Heterocyclic Synthesis with Nitriles: Synthesis of some novel pyrrolo [2,1-b]thiadiazoline,pyrrolo[2,1-b]thiadiazolo[3,2-a]pyrimidine and pyridine derivatives

α-(Bromothiocyanatomethyl)benzylidenemalononitrile ( 1 ) reacts with the hydrazides 2a – c , cyanoacethoydrazide ( 2d ,) cyanoacetamide ( 3a ) and cyanoacetanilides 3b – d to afford pyrrolo[2,1-b]thiadiazolines 5a – c , pyrrolo[2,1-b]thia-diazolo[3,2-a]pyrimidine ( 8 ) and the pyridone derivatives 11a – d . Structures and conceivable mechanisms are discussed.     

6-甲基-4-羟基-噻嗯并[2,3-b]噻喃-2-磺酰胺的合成

以2-巯基噻吩和巴豆酸为起始原料,经加成缩合制得3-(2-噻吩巯基)丁酸;在P2O5催化下环合制得6-甲基-4-氧-噻嗯并[2,3-b]噻喃;再用氯磺酸进行氯磺化、氨水氨解制得6-甲基-4-氧-噻嗯并[2,3-b]噻喃-2-磺酰胺;最后用硼氢化钠还原得到盐酸杜塞酰胺的中间体6-甲基-4-羟基-噻嗯并[2,3-b]噻喃-2-磺酰胺,合成总收率为16.0%。其化学结构经IR,1H NMR,MS得以确证。     

Synthesis of pyrazolo[4′,3′:5,6]pyrazino[2,3-c]pyrazoles and pyrazolo[4′,3′:5,6]pyrazino[2,3-d]pyrimidines and their application to polyester fibres

4-Nitroso-1-phenyl-3-methyl-5-aminopyrazole ( 1 ) was condensed with ethylcyanoacetate ( 2 ), malononitrile ( 4a ) and 2-cyanomethylbenzimidazole ( 4b ) to yield 6-hydroxy-5-cyano, 6-amino-5-cyano and 6-amino-5-(benzimidazol-2-yl)-3-methylpyrazolo [3,4-b]pyrazines 3, 5a and 5b , respectively. 5-Cyano-6-chloro derivative 6 obtained from 3 was converted to 3-aminopyrazolo[4′,3′:5,6]pyrazino[2,3-c]pyrazoles 8a and 8b by the treatment with hydrazin hydrate ( 7a ) and phenylhydrazine ( 7b ), respectively. Compound 5a was treated with formamide ( 9a ), urea ( 9b ) and thiourea ( 9c ) to give 4-aminopyrazolo[4′,3′:5,6]pyrazino[2′3′-d]pyrimidines 10a–10c. With refluxing acetic anhydride compounds 8a, 8b and 10a gave corresponding acetamido derivatives 8c, 8d and 10d. Compound 5a was treated with ethylorthoformate ( 11 ), acetic anhydride ( 12 ) or benzoylchloride ( 13 ) to give fused benzimidazopyrazolo[4′,3′:5,6]pyrazino[2′,3′-d]pyrimidines, viz., benzimidazol[1,2-c]pyrazolo[4,3-g]pteridines ( 14a–14c ). Some of the compounds 8, 10 and 14 were applied to polyester as disperse dyes and their fastness properties were studied.     

5,6-二氢-4H-6-甲基噻嗯并[2,3-b]噻喃-4-酮-2-磺酰胺的合成

以丁烯酸和2-巯基噻吩为原料,经加成缩合制得3-(2-噻吩硫基)丁酸(2);以氯化亚砜氯化,三氯化铝催化环合得5,6-二氢-4H-6-甲基噻嗯并[2,3-b]噻喃-4-酮(3);再经磺化、氯化、氨解反应合成得5,6-二氢-4H-6-甲基噻嗯并[2,3-b]噻喃-4-酮-2-磺酰胺(1)。其中经均匀设计优化了环合反应条件为:n(2)∶n(氯化亚矾)∶n(三氯化铝)=1∶3∶1.5,于20℃反应2h。以2-巯基噻吩计,1合成总收率为30.49%,结构经IR、MS、1HNMR确证。     

Some reactions with 3-Methyl-1H-naphtho[2,1-b]pyran-1-one

3-Methyl-1H-naphtho[2,1-b]pyran-1-one 1 has been shown to react with various aldehydes to give the styryl derivatives 2 . Reaction of 1 with P₂S₅ gave the thio-derivative 3 which reacted with aldehydes giving the thiostyryl-derivatives 4 . Hydroxylamine reacted with 1 giving the isoxazole derivative 5 . Hydrazine reacted with 2 giving the pyrazole derivative 6 . Compounds 2 have been shown to undergo DIELS -ALDER reaction to give the adducts 7, 8 and 9 . When 1 was allowed to react with different dicarboxylic acid anhydrides, the phthalide derivatives 10 were obtained, which on reaction with phenol, gave the dihydroxyphthalophenones 11 .     

Reaction of ethyl N-(6-ethoxycarbonyl-2-methylthiothieno[2,3-d]-pyrimidin-5-yl) formimidate with alkyl- and arylhydrazines: Formation of modified thieno[2,3-d]pyrimidines and thieno[2,3-d:4,5-d]dipyrimidin-4-ones

The reaction of ethyl N-(6-ethoxycarbonyl-2-methyl-thiothieno[2,3-d]pyrimidin-5-yl)formimidate ( 1 ) with methyl-hydrazine, N,N′-dimethyl- and N,N′-diphenylhydrazines separately in refluxing ethanol resulted in hydrolysis of formimidate group to give ethyl 5-amino-2-methylthiothieno[2,3-d] pyrimidine-6-carboxylate ( 2 ). The reaction on 1 with methyl-hydrazine without solvent afforded ethyl 5-amino-2-(1-methyl-hydrazino)thieno[2,3-d]pyrimidine-6-carboxylate ( 3 ), which underwent hydrazone formation with p-nitrobenzaldehyde to give 4 . Treatment of 1 with N,N-dimethylhydrazine afforded a mixture of 3-dimethylamino-7-methylthiothieno[2,3-d:4,5-d']dipyrimidin-4(3H)-one ( 5 ) and 2 . Displacement of methylthio group in 5 with morpholine, piperidine and 4-methylpiperazine gave the corresponding 7-substituted derivatives 6a-c . The reaction of 1 with para-substituted phenylhydrazines resulted in the formation of 3-(p-substituted phenylamino)7-methylthiothieno[2,3-d:4,5-d']dipyrimidin-4 (3H)ones ( 7a-c ).     

2,3-二氢-2-苯基咪唑[2,1-b]苯并噻唑的合成研究

以2-氯苯并噻唑为原料,在N,N-二异丙基乙基胺存在下与D或L-苯甘氨醇反应后,不经分离直接与甲磺酰氯在N,N-二异丙基乙基胺作用下关环,一锅法合成了(R)或(S)-2,3-二氢-2-苯基咪唑[2,1-b]苯并噻唑,利用IR、~1HNMR、MS谱和旋光度对其结构进行了表征.通过优化研究2,3-二氢-2-苯基咪唑[2,1-b]苯并噻唑的合成工艺条件,可得到总收率为80%的(R)或(S)-2,3-二氢-2-苯基咪唑[2,1-b]苯并噻唑.     

Synthesis of Thiazolo(4,5-b)-quinoxalines and related compounds

The reaction of 2,3,7-trichloroquinoxaline ( 1 ) or 2,3-dichloro-7-bromoquinoxaline ( 2 ) with thiourea in DMSO gave 6,6′-dichloro- or 6,6′-dibromodiquinoxalino[2,3-b:2′:3′-e]1,4-dithiien ( 3 or 4 ). However, 1 or 2 reacts with thiourea in ethanol to give ( 3 or 4 ) beside 7-chloro- or 7-bromo-2-imino-2,3-dihydrothiazolo[4,5-b] quinoxaline ( 5 or 6 ) respectively. Interaction of 1 or 2 with acetone thiosemicarbazone gave 7-chloro- or 7-bromo-3-amino-2-imino-2,3-dihydro-thiazolo[4,5-b] quinoxaline hydrochloride ( 13 or 14 ) respectively. Cyclization of 7-chloro- or 7-bromo-3-amino-2-imino-2,3-dihydrothiazolo[4,5-b]quinoxaline ( 15 or 16 ) on treatment with aromatic acid chlorides or isothiocyanates succeeded to give 19—21 or 28 and 29 .     

3-Amino-thieno[2,3-b]furane und 3-Amino-thieno[3,2-b]furane

3-Amino-thieno[2,3-b]furans and 3-Amino-thieno[3,2-b]furans The O-alkylation of 2-hydroxy-thiophene-3-carbonitriles ( 1 ) with α-bromocarbonyl compounds yields the 2-alkoxy-thiophene-3-carbonitriles ( 2a–f ) among them 2-benzoylmethoxy-thiophene-3-carbonitriles ( 2a–c ) which undergo Thorpe-Ziegler-cyclization to form the 3-amino-2-benzoyl-thieno[2,3–b]furans ( 3 ) in low yields. The 2-acyl-3-amino-thieno[3,2–b]furans and ethyl 3-amino-thieno[3,2–b]furan-2-carboxylates ( 6 ) are synthesized in similar manner from 3-hydroxy-thiophene-2-carbonitriles ( 4 ) and α-halogencarbonyl compounds via 3-acylmethoxy- and 3-ethoxycarbonylmethoxy-thiophene-2-carbonitriles ( 5 ) with high yields.     

Reactions with Thiazolo[3,2-b]-s-triazol-3(2H)-ones

5-Aryl-3-carboxymethylthio-1,2,4-triazoles 2 are cyclised to 6-arylthiazolo[3,2-b]-s-triazol-3(2H)-ones 3 . This structural assignment has been based on IR and NMR spectra. 2-Arylmethylene-6-arylthiazolo[3,2-b]-s-triazol-3(2H)-ones 7 were prepared by several methods. Compounds 3 coupled with diazotised anilines to give 2,3-dihydro-6-arylthiazolo[3,2-b]-s-triazole-2,3-dione 2-arylhydrazones 8 . The action of amines on 3a opens the thiazolone ring with the formation of substituted (5-phenyltriazol-3-ylthio)-acetamides 9 .     

Synthesis and Dyeing Examinations of 7H, 9H-Quinazolino [3,2-b] benz [d,e] isoquinolin-7-one

The synthesis and application of a representative compound of the new group of disperse dyes derived from 7H,9H-quinazolino[3,2-b] benz[d, e] isoquinolin-7-one (II) have been investigated. The MS, IR and NMR spectra of compound (II) are analysed, and its dyeing and colour properties are compared with 7H-benzimidazo-[2,1-a] benz [d.e] isoquinolin-7-one (I).     

Pyryliumverbindungen. XIV. Zur Lichtabsorption von 1,2-Benzoxalenen (Indeno[2,1-b]pyranen)

Pyrylium Compounds. XIV. The Light Absorption of 1,2-Benzoxalenes (Indeno[2,1-b]pyrans) The iso-π-electronic relationship between azulene A and the heterocyclic pseudoazulene B is reflected by the same dependence of the N V₁ transition from the substituents: Many examples ( 1 – 27 ) show that pseudo-azulenes of the 1,2-benzoxalene type (indeno[2,1-b]pyran) C undergo a bathochromic shift by alkyl substitution at C³ and C⁶, but an hypsochromic shift by alkyl substitution at C⁷. Second order substituents effect an opposite influence (examples 92 – 98 ). The conjugative effect of substituents causes a bathochromic shift in all positions (examples 49 – 58 ), which may rise to a remarkable amount with the extension of the conjugated system (examples 59 – 91 ). The relations obtained correspond to the results of quantum-chemical calculations (examples 28 – 48 ).     

6-甲基-2-苯基咪唑[2,1-b]并-1,3,4-噻二唑-5-N'-取代苯基亚甲基碳酰肼的设计与合成

根据已有的具有抗肿瘤活性的咪唑[2,1-b]并-1,3,4-噻二唑类化合物的结构及其构效关系,以2-氨基-5-苯基-1,3,4-噻二唑和溴代乙酰乙酸乙酯为原料设计并合成了8个6-甲基-2-苯基咪唑[2,1-b]并-1,3,4-噻二唑-5-碳酰肼的腙类衍生物.通过1HNMR、LC-MS、IR等方法对其结构进行了确证.     

Ring closure reaction of 5-hydroxy-pyrido[2,3-d]pyrimidine-2,4,7-triones to benzo[b]pyrimido[4,5-h]1,6-naphthyridine-1,3,6-triones

N-Substituted aminouracils ( 1 ) react with malonates by cyclocondensation to 5-hydroxy-pyrido[2,3-d]pyrimidine-2,4,7-triones ( 2 ), which give with triethylorthoformate and aniline 6-(phenylaminomethylene)-pyrido[2,3-d]pyrimidine-tetraone ( 3 ). Halogenation of 2a - d (with R² = Me) with phosphorylchloride leads to 5,7-dichloro-pyrido[2,3-d]pyrimidine-2,4-diones ( 4 ) by cleavage of the methyl group at N-8, whereas Vilsmeier reaction of 2 affords 5-chloro-6-formyl derivatives ( 6 ), which cyclize with arylamines to give benzo[b]pyrimido[4,5-h] 1,6-naphthyridines ( 9 ). Compounds 9 were obtained independently by amination of the tosylates 5 to the 5-arylamino compounds 8 , and Vilsmeier formylation to yield 9 .     

N-羟甲基-2,3-二丁硫基四硫富瓦烯并[6,7-c]吡咯的合成

从4,5-二丁硫基-1,3-二硫杂环戊二烯-2-酮和N-对苯磺酰基-2-硫代-1,3-二硫杂环戊二烯并[4,5-c]吡咯出发,经交叉偶联、去保护得2,3-二丁硫基四硫富瓦烯并[6,7-c]吡咯(4)。化合物4在碱存在下与甲醛水溶液(37%)反应生成N-羟甲基化的产物。用核磁共振氢谱研究了标题化合物在不同极性溶剂中的偶合行为。     

Synthese und 13C-NMR-Spektroskopie einiger Pyrrolo[2,1-b]chinazoline

Synthesis and ¹³C-N.M.R.-Spectroscopy of Pyrrolo-[2,1,-b]quinazoline In 6- or 7-position substituted pyrrolo-[2,1-b]quinazoline derivatives were synthesized by reacting substituted anthranilic acid derivatives with either 4-amino-butyric acid or 2-methoxy-Δ¹-pyrroline. Furthermore some at C-3 substituted desoxyvasicinone derivatives were prepared. Using these compounds and different n.m.r. spectroscopie techniques the ¹³C resonance signals of all carbon atoms in peganine were assigned.     

Action of acrylonitrile on 4-cyano- and 4-carbethoxy pyridazin-3(2H)-ones and their 3-mercapto derivatives. A novel Synthesis of Pyrano and Thiinopyridazines

Reaction of acrylonitrile with 4-cyano-5,6-diphenyl pyridazin-3(2H)-one and 3(2H)-thione derivative ( 1a, b ) at elevated temperature gave 7H-5-amino-6-cyano-3,4-diphenylpyrano and thiino [2,3-c] pyridazines ( 2a, b ), respectively. However, the reaction of 4-carbethoxy pyridazine derivatives ( 1c, d ) with the same reagent, under the same conditions afforded 6H, 7H-6-cyano-3,4-diphenyl-5-oxopyrano ( 3a ) and thiino [2,3-c] pyridazine ( 3b ), respectively. In addition, treatment of ( 1a, c ) and ( 1b, d ) with acrylonitrile ar reflux in alkaline medium give the respective 3-(2′-cyanoethyloxo) ( 7a, c ) and 3-2′-cyanoethylthio ( 7b, d ) pyridazine derivatives. Prolonged alkaline hydrolysis of either ( 1a, c ) or ( 7a, c ) yielded the same product ( 8a ). Also hydrolysis of ( 1b, d ) and ( 7b, d ) afforded one and the same product ( 8b ). The structures of the products were assigned on the basis of satisfactory analytical and spectroscopic data.     

萘并吡喃并[2,3-d]嘧啶-4(3H)-酮衍生物的合成与表征

通过氮杂Wittig反应合成了7种萘并吡喃并[2,3-d]嘧啶-4(3H)-酮衍生物。首先用2-萘酚、氰乙酸乙酯和芳醛通过Knoevenagl-Cope缩合得到2-氨基萘并吡喃(Ⅰ),(Ⅰ)再与三苯基膦反应得到膦亚胺中间体(Ⅱ)。(Ⅱ)与芳基异氰酸酯采用aza-Wittig反应得到碳二亚胺(Ⅲ)。(Ⅲ)再分别与胺、醇、酚反应合成了萘并吡喃并[2,3-d]嘧啶-4(3H)-酮Ⅳ(a-g)。目标化合物结构经1H-NMR、MS和IR进行了表征。试验考察了亲核试剂及反应条件对产品收率的影响。结果表明,亲核试剂空间位阻小反应速度较快,收率高;若有吸电子基团时,反应时间缩短。     

Pd2(dba)3-catalyzed amination of C5-bromo-imidazo[2,1-b][1,3,4] thiadiazole with substituted anilines at conventional heating in Schlenk tube

ABSTRACT

An efficient Pd₂(dba)₃-catalyzed amination of C5-bromo-imidazo[2,1-b][1,3,4]thiadiazole using conventional heating is reported. The C5-bromoimidazo[2,1-b][1,3,4]thiadiazole was synthesized using a multistep approach which started by cyclization of thiosemicarbazide with a carboxylic acid to give 2-amino[1,3,4]thiadiazoles which were further treated with 2-haloketones to give imidazo[2,1-b][1,3,4]thiadiazoles. Then, the bromination of imidazothiadiazole was done using N-bromosuccinimide to give the C5-bromo-imidazo[2,1-b][1,3,4]thiadiazole. Afterward, various C-N bond-forming approaches were attempted such as S_NAr, Cu(I), Cu(II), Pd(OAc)_2, Pd₂(dba)₃ catalyst with different ligand, additive, base, solvent and temperature conditions. Out of various approaches used, only Buchwald Hartwig amination, performed with conventional heating, gave N-arylamine-5-imidazothiadiazoles. Then, 10 different anilines with different electron-withdrawing and donating groups at different positions were employed to examine the scope and limitations of the method. Salient features of this method include conventional heating in a Schlenk tube as the reaction condition, the absence of the use of toxic isocyanides, the wide nature of substituent tolerance with anilines, and moderately good product yields.     

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.