An Efficient Synthesis of 1-Thia-5-azaspiro[5.5]undec-2-ene and its Recyclization to 1,5-Diazaspiro[5.5]undec-2-ene and/or Spiro-Thieno[2,3-d]pyrimidin-4(1H)-one Derivatives

Synthesis and In Vitro Anticancer Evaluation of Symmetrically Bridged 1,3‐thiazine Derivatives

“…It is noteworthy that symmetrical bis ‐1,3‐thiazines with rigid phenyl linkages have been reported from the condensation reactions of terephthalaldehyde with 3‐arylamino‐2‐cyano‐3‐mercapto‐acrylamide . To the best of our knowledge, bis ‐1,3‐thiazines connected through flexible alkyl bridges were not frequently discussed in the literature with only one exceptional case reported by Wang and co‐workers .…”

“…As part of our growing interest in synthesizing bis ‐heterocyclic compounds of interesting biological activities , we report here the versatile and hitherto unreported synthesis of a series of symmetrically functionalized bis ‐thiazines, in which the two substituted heterocycles were linked together through a flexible bridge of alkyl chains with variable number of methylene moieties and their anticancer activities were evaluated against various cancer cells. The bis ‐aldehydes 1a–c were chosen as ideal candidates for the synthesis of the target bis ‐thiazine scaffolds 3a–c because they can undergo nucleophilic attack upon reaction with the bis ‐nucleophile 2a–c followed by subsequent facial cyclization.…”

Synthesis of novel 1-thia-5,9-diaza-spiro[5.5]undec-2-ene and its recyclization to 1,5,9-triaza-spiro[5.5]undec-2-ene and/or spiro(piperidine-4,2’-thieno[2,3-d]pyrimidine)

“…Elemental analyses were measured with a Vario EL III CHNOS Elemental Analyzer, Germany, in the Microanalytical Center of Cairo University. Compounds 1, 37 7a, 38 and 7b, 21 were synthesized using the published procedures.…”

“…15 Furthermore, 1,3-thiazines are an important type of heterocycles showing a wide variety of pharmacological properties. [16][17][18][19][20] Prompted by the aforesaid biological and pharmaceutical activities, and as a part of our continuing interest on the synthesis of new polyfunctionally substituted heterocyclic [21][22][23][24][25][26][27][28][29][30] and spiro heterocyclic compounds [31][32][33][34] of expected biological activity, we now report the versatile and hitherto unreported synthesis of 1-thia-5,9-diazaspiro [5.5]undec-2-ene, and its base-catalyzed recyclization to 1,5,9-triaza-spiro [5.5]undec-2-ene and spiro(piperidine-4,2'-thieno [2,3-d]pyrimidine) derivatives with the purpose of investigating in the future their possible biological activity. Scheme 1 outlines the synthesis of the ethyl ester of 3-cyano-4-oxo-2-phenylamino-1-thia-5,9-diaza-spiro [5.5]undec-2-ene-9-carboxylic acid 3a,b from the cyclocondensation of 2-cyano-3-mercapto-3-phenylamino-acrylamide 1 with ethyl 4-oxo-piperidine-1-carboxylate 2a and/or 1-benzylpiperidin-4-one 2b in the presence of catalytic amounts of p-toluenesulfonic acid (p-TSA) in boiling ethanol.…”

Synthesis of Thiazine and Thiazepine Derivatives from (Z)-2-Cyano-3-Mercapto-3-(Phenylamino)Acrylamide

“…14 We have found that 2-cyano-3-mercaptoacrylamide derivative reacts with a variety of carbonyl compounds in boiling ethanol to yield different heterocyclic compounds. 15,16 Very recently we have found that the reaction of acrylamide derivative 1 with ethyl chloroacetate and ω-chloroacetophenone gives ethyl 3-amino-4-carbamoyl-5-(phenylamino)thiophene-2-carboxylate and 4-amino-5-benzoyl-2-(phenylamino)thiophene-3-carboxamide, respectively. 17 The formation of charge transfer complexes (CT-complexes) has long been recognised as an important phenomenon in many chemical processes.…”