YENİ METİL 1H-BENZİMİDAZOL-5-KARBOKSİLAT TÜREVLERİNİN SENTEZİ VE YAPILARININ AYDINLATILMASI

Year 2023, , 490 - 496, 20.05.2023

Fatıma Doğanç

https://doi.org/10.33483/jfpau.1249200

Abstract

Amaç: Bu çalışma kapsamında daha önce bölümümüzde sentezlenen bileşiklere ek olarak bazı yeni metil 1H-benzimidazol-5-karboksilat türevlerinin sentezi gerçekleştirilmiştir. Antibakteriyel aktiviteyi artırmak için benzimidazol halkasının 2. konumu 4-metilpiperidinil grubuyla modifiye edilmiştir.
Gereç ve Yöntem: Tasarlanan metil 1H-benzimidazol-5-karboksilat bileşikleri, o-fenilendiamin türevlerinin üre ile reaksiyonu sonucu sentezlenmiştir. 2. konumda bulunan oksijen atomu POCl3 varlığında klor ile yer değiştirmiştir. Son olarak, 4-metil piperidin ile nükleofilik sübstitüsyonla hedeflenen bileşiklere ulaşılmıştır. Elde edilen bileşiklerin yapıları 1H-13C-NMR ve LC-MS teknikleriyle aydınlatılmıştır.
Sonuç ve Tartışma: Bu çalışmada daha iyi in vitro antibakteriyel aktivite elde etmek için 2. konumda 4-metilpiperidinil grubu taşıyan metil 1H-benzimidazol-5-karboksilat türevleri sentezlenmiştir. Bu çalışmada sentezlenen bileşiklerin in vitro antibakteriyel etkileri araştırılmaktadır.

Keywords

1H-13C-NMR, 1H-benzimidazol, 4-metilpiperidin, metil 1H-benzimidazol-5-karboksilat

SYNTHESIS AND STRUCTURE ELUCIDATION OF NEW METHYL 1H-BENZIMIDAZOLE-5-CARBOXYLATE DERIVATIVES

Abstract

Objective: In this study, in connection with previous works in our department, some methyl 1H-benzimidazole-5-carboxylate derivatives were synthesized for the first time. Compounds were modified by substituting the second position of the benzimidazole ring with 4-methylpiperidinyl groups for increasing antibacterial activity.
Material and Method: The targeted methyl 1H-benzimidazole-5-carboxylates were synthesized by the reaction of o-phenylendiamine derivatives with urea. Oxygen at the 2nd position was converted to chlorine in the presence of POCl3. Finally, the resulting products were obtained by the nucleophylic substitution with 4-methylpiperidine. Structures of synthesized compounds were elucidated with 1H- 13C-NMR and LC-MS techniques.
Result and Discussion: Methyl 1H-benzimidazole-5-carboxylate derivatives bearing 4-methyl piperidinyl groups at the 2nd position were synthesized to improve better in vitro antibacterial activity profiles. In vitro antibacterial activity of the synthesized compounds in this study is under investigation.

Keywords

1H-13C-NMR, 1H-benzimidazole, 4-methylpiperidine, methyl 1H-benzimidazole-5-carboxylates

References

• 1. Walia R., Headitullah M.D., Naaz S.F., Iqbal K., Lamba H.S. (2011). Benzimidazole derivatives-an overview. International Journal of Research in Pharmacy and Chemistry, 1(3), 565-574.
• 2. Hisano T., Ichikawa M., Tsumoto K., Tasaki M. (1982). Synthesis of benzoxazoles, benzothiazoles and benzimidazoles and evaluation of their antifungal, insecticidal and herbicidal activities. Chemical and Pharmaceutical Bulletin, 30(8), 2996-3004.
• 3. Göker H., Tunçbilek M., Ayhan G., Altanlar N. (1988). Synthesis of some new benzimidazolecarboxamide and evaluation of their antimicrobial activity. Il Farmaco, 53, 415-420.
• 4. Lazer E.S., Matteo M.R., Possanza G.J. (1987). Benzimidazole derivatives with atypical antiinflammoatory activity. Journal of Medicinal Chemistry, 30, 726-729.
• 5. Bansal Y., Silakari O. (2012). The therapeutic journey of benzimidazoles: A review. Bioorganic & Medicinal Chemistry, 20, 6208-6236. [CrossRef]
• 6. Yadav G., Ganguly S. (2015). Structure activity relationship (SAR) study of benzimidazole scaffold for different biological activities: A mini-review. European Journal of Medicinal Chemistry, 97, 419-443. [CrossRef]
• 7. Pintilie L., Oniscu C., Voiculescu G.H., Draghici C., Caproiu M.T., Alexandru N., Paraschiv I., Damian E., Dobrovolschi D., Diaconu L. (2003). Synthesis and antibacterial activity of some novel fluoroquinolones. Romanian Biotechnological Letters, 8(2), 1197-1204.
• 8. Shahzadi S., Ali S., Bhatti M.H., Fettouhi M., Athar M. (2006). Chloro-diorganotin(IV) complexes of 4-methyl-1-piperidine carbodithioic acid: Synthesis, X-ray crystal structures, spectral properties and antimicrobial studies. Journal of Organometallic Chemistry, 691, 1797-1802. [CrossRef]
• 9. Khan H.N., Ali S., Shahzadi S., Sharma S.K., Qanungo K. (2010). Synthesis, spectroscopy, semiempirical, phytotoxicity, antibacterial, antifungal, and cytotoxicity of diorganotin(IV) complex derived from Bu2Sn(Acac)2 and 4-methyl-1-piperidinecarbodithioic acid1. Russian Journal of Coordination Chemistry, 36(4), 310-316. [CrossRef]
• 10. Özden S., Atabey D., Yıldız S., Göker H. (2005). Synthesis and potent antimicrobial activity of some novel methyl or ethyl 1H-benzimidazole-5-carboxylates derivatives carrying amide or amidine groups. Bioorganic & Medicinal Chemistry, 13, 1587-1597. [CrossRef]
• 11. Xu Y.L., Lin H.Y., Ruan X., Yang S.G., Hao G.F., Yang W.C., Yang G.F. (2015) Synthesis and bioevaluation of pyrazole-benzimidazolone hybrids as novel human 4-hydroxyphenylpyruvate dioxygenase inhibitors. European Journal of Medicinal Chemistry, 92, 427-438. [CrossRef]
• 12. Claremon D.A., Dillard L.W., Fan Y., Lotesta S.D., Singh S.B., Tice C.M., Zhao W., Zhuang L. (2017) Modulators of ror-gamma. WO 2017/024018 A1.
• 13. Göker H., Ayhan-Kılcıgil G., Tunçbilek M., Kus C., Ertan R., Kendi E., Özbey S., Fort M., Garcia C., Farre A.J. (1999) Synthesis and antihistaminic H1 activity of 1,2,5(6)-trisubstituted benzimidazoles. Heterocycles 51(11), 2561-2573.