Organocatalysis in heterocyclic synthesis: DABCO as a mild and efficient catalytic system for the synthesis of a novel class of quinazoline, thiazolo [3,2-a]quinazoline and thiazolo[2,3-b] quinazoline derivatives

Chemistry Central Journal

Haider Behbehani²  Hamada Mohamed Ibrahim¹ 

[1] Chemistry Department, Faculty of Science, Fayoum University, Fayoum 63514, A. R, Egypt

[2] Chemistry Department, Faculty of Science, Kuwait University, P.O. Box 5969, Safat 13060, Kuwait

关键词: Thiazolo[2,3-b]quinazoline;    Thiazolo[3,2-a] quinazoline;    Quinazoline;    DABCO;    Organocatalysis;   

Others  :  787911
DOI  :  10.1186/1752-153X-7-82

 received in 2013-02-27, accepted in 2013-04-18,  发布年份 2013

【 摘 要 】

Background

There are only limited publications devoted to the synthesis of especially thiazolo[3,2-a]quinazoline which involved reaction of 2-mercaptopropargyl quinazolin-4-one with various aryl iodides catalyzed by Pd-Cu or by condensation of 2-mercapto-4-oxoquinazoline with chloroacetic acid, inspite of this procedure was also reported in the literature to afford the thiazolo [2,3-b] quinazoline. So the multistep synthesis of the thiazolo[3,2-a]- quinazoline suffered from some flaws and in this study we have synthesized a novel class of thiazoloquinazolines by a simple and convenient method involving catalysis by 1,4-diazabicyclo[2.2.2]octane (DABCO).

Results

A new and convenient one-pot synthesis of a novel class of 2-arylidene-2H-thiazolo[3,2-a]quinazoline-1,5-diones 9a-i was established through the reaction between methyl-2-(2-thio-cyanatoacetamido)benzoate (4) and a variety of arylidene malononitriles 8a-i in the presence of DABCO as a mild and efficient catalytic system via a Michael type addition reaction and a mechanism for formation of the products observed is proposed. Moreover 4 was converted to ethyl-2-[(4-oxo-3,4-dihydroquinazolin-2-yl)thio]acetate (10) upon reflux in ethanol containing DABCO as catalyst. The latter was reacted with aromatic aldehydes and dimethylformamide dimethylacetal (DMF-DMA) to afford a mixture of two regioselectively products with identical percentage yield, these two products were identified as thiazolo[3,2-a]quinazoline 9,13 and thiazolo[2,3-b]quinazoline 11,12 derivatives respectively. The structure of the compounds prepared in this study was elucidated by different spectroscopic tools of analyses also the X-ray single crystal technique was employed in this study for structure elucidation, Z/E potential isomerism configuration determination and to determine the regioselectivity of the reactions.

Conclusion

A simple and efficient one-pot synthesis of a novel class of 2-arylidene-2H-thiazolo[3,2-a]quinazoline-1,5-diones 9a-i was established through DABCO catalyzed Michael type addition reaction. In addition many fused quinazoline and quinazoline derivatives were synthesized which appeared as valuable precursors in synthetic and medicinal chemistry.

【 授权许可】

   
2013 Behbehani and Ibrahim; licensee Chemistry Central Ltd.

【 图 表 】

Scheme 1

Scheme 2

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

Figure 7.

Figure 8.

Scheme 3

Scheme 4

Figure 9.

Scheme 5

Figure 10.

Figure 11.

Scheme 6

【 参考文献 】

• [1]Wu J, Sun X, Li Y: DABCO: An efficient organocatalyst in the ring-opening reactions of aziridines with amines or thiols. Eur J Org Chem 2005, 20:4271-4275.
• [2]Yamguchi K, Eto M, Higashi K, Yoshitake Y, Harano K: DABCO-triggered mild cascade reaction of electron-eficient cyclopentadienone: facile and efficient synthesis of condensed carbocycles. Tetrahedron Lett 2011, 52:6082-6085.
• [3]Wu J-W, Li F, Zheng Y, Nie J: DABCO-mediated one-pot sequential transformation: convenient access to fluorinated 1H-pyrazol-5(4H)-ones. Tetrahedron Lett 2012, 53:4828-4831.
• [4]Palomo C, Oiarbide M, Mielgo A: Unveiling reliable catalysts for the asymmetric nitroaldol (Henry) reaction. Angew Chem Int Ed 2004, 43:5442-5444.
• [5]Wang R, Yue L, Pan W, Zhao J-J: Direct transition metal-free C–S bond formation: synthesis of 2-aminobenzothiazole derivatives via base-mediated approach. Tetrahedron Lett 2012, 53:4529-4531.
• [6]Abdel Gawad NM, Georgey HH, Youssef RM, El-Sayed NA: Synthesis and antitumor activity of some 2,3-disubstituted quinazolin-4(3H)-ones and 4,6-disubstituted-1,2,3,4-tetrahydro- quinazolin-2H-ones. Eur J Med Chem 2010, 45:6058-6067.
• [7]Chandrika PM, Yakaiah T, Rao AR, Narsaiah B, Reddy NC, Sridhar V, Rao JV: Synthesis of novel 4,6‒disubstituted uinazoline derivatives, their anti-inflammatory and anti‒cancer activity (cytotoxic) against U937 leukemia cell lines. Eur J Med Chem 2008, 43:846-852.
• [8]Al-Omary FAM, Hassan GS, El-Messery SM, El-Subbagh HI: Substituted thiazoles V. Synthesis and antitumor activity of novel thiazolo[2,3-b]quinazoline and pyrido[4,3-d]thiazolo[3,2-a]- pyrimidine analogues. Eur J Med Chem 2012, 47:65-72.
• [9]Marvania B, Lee P-C, Chaniyara R, Dong H, Suman S, Kakadiya R, Chou T-C, Lee T-C, Shah A, Su T-L: Design, synthesis and antitumor evaluation of phenyl N-mustard-quinazoline conjugates. Bioorg Med Chem 2011, 19:1987-1998.
• [10]Decker M, Kraus B: Design, synthesis and pharmacological evaluation of hybrid molecules out of quinazolinimines and lipoic acid lead to highly potent and selective butyrylcholinesterase inhibitors with antioxidant properties. Bioorg Med Chem 2008, 16:4252-4261.
• [11]El-Gazzar ABA, Youssef MM, Youssef AMS, Abu-Hashem AA, Badria FA: Design and synthesis of azolopyrimidoquinolines, pyrimidoquinazolines as anti-oxidant, anti-inflamm- atory and analgesic activities. Eur J Med Chem 2009, 44:609-624.
• [12]Kumar A, Sharma S, Bajaj AK, Sharma S, Panwar H, Singh T, Srivastava VK: Some new 2,3,6-trisubstituted quinazolinones as potent anti-inflammatory, analgesic and COX-II inhibitors. Bioorg Med Chem 2003, 11:5293-5299.
• [13]Aly MM, Mohamed YA, El-Bayouki KM, Basyouni WM, Abbas SY: Synthesis of some new 4(3H)-quinazolinone-2-carboxaldehyde thiosemicarbazones and their metal complexes and a study on their anticonvulsant, analgesic, cytotoxic and antimicrobial activities. Eur J Med Chem 2010, 45:3365-3373.
• [14]Pandeya SN, Sriram D, Nath G, Clercq ED: Synthesis antibacterial antifungal and anti-HIV evaluation of Schiff and Mannich bases of isatin derivatives with 3-amino-2-methylmercapto quinazolin-4(3H)-one. Pharm Acta Helv 1999, 74:11-17.
• [15]Selvam P, Girija K, Nagarajan G, De Clerco E: Synthesis, antibacterial, and anti-HIV activities of 3-[5-amino-6-(2,3-dichlorophenyl)-[1,2,4]triazin-3-yl]-6,8-dibromo-2-substituted-3H-quin- azolin-4-one. Indian J Pharm Sci 2005, 67:484-487.
• [16]Ghorab MM, Abdel-Gawad SM, El-Gaby MSA: Synthesis and evaluation of some new fluorinated hydroquinazoline derivatives as antifungal agents. II Farmaco 2000, 55:249-255.
• [17]Cakici M, Catir M, Karabuga S, Kilic H, Ulukanli S, Gulluce M, Orhan F: Synthesis and biological evaluation of (S)-4-aminoquinazoline alcohols. Tetrahedron-Asymmetr 2010, 21:2027-2031.
• [18]Alagarsamy V, Pathak US: Synthesis and antihypertensive activity of novel 3-benzyl-2-substituted-3H-[1,2,4]triazolo[5,1-b]quinazolin-9-ones. Bioorg Med Chem 2007, 15:3457-3462.
• [19]Agarwal KC, Sharma V, Shakya N, Gupta S: Design and synthesis of novel substituted quinazoline derivatives as antileishmanial agents. Bioorg Med Chem Lett 2009, 19:5474-5477.
• [20]Kashawa SK, Kashawa V, Mishra P, Jain NK, Stables JP: Synthesis, anticonvulsant and CNS depressant activity of some new bioactive 1-(4-substituted-phenyl)-3-(4-oxo-2- phenyl/ethyl-4H-quinazolin-3-yl)urea. Eur J Med Chem 2009, 44:4335-4343.
• [21]Liesen AP, Aquino TM, Carvalho CS, Lima VT, Araujo JM, Lima JG, Faria AR, Melo EJT, Alves AJ, Alves EW, Alves AQ, Goes AJS: Synthesis and evaluation of anti-Toxoplasma gondii and antimicrobial activities of thiosemicarbazides, 4-thiazolidinones and 1,3,4-thiadiazoles. Eur J Med Chem 2010, 45:3685-3691.
• [22]Omar K, Geronikaki A, Zoumpoulakis P, Camoutsis C, Sokovic M, Ciric A, Glamoclija J: Novel 4-thiazolidinone derivatives as potential antifungal and antibacterial drugs. Bioorg Med Chem 2010, 18:426-432.
• [23]Liu X, Zheng C, Sun L, Liu X, Piao H: Synthesis of new chalcone derivatives bearing 2,4-thiazolidinedione and benzoic acid moieties as potential anti-bacterial agents. Eur J Med Chem 2011, 46:3469-3473.
• [24]Upadhyay A, Srivastava SK, Srivastava SD: Conventional and microwave assisted synthesis of some new N-[(4-oxo-2-substituted aryl-1,3-thiazolidine)acetamidyl]-5-nitroindazoles and its antimicrobial activity. Eur J Med Chem 2010, 45:3541-3548.
• [25]Vintonyak VK, Warburg K, Kruse H, Grimme S, Hubel K, Rauh D, Waldmann H: Indentification of thiazolidinones spiro-fused to indolin-2-ones as potent and selective inhibitors of the mycobacterium tuberculosis protein tyrosine phosphatase B. Angew Chem 2010, 122:6038-6041.
• [26]Wang S, Zhao Y, Zhang G, Lv Y, Zhang N, Gong P: Design, synthesis and biological evaluation of novel 4-thiazolidinones containing indolin-2-one moiety as potential antitumor agent. Eur J Med Chem 2011, 46:3509-3518.
• [27]Lv P, Zhou C, Chen J, Liu P, Wang K, Mao W, Li H, Yang Y, Xiong J, Zhu H: Design, synthesis and biological evaluation of thiazolidinone derivatives as potential EGFR and HER-2 kinase inhibitors. Bioorg Med Chem 2010, 18:314-319.
• [28]Havrylyuk D, Mosula L, Zimenkovsky B, Vasylenko O, Gzella A, Lesyk R: Synthesis and anticancer activity evaluation of 4-thiazolidinones containing benzothiazole moiety. Eur J Med Chem 2010, 45:5012-5021.
• [29]Maccari R, Corso AD, Giglio M, Moschini R, Mura U, Ottana R: In vitro evaluation of 5-arylidene-2-thioxo-4-thiazolidinones active as aldose reductase inhibitors. Bioorg Med Chem Lett 2011, 21:200-203.
• [30]Rawal RK, Tripathi R, Katti SB, Pannecouque C, De Clercq E: Design and synthesis of 2-(2,6-dibromophenyl)-3-heteroaryl-1,3-thiazolidin-4-ones as anti-HIV agents. Eur J Med Chem 2008, 43:2800-2806.
• [31]Mobinikhaledi A, Foroughifar N, Ebrahimi S, Rahimi F, Zandi F: Synthesis of some novel 2-aryl- idene thiazoloquinazolinone derivatives via one-pot, three-component reaction. Phosphorus Sulfur Silicon Relat Elem 2011, 186:457-463.
• [32]Feng Y, Ding X, Chen T, Chen L, Liu F, Jia X, Luo X, Shen X, Chen K, Jiang H, Wang H, Liu H, Liu D: Design, synthesis, and interaction study of quinazoline-2(1H)-thione derivatives as novel potential Bcl-xL inhibitors. J Med Chem 2010, 53:3465-3479.
• [33]Bouillon I, Krchnak V: Efficient solid-phase synthesis of 3-substituted-5-Oxo-5H-thiazolo[2,3-b]quinazoline-8-carboxamides under mild conditions with two diversity positions. J Comb Chem 2007, 9:912-915.
• [34]Loge C, Testard A, Thierry V, Lozach O, Blairvacq M, Robert J-M, Meijer L, Besson T: Novel 9-oxo-thiazolo[5,4-f]quinazoline-2-carbonitrile derivatives as dual cyclin-dependent kinase 1 (CDK1)/glycogen synthase kinase-3 (GSK-3) inhibitors: synthesis, biological evaluation and molecular modeling studies. Eur J Med Chem 2008, 43:1469-1477.
• [35]Testard A, Loge C, Leger B, Robert J-M, Lozach O, Blairvacq M, Meijer L, Thiery V, Besson T: Thiazolo[5,4-f]quinazolin-9-ones, inhibitors of glycogen synthase kinase-3. Bioorg Med Chem Lett 2006, 16:3419-3423.
• [36]McIntyre NA, McInnes C, Griffiths G, Barnett AL, Kontopidis G, Slawin AMZ, Jackson W, Thomas M, Zheleva DI, Wang S, Blake DG, Westwood NJ, Fischer PM: Design, synthesis, and evaluation of 2-methyl- and 2-amino-N-aryl-4,5-dihydrothiazolo[4,5-h]quinazolin-8-amines as ring-constrained 2-anilino-4-(thiazol-5-yl)pyrimidine cyclin-dependent kinase inhibitors. J Med Chem 2010, 53:2136-2145.
• [37]Mrkvicka V, Klasek A, Kimmel R, Pevee A, Kosmrlj J: Thermal reaction of 3aH,5H-thiazolo[5,4-c]quinoline-2,4-diones an easy pathway to 4-amino-1H-quinoline-2-ones and novel 6H-thiazolo[3,4-c]quinazoline-3,5-diones. ARKIVOC 2008, 14:289-302.
• [38]Grasso S, Micale N, Monforte A-M, Monforte P, Polimeni S, Zappala M: Synthesis and in vitro antitumour activity evaluation of 1-aryl-1H,3H-thiazolo[4,3-b]quinazolines. Eur J Med Chem 2000, 35:1115-1119.
• [39]Bakherad M, Keivanloo A, Kalantar Z, Keley V: Regioselective syntheses of 1-aryl-substituted-5H-[1,3]thiazolo[3,2-a]quinazoline-5-ones during Sonogashira coupling. Phosphorus Sulfur Silicon Relat Elem 2011, 186:464-470.
• [40]Jain KK, Rout SP, Pujari HK: Heterocyclic systems containing bridgehead nitrogen atom. Part LXIV. Synthesis of 7-methylthiazolo[3,2-a]quinazolines. Indian J Chem Sect B 1990, 29B:379-80.
• [41]Behbehani H, Ibrahim HM, Makhseed S, Mahmoud H: Applications of 2-arylhydrazononitriles in synthesis: preparation of new indole containing 1,2,3-triazole, pyrazole and pyrazolo[1,5-a]pyrimidine derivatives and evaluation of their antimicrobial activities. Eur J Med Chem 2011, 46:1813-1820.
• [42]Behbehani H, Ibrahim HM, Makhseed S, Elnagdi MH, Mahmoud H: 2-Aminothiophenes as building blocks in heterocyclic synthesis: synthesis and antimicrobial evaluation of a new class of pyrido[1,2-a]thieno[3,2-e]pyrimidine, quinoline and pyridin-2-one derivatives. Eur J Med Chem 2012, 52:61-65.
• [43]Behbehani H, Ibrahim HM: 4-Thiazolidinones in heterocyclic synthesis: synthesis of novel enaminones, azolopyrimidines and 2-Arylimino-5-arylidene-4-thiazolidinones. Molecules 2012, 17:6362-6385.
• [44]Vicini P, Geronikaki A, Anastasia K, Incerti M, Zani F: Synthesis and antimicrobial activity of novel 2-thiazolylimino-5-arylidene-4-thiazolidinones. Bioorg Med Chem 2006, 14:3859-3864.
• [45]Gruner M, Rehwald M, Eckert K, Gewald K: New synthesis of 2-alkylthio-4-oxo-3,4-dihydroquinazolines, 2-alkylthioquinazolines, as well as, their hetero analogues. Heterocycles 2000, 53:2363-2377.
• [46]Crystallographic data for 3 (ref. CCDC 916675) can be obtained on request from the director. 12 Union Road, Cambridge CB2 1EW, UK: Cambridge Crystallographic Data Center;
• [47]Crystallographic data for 4 (ref. CCDC 916665) can be obtained on request from the director. 12 Union Road, Cambridge CB2 1EW, UK: Cambridge Crystallographic Data Center;
• [48]Crystallographic data for 5 (ref. CCDC 916666) can be obtained on request from the director. 12 Union Road, Cambridge CB2 1EW, UK: Cambridge Crystallographic Data Center;
• [49]Crystallographic data for 9a (ref. CCDC 916667) can be obtained on request from the director. 12 Union Road, Cambridge CB2 1EW, UK: Cambridge Crystallographic Data Center;
• [50]Crystallographic data for 9c (ref. CCDC 916674) can be obtained on request from the director. 12 Union Road, Cambridge CB2 1EW, UK: Cambridge Crystallographic Data Center;
• [51]Crystallographic data for 9d (ref. CCDC 916671) can be obtained on request from the director. 12 Union Road, Cambridge CB2 1EW, UK: Cambridge Crystallographic Data Center;
• [52]Crystallographic data for 9f (ref. CCDC 916670) can be obtained on request from the director. 12 Union Road, Cambridge CB2 1EW, UK: Cambridge Crystallographic Data Center;
• [53]Crystallographic data for 9h (ref. CCDC 916673) can be obtained on request from the director. 12 Union Road, Cambridge CB2 1EW, UK: Cambridge Crystallographic Data Center;
• [54]Crystallographic data for 10 (ref. CCDC 916672) can be obtained on request from the director. 12 Union Road, Cambridge CB2 1EW, UK: Cambridge Crystallographic Data Center;
• [55]Crystallographic data for 12 (ref. CCDC 916668) can be obtained on request from the director. 12 Union Road, Cambridge CB2 1EW, UK: Cambridge Crystallographic Data Center;
• [56]Crystallographic data for 13 (ref. CCDC 916669) can be obtained on request from the director. 12 Union Road, Cambridge CB2 1EW, UK: Cambridge Crystallographic Data Center;