Next Article in Journal
2-(4-(2-Chloroacetamido)-1-methyl-1H-pyrrole-2-carboxamido)ethyl Acetate
Previous Article in Journal
[7-(Fluoromethyl)-2-naphthyl]methanol
Article Menu

Export Article

Molbank 2014, 2014(1), M819; doi:10.3390/M819

Short Note
N,N-Dibenzyl-1-(1-[(4-methyl-2-phenyl-4,5-dihydrooxazol-4-yl)methyl)]-1H-1,2,3-triazol-4-yl)methanamine
Aouine Younas, El Hallaoui Abdelilah and Alami Anouar *
Laboratoire de Chimie Organique, Faculté des Sciences Dhar El Mahraz, Université Sidi Mohamed Ben Abdellah, B.P. 1796 Fès-Atlas, 30003, Morocco
*
Author to whom correspondence should be addressed; Tel./Fax: +212-5-3573-3171.
Received: 5 January 2014 / Accepted: 18 February 2014 / Published: 3 March 2014

Abstract

:
The title compound, N,N-dibenzyl-1-(1-[(4-methyl-2-phenyl-4,5-dihydrooxazol-4-yl)methyl)]-1H-1,2,3-triazol-4-yl)methanamine was synthesized in high yield by 1,3-dipolar cycloaddition reaction of 4-(azidomethyl)-4-methyl-2-phenyl-4,5-dihydrooxazole and N,N-dibenzylprop-2-yn-1-amine in toluene at reflux. The structure of this product was established on the basis of NMR spectroscopy (1H, 13C), Elemental Analysis and MS data.
Keywords:
oxazoline; 1,2,3-triazole; 1,3-dipolar cycloaddition
Triazoles constitute an important class of biologically active heterocyclic compounds that have received a great deal of attention since their discovery. Diverse compounds containing the 1,2,3-triazole moiety have a wide spectrum activities including antimicrobial activities [1,2], anti-HIV agents, antimicrobial, anticancer, antibacterial, antifungal, anti-tubercular compounds [3,4] and corrosion inhibitors [5].
Continuing our investigations in the use of oxazoline derivatives [6,7,8] in heterocyclic synthesis, we present in this short note a convenient and easy procedure for the preparation of N,N-dibenzyl-1-(1-[(4-methyl-2-phenyl-4,5-dihydrooxazol-4-yl)methyl)]-1H-1,2,3-triazol-4-yl)methanamine 3, a new oxazolinic precursors of heterocyclic amino acids.
For the first time, we prepared the terminal alkyne N,N-dibenzylprop-2-yn-1-amine 2 by the reaction of N-alkyaltion of propargyl bromide by dibenzylamine in anhydrous acetone at room temperature in the presence of K2CO3 as base [9]. The intermediate 2 is obtained with a 92% yield as colorless oil, and then it was submitted to cycloaddition reaction with azide 1.
This reaction leads normally to the formation of two regioisomers (1,4-isomer and 1,5-isomer) with prevalence of the 1,4-isomer [10]. We isolated after column chromatography on silica gel two isomers with a total yield of about 84%. The cycloadduct 3 was synthesized as shown in Scheme 1.
A mixture of 0.65 mmol of 4-(azidomethyl)-4-methyl-2-phenyl-4,5-dihydrooxazole 1 and 0.65 mmol of N,N-dibenzylprop-2-yn-1-amine 2 in 5mL of toluene, was heated at reflux with constant stirring for 72 h. After reaction, the solvent was evaporated under vacuum and the residue was extracted with ether. The organic layer was washed with water, dried with sodium sulfate (Na2SO4), and the solvent was removed. The products were purified by column chromatography on silica gel using ether/hexane (1/2) as eluent to afford pure products. The major product 3, the 1,4-isomer, was obtained as a white solid. The structures of the products were established on the basis of NMR spectroscopy (1H, 13C), Elemental analysis and MS data [11].
Description of the majority compound 3: White solid; Proportion of isomer = 80%; Rf (ether) = 0.51; Melting point: 100–102 °C.
1H-NMR (Bruker, 300.13 MHz, CDCl3): δ (ppm) 1.42 (3H, CH3, s); 3.37–3.47 (4H, dibenzyl, AB system, J = 13.47 Hz); 3.66–3.73 (2H, CH2N(Bn)2, AB system, J = 14.64 Hz); 4.06–4.52 (2H, 4,5-dihydrooxazole, AB system, J = 8.92 Hz); 4.45–4.53 (2H, CH2-triazole, AB system, J = 14.10 Hz); 7.18–7.91 (15Harom, m); 7.61 (1H51,2,3-triazole, s).
13C-NMR (Bruker, 75.47 MHz; CDCl3): δ (ppm) 25.1 (1C, CH3); 47.6 (1C, CH2N(Bn)2); 57.3 (2C, dibenzyl); 57.4 (1C, 4,5-dihydrooxazole); 70.7 (1C, CH2-triazole); 74.7 (1C, CH2(4,5-dihydrooxazole)); 132.0 and 150.3 (2C, C4 and C5 of 1,2,3-triazole); 124.6–139.5 (18Carom); 164.6 (1C, C=N of 4,5-dihydrooxazole).
Anal. calcd. for C28H29N5O: C, 74.47%; H, 6.47%; N, 15.51%. Found: C, 74.87%; H, 6.18%; N, 15.11%.
MS (EI): m/z (rel. int. %) = 451 (100%) (M+).

Supplementary materials

Supplementary File 1Supplementary File 2Supplementary File 3

References and Notes

  1. Xu, W.; Song, B.; Bhadury, P.; Song, Y.; Hu, D. Synthesis and crystal structure of novel sulfone derivatives containing 1,2,4-triazole moieties. Molecules 2010, 15, 766–779. [Google Scholar] [CrossRef] [PubMed]
  2. Karabasanagouda, T.; Adhikari, A.V.; Shetty, N.S. Synthesis and antimicrobial activities of some novel 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles and 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines carrying thioalkyl and sulphonyl phenoxy moieties. Eur. J. Med. Chem. 2007, 42, 521–529. [Google Scholar] [CrossRef] [PubMed]
  3. Agalave, S.G.; Maujan, S.R.; Pore, V.S. Click chemistry: 1,2,3-Triazoles as pharmacophores. Chem. Asian J. 2011, 6, 2696–2718. [Google Scholar] [CrossRef] [PubMed]
  4. Ganesh, A. Potential biological activity of 1,4-sustituted-1H-[1,2,3]triazoles. Int. J. Chem. Sci. 2013, 11, 573–578. [Google Scholar]
  5. González-Olvera, R.; Espinoza-Vázquez, A.; Negrón-Silva, G.E.; Palomar-Pardavé, M.E.; Romero-Romo, M.A.; Santillan, R. Multicomponent click synthesis of new 1,2,3-triazole derivatives of pyrimidine nucleobases: promising acidic corrosion inhibitors for steel. Molecules 2013, 18, 15064–15079. [Google Scholar] [CrossRef] [PubMed]
  6. Atmani, A.; El Hajji, S.; El Hallaoui, A.; Roumestant, M.L.; Viallefont, P. From oxazolines to precursors of aminoacids. Synth.Commun. 1991, 21, 2383–2390. [Google Scholar] [CrossRef]
  7. Zaid, F.; El Hajji, S.; El Hallaoui, A.; Elachqar, A.; Kerbal, A.; Roumestant, M.L.; Viallefont, P. Synthesis of heterocyclic β-aminoalcohol precursors of heterocyclic α-aminoacids. Prep. Biochem. Biotechnol. 1998, 28, 137–153. [Google Scholar] [CrossRef] [PubMed]
  8. Zaid, F.; El Hajji, S.; El Hallaoui, A.; Elachqar, A.; Alami, A.; Roumestant, M.L.; Viallefont, P. Synthesis of heterocyclic α-aminoaldehyde and α-aminoacid analogues of Histidines. Prep. Biochem. Biotechnol. 1998, 28, 155–165. [Google Scholar] [CrossRef] [PubMed]
  9. Aouine, Y.; Faraj, H.; Alami, A.; El Hallaoui, A.; Elachqar, A.; El Hajji, S.; Kerbal, A.; Labriti, B.; Martinez, J.; Rolland, V. Synthesis of new compounds, precursors of biheterocyclic amino acids. J. Mar. Chim. Heterocycl. 2008, 7, 44–49. [Google Scholar]
  10. Huisgen, R. Kinetics and mechanism of 1,3-dipolar cycloadditions. Angew. Chem. Int. Ed. 1963, 2, 633–645. [Google Scholar] [CrossRef]
  11. Description of the minority compound: Yellow oil; Rf (ether) = 0.63. 1H-NMR (Bruker, 300.13 MHz, CDCl3): δ (ppm) 1.30 (3H, CH3, s); 3.46–3.56 (4H, dibenzyl, AB system, J = 13.45 Hz); 3.63–3.92 (2H, CH2N(Bn)2, AB system, J = 14.49 Hz); 5.04–5.65 (2H, 4,5-dihydrooxazole, AB system, J = 8.91 Hz); 6.46 (2H, CH2-triazole, s); 7.06–7.91 (15Harom, m); 7.58 (1H41,2,3-triazole, s). 13C-NMR (Bruker, 75.47 MHz; CDCl3): δ (ppm) 25.1 (1C, CH3); 46.7 (1C, CH2N(Bn)2); 55.1 (1C, 4,5-dihydrooxazole); 58.3 (2C, dibenzyl); 71.2 (1C, CH2-triazole); 75.5 (1C, CH2(4,5-dihydrooxazole)); 131.7 and 150.0 (2C, C4 and C5 of 1,2,3-triazole); 127.0–138.3 (18Carom); 164.0 (1C, C=N of 4,5-dihydrooxazole). MS (EI): m/z (rel. int. %) = 451.2 (100%) (M+).
Scheme 1. Synthesis of compounds 3.
Scheme 1. Synthesis of compounds 3.
Molbank 2014 m819 sch001
Molbank EISSN 1422-8599 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top