Aromatic chlorination of ω-phenylalkylamines and ω-phenylalkylamides in carbon tetrachloride and α,α,α-trifluorotoluene

Abstract

The aromatic halogenation of simple alkylbenzenes with chlorine proceeds smoothly in acetic acid but is much less efficient in less polar solvents. By contrast chlorination of omega-phenylalkylamines, such as 3-phenylpropylamine, occurs readily in either acetic acid, carbon tetrachloride or alpha,alpha,alpha-trifluorotoluene, and in the latter solvents gives high proportions of ortho-chlorinated products. These effects are attributable to the involvement of N-chloroamines as reaction intermediates, with intramolecular delivery of the chlorine electrophile. Omega-phenylalkylamides, such as 3-phenylpropionamide, also easily undergo aromatic chlorination in carbon tetrachloride and alpha,alpha,alpha-trifluorotoluene. These reactions generally show a first-order dependence on the substrate concentration, but not on the amount of chlorine. With carbon tetrachloride, very similar reaction rates are observed with chlorine concentrations ranging from 0.1-1.5 M. In alpha,alpha,alpha-trifluorotoluene, the rates reach a plateau at a chlorine concentration of approximately 0.2 M. These features indicate that the reactions proceed via the formation of intermediates which evidence suggests may be the corresponding O-chloroimidates. Irrespective of the mechanistic details, the reactions are remarkably rapid, being faster than analogous reactions in acetic acid and three to four orders of magnitude more rapid than reactions of simple alkylbenzenes in carbon tetrachloride. Therefore, chlorination of the amines and amides may be accomplished without the need for highly polar solvents, added catalysts or large excesses of chlorine, which are often employed for electrophilic aromatic substitutions. Although the use of carbon tetrachloride is becoming increasingly impractical due to environmental concerns, the trifluorotoluene is a suitable alternative.

Nitrogen Modified Carbon Nano-Materials as Stable Catalysts for Phosgene Synthesis

“…1,4-Diaminobenzene, for example, reacted readily with Cl 2 , results in the immediate formation of chlorination products (Figure S15). Overall, aromatic amines promote the irreversible consumption of Cl 2 via secondary reaction pathways. , Chlorination of aromatic amines does not need highly polar solvents or an added catalyst, frequently required for other electrophilic aromatic substitutions . The formation of a N-chloramine as a reaction intermediate facilitates the electrophilic Cl δ+ via the heterolytic cleavage of N–Cl bond, able to further promote the substitution of H for Cl.…”

“…The linear dependence of the irreversible Cl 2 uptake from the concentration of nucleophilic carbon at ortho and para positions of the aromatic rings in polymer A, C, and D suggests that these sites favor electrophilic Cl 2 adsorption and formation of strong C–Cl covalent bonds (Scheme ). − …”

“…51,52 Chlorination of aromatic amines does not need highly polar solvents or an added catalyst, frequently required for other electrophilic aromatic substitutions. 51 The formation of a Nchloramine as a reaction intermediate facilitates the electrophilic Cl δ+ via the heterolytic cleavage of N−Cl bond, able to further promote the substitution of H for Cl. In the current experiments, the initial Cl 2 uptake and the number of free accessible aromatic sp 2 carbon sites at vicinal ortho and para positions to an amine or nitrile functionality were directly correlated (Figure 5a).…”

Brønsted Acidic Ionic Liquid Accelerated Halogenation of Organic Compounds with N-Halosuccinimides (NXS)

“…p-Chlorotoluene+o-Chlorotoluene ( 38c , 39c ). One mmol of substrate, 3 mmol IL-A, 1.1 mmol NCS, r.t. = 180 min, 70 °C; 1 H-NMR (CDCl 3 ): δ 7.37–7.31 (m, 1H), 7.25–7.07 (m, 7H), 2.39 (s, 3H), 2.32 (s, 3H) [ 73 ].…”

Fluorous Organic Hybrid Solvents for Non-Fluorous Organic Synthesis

“…Easton and his co-workers performed aromatic chlorination of ophenylalkylamine and o-phenylalkylamide with chlorine gas in BTF as a solvent (Scheme 3) [12]. The rate constant of chlorination of 3-phenylpropionamide (13) in BTF was determined to be 8.8 Â 10 À3 M À1 s À1 , which is slightly larger than that in carbon tetrachloride (1.3 Â 10 À3 M À1 s À1 ) and two orders of magnitude larger than that in acetic acid.…”