Journal of Chemical Crystallography

, Volume 47, Issue 5, pp 166–172 | Cite as

Structure Determination of 2-(3,4-Dihydroisoquinolin-2(1H)-yl)-2-[4-(dimethylamino)phenyl]acetonitrile, an α-Amino Nitrile Obtained by a Modified Strecker Reaction

  • Aurora L. Carreño Otero
  • José H. Quintana
  • José Antonio Henao
  • Vladimir V. Kouznetsov
  • José Miguel Delgado
  • Graciela Díaz de DelgadoEmail author
Original Paper


Modified Strecker synthesis between 4-(dimethylamino)benzaldehyde (1), 1,2,3,4-tetrahydroisoquinoline (2), and potassium cyanide in the presence of silica-supported sulfuric acid in MeCN at room temperature produced the new compound 2-(3,4-dihydroisoquinolin-2(1H)-yl)-2-[4-(dimethylamino)phenyl]acetonitrile (3). The yellow prisms obtained from petroleum ether:ethyl acetate (30:1) mixture at 25 °C are monoclinic, space group P21/c, with a = 13.2197(9) Å, b = 6.4454(4) Å, c = 19.1092(13) Å, β = 95.051(8)°, V = 1621.90(19) Å3, Z = 4. The refinement converged to R = 0.0434, wR 2  = 0.1247, S = 1.02. Molecules of 3 interact via C–H⋯N and C–H⋯π contacts to form zig-zag ribbons that run along the a-axis and stack along the c-axis, connected by van der Waals interactions.

Graphical Abstract

Zig-zag ribbons connected by C–H⋯N and C–H⋯π interactions dominate the structure of the new α-amino nitrile 2-(3,4-dihydroisoquinolin-2(1H)-yl)-2-[4-(dimethylamino)phenyl]acetonitrile synthesized by a one-pot Strecker reaction.


α-Amino nitriles Multi-component reactions (MCRs) Three component Strecker reaction Girgensohnine analogues 



The authors thank Vicerrectoría de Investigación y Extensión, Universidad Industrial de Santander (UIS) and Laboratorio de Rayos-X-Parque Tecnológico Guatiguará, UIS, Piedecuesta, Santander, Colombia, for the support to the diffraction data acquisition facilities. Financial support from Departamento Administrativo de Ciencia, Tecnología e Innovación de Colombia, COLCIENCIAS, RC-Contract 624-2014, is gratefully acknowledged. A.L.C.O. thanks COLCIENCIAS for the fellowship No. 567/2012 to carry out Doctoral studies.


  1. 1.
    Dömling A, Wang W, Wang K (2012) Chemistry and biology of multicomponent reactions. Chem Rev 112(6):3083–3135. doi: 10.1021/cr100233r CrossRefGoogle Scholar
  2. 2.
    Biggs-Houck JE, Younai A, Shaw JT (2010) Recent advances in multicomponent reactions for diversity-oriented synthesis. Curr Opin Chem Biol 14(3):371–382. doi: 10.1016/j.cbpa.2010.03.003 CrossRefGoogle Scholar
  3. 3.
    Ramón DJ, Yus M (2005) Asymmetric multicomponent reactions (AMCRs): the new frontier. Angew Chem Int Ed 44(11):1602–1634. doi: 10.1002/anie.200460548 CrossRefGoogle Scholar
  4. 4.
    Gröger H (2003) Catalytic enantioselective Strecker reactions and analogous syntheses. Chem Rev 103(8):2795–2828. doi: 10.1021/cr020038p CrossRefGoogle Scholar
  5. 5.
    Vargas Mendez LY, Kouznetsov VV (2013) First girgensohnine analogs prepared through InCl3-catalyzed Strecker reaction and their bioprospection. Curr Org Synth 10(6):969–973. doi: 10.2174/157017941006140206105449 CrossRefGoogle Scholar
  6. 6.
    Harusawa S, Hamada Y, Shioiri T (1979) Diethyl phosphorocyanidated (DEPC). A novel reagent for the classical Strecker’s α-amino nitrile synthesis. Tetrahedron Lett 20(48):4663–4666. doi: 10.1016/S0040-4039(01)86677-6 CrossRefGoogle Scholar
  7. 7.
    Nakamura S, Sato N, Sugimoto M, Toru T (2004) A new approach to enantioselective cyanation of imines with Et2AlCN. Tetrahedron 15(9):1513–1516. doi: 10.1016/j.tetasy.2004.03.040 CrossRefGoogle Scholar
  8. 8.
    Li Z, Ma Y, Xu J, Shi J, Cai H (2010) One-pot three-component synthesis of α-aminonitriles using potassium hexacyanoferrate(II) as an eco-friendly cyanide source. Tetrahedron Lett 51(30):3922–3926. doi: 10.1016/j.tetlet.2010.05.088 CrossRefGoogle Scholar
  9. 9.
    Rueping M, Sugiono E, Azap C (2006) A highly enantioselective Brønsted acid catalyst for the Strecker reaction. Angew Chem Int Ed 45(16):2617–2619. doi: 10.1002/anie.200504344 CrossRefGoogle Scholar
  10. 10.
    Reddy SS, Reddy BRP, Reddy PVG (2015) Propylphosphonic anhydride (T3P®) catalyzed one-pot synthesis of α-aminonitriles. Chin Chem Lett 26(6):739–743. doi: 10.1016/j.cclet.2015.03.021 CrossRefGoogle Scholar
  11. 11.
    Zhang G-W, Zheng D-H, Nie J, Wang T, Ma J-A (2010) Bronsted acid-catalyzed efficient Strecker reaction of ketones, amines and trimethylsilyl cyanide. Org Biomol Chem 8(6):1399–1405. doi: 10.1039/B924272D CrossRefGoogle Scholar
  12. 12.
    Ranu BC, Dey SS, Hajra A (2002) Indium trichloride catalyzed one-step synthesis of α-amino nitriles by a three-component condensation of carbonyl compounds, amines and potassium cyanide. Tetrahedron 58(13):2529–2532. doi: 10.1016/S0040-4020(02)00132-1 CrossRefGoogle Scholar
  13. 13.
    Bakherad M, Keivanloo A, Siavashi M, Omidian M (2014) Three-component synthesis of imidazo[1,2-c]pyrimidines using silica sulfuric acid (SSA). Chin Chem Lett 25(1):149–151. doi: 10.1016/j.cclet.2013.10.013 CrossRefGoogle Scholar
  14. 14.
    Kantam ML, Mahendar K, Sreedhar B, Choudary BM (2008) Synthesis of α-amino nitriles through Strecker reaction of aldimines and ketoimines by using nanocrystalline magnesium oxide. Tetrahedron 64(15):3351–3360. doi: 10.1016/j.tet.2008.01.128 CrossRefGoogle Scholar
  15. 15.
    Resnick L, Galante RJ (2006) A practical synthesis of 3-ethyl-l-norvaline. Tetrahedron 17(5):846–849. doi: 10.1016/j.tetasy.2006.02.002 CrossRefGoogle Scholar
  16. 16.
    Veisi H (2010) Silica sulfuric acid (SSA) as a solid acid heterogeneous catalyst for one-pot synthesis of substituted pyrroles under solvent-free conditions at room temperature. Tetrahedron Lett 51(16):2109–2114. doi: 10.1016/j.tetlet.2010.02.052 CrossRefGoogle Scholar
  17. 17.
    Wu H, Shen Y, Fan L-y, Wan Y, Shi D-q (2006) Solid silica sulfuric acid (SSA) as a novel and efficient catalyst for acetylation of aldehydes and sugars. Tetrahedron 62(34):7995–7998. doi: 10.1016/j.tet.2006.06.038 CrossRefGoogle Scholar
  18. 18.
    Wu H, Shen Y, Fan L-y, Wan Y, Zhang P, Chen C-f, Wang W-x (2007) Stereoselective synthesis of β-amino ketones via direct Mannich-type reaction catalyzed with silica sulfuric acid. Tetrahedron 63(11):2404–2408. doi: 10.1016/j.tet.2007.01.015 CrossRefGoogle Scholar
  19. 19.
    Carreño Otero AL, Vargas Méndez LY, Duque L JE, Kouznetsov VV (2014) Design, synthesis, acetylcholinesterase inhibition and larvicidal activity of girgensohnine analogs on Aedes aegypti, vector of dengue fever. Eur J Med Chem 78:392–400. doi: 10.1016/j.ejmech.2014.03.067 CrossRefGoogle Scholar
  20. 20.
    Groom CR, Bruno IJ, Lightfoot MP, Ward SC (2016) The Cambridge structural database. Acta Crystallogr Sect B 72 (2):171–179. doi: 10.1107/S2052520616003954 CrossRefGoogle Scholar
  21. 21.
    Rigaku/MSC I (2000) CRYSTALCLEAR, Software Users Guide, version 1.3.6. Rigaku/MSC I, The WoodlandsGoogle Scholar
  22. 22.
    Sheldrick GM (2015) SHELXT—Integrated space-group and crystal-structure determination. Acta Crystallogr Sect A 71(1):3–8. doi: 10.1107/S2053273314026370 CrossRefGoogle Scholar
  23. 23.
    Sheldrick GM (2015) Crystal structure refinement with SHELXL. Acta Crystallogr Sect C 71(1):3–8. doi: 10.1107/S2053229614024218 CrossRefGoogle Scholar
  24. 24.
    Dolomanov OV, Bourhis LJ, Gildea RJ, Howard JAK, Puschmann H (2009) OLEX2: a complete structure solution, refinement and analysis program. J Appl Crystallogr 42(2):339–341. doi: 10.1107/S0021889808042726 CrossRefGoogle Scholar
  25. 25.
    Brandenburg K (1999) DIAMOND. 3.0 edn. Crystal Impact GbR, BonnGoogle Scholar
  26. 26.
    Spek AL (2009) Structure validation in chemical crystallography. Acta Crystallogr Sect D 65(2):148–155. doi: 10.1107/S090744490804362X CrossRefGoogle Scholar
  27. 27.
    Allen FH, Johnson O, Shields GP, Smith BR, Towler M (2004) CIF applications. XV. enCIFer: a program for viewing, editing and visualizing CIFs. J Appl Crystallogr 37(2):335–338. doi: 10.1107/S0021889804003528 CrossRefGoogle Scholar
  28. 28.
    Boeyens JCA (1978) The conformation of six-membered rings. J Cryst Mol Struct 8(6):317–320. doi: 10.1007/bf01200485 CrossRefGoogle Scholar
  29. 29.
    Etter MC, MacDonald JC, Bernstein J (1990) Graph-set analysis of hydrogen-bond patterns in organic crystals. Acta Crystallogr Sect B 46(2):256–262. doi: 10.1107/S0108768189012929 CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Aurora L. Carreño Otero
    • 1
  • José H. Quintana
    • 2
    • 4
  • José Antonio Henao
    • 2
    • 4
  • Vladimir V. Kouznetsov
    • 1
  • José Miguel Delgado
    • 3
    • 4
  • Graciela Díaz de Delgado
    • 3
    • 4
    Email author
  1. 1.Laboratorio de Química Orgánica y Biomolecular, Escuela de QuímicaUniversidad Industrial de SantanderBucaramanga A.A. 678Colombia
  2. 2.Grupo de Investigación en Química Estructural (GIQUE), Escuela de QuímicaUniversidad Industrial de SantanderBucaramanga A.A. 678Colombia
  3. 3.Laboratorio de Cristalografía-LNDRX, Departamento de Química, Facultad de CienciasUniversidad de Los AndesMéridaVenezuela
  4. 4.Red Suramericana de Caracterización Estructural de Farmacóforos, Catalizadores y SemiconductoresUniversidad Industrial de SantanderBucaramanga A.A. 678Colombia

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