Synlett 2013; 24(9): 1162-1163
DOI: 10.1055/s-0033-1338942
spotlight
© Georg Thieme Verlag Stuttgart · New York

2-Cyanoacetamide

Anna Zdzienicka
Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Łódź, Muszyńskiego 1, 90-151 Łódź, Poland   Email: anna.zdzienicka@umed.lodz.pl
› Author Affiliations
Further Information

Publication History

Publication Date:
08 May 2013 (online)

 
Zoom Image

Anna Zdzienicka was born in Łódź (Poland) in 1987. She received her M.Sc. degree in chemistry in 2011 working in the group of Professor Janusz Zakrzewski at the Department of Organic Chemistry, University of Łódź. Currently, she is continuing her research at the Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Łódź, working in the group of Professor Andrzej E. Wróblewski. Her research interests focus on synthesis of new 1,2,3-triazolylalkylphosphonates.

Introduction

Cyanoacetic acid derivatives are important intermediates in the synthesis of various organic heterocyclic compounds. Among these derivatives, 2-cyanoacetamide deserves attention since it is a useful reagent for the synthesis of a variety of novel compounds possessing ­biological activity and other special properties.[1]

It possesses electrophilic C1 and C3 carbons and nucleophilic C2 and NH centers responsible for the high reactivity and importance of this compound. The acidic C2 hydrogen prompts an extensive application in a variety of condensation and cycloaddition reactions. Moreover, 2-cyanoacetamide can take part in substitution reactions.[2]


#

Preparation:

2-Cyanoacetamide (1) is commercially available. It can be prepared by several literature procedures from: cyanoacetates 2 and ammonia, from cyanoacetic acid (3) and NH4OH, and from chloracetamide (4) and NaCN.[1]

Zoom Image
Scheme 1

#

Abstracts

(A) 2-Cyanoacetamide (1) can be readily alkylated at C2. Nucleophilic substitution in (benzamidomethyl)triethylammonium chloride (5) occurred under mild conditions in aqueous media and at ambient temperature to give disubstituted cyanoacetamide 6 without any catalyst.[3]

(B) Triarylstibine-modified Co2(CO)8 appeared to be an efficient homogeneous catalytic system for the synthesis of secondary amides by direct reductive N-alkylation of a variety of substituted aryl aldehydes with aryl-, heteroaryl- and aliphatic primary amides. Reaction of 4-tert-butyl benzaldehyde (7) and 2-cyanoacetamide (1) gave compound 8 in 90% yield.[4]

(C) The triethylamine-catalyzed alkylation of 2-cyanoacetamide (1) with 2-chloroacetoacetate (9) followed by nucleophilic attack of the amide nitrogen on the carbonyl group and acid-catalyzed dehydration led to the formation of substituted pyrrole 10 in good yield.[5]

(D) The Gewald reaction of a ketone or aldehyde with 2-cyano­acetamide in the presence of a base and elemental sulfur affords sub­stituted 2-aminothiophenes. T. Horiuchi and co-workers described the preparation of thiophene 12 from butyraldehyde (11), 2-cyanoacetamide (1) and elemental sulfur in DMF.[6]

(E) α,β-Unsaturated nitrile derivatives (Knoevenagel condensation products) are among the most important precursors of heterocycles. Various aliphatic, aromatic and heteroaromatic aldehydes 13 reacted with 2-cyanoacetamide (1) in the presence of N-methylpiperazine under solvent-free conditions to give the Knoevenagel condensation products 14.[7]

(F) 1,4-Conjugate addition (Michael reaction) of 2-cyanoacetamide (1) to butenonyl C-glycoside 15 was carried out in the presence of various organic bases in organic solvents and under a nitrogen atmosphere followed by oxidative aromatization to form glycopyranosyl methylpyridone 16.[8]

(G) [3+2] Dipolar cycloaddition of azides and 2-cyanoacetamide gave substituted 5-amine-4-carbamoyl-1,2,3-triazoles. Cycloaddition of diethyl (R)-3-azidophosphonate 17 and 2-cyanoacetamide (1) in DMSO in the presence of potassium carbonate provided phosphonate 18 in 70% yield.[9]


#
#
  • References

  • 1 Litvinov VP. Russ. Chem. Rev. 1999; 68: 737
  • 2 Fadda AA, Bondock S, Rabie R, Etman HA. Turk. J. Chem. 2008; 32: 259
  • 3 Mateska A, Stojkovic G, Mikhova B, Mladenowska K, Popovski E. ARKIVOC 2009; (x): 131
  • 4 Rubio-Pérez L, Sharma P, Pérez-Flores FJ, Velasco L, Arias JL, Cabrera A. Tetrahedron 2012; 68: 2342
  • 5 Dawadi PB. S, Lugtenburg J. Tetrahedron Lett. 2011; 52: 2508
  • 6 Horiuchi T, Chiba J, Uoto K, Soga T. Bioorg. Med. Chem. Lett. 2009; 19: 305
  • 7 Mukhopadhyay C, Datta A. Synth. Commun. 2008; 38: 2103
  • 8 Bisht SS, Jaiswal N, Sharma A, Fatima S, Sharma R, Rahuja N, Srivastava AK, Baipai V, Kumar B, Tripathi RP. Carbohydr. Res. 2011; 346: 1191
  • 9 Głowacka IE. Tetrahedron: Asymmetry 2009; 20: 2270

  • References

  • 1 Litvinov VP. Russ. Chem. Rev. 1999; 68: 737
  • 2 Fadda AA, Bondock S, Rabie R, Etman HA. Turk. J. Chem. 2008; 32: 259
  • 3 Mateska A, Stojkovic G, Mikhova B, Mladenowska K, Popovski E. ARKIVOC 2009; (x): 131
  • 4 Rubio-Pérez L, Sharma P, Pérez-Flores FJ, Velasco L, Arias JL, Cabrera A. Tetrahedron 2012; 68: 2342
  • 5 Dawadi PB. S, Lugtenburg J. Tetrahedron Lett. 2011; 52: 2508
  • 6 Horiuchi T, Chiba J, Uoto K, Soga T. Bioorg. Med. Chem. Lett. 2009; 19: 305
  • 7 Mukhopadhyay C, Datta A. Synth. Commun. 2008; 38: 2103
  • 8 Bisht SS, Jaiswal N, Sharma A, Fatima S, Sharma R, Rahuja N, Srivastava AK, Baipai V, Kumar B, Tripathi RP. Carbohydr. Res. 2011; 346: 1191
  • 9 Głowacka IE. Tetrahedron: Asymmetry 2009; 20: 2270

Zoom Image
Zoom Image
Scheme 1