Conversion of Carboxamides to Nitriles Using Trichloroacetyl Chloride/Triethylamine as a Mild Dehydrating Agent

Bidirectional Association of Branched Noncovalent Complexes of Tetrazoles and 1,3,5-Tris(4,5-dihydroimidazol-2-yl)benzene in Solution

“…Nitriles 2 and 4 were prepared by alkylation of commercially available mono- and dihydroxybenzonitriles (Scheme ). Nitrile 7 was derived from an acid chloride precursor that was first converted to an amide and then dehydrated using a literature procedure after replacing the iodide by CN using copper(I) cyanide in boiling N -methylpyrrolidone (NMP).…”

A convenient new procedure for converting primary amides into nitriles

“…More intriguingly, N-containing heteroaromatic carboxamides including those containing a pyrrolic N-hydrogen (Entries 8-12) are readily converted into the corresponding nitriles in good to high yields. Especially, when nicotinamide (Entry 8) was employed as a starting substrate, a substantially high yield of the corresponding 3-cyanopyridine (90%) was obtained compared to other reported methods such as trichloromethyl chloroformate (0%), 17 trichloroacetyl chloride/triethylamine (77%), 15 and titanium tetrachloride/ triethylamine (78%). 5 Alkyl or arakyl carboxamides bearing various functionalities are also allowed to provide the corresponding nitriles in high yields (80-92%) under this newly developed protocol (Entries 13-16).…”

“…The new dehydration process is facilitated by the ease of primary amides to undergo coupling with ethyl dichlorophosphate (EtOPOCl 2 ) or phenyl dichlorophosphate (C 6 H 5 OPOCl 2 ) followed by rapid elimination with 1,8-diazabicyclo [5.4.0]undec-7-ene (DBU) to form the corresponding nitriles. While a wealth of dehydrating agents are available to effect this transformation, [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] the mild reagent, either EtOPOCl 2 or C 6 H 5 OPOCl 2 , applied in this newly developed methodology, to our knowledge, are unprecedented. Compiled in Table 1 are results for the initial model study by the use of benzamide (1) as a substrate under treatment with each hitherto unexplored dehydrating agents, including ethyl dichlorophosphate (EtOPOCl 2 ),{ phenyl dichlorophosphate (C 6 H 5 OPOCl 2 ),{ N,N-dimethylphosphoramidic dichloride [(CH 3 ) 2 NPOCl 2 ],{ and N,N-dimethylphosphoramidous dichloride [(CH 3 ) 2 NPCl 2 ]{ in the presence of different bases to afford benzonitrile (2).…”

Functionalization of pyridines. 2. Synthesis of acylpyridines, pyridinecarboxylic acids, and their derivatives. Review

“…Anhydrides of strong organic acids and sulfonic acids in the presence of trimethylamine may be used as the dehydration agents. Thus, trichloroacetyl chloride in the presence of triethylamine has been used to convert amide L into nitrile XLIX under very mild conditions [100]: Trifluoromethanesulfonic acid anhydride has been used for the conversion of picolinamide into the corresponding nitrile [101]:…”