Bis(α‐bromo ketones): Versatile Precursors for Novel Bis(s‐triazolo[3,4‐b][1,3,4]thiadiazines) and Bis(thiazoles)

A synthesis of novel bis(s-triazolo[3,4-b][1,3,4]thiadiazines) in which the triazolothiadiazine is linked to the benzene core through the thiadiazine ring via phenoxymethyl spacers was reported. First attempt to synthesize by the reaction of the appropriate bis(acetophenones) with 4-amino-3-mercapto-1,2,4-triazole derivatives using an acidified acetic acid method were unsuccessful. On the other hand, reaction of the corresponding bis(α-bromoketones) with 4-amino-3-mercapto-1,2,4-triazole derivatives afforded in good yields. The reaction pathway is assumed to involve S-alkylation to give bis(aminotriazole) intermediates, followed by intramolecular cyclocondensation to give . The successful isolation of the corresponding bis(aminotriazole) intermediates provides strong evidence for the proposed mechanism. The novel bis(thiazoles) , linked to alkyl or aryl spacers can also be synthesized by reaction of the appropriate bis(bromoacetyl) compounds and with the corresponding thioamide derivatives .

[1]  K. Khalil,et al.  A Convenient Ultrasound-Promoted Synthesis of Some New Thiazole Derivatives Bearing a Coumarin Nucleus and Their Cytotoxic Activity , 2012, Molecules.

[2]  M. Shaaban,et al.  Bis(α‐bromo ketones): Versatile Precursors for Novel Bis(s‐triazolo[3,4‐b][1,3,4]thiadiazines) and Bis(as‐triazino[3,4‐b][1,3,4]thiadiazines) , 2012 .

[3]  P. Sharma,et al.  Thiazoles: having diverse biological activities , 2012, Medicinal Chemistry Research.

[4]  A. Geronikaki,et al.  Thiazole-based chalcones as potent antimicrobial agents. Synthesis and biological evaluation. , 2011, Bioorganic & medicinal chemistry.

[5]  S. Prabhu,et al.  Characterization of a novel lyophilized chitosan hydrogel complex for the controlled release of a highly water soluble drug, niacinamide , 2011 .

[6]  A. EL-Mahdy,et al.  Novel Method for the Synthesisof s-Triazolo[3,4-b][1,3,4]thiadiazines , 2010 .

[7]  A. Abu‐Hashem,et al.  Synthesis of 3-((2,4-dichlorophenoxy)methyl)-1,2,4-triazolo(thiadiazoles and thiadiazines) as anti-inflammatory and molluscicidal agents. , 2010, European journal of medicinal chemistry.

[8]  P. Naik,et al.  Synthesis and antitumor activity studies of some new fused 1,2,4-triazole derivatives carrying 2,4-dichloro-5-fluorophenyl moiety. , 2009, European journal of medicinal chemistry.

[9]  S. Ünüvar,et al.  Synthesis of 3,6-disubstituted 7H-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines as novel analgesic/anti-inflammatory compounds. , 2009, European journal of medicinal chemistry.

[10]  Mousa L. Al-Smadi,et al.  Synthesis, characterization, and reactions of selected multichalcone derivatives , 2009 .

[11]  A. Mavrova,et al.  Synthesis, cytotoxicity and effects of some 1,2,4-triazole and 1,3,4-thiadiazole derivatives on immunocompetent cells. , 2009, European journal of medicinal chemistry.

[12]  H. Kumar,et al.  Condensed bridgehead nitrogen heterocyclic system: synthesis and pharmacological activities of 1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazole derivatives of ibuprofen and biphenyl-4-yloxy acetic acid. , 2008, European journal of medicinal chemistry.

[13]  S. Saraf,et al.  4-thiazolidinone--a biologically active scaffold. , 2008, European journal of medicinal chemistry.

[14]  B. Poojary,et al.  Synthesis, antimicrobial and anti-inflammatory activities of some 1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles and 1,2,4-triazolo[3,4-b][1,3,4]thiadiazines bearing trichlorophenyl moiety. , 2008, European journal of medicinal chemistry.

[15]  A. Amr,et al.  Synthesis and reactions of thiosemicarbazides, triazoles, and Schiff bases as antihypertensive α-blocking agents , 2008 .

[16]  Z. Kaplancıklı,et al.  New triazole and triazolothiadiazine derivatives as possible antimicrobial agents. , 2008, European journal of medicinal chemistry.

[17]  N. Park,et al.  New oxime reactivators connected with CH2O(CH2)nOCH2 linker and their reactivation potency for organophosphorus agents-inhibited acetylcholinesterase. , 2007, Bioorganic & medicinal chemistry.

[18]  G. Tarzia,et al.  Synthesis and biological activity of new melatonin dimeric derivatives. , 2007, Bioorganic & medicinal chemistry.

[19]  C. Olsen,et al.  Synthesis of Some Novel bis‐Spiro[indole‐pyrazolinyl‐thiazolidine]‐2,4′‐diones , 2006 .

[20]  B. Sarojini,et al.  Synthesis and studies on some new fluorine containing triazolothiadiazines as possible antibacterial, antifungal and anticancer agents. , 2006, European journal of medicinal chemistry.

[21]  E. De Clercq,et al.  Synthesis and biological activity of 4-thiazolidinones, thiosemicarbazides derived from diflunisal hydrazide. , 2006, European journal of medicinal chemistry.

[22]  S. Khanum,et al.  Synthesis and antimicrobial study of novel heterocyclic compounds from hydroxybenzophenones. , 2005, European journal of medicinal chemistry.

[23]  G. Turan‐Zitouni,et al.  Synthesis and antimicrobial activity of 4-phenyl/cyclohexyl-5-(1-phenoxyethyl)-3-[N-(2-thiazolyl)acetamido]thio-4H-1,2,4-triazole derivatives. , 2005, European journal of medicinal chemistry.

[24]  A. Elwahy,et al.  1,ω-Bis(4-amino-1,2,4-triazole-5(1H)-thion-3-ylsulfanyl)alkanes: Versatile precursors for novel bis(S-triazolo[3,4-b][1,3,4]thiadiazines) as well as novel bis(macrocyclic schiff bases) , 2005 .

[25]  A. Elwahy,et al.  A facile and efficient synthetic approach to novel lariat macrocyclic diamides and bis macrocyclic diamides , 2005 .

[26]  A. Shafiee,et al.  Synthesis and anticonvulsant activity of new 2-substituted-5- [2-(2-fluorophenoxy)phenyl]-1,3,4-oxadiazoles and 1,2,4-triazoles. , 2004, Bioorganic & medicinal chemistry letters.

[27]  Mousa L. Al-Smadi,et al.  New many fold 1,2,3-selenadiazole aromatic derivatives , 2004 .

[28]  J. Suwiński,et al.  Synthesis and anti-tuberculosis activity of N-aryl-C-nitroazoles. , 2004, European journal of medicinal chemistry.

[29]  K. Shikha,et al.  Synthesis and anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation activities of some new 2-[(2,6-dichloroanilino) phenyl]acetic acid derivatives. , 2004, European journal of medicinal chemistry.

[30]  Yaseen A Al-Soud,et al.  Synthesis and properties of new substituted 1,2,4-triazoles: potential antitumor agents. , 2003, Bioorganic & medicinal chemistry.

[31]  U. Holzgrabe,et al.  Elevation of ligand binding to muscarinic M(2) acetylcholine receptors by bis(ammonio)alkane-type allosteric modulators. , 2002, Journal of medicinal chemistry.

[32]  B. S. Holla,et al.  New bis-aminomercaptotriazoles and bis-triazolothiadiazoles as possible anticancer agents. , 2002, European journal of medicinal chemistry.

[33]  J. N. Low,et al.  Control of the reaction between 2-aminobenzothiazoles and Mannich bases. Synthesis of pyrido[2,1-b][1,3]benzothiazoles versus [1,3]benzothiazolo[2,3-b]quinazolines , 2002 .

[34]  M. Stevens,et al.  Antitumor benzothiazoles. 16. Synthesis and pharmaceutical properties of antitumor 2-(4-aminophenyl)benzothiazole amino acid prodrugs. , 2002, Journal of medicinal chemistry.

[35]  B. S. Holla,et al.  Synthesis of some new biologically active bis-(thiadiazolotriazines) and bis-(thiadiazolotriazinyl) alkanes. , 2001, Il Farmaco.

[36]  J. Rudolph,et al.  seco-Cyclothialidines: new concise synthesis, inhibitory activity toward bacterial and human DNA topoisomerases, and antibacterial properties. , 2001, Journal of medicinal chemistry.

[37]  G. Ramesh,et al.  Synthesis of novel non-cross-linking pyrrolobenzodiazepines with remarkable DNA binding affinity and potent antitumour activity , 2001 .

[38]  B. S. Holla,et al.  Synthesis and antibacterial studies of a new series of 1,2-bis(1,3, 4-oxadiazol-2-yl)ethanes and 1,2-bis(4-amino-1,2, 4-triazol-3-yl)ethanes. , 2000, European journal of medicinal chemistry.

[39]  R. Shaker.  ONE-POT SYNTHESIS OF NOVEL 1,1′- AND 1,4-BRIDGED BIS-THIAZOLIDINONE DERIVATIVES AND THEIR ANTIMICROBIAL ACTIVITY , 1999 .

[40]  S. Neidle,et al.  Synthesis of Sequence-Selective C8-Linked Pyrrolo[2,1-c][1,4]benzodiazepine DNA Interstrand Cross-Linking Agents. , 1996, The Journal of organic chemistry.

[41]  F. Toda,et al.  Oligomers and Polymers Containing Triple Bonds. III. Derivatives of α,ω-Bis(4-ethynylphenoxy)alkane , 1964 .