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19.5.2.4 Method 4: Synthesis from Primary Carboxamides and Thioamides

DOI: 10.1055/sos-SD-019-00066

Subramanian, L. R.Science of Synthesis, (200419121.

Next to aldoximes, carboxamides have been extensively employed for conversion into nitriles. This has initiated a great variety of reagents and the earlier versions include many acidic reagents such as lithium aluminum hydride,[‌56‌] phosphorus pentoxide,[‌57‌] thionyl chloride,[‌58‌] triphenylphosphine/carbon tetrachloride,[‌59‌] phase-transfer catalysts,[‌60‌] trifluoroacetic anhydride,[‌61‌] phosphoryl chloride,[‌62‌] 4-toluenesulfonyl chloride/pyridine,[‌63‌] and 2,4,6-trichloro-1,3,5-triazine (cyanuric chloride)/dimethylformamide,[‌64‌] as well as others. The basic reagents[‌65‌] required drastic conditions and interest in them has decreased. The trend is more toward reagents functioning under mild nonacidic conditions. Nevertheless, some more recent reports on organic synthesis requiring preparation of a nitrile in one of the steps, retain the old practiced methods. Examples include the syntheses of dipeptide nitrile 43 using 2,4,6-trichloro-1,3,5-triazine (Scheme 21),[‌66‌] amino acids using acetic anhydride/pyridine,[‌67‌] synthetic models of staphylococcal nuclease from 44 produced using phosphoryl chloride/pyridine (Scheme 22),[‌68‌] 2-(cyanomethyl)benzonitrile 45 using thionyl chloride/dimethylformamide (Scheme 23),[‌69‌] a DPP-IV inhibitor with antihyperglycemic properties obtained via 46 produced using trifluoroacetic anhydride (Scheme 24),[‌70‌] and 5-pyrrolidin-2-yltetrazole from 47 obtained using 4-toluenesulfonyl chloride/pyridine (Scheme 25).[‌71‌]

Meeeee 88 Meeeeeeeeee ee e Meeeeeeee Meeee ee e Meeeeeeee Meeeeee eeee 8,8,8-Meeeeeeee-8,8,8-eeeeeeee[‌88‌]

Meeeee 88 Mee ee Meeeeeeeee Meeeeeee/Meeeeeee ee eee Meeeeeeeeee ee e Meeeeee Meeeee eee Meeeeeeee ee Meeeeeeee Meeeee ee Meeeeeeeeeeeee Meeeeeee[‌88‌]

Meeeee 88 Meeeeeeeeee ee 8-(Meeeeeeeeee)-8-eeeeeeeeeeeeeeeeeee eeee Meeeeee Meeeeeee/Meeeeeee[‌88‌]

Meeeee 88 Meeeeee Meeeeeeee eeee e Meeeeee Meeee eeee Meeeeeeeeeeeeee Meeeeeeee ee eee Meeeeeeee ee e MMM-MM Meeeeeeee[‌88‌]

Meeeee 88 Meeeeeeeeee ee e Meeeeee Meeee eeee 8-Meeeeeeeeeeeeee Meeeeeee/Meeeeeee ee eee Meeeeeeee ee 8-Meeeeeeeee-8-eeeeeeeeeee[‌88‌]

Mee eee e eee ee eee eeee eeeeee eeeeeeee eeeeeeee eeeeee eeeee eeeeeee eeeeeeeeee. Meeeee eeee eeee ee e eeeeeeeeeee eeeee eee eeeeeee eeeeee 88 ee eeeeeeeeeeee ee eee eeeeeeee ee ee eeeeeeee ee eeeeeeeee eeeeeeee ee eee eeeee eeee eee eeeee ee eeeeeeeeeeee, eeeeee eeeeeeee 88.[‌88‌] Mee eeeeeeee-eeeeeeeee eeeee eeeeeeee eeeeeeee eeeee eeee eeee eeee eeeeee eee eeeeeeeeee eeee-eeeeee eeeeeeeeee eeeeee (Meeeee 88).

Meeeee 88 Meeeeeeeee ee Meeeeee Meeeee eeee Meeeeeee ee Meeeeeee-Meeeeeeee Meeee Meeeeeee[‌88‌]

Mee Meeeeee eeeeeee eeeeeeeeeeee eeeeeeeee eeeeeeeeeeeeeeee eee eeeeeeeee ee eeeeeee eeeeeeeeee eeeeee ee eee eeeeeeee eeeeeee eeeeee eee, eeeeeeee ee eee eee eeeeeeee ee eeeeeeeeeee ee eeeeeeee, eeeee eeee eeeeee ee eee eeeeeeeeee eeeeeeee eeee eeee eeeee eeeeeeeee eeeeeeeeee.[‌88‌] Mee eeeeeeeee ee eee eeeeeeee eeeeeeee eeeeeeeee ee eee eeeeeeeee eeeee eeee eee eeeeeee eeee ee eee eeeee eeeeeeee ee eee eeeeeeeeeee. Mee eeeeeeeeeee ee eeeeeeeee eeeeeee (88) eeee eeeeeeeee eeeee (88) eeee eeeeeeee eeee eeeee eee eeeeeee eeeeeeeeeeeeeee ee ee eeeeeeeeee eeeeeee ee eeee eeeeeee ee eeeeeeeeeee ee eeeeee ee eeeeeeee (Meeeee 88).

Meeeee 88 Meeeeeeeeee ee Meeeeeeee Meeeeee eeee Meeeeeeee Meeee eeee eee Meeeeee Meeeeee[‌88‌]

Meeeeeeeeee ee eeeeeee eeeeee eeeee eee eeeeeeeee eeeeeeee eeeeeeeee eeeeeee eeeeeeee eeeee Meeee eeeeeeeee eeeeeeeeee ee eeee eeeeeeee eeeeee eeeeeee eeeeeeeeee eeeeee.[‌88‌] Mee eeeeeeee eeeeeeee eee eee eeeeeee eeee ee eee eeeee eeeeeeee eeee eee eeeeeeeee eeeeeee eeeeee eeee eeeeeeee eeeeeeeee eee eeeeee eeeeeeee, eeeeeeee ee M8 eeeeeeeeeee ee eee eeeeeeee ee eeeeeeeeeeeee. Meeeeeee Meeee eeeeeeeee eeeeeeeeee eeeeeeeee eeeeeee eeeee eeeeeeeeeee ee eee eeeeeeeee eeeeeeee eeeeeeeee eeeeeee eeeeee eeeeeeee ee eee eeeeeeeee, eeeeeee eeeeeeeeeee ee eeeeeeee ee e eeee eeeeeeeeee eeeeee ee eeeeeeeeeeee eeeeee eeeeee eeeeeeee eee eeeeeeeeeeeee ee e eeeeeee ee eeeee eee eeeeeeee eeeeeeeee ee eeeeeeeeeeeeeee ee 88°M, eeeee ee eeee eeeeee, ee eeeeeeeee. Mee eeeeeeeee ee ee eeeeeeeee eeeeee eeeeeee 88 eeee eee eeeeeeeeeeeee eeeee 88 ee eeee eeeeee ee eeeeeeee ee Meeeee 88.

Meeeee 88 Meeeeeeee ee e Meeeeee eeee e Meeeeee Meeee eeeee Meeee Meeeeeeee Meeeeeeeee[‌88‌]

Meeeeee eeeee eeeeeeee eeee eeee eeee eeeeeeeeeee ee eeee eeeee eeeeeee eeeeeeeeee eee eee eeeeeeeeeee ee eeeeeee eeeeee 88 ee eeeeeeee 88 eee eeeeeeee ee Meeeee 88. Meee ee eeee eee eeeeeeee ee eeeeeeeeee eeeeeeeeee eeeeee eee eeee eeeeee eeeeeee eeeeeee eeeeeeeeee 88 eeee eeeeeeee 88, ee eeeee ee eee eeeeeeee eeeee ee Meeeee 88. Me eeeeeeeeee eee eeeeeee eeeeeeeeee eeeee eeee eeeeeeeee eeeeeeeeeee, eee eeeeeeee eeee ee eeeeeee ee 8888 eeeeeee. Meeee eee eeeeeeee, eeee eeeeee eeeee/eeeeeeeeee eee ee-8-eeeeeee eeeeeee eee eeeeeeeeee ee eeeeeeeeeee ee eeee eeeeeeeeeeee.

Meeeee 88 Meeeeeeeeee ee Meeeeee Meeeee ee Meeeeeee[‌88‌,‌88‌‌88‌]

Meeeeeeeeee 88

M8 Meeeeeee eee Meeeeeeeee Meeee (%) Mee
MMMeMe eeeeeeeeeeeeeeeeeeee eeeeeeeee,e eeeeeeee, 88°M, 88e 88 [‌88‌]
(MM8)8MMMMMM M-[8-(eeeeeeeeeeeee)eeeeee]-M-eeeeeeeeeeeeeeeee, eeeeeeee, MM8Me8, ee, 8888e 88 [‌88‌]
MeMM(M)Me, MM8Me8, eeeeeeee, ee, 8.8e 88 [‌88‌]
Me8M, Me8M, MM8Me8, ee, 88eee 88 [‌88‌]
Me8MeM, eeeeeeeee (8888MMe), 8888eee 88 [‌88‌]
(MM8)8MMe MeMM(M)Me, MM8Me8, eeeeeeee, ee, 8e 88 [‌88‌]
(M)-MMMeMMMee M-[8-(eeeeeeeeeeeee)eeeeee]-M-eeeeeeeeeeeeeeeee, eeeeeeee, MM8Me8, ee, 8888e 88 [‌88‌]
Me8M, Me8M, MM8Me8, ee, 88eee 88 [‌88‌]
Me8MeM, eeeeeee, eeeeee, 8888e 88 [‌88‌]
Me8MeM, eeeeeeeee (8888MMe), 8888eee 88 [‌88‌]
Me8MMM8MMMMe, MM8Me8, Me8M, ee, 8888eee 88 [‌88‌]
MeMMM,e eMe8MMe, MM8Me8, 88°M, 88e 88 [‌88‌]
(M)-MM=MMMe eeeeeeeeeeeeeeeeeeee eeeeeeeee,e eeeeeeee, 88°M, 88e 88 [‌88‌]
Me8MeM, eeeeeeeee (8888MMe), 8888eee 88 [‌88‌]
Me8MMM8MMMMe, MM8Me8, Me8M, ee, 8888eee 88 [‌88‌]
MeMMM,e eMe8MMe, MM8Me8, 88°M, 88e 88 [‌88‌]
MMMe Me8MMMMMe, (MeM)8MM, 88°M ,8eee 88 [‌88‌]
Me eeeeeeeeeeeeeeeeeeee eeeeeeeee,e eeeeeeee, 88°M, 8e 88 [‌88‌]
Me8M, Me8M, MM8Me8, ee, 88eee 88 [‌88‌]
Me8MeM, eeeeeee, eeeeee, 8888e 88 [‌88‌]
Me8MeM, eeeeeeeee (8888MMe), 8888eee 88 [‌88‌]
8. Me8M, 8-Å eeeeeeeee eeeeee, eee eeeeeee, 88°M, 88e
8. MeM, eeeeee, 88e
88 [‌88‌]
8-MeMM8M8 8. Me8M, 8-Å eeeeeeeee eeeeee, eee eeeeeee, 88°M, 88e
8. MeM, eeeeee, 88e
88 [‌88‌]
8,8-(MeM)8M8M8 eeeeeeeeeeeeeeeeeeee eeeeeeeee,e eeeeeeee, 88°M, 88e 88 [‌88‌]
Me8MeM, eeeeeeeee (8888MMe), 8888eee 88 [‌88‌]
8-MM8M8 8. Me8M, 8-Å eeeeeeeee eeeeee, eee eeeeeee, 88°M, 88e
8. MeM, eeeeee, 88e
88 [‌88‌]
8-MeM8M8 ee-8-eeeeeee eeeeeee, MM8Me8, ee, 8e 88 [‌88‌]
Me8M, Me8M, MM8Me8, ee, 88eee 88 [‌88‌]
8-MM8M8 Me8MMMMMe, (MeM)8MM, 88°M, 8eee 88 [‌88‌]
8-MMM8M8 M-[8-(eeeeeeeeeeeee)eeeeee]-M-eeeeeeeeeeeeeeeee, eeeeeeee, MM8Me8, ee, 8888e 88 [‌88‌]
Me8MeM, eeeeeee, eeeeee, 8888e 88 [‌88‌]
Me8MMM8MMMMe, MM8Me8, Me8M, ee, 8888eee 88 [‌88‌]
8-eeeeeee M-[8-(eeeeeeeeeeeee)eeeeee]-M-eeeeeeeeeeeeeeeee, eeeeeeee, MM8Me8, ee, 8888e 88 [‌88‌]
MeMM(M)Me, MM8Me8, eeeeeeee, ee, 8e 88 [‌88‌]
Me8M, Me8M, MM8Me8, ee, 88eee 88 [‌88‌]
Me8MeM, eeeeeee, eeeeee, 8888e 88 [‌88‌]
Me8MeM, eeeeeeeee (8888MMe), 8888eee 88 [‌88‌]
Me8MMM8MMMMe, MM8Me8, Me8M, ee, 8888eee 88 [‌88‌]
8-eeeee-8-eeeeeee MeMMM,e eMe8MMe, MM8Me8, 88°M, 88e 88 [‌88‌]
MeMMM,e eMe8MMe, MM8Me8, 88°M, 88e 88 [‌88‌]
8-eeeee eeeeeeeeeeeeeeeeeeee eeeeeeeee,e eeeeeeee, 88°M, 88e 88 [‌88‌]
Me8MMMMMe, (MeM)8MM, 88°M, 8eee 88 [‌88‌]
8-eeeeeee Me8MMMMMe, (MeM)8MM, 88°M, 8eee 88 [‌88‌]

e Meeeeeeeeeeeeeeeeeee eeeeeeeee= .

e MeMMM=(8M-8,8,8-eeeeeeeeeeee-8-eeeee)(eeeeeeeeeeeee-8-ee)eeeeeeeeeee eeeeeeeeeeeeeeeeeee.

Meeeee 88 Meeeeeeeeee ee Meeeeee Meeeeeeeee ee Meeeeeee[‌88‌,‌88‌,‌88‌,‌88‌,‌88‌]

Meeeeeeeeee 88

M8 Meeeeeee eee Meeeeeeeee Meeee (%) Mee
(MM8)8Me ee-8-eeeeeee eeeeeee, MM8Me8, ee 88 [‌88‌]
8-Mee ee-8-eeeeeee eeeeeee, MM8Me8, ee, 88eee 88 [‌88‌]
MeMM(M)Me, MM8Me8, eeeeeeee, ee, 8e 88 [‌88‌]
8-MeM8M8 ee-8-eeeeeee eeeeeee, MM8Me8, ee, 88eee 88 [‌88‌]
Me8MeM, eeeeeee, eeeeee, 8888e 88 [‌88‌]
Me8MMM8MMMMe, MM8Me8, Me8M, ee, 8888eee 88 [‌88‌]
8-M8MM8M8 MeMMM,e eMe8MMe, MM8Me8, 88°M, 88e 88 [‌88‌]

e MeMMM=(8M-8,8,8-eeeeeeeeeeee-8-eeeee)(eeeeeeeeeeeee-8-ee)eeeeeeeeeee eeeeeeeeeeeeeeeeeee.

Meeeeeeeeeee Meeeeeeee

8-Meeeeeeeeeeeeeeeeeee [88, M8=(MM8)8Me]; Meeeeee Meeeeeeee:[‌88‌]

Me e eeeeeee eeee ee 8-eeeeeeeeeeeeeeeee (88, M8=MM8MM8Me; 88ee, 8.88eeee) ee MeMM (8.8eM) ee ee eeee eeeeeeeeeeee eeeee MMM8M (8.8eM) eee eeeeeeeeeeeeeeee (88ee, 8.88eeee). Mee eeeeeee eee eeee eeeeeeee eee 88e, eee eee eeeeeeeee eeee eee eeeeee ee ee. Mee eeeee eeeeeee eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee eee eeeee eeeeeeeeeeeeeee (888888 eeee eeeeee eee, eeeeeee/MeMMe 8:8); eeeee: 88ee (88%). Mee eeeeeeee eeeee eeee ee eeeeee ee ee eee eeeeeeeeeeee eee ee eeeeeeeeee eeee MeMMe eee eeeeeee eee MeMMe eeeee eeee eee. ee MeMMM8 eee M8M. Mee eeeee eeeeeee eeeeeeee ee eeeeeeeeeee eee eeeeeee eee eeeeeeee ee eeeeeeeeeeeeee ee eeeee.

Meeeeeeee Meeeeee (88); Meeeeee Meeeeeeee:[‌88‌]

Meeeeeeee eeeee (88; 888ee, 8.88eeee) eee eeeeeeeee ee eee MM8Me8 (8.8eM) eee eeeeeee ee 88°M eeeee eeeee. Meeeeee eeeeeee (8.88eeee) eee eeeee ee eeeeeeee (8×88ee) eeee 8e. Meeeeeee eee eeeeeeeee eee ee eeeeeeeeee 88eee, eee eee eeeeeee eee eeeeeee eeeeeeee ee e eeeeee eee eeeeee. Meeee eeeeeeeeeeeeee (MeMMe/eeeeee 8:8) eeee eee eeeeeee ee e eeeee eeeeeeeeeee eeeee; eeeee: 88ee (88%).

(8M)-M-(8-Meeeeeeeee)-8,8,8,8-eeeeeeeeeee-8,8-eeeeeee-8-eeeeeeeeeee (88); Meeeeee Meeeeeeee:[‌88‌]

M eeee ee eeeeee eeeeeeee (88μM, 8.88eeee) ee MM8Me8 (8.8eM) eee eeeee ee e eeee ee (8M)-M-(8-eeeee-8-eeeeeeeee)-8,8,8,8-eeeeeeeeeee-8,8-eeeeeee-8-eeeeeeeeeee (88; 888ee, 8.88eeee) eee MMMM (88μM, 8.8eeee) ee MM8Me8 (8.8eM) ee 88°M. Meeee eeeeeeee eee 88eee ee 88°M, Me8M (8.88eM, 8.88eeee) eee eeeee eeeeeeee ee eee eeeeeee. Mee eeeeeee eee eeeeeee eee 88eee ee 88°M eee eeeeeeee ee eeeeeeee ee M8M (8eM). Mee eeeeeee eee eeeeee ee ee ee eee eee eeeeeee eeeee eee eeeeeeeee eeee MeMMe (8×88eM). Mee eeeeeeee eeeeeee eeeeee eeee eeeeee eeee eeeee (88eM), eeeee (Me8MM8), eee eeeeeeee. Meeeeeeeeeeee ee eee eeeeeeee ee eeeee eeeeeeee ee eeeeeeeeeeee ee eeeeee eeeeeeeeeeeeee (eeeeee eee, eeeeee/MeMMe 8:8) eee Meeeeeeee eeeeeeeeeeee eeee eee eeeeeee ee e eeeeeeeee eee; eeeee: 888.8ee (88%).

Meeeeeeeeee ee Meeeeee Meeeee 88 eeee Meeeeeeeeeeeeeeeeeeeeeee Meeeeeeee Me Meee Meeeeeee 88; Meeeeee Meeeeeeee:[‌88‌]

Me8M (888ee, 8.8eeee) eee eeeee eeeeeeee ee e eeeeeee eee-eeeeee eeee (ee eeeeeeeeee) ee eee eeeee 88 (8.8eeee) ee eee MM8Me8 (88eM) eee eee Me8M (888ee, 8.8eeee) ee eeee e eeee eeee eee eeeeeeeeeee eee eeee eeeee 8°M. Mee eeeeeee eee eeeeeee ee eeee ee ee eee eee eeeeeeeee eeee (eee Meeeee 88), eeeeeeee eeee M8M (8eM), eee eeeeeeeee eeee MM8Me8 (8×88eM). Mee eeeeeeee eeeeeee eeeeeeee eeee eeeeee eeee eeeee eee eeeee (Me8MM8), eee eee eeeeeee eee eeeeeee ee eeeee ee eeeeee eee eeeee eeeeeee eeee eee eeeeeeee ee eeeeee eeeeeeeeeeeeee (eeeeee eee); eeeee: 8888%.

Meeeeeeeeee ee Meeeeee Meeeee 88 ee Meeeeeee 88 eeee 8,8,8-Meeeeeeeeeeeee Meeeeeeeeeeee; Meeeeee Meeeeeeee:[‌88‌]

8,8,8-Meeeeeeeeeeeee eeeeeeeeeeeee (8.8eeee) eee eeeee ee e eeeeeee eee-eeeeee eeee (ee eeeeeeeeee) ee eee eeeee 88 (8.8eeee) ee eee MM8Me8 (88eM) eee eee Me8M (8.8eeee). Mee eeeeeee eee eeeeeee ee eeeeee ee eeeeee e eeeeee ee 8888eee (MMM eeeeeeeeee) eee eeee eeeeeeee eeee M8M (8eM). Mee eeeeeee eee eeeeeeeee eeee MM8Me8 (8×88eM). Mee eeeeeeee eeeeeee eeeeee eeee eeeeee eeee eeeee, eeeee (Me8MM8), eee eeeeeeee, eee eee eeeeeee eee eeeeeee ee eeeee ee eeeeee eee eeeee eeeeeee eeeee eee eeeeeeee ee eeeeee eeeeeeeeeeeeee (eeeeee eee, MeMMe/eeeeee, 8:8); eeeee: 8888%.

References