Vilsmeier-Haack Reagent (Halomethyleneiminium Salt)

Biographical Sketches

Mrs. Tasneem received her Bachelor Degree from Osmania University, Hyderabad, India and a Masters degree from the University of Hyderabad. After completion of her MSc, she joined Prof. K. C. Rajanna (Osmania University) to pursue her research work leading to a PhD. She has been assigned to carry out micellar-mediated kinetic studies of organic substitution reactions such as formylation, acetylation and nitration. At present, she is actively engaged in the field of kinetic and mechanistic studies of Vilsmeier-Haack reactions under various conditions.

Introduction

The Vilsmeier-Haack reagent (halomethyleneiminium salt) formed from the interaction of dialkyl formamides such as DMF with POCl₃ has attracted the attention of synthetic organic chemists since its discovery in 1927. [1] It is one of the most commonly used reagents for the introduction of an aldehydic (CHO) group into aromatic and heteroaromatic compounds. [2]

Some interesting cyclisation reactions have also been reported under Vilsmeier conditions. [3] In addition, certain striking applications eg halogenation, alkylation (methylation) and haloalkylation have been recently reported. [4]

Abstract

(A) Rajanna et al reported that acetanilides, particularly deactivated acetanilides, undergo Vilsmeier-Haack cyclisation in micellar media to afford the corresponding 2-chloro-3-formyl quinoline derivatives in good yields. This procedure works efficiently in the presence of micelles i.e. CTAB (cetyltrimethylammonium bromide), SDS (sodium dodecylsulfate) and TX (Triton-X-100) under reflux conditions. Surprisingly, the reaction time was reduced up to 10-fold in the present method. [5] Under ultrasonic irradiation, the reaction times were even more reduced with dramatic enhancement in the yield of reaction products. [6]
(B) Alkyl diacylacetalates are efficiently converted into 2,6-dichloro-3-formyl benzoates using the Vilsmeier-Haack reagent under microwave irradiation. The reaction time has been decreased from hours to seconds. [7]
(C) Cheng et al. reported the formation of unexpected products from the formylation of N,N-dimethylanilines with 2-formamidopyridine in POCl3 under Vilsmeier-Haack reaction conditions. 2-Formamidopyridine in POCl3 solution reacts with N,N-dime­thylaniline to give tris(4-dimethylaminophenyl)methane in 80% yield, whereas with 4-N,N-dimethylaniline it gives 2-dimethylamino-5-phenyl(2-N-methylformamido-5X-Phenyl)(2-pyridyloamino)methane. [8]
(D) 2-Chloro-3-pyridine carboxaldehydes were synthesised for the first time by Vilsmeier-Haack reaction of 4-aryl-3-buten-2-one oxime. The reaction proceeds via the formation of N-(2-arylethenyl) acetamides as intermediates. [9]
(E) Lellouche et al reported that the two electrophilic Vilsmeier-Haack complexes formed from POCl3-DMF or (CF3SO2)2O-DMF react with C 2-symmetrical dialkoxysilanes R1O-Si(R2)2-OR1 affording the corresponding formates R1CHO in low/medium to high yields depending on conditions and substrates. [10]
(F) POCl3-DMF over silica gel has been used for the synthesis of β-chlorovinylaldehydes, 2-aryl-3-formylindoles, 2-chloro-3-formylquinolines and other aromatic aldehydes using solvent-free conditions and microwave irradiation. The Vilsmeier-Haack reaction was performed in 1.5-2.5 minutes under microwave irradiation in solvent-free conditions with good yields. Furthermore, the present method is rapid and efficient and avoids the use of the reagent as solvent and thus is environmentally friendly. [11]

References

1 Vilsmeier A. Haack A. Berichte  1927,  60:  119 

2a Massa CM. Tetrahedron  1992,  48:  3659 

2b Jutz C. In Advances in Organic Chemistry   9:  Taylor EC. Wiley; New York: 1976.  p.225 

2c Seshadri S. J. Sci. Ind. Res.  1973,  32:  128 

3a Meth-Cohn O. Tarnowshi B. Adv. Heterocycl. Chem.  1982,  31:  207 

3b Meth-Cohn O. Taylor DL. J. Chem. Soc., Chem Commun.  1995,  1463 

3c Jackson A. Meth-Cohn O. J. Chem. Soc., Chem Commun  1995,  1319 

4a Selvi S. Perumal PT. Org. Prep. Proced. Int.  2001,  33:  194 

4b Dinakaran K. Perumal PT. Ind. J. Chem., Sect. B.  2000,  39:  135 

4c Krapivin GD. Kozhina ND. Chernousenko LAZavodnikVE. Chem. Heterocycl. Compd.  1999,  35:  23 

5 Ali MM. . Rajanna KC. Saiprakash PK. Synlett  2001,  251 

6 Ali MM. Sana Sariah. . Rajanna KC. Saiprakash PK. Synth. Commun.  2002,  32:  1351 

7 Selvi S. Perumal PT. Synth. Commun.  2000,  30:  3925 

8 Cheng Y. Jiao P. Williams DJ. Meth-Cohn O. J. Chem. Soc., Perkin Trans. 1  2001,  44 

9 Perumal PT. Amaresh RR. Synth. Commun.  2000,  30:  2269 

10 Cohen Y. Kotlyar V. Koeller S. Lellouche JP. Sylett  2001,  1543 

11 Paul S. Gupta M. Gupta R. Synlett  2000,  1115