reacted with different nitrones to afford new l,2,4-oxadiazolidin-5-ylidene-aminothiophenes 5a-c. Treatment of 4 with absolute EtOH at room temperature gave methyleneamino-5-(methylthio)thiophene 7,(methylthio)-3-(3- phenylureidothiophene)-2-carboxylate 8 or thienopyrimidine 9 and 10 at refluxing temperature.Finally reaction of carbodiimide intermediate 4 with different secondary amines gave the new thienopyrimidines 11a-c.     

Condensed thiophenes and selenophenes: thionyl chloride and selenium oxychloride as sulfur and selenium transfer reagents

3,4-Cyanomethyl substituted thiophenes reacted with thionyl chloride in the presence of base to give dicyano substituted thieno(3,4-c)thiophenes. The use of selenium oxychloride furnished the corresponding cyano substituted seleno(3,4-c)thiophene. 1,2-Phenylenediacetonitriles gave the corresponding cyano substituted benzo(c)thiophenes and benzo(c)selenenophenes, respectively, upon reaction with thionyl chloride and selenium oxychloride in the presence of base.     

TFAA/H3PO4‐Mediated C‐2 Acylation of Thiophene: A Direct Synthesis of Known and Novel Thiophene Derivatives of Pharmacological Interest

A number of aliphatic and aromatic carboxylic acids were reacted with thiophene in the presence of trifluoroacetic anhydride and H₃PO₄ to give a variety of acylated thiophenes in good to excellent yields. The methodology was used to prepare known nonsteroidal anti‐inflammatory drug‐based novel compounds of potential pharmacological significances. Molecular modeling studies were carried out by using nonsteroidal anti‐inflammatory drug‐based thiophene derivatives to assess their cyclooxygenase inhibiting potential in silico. On the basis of docking studies followed by subsequent in vitro assay, indomethacin‐based thiophene derivative was identified as a novel cyclooxygenase‐2 inhibitor with balanced selectivity.     

催化裂化汽油中硫化物类型分布的气相色谱-硫化学发光检测的方法研究

采用气相色谱-硫化学发光检测器(GC-SCD),建立了催化裂化汽油(FCC汽油)中各种硫化物类型分布的分析方法。考察了色谱条件对催化裂化汽油中各种硫化物分离的影响,定性了某催化裂化汽油中的58个硫化物。采用该方法,硫化物中的硫在其质量浓度为0.5~800.0 mg/L时,其峰面积与质量浓度呈较好的线性关系,相关系数达0.999,其响应与硫化物的类型无关。FCC汽油中几种主要硫化物(噻吩、正丁硫醇、2-甲基噻吩、3-甲基噻吩、2,4-二甲基噻吩)的浓度测定值的相对标准偏差(RSD)均小于5.0%。当信噪     

Synthesis, properties, and redox behavior of mono-, bis-, and tris[1,1,4,4,-tetracyano-2-(1-azulenyl)-3-butadienyl] chromophores binding with benzene and thiophene cores

Mono-, bis-, tris-, and tetrakis(1-azulenylethynyl)benzene and mono- and bis(1-azulenylethynyl)thiophene derivatives 5-10 have been prepared by Pd-catalyzed alkynylation of ethynyl arenes with 1-iodoazulene derivative or the 1-ethynylazulene derivative with tetraiodobenzene and iodothiophenes under Sonogashira-Hagihara conditions. Compounds 5-10 reacted with tetracyanoethylene in a [2+2] cycloaddition reaction to afford the corresponding 1,1,4,4,-tetracyano-2-(5-isopropyl-3-methoxycarbonyl-1-azulenyl)-3-butadienyl chromophores 12-16 in excellent yields, except for the reaction of the tetrakis(1-azulenylethynyl)benzene derivative. 1,1,4,4,-Tetracyano-2,3-bis(1-azulenyl)butadiene (17) was also prepared by the similar reaction of bis(1-azulenyl)acetylene (11) with tetracyanoethylene (TCNE). The redox behavior of novel azulene derivatives 12-17 was examined by cyclic voltammetry (CV) and differential pulse voltammetry (DPV), which revealed multistep electrochemical reduction properties. Moreover, a significant color change was observed by visible spectroscopy under electrochemical reduction conditions.     

Studies on polycyclic thiaarenes: Part II. An improved synthesis of phenanthro[1,2-b]thiophene and a synthesis of acenaphtho[1,2-b]naphtho-[2,3-d]thiophene,a novel polynuclear thiaarene

An improved synthesis of phenanthro[1,2-b]thiophene ( 6 ) from 1-chloro-3,4-dihydrophenanthrene-2-aldehyde ( 2 ) by condensation with thioglycolate followed by hydrolysis, decarboxylation and dehydrogenation is described. A new polycyclic thiophene derivative 14 has also been prepared from acenaphthothiophene ( 7 ) by Friedel-Craft's reaction with phthalic anhydride followed by lactonisation of the keto carboxylic acid 9 and then reduction and finally cyclisation of the resultant aldehyde 13 .     

Stepwise Oxidation of Thiophene and Its Derivatives by Hydrogen Peroxide Catalyzed by Methyltrioxorhenium(VII)

The oxidation of thiophene derivatives by hydrogen peroxide is catalyzed by methyltrioxorhenium(VII) (CH(3)ReO(3)). This compound reacts with hydrogen peroxide to form 1:1 and 1:2 rhenium peroxides, each of which transfers an oxygen atom to the sulfur atom of thiophene and its derivatives. Complete oxidation to the sulfone occurs readily by way of its sulfoxide intermediate. The rates for each oxidation step of dibenzothiophenes, benzothiophenes, and substituted thiophenes were determined. The rate constants for the oxidation of the thiophenes are 2-4 orders of magnitude smaller than those for the oxidation of aliphatic sulfides, whereas the rate constants are generally the same for the oxidation of the thiophene oxides and aliphatic sulfoxides. The rate constant for conversion of a sulfide to a sulfoxide (thiophene oxide) increases when a more electron-donating substituent is introduced into the molecule, whereas the opposite trend was found for the reaction that converts a sulfoxide to a sulfone (thiophene dioxide). Mechanisms consistent with this are proposed. The first trend reflects the attack of the nucleophilic sulfur atom of a thiophene center on a peroxide that has been electrophilically activated by coordination to rhenium. The second, more subtle, trend arises when both sulfoxide and peroxide are coordinated to rhenium; the inherently greater nucleophilicity of peroxide then takes control.     

AM1 semiempirical searching for suitable thiophene derivatives that will enable thiophenes to act as a diene in the diels-alder reactions

The AM1 semiempirical method was used for theoretical searching of activation of thiophene as a diene for the Diels-Alder reaction. The reactivity of thiophene, electron-withdrawing and electron-donating substituted thiophenes, as well as the S-methylthiophenium ion were studied as the diene for Diels-Alder reactions by evaluating their frontier orbital energies and by calculating reaction barriers with activated and deactivated dienophiles. It was demonstrated that slight activation of the thiophene ring can be obtained with both electron-donating and electron-withdrawing groups attached to the thiophene ring. It was predicted that the actual transformation of thiophenes into the corresponding S-methylthiophenium anions is the best means of activating the thiophenes. The calculated activation energies for normal (non-activated) dienophiles are moderate so mild reaction conditions are predicted. If dienophiles are activated with electron-donating substituents, AM1 calculations predict a two step cycloaddition reaction with a very small activation barrier.     

Thiophenes as traps for benzyne. 3. Diaryl sulfides and the role of dipolar intermediates

The reactions of seven thiophenes with benzyne generated from diphenyliodonium-2-carboxylate (DPIC) under a standard set of conditions led among other products to the formation of alpha- and beta-naphthyl phenyl sulfides 2a and 2b from thiophene (1a) and of 2c and 2d from 2-methylthiophene (1b). Dithienyl sulfides 4a-f were produced from the halothiophenes 1c-g. The structures of the naphthyl sulfides were proven by comparison with authentic samples of 2a-f, thus eliminating one of two possible mechanisms of formation. The remaining mechanism involves [4+2]-cycloaddition of benzyne to thiophene or to an S-phenylthiophenium ylide 10 to give the dipolar 2:1 benzyne/thiophene adduct 8 followed by ring-opening. Stevens-like rearrangements of 11, formed from 10 by proton transfer, may also explain the origin of arylated thiophenes such as 12 and 3 found in some reactions of benzynes with thiophene.     

5-(2-Thienylsulfanyl)thiophene-2-carbaldehyde: Thioacetalization,chloromethylation, and oxidation

5-(2-Thienylsulfanyl)thiophene-2-carbaldehyde reacted with propane-1-thiol and propane-1,3-dithiol in the presence of chloro(trimethyl)silane to give previously unknown 5-[bis(propylsulfanyl)methyl]-2-(2-thienylsulfanyl)thiophene and 2-[5-(2-thienylsulfanyl)thiophen-2-yl]-1,3-dithiane. Chloromethylation of 5-(2-thienylsulfanyl)thiophene-2-carbaldehyde with formaldehyde in a stream of hydrogen chloride in the presence of zinc chloride resulted in the formation of an oligomeric product consisting of thiophene rings connected alternately by sulfur and methylene bridges. The oligomer is formed via fast polycondensation of the primary chloromethylation product with the initial aldehyde. 5-(2-Thienylsulfanyl)thiophene-2-carbaldehyde was oxidized at the sulfide and aldehyde groups with 30% hydrogen peroxide in glacial acetic to produce 5-(2-thienylsulfonyl)thiophene-2-carboxylic acid.     

Iridium‐Catalyzed Annulation Reactions of Thiophenes with Carboxylic Acids: Direct Evidence for a Heck‐type Pathway

The functionalization of thiophenes is a fundamental and important reaction. Herein, we disclose iridium‐catalyzed one‐pot annulation reactions of (benzo)thiophenes with (hetero)aromatic or α,β‐unsaturated carboxylic acids, which afford thiophene‐fused coumarin‐type frameworks. Dearomatization reactions of 2‐substituted thiophenes with α,β‐unsaturated carboxylic acids deliver various thiophene‐containing spirocyclic products. The occurrence of two interconnected reactions provides direct evidence for a Heck‐type pathway. The mechanistic scenario described herein is distinctly different from the S_EAr and concerted metalation–protodemetalation (CMD) pathways encountered in the well‐described oxidative C?H/C?H cross‐coupling reactions of thiophenes with other heteroarenes.     

Palladium-catalysed direct 3- or 4-arylation of thiophene derivatives using aryl bromides

The palladium-catalysed direct 3- or 4-arylation of 2,5-disubstituted thiophenes using aryl bromides gives a simple access to a variety of 3- or 4-arylthiophene derivatives. Moderate to good yields of 3-arylated thiophenes were obtained using 2,5-dimethylthiophene. In the presence of unsymmetrically disubstituted, 2-acetyl-5-methylthiophene, a regioselective arylation on carbon 4 of thiophene was observed. This reaction provides only HX associated to the base as by-product and reduces the number of steps to prepare these compounds.     

Reactions of a Ruthenium Complex with Substituted N‐Propargyl Pyrroles

In an investigation into the chemical reactions of N‐propargyl pyrroles 1 a – c , containing aldehyde, keto, and ester groups on the pyrrole ring, with [Ru]?Cl ([Ru]=Cp(PPh₃)₂Ru; Cp=C₅H₅), an aldehyde group in the pyrrole ring is found to play a crucial role in stimulating the cyclization reaction. The reaction of 1 a , containing an aldehyde group, with [Ru]?Cl in the presence of NH₄PF₆ yields the vinylidene complex 2 a , which further reacts with allyl amine to give the carbene complex 6 a with a pyrrolizine group. However, if 1 a is first reacted with allyl amine to yield the iminenyne 8 a , then the reaction of 8 a with [Ru]?Cl in the presence of NH₄PF₆ yields the ruthenium complex 9 a , containing a cationic pyrrolopyrazinium group, which has been fully characterized by XRD analysis. These results can be adequately explained by coordination of the triple bond of the propargyl group to the ruthenium metal center first, followed by two processes, that is, formation of a vinylidene intermediate or direct nucleophilic attack. Additionally, the deprotonation of 2 a by R₄NOH yields the neutral acetylide complex 3 a . In the presence of NH₄PF₆, the attempted alkylation of 3 a resulted in the formation the Fischer‐type amino–carbene complex 5 a as a result of the presence of NH₃, which served as a nucleophile. With KPF₆, the alkylation of 3 a with ethyl and benzyl bromoacetates afforded the disubstituted vinylidene complexes 10 a and 11 a , containing ester groups, which underwent deprotonation reactions to give the furyl complexes 12 a and 13 a , respectively. For 13 a , containing an O‐benzyl group, subsequent 1,3‐migration of the benzyl group was observed to yield product 14 a with a lactone unit. Similar reactivity was not observed for the corresponding N‐propargyl pyrroles 1 b and 1 c , which contained keto and ester groups, respectively, on the pyrrole ring.