Insights into the chemistry and therapeutic potential of acrylonitrile derivatives

Abstract

Acrylonitrile is a fascinating scaffold widely found in many natural products, drugs, and drug candidates with various biological activities. Several drug molecules such as entacapone, rilpivirine, teriflunomide, and so forth, bearing an acrylonitrile moiety have been marketed. In this review, diverse synthetic strategies for constructing desired acrylonitriles are discussed, and the different biological activities and medicinal significance of various acrylonitrile derivatives are critically evaluated. The information gathered is expected to provide rational guidance for the development of clinically useful agents from acrylonitriles.

Transition-Metal-Free and Selective Deconstructive Carbonyl Olefination of α-Hydroxy Ketones: A Complementary Approach to Knoevenagel Reaction

“…12 With these research backgrounds, herein, we report Knoevenagel-type deconstructive carbonyl olefination of α-hydroxy ketones using arylacetonitriles to access 2,3-diaryl acrylonitriles (Scheme 1b), an important class of α,β-unsaturated nitriles. 13 We started our investigations by selecting 2-hydroxy-1,2,2triarylethanone (1a) as the model substrate (Table 1). A solution of 1a and 4-methoxyphenylacetonitrile (2a, 2.0 equivalents) was treated with NaOH (1.5 equivalents) in MeOH at 80 C under air atmosphere (entry 1).…”

“…IR spectra (in wavenumber) were recorded with Thermo Scientific (NICOLET IS 50) FT-IR spectrophotometer. 1 H NMR and 13 C NMR spectra were recorded in CDCl3 with a Bruker Avance NEO 500 NMR spectrometer operating at 500 MHz and 125.77 MHz respectively. Chemical shifts (δ) are reported in parts per million downfield from tetramethylsilane as an internal standard.…”

“…1 H NMR (CDCl3, 500 MHz): ẟ = 7.10-7.14 (m, 2H, ArH), 7.41-7.47 (m, 4H, ArH and olefinic H), 7.62-7.66 (m, 2H, ArH), 7.85 ppm (dd, J = 7.9, 1.7 Hz, 2H, ArH). 13 2-(3-methoxyphenyl)-3-phenylacrylonitrile (9) 20 White solid; Yield: 166 mg (75 %); Rf = 0.4 (n-hexane/EtOAc, 9.5:0.5); mp: 68-69 ⁰C. IR (neat) = 3040, 2945, 2837, 2214 (CN), 1587, 1487, 1429, 1269 cm -1 .…”

“…1 H NMR (CDCl3, 500 MHz): ẟ = 3.84 (s, 3H, OCH3), 6.91 (dd, J = 7.7, 2.5 Hz, 1H, ArH), 7.18 (t, J = 2.2 Hz, 1H, ArH), 7.23-7.26 (m, 1H, ArH), 7.33 (t, J = 7.9 Hz, 1H, ArH), 7.39-7.46 (m, 3H, ArH and olefinic H), 7.51 (s, 1H, ArH), 7.86 ppm (dd, J = 8.3, 1.6 Hz, 2H, ArH). 13 C NMR (CDCl3, 125.77 MHz): ẟ = 55. 5 13 C NMR (CDCl3, 125.77 MHz): ẟ = 110.3, 117.5 (CN), 123.8 (q, 1 JCF = 270 Hz), 126.1 (q, 3 JCF = 3.8 Hz), 126.3, 129.1, 129.5, 131.0 (q, 2 JCF = 32.7 Hz), 131.2, 133.2, 137.9, 144.2 ppm.…”

“…13 C NMR (CDCl3, 125.77 MHz): ẟ = 55. 5 13 C NMR (CDCl3, 125.77 MHz): ẟ = 110.3, 117.5 (CN), 123.8 (q, 1 JCF = 270 Hz), 126.1 (q, 3 JCF = 3.8 Hz), 126.3, 129.1, 129.5, 131.0 (q, 2 JCF = 32.7 Hz), 131.2, 133.2, 137.9, 144.2 ppm. 19 White solid; Yield: 163 mg (79 %); Rf = 0.54 (n-hexane/EtOAc, 9.5:0.5); mp: 65-66 ⁰C.…”