Next Article in Journal
2-(4-Fluoro-3-nitrophenyl)-6-(4-methoxyphenyl)imidazo[2,1-b]-1,3,4-thiadiazole
Previous Article in Journal
Ethyl 7-Methyl-5-(4-methylphenyl)-3-oxo-2-{[3-(3,4-dichlorophenyl)-1-phenyl-1H-pyrazol-4-yl]methylidene}-2,3-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidine-6-carboxylate
 
 
Short Note

Methyl 2-Benzamido-2-(1H-benzimidazol-1-ylmethoxy)acetate

Laboratory of Organic Chemistry, Faculty of Sciences Dhar El Mehraz, University Sidi Mohamed Ben Abdellah, B.P. 1796, Fez, Morocco
Molbank 2012, 2012(3), M777; https://doi.org/10.3390/M777
Received: 14 August 2012 / Accepted: 7 September 2012 / Published: 21 September 2012

Abstract

The heterocyclic carboxylic α-aminoester methyl 2-benzamido-2-(1H-benzimidazol-1-ylmethoxy)acetate is obtained by O-alkylation of methyl α-azido glycinate N-benzoylated with 1H-benzimidazol-1-ylmethanol.
Keywords: α-aminoesters; O-alkylation; methyl α-azidoglycinate α-aminoesters; O-alkylation; methyl α-azidoglycinate

1. Introduction

It is interesting to note that amino acids are components of living organisms and are precursors for protein formation. Several researchers have investigated the inhibitory potential of some amino acids and the results obtained from such studies have given some hope for the use of amino acids as green corrosion inhibitors [1,2,3,4].
Recently, benzimidazole derivatives are a key part of many drugs [5] for their potency and activation [6,7,8]. Both telmisartan (TST) and candesartan (CST) are potent angiotensin II type 1 (AT1) receptor blockers (ARBs), which have been widely used in the treatment of hypertension and also found to display some other pharmacologic effects in treating diabetes [9] and heart disease [10], while DB921 with diamidine in terminal can strongly bind to the DNA groove and cause rapid destruction of the mitochondrial kinetoplast [11].
For this reason, we considered it interesting to synthesize new compounds containing 1H-benzimidazol-1-ylmethanol fused with a derivative of amino acid, in order to study their biological activities.
Following the research done on the synthesis of new α-carboxylic aminoesters [12] and in the synthesis of heterocyclic systems of benzimidazole derivatives, we reported in this paper another part of our investigations concerning the preparation of methyl 2-benzamido-2-(1H-benzimidazol-1-ylmethoxy)acetate. Our strategy is based on the O-alkylation of methyl α-azido glycinate N-benzoylated with 1H-benzimidazol-1-ylmethanol. The product synthesized with a satisfactory yield was characterized by nuclear magnetic resonance and mass spectrometry (Scheme 1).

2. Results and Discussion

Our strategy is based on the O-alkylation of alcohol 1H-benzimidazol-1-ylmethanol with methy α-azidoglycinate 1 (Scheme 1). Azide derivative 1 was prepared using Steglich method [13] and Achamlale’s procedure [14].
Methyl α-azido glycinate N-benzoylated 1 was obtained by the reaction [14] of sodium azide with the methyl α-bromo glycinate. The title compound is stable and can be stored for an unlimited time without any signs of decomposition. The methyl α-bromo glycinate also can be used and gives satisfactory results; the azide 1 is used especially for its stability.
As shown in Scheme 1, the reaction of 1H-benzimidazol-1-ylmethanol on azide 1 results in formation of the new racemic α-heterocyclic α-carboxylic aminoester 2 carrying 1H-benzimidazol-1-ylmethoxy group or substituent in position α.
As a first step and to optimize the different reaction conditions (choice of base, solvent ...), we conducted several test reactions. For all these tests, the reactions were followed by TLC and 1H-NMR. Yields are given as pure product after column chromatography on silica gel.
After several attempts of reactions without base or in the presence of bases such as triethylamine, reaction with diisopropylethylamine (DIPEA) gave the best results. The reaction was carried out in dry acetone at room temperature for 48 h. Results are summarized in Table 1.
The product 2 was obtained in 30% overall yield from 1 and was characterized by MS, 1H-NMR and 13C-NMR spectroscopy.
Comparing these results with the work done by our team [12,15,16], we see that we have obtained almost the same results.

3. Experimental

To a stirred solution of 2.86 mmol of alcohol (oxygen compound) and 3.12 mmol of diisopropylethylamine in 10 mL of dry acetone, 2.6 mmol of α-azido glycinate were added. The mixture was stirred at room temperature and the reaction was followed by TLC (Kiesegel Merck 60F254). The solvent was evaporated under reduced pressure. The residue was quenched with saturated aqueous solution of ammonium chloride (20 mL) and extracted with dichloromethane (20 mL × 3). The organic phase was dried in sodium sulfate (Na2SO4) and the solvent was removed under reduced pressure. The product was purified by column chromatography on silica gel using ether/hexane as eluant to afford pure O-alkylated product.
White solide: yield = 30%; Melting point (ether/hexane): 116–118 °C; Rf = 0.60 (ether).
1H-NMR (Bruker, 300.13 MHz, CDCl3): δ (ppm) = 3.87 (s, 3H, OCH3), 5.37 (sbr, 1H, Hα), 5.81 (s, 2H, OCH2), 7.00–7.82 (m, 9H, Harom), 8.02 (sbr, 1H, NHamid), 8.35 (s, 1H, Himid).
13C-NMR (75.47 MHz; CDCl3): δ (ppm) = 54.2 (OCH3), 60.8 (OCH2N), 84.1(–CH–), 110.0 (2C), 123.2 (2C), 124.05 (2C), 127.4 (2C), 128.8, 132.7 (C6H5 aromatic carbons), 134.1 (=CqN–), 138.2 (=CqN–), 143.0 (–CHimid), 167.3 (CO), 171.4 (CO).
MS (electrospray) m/z: 362 (M+H++Na+, 19%), 340 (M+H+, 100%), 296 (11%), 221 (20%), 219 (9%), 192 (33%).
Anal Calcd. for C18H17N3O4: C, 63.71%; H, 5.05%; N, 12.38%. Found: C, 63.68%; H, 5.01%; N, 12.31%.

Supplementary materials

Supplementary File 1Supplementary File 2Supplementary File 3

References and Notes

  1. Ebenso, E.E.; Isabirye, D.A.; Eddy, N.O. Adsorption and quantum chemical studies on the inhibition potentials of some thiosemicarbazides for the corrosion of mild steel in acidic medium. Int. J. Mol. Sci. 2010, 11, 2473–2498. [Google Scholar] [CrossRef] [PubMed]
  2. Eddy, N.O.; Ebenso, E.E.; Ibok, U.J. Adsorption, synergistic inhibitive effect and quantum chemical studies of ampicillin (AMP) and halides for the corrosion of mild steel in H2SO4. J. Appl. Electrochem. 2010, 40, 445–456. [Google Scholar] [CrossRef]
  3. Eddy, N.O.; Ibok, U.J.; Ebenso, E.E.; El Nemr, A.; El Ashry, E.S.H. Quantum chemical study of the inhibition of the corrosion of mild steel in H2SO4 by some antibiotics. J. Mol. Model. 2009, 15, 1085–1092. [Google Scholar] [CrossRef] [PubMed]
  4. Eddy, N.O. Experimental and theoretical studies on some amino acids and their potential activity as inhibitors for the corrosion of mild steel, part 2. J. Adv. Res. 2011, 2, 35–47. [Google Scholar] [CrossRef]
  5. Li, J.; Shi, R.; Yang, C.; Zhu, X. Exploration of the binding of benzimidazole-biphenyl derivatives to hemoglobin using docking and molecular dynamics simulation. Int. J. Biol. Macromol. 2011, 48, 20–26. [Google Scholar] [CrossRef] [PubMed]
  6. Goebel, M.; Staels, B.; Unger, T.; Kintscher, U.; Gust, R. Characterization of new PPARgamma agonists: Benzimidazole derivatives - the importance of position 2. Chem. Med. Chem. 2009, 4, 1142–1136. [Google Scholar] [CrossRef] [PubMed]
  7. Moss, N.; Choi, Y.; Cogan, D.; Flegg, A.; Kahrs, A.; Loke, P.; Meyn, O.; Nagaraja, R.; Napier, S.; Parker, A.; et al. A new class of 5-HT2B antagonists possesses favorable potency, selectivity, and rat pharmacokinetic properties. Bioorg. Med. Chem. Lett. 2009, 19, 2206–2210. [Google Scholar] [CrossRef] [PubMed]
  8. Demirayak, S.; Kayagil, I.; Yurttas, L. Microwave supported synthesis of some novel 1,3-Diarylpyrazino[1,2-a]benzimidazole derivatives and investigation of their anticancer activities. Eur. J. Med. Chem. 2011, 46, 411–416. [Google Scholar] [CrossRef] [PubMed]
  9. Cheng, Q.; Law, P.K.; de Gasparo, M.; Leung, P.S. Combination of the Dipeptidyl Peptidase IV Inhibitor LAF237 [(S)-1-[(3-Hydroxy-1-adamantyl)ammo]acetyl-2-cyanopyrrolidine] with the Angiotensin II Type 1 Receptor Antagonist Valsartan [N-(1-Oxopentyl)-N-[[2'-(1H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl]methyl]-L-valine] Enhances Pancreatic Islet Morphology and Function in a Mouse Model of Type 2 Diabetes. J. Pharmacol. Exp. Ther. 2008, 327, 683–691. [Google Scholar] [PubMed]
  10. Pfeffer, M.A.; McMurray, J.J.; Velazquez, E.J.; Rouleau, J.L.; Køber, L.; Maggioni, A.P.; Solomon, S.D.; Swedberg, K.; van de Werf, F.; White, H.; et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N. Engl. J. Med. 2003, 349, 1893–1906. [Google Scholar] [CrossRef] [PubMed]
  11. Ismail, M.A.; Batista-Parra, A.; Miao, Y.; Wilson, W.D.; Wenzler, T.; Brun, R.; Boykin, D.W. Dicationic near-linear biphenyl benzimidazole derivatives as DNA-targeted antiprotozoal agents. Bioorg. Med. Chem. 2005, 13, 6718–6726. [Google Scholar] [CrossRef] [PubMed]
  12. El Houssine, M.; Abdelrhani, E.; Anouar, A.; Abdelilah, E.H. Synthesis of New Racemic α,α-Diaminocarboxylic Ester Derivatives. Molecules 2010, 15, 9354–9363. [Google Scholar] [CrossRef]
  13. Kober, R.; Steglich, W. Untersuchungen zur Reaktion von Acylaminobrommalonestern und Acylaminobromessigestern mit Trialkylphosphiten-eine einfache Synthese von 2-Amino-2-(diethoxyphosphoryl) Essigsäure Ethylester. Liebigs Ann. Chem. 1983, 4, 599–609. [Google Scholar] [CrossRef]
  14. Achamlale, S.; Elachqar, A.; El Hallaoui, A.; El Hajji, S.; Roumestant, ML.; Viallefont, P.H. Synthesis of α-triazolyl α-aminoacid derivatives. Amino Acids 1997, 12, 257–263. [Google Scholar] [CrossRef]
  15. Boukallaba, K.; Elachqar, A.; El Hallaoui, A.; Alami, A.; El Hajji, S.; Labriti, B.; Martinez, J.; Rolland, V. Synthesis of new α-heterocyclic α-aminophosphonates. Phosphorus Sulfur Silicon Relat. Elem. 2006, 181, 819–823. [Google Scholar] [CrossRef]
  16. Mabrouk, E.H.; Abdelrhani, E.; Abdelilah, E.H.; Anouar, A.; Soumia, E.H.; Jean, M.; Vallery, R. Synthesis of new racemic α-heterocyclic α,α-diaminoesters and α-aminoester carboxylic. Arab. J. Chem. 2010. [Google Scholar] [CrossRef]
Scheme 1. O-alkylation of 1H-benzimidazol-1-ylmethanol with methy α-azidoglycinate.
Scheme 1. O-alkylation of 1H-benzimidazol-1-ylmethanol with methy α-azidoglycinate.
Molbank 2012 m777 sch001
Table 1. Synthesis of Methyl 2-benzamido-2-(1H-benzimidazol-1-ylmethoxy)acetate 2.
Table 1. Synthesis of Methyl 2-benzamido-2-(1H-benzimidazol-1-ylmethoxy)acetate 2.
Nu-HProductM.P. (°C)Reaction Time (h)-DCMEt3N DCMEt3N AcetoneDIEPA DCMDIPEA Acetone
Yield (%)Yield (%)Yield (%)Yield (%)Yield (%)
1H-benzimidazol-1-ylmethanolMethyl 2-benzamido-2-(1H-benzimidazol-1-ylmethoxy)acetate 2116–11848010152230
Back to TopTop