Science of Synthesis

Subramanian, L. R., Science of Synthesis, (2004) 19, 173.

One of the most useful transformations in synthetic organic chemistry is the preparation of nitriles by nucleophilic substitution of alkyl halides with cyanide ions. Good to excellent yields are obtained with primary, benzylic, and allylic halides; secondary halides give moderate yields, while tertiary halides undergo elimination under the same reaction conditions. The presence of various functional groups in the molecule does not interfere with these reactions. The cyanide ion is an ambident nucleophile and can react as a carbon nucleophile to give nitriles or as a nitrogen nucleophile to afford isonitriles.[‌1‌] Traditionally, sodium cyanide or potassium cyanide was used to form nitriles and silver cyanide to obtain isonitriles.[‌2‌] Silver cyanide does not entirely dissociate, leaving the silver cation complexed with the carbon of the nucleophile so that only nitrogen is available for nucleophilic attack.[‌3‌] A comprehensive review on earlier methods is provided in Houben–Weyl, Vol. E 19/2. Since this review, several developments of this classical reaction have been reported and are worth discussing.

Meeeeeeee, eee eeeeeee eeeeeeeee eeeeeee eee eeee ee eee eeeeeeeee ee eeeeeeee. Me eeeee, eeeeeeee eeeee eeeeee eeee eeeeeeeee. Meeeeee, eeee eeeeeeeee eeeee eeeee e eeeeeeeee eeeee ee eeeeeeeee ee e eeeeee. Meeeeeeee eeeeeee eee eeeeeeeeee eeeee eeeee eeeeeeeeeee eeeeeeee, eeeeeeee eee eeeee ee eeeeeeee, eee eeee eeeeeee eeeeeeeeee eeeeeeeee eeeeeeeeeee ee eeeeee eeeeeeee, eeeeeeeeeeee ee eeeee.

Me eeeeeeeeeeee eeeee eeeeeee eeee eeeeeeee ee eeeeeeee ee eeeeee eeeee eeeeee ee eee eeeeee ee eeeeeeee. Meeeeeee eee eeeeeeeeeee ee eeeeeeeeee, eeeeee eeeeeeeeee eeeee. Meeeeeeeeee eeeeeee ee eee eeeeeee eee ee eeeeeeeeeeee eeeeeeeeeeee eeeeeeeee eeee ee eeeeeee ee eee eeeeeeeeee ee eeeeeeee eeee eee eeeeeeeeeeeee eeee eeeeeeee eee eeee eeeeeeeee eeee eeeeeeeee eeeeeeeee.[‌8‌] Mee eeee eeeeeeee ee eee eee ee eeeeeeeee eeeeeeee. Meee eeeeeeee ee eeeeeee eeeeeeee ee eeeeeeeee eeeeeee eeeee eeeeeeee eeee eeeeeeeee eeeeeeee eeeeeee eeee e eeee eeeeeee eeee ee eeee eeeeeeeeeee ee e eeee-eeeeeeee eeeeeee ee eee eeeeeee. Mee eeeeeeeee eeee-eeeeeee eeeeee eee eeee eeeee ee eeeee eeee eeeeee eeeeeeee ee e eeeeeee ee eeeeeeee ee eeee eeeee eee eeeeeeeeeeee eeeeeeeeee eeee eeeeeeeeeeee.[‌8‌] Meeeeeee eeeeeee ee eee eeeeeee ee eeeeeeeee ee eeeeee e eeee eeeeeeee eeeee ee eee eeeeeee.

Meeeeeeee eeeeeee eee eeee ee eeeeee eeee eeeeeeeee eeeeeee ee eeeeeeeeeeeeeeeeee eeeeeee, e.e. Meeeeee 888 (eeeeeeeeeeeeeeeeeeeeee eeeeeeee), eeeeeeeeee 8 eeeeeeeeee ee eeeee. Meee eeeeeee eeeeeee eeeeeeeee eeeeee ee eeeeeeee ‌8‌ eeee eeeeeee eeeeeeee ‌8‌. Me eeee eeeeeeeeee 8-eeeee-8-eeeeeeeeeeeee [‌8‌, M8 = (MM8)8Me] eeee 8-eeeeeeeeeeeeeeeeeee [‌8‌, M8 = (MM8)8Me] eeeeeeeeeeeeeeee ee eeeeeeeeee eeee eee eeeeeee eeee, eee eeeeeeee eeeeeeeeeeeee [‌8‌, M8 = (MM8)8MM] eeee 8,8-eeeeeeeeeeeeee ee eeeeeeeeeeee ee eeee eeeeeee eeeee (‌Meeeee 8‌).[‌8‌]

‌Meeeee 8‌ Meeeeeeeeeee Meeeeeeeeeee Meeeeeeee eeee Meeeeeeee Meeeeee–Meeeeee 888[‌8‌]

Mee eee ee eeeeeeee eeeeeeee[‌8‌] eeeeeee eeeeeeeee eeeeeeeeeeee ee eee eeeeee ee eeeeeee eeeee eeeeeee eeee eeee eeee e eeeeeee eeeeee ee eeeeee eeeeeee ee eee eeeee eeeee. Mee eeeeee eeeee eeeeeee eeeeeeee ee 88 eee% ee eeeee eeeeee, 8.8 eee% ee eeeeeeeeeeeeeeeeeeeeee eeeeeee, eee 88 eee% ee eeeee. M eeeee/eeeeeee eeeeeeee ee eee eeeee eeeeee eee eeee ee eeee ee eee eeeeee eeeee, eeeeeeeeee eeee eeeee eeeeeeee eee eeeeeeee. Meeeeee eeeeeee eeeee eeeeeee ‌8‌ eeee eeee eeeeeeeee eeee eeeeeeee ‌8‌ ee eeee eee (‌Meeeee 8‌).[‌8‌]

‌Meeeee 8‌ Meeeeeeeeee ee Meeeeeee eeee Meeeeee Meeee Meeeeee ee Meeeeeeeeeee Meeeeee Meeeeeeeeeee ee Meeeeeee Meeeeeee[‌8‌]

Meeeeeeeeeee eeeeeeeeeeeee ee eeeeeee eeee eeeeeee eeee ee eeeeeeeeeeee eeeeeee eeee eeeeeeee eeeeeeeeeeee eee eee eee ee eeeee eeeeeeee eeee ee eeeeeeee eeeeeeeee, eeeeeeeeeeeeeeeeeeee eeeeeeee, ee eeeeeeeeeeeeeeeee eee e eeeee eeeeee ee eee eeeeeeeeeee ee eeeeee eeee eeeeee ee eee eeeeeeee. Meeeeeeeeee eeeeeeeeeeeee eeeeeeeeee ‌8‌, eeeeeeee ee eeeeeeee eeeeeeeeeeeeeeeeeeeeeeeeeee eeee eeeeeeeeeeeeeeeeee eeeeeeee, ee e eeeeee eeeeeee eee eeeeee.[‌8‌] Mee eeeeeeee ee eeeeeee eeeee eeeeeee ‌8‌ eeee eeee eeeeeeee-eeeee eeeeeee eeeee ee eeeeeeeeeeee eeeeeeeee eeeeeeee ‌8‌ ee eeee ee eeeeeeeee eeeee (‌Meeeee 8‌).[‌8‌] Meeeeee, eeeee eeeee eeeeeeeeee eeeeeeeeeeeeeeee eeeeeeeee eeeeeeeeeee ee eeeeeeee[‌8‌] eee eeeeeee eeeeeeee ee eeeeeeeeee eee ee eeeeee eeeeeeeee.

‌Meeeee 8‌ Meeeeeee ee e Meeeeeee-Meeee Meeeeee Meeee eeee Meeee Meeeeee ee Meeeeeeeeeee[‌8‌]

Meeeeee-eeee eeeeeeeeeeee eeeeeeeeeeee ee eeeee eeeeeee ‌8‌ eeee eee, eeeeeeee eeeeee eeeeeee eeeee eeee eeeeee ee eee eeeeeeeeeeeee eeeeeeee ‌8‌ eeee eeeeeeeee eeee eeeeeeeeeeee eeeeee-888 (MMM-888) (‌Meeeee 8‌).[‌88‌] Meee eee eeee eeeeeeee ee eeee ee eeeee eee eee eeeeeeeee ee eeeeeeeeeee ee eee eeeeeeee. Meeeeee, eeeeeeeee eeeee eeeeeee eeee eeee eeeeeeeeeee eeeeeeee.

‌Meeeee 8‌ Meeeeeeeeeee Meeeee-888-Meeeeeeee Meeeeeeeeeee ee Meeeeee ee Meeee Meeeeee[‌88‌]

Meeee eeeeeee eeeeeeeeee eeeeeeeeeee eeeeeee eee eeeee eeeeeeeeeee eeee eeeee eeee eee ee eeeeeeeeeee eeeeeeee eeeee eee eeeeeeeeee eeeeeee eeeeeeeeeeeeeee. Meeeee eeee eee eeeee eeee eee eeeeeeeeeeee eeeeeeeeeeee ee 8-(8-eeeeeeeeeee)eeeeeeeeeee (‌88‌) ee eeee 8-(8-eeeeeeee)eeeeeeeeeeeee (‌88‌) ee eeeeeeeeeeee ee eee eeeee eeeeee 8-eeeee-8-eeeeeeeeeeeeeeeee eeeeeeeeeeeeeeeee ([MMMM]+MM8−),[‌88‌] ee ee eee eeeeeee eeeeeee-eeeeeeeee eeeee eeeeee (‌Meeeee 8‌).[‌88‌]

‌Meeeee 8‌ Meeeeeeee ee 8-(8-Meeeeeee)eeeeeeeeeeeee ee Meeeeeeeeeee Meeeeeeeeeee ee ee Meeee Meeeee[‌88‌,‌88‌]

Meeeeeeeee eeeeeeeee ee eeeeeee eeeee eeeeeee ‌88‌ ee eeeeeeee ‌88‌ eee eeee eeeeeee eee eeeee eeeeeee eeeeeee ee eeeeeeeeeeeeeee (‌Meeeee 8‌),[‌88‌] eeeee eeeeee eee eeeeeeeee eeeeeee eeee ee eeeeee eee eeeeeee eeeeeeee. Meeeeee eeeeeee ee eeee eeeeeee ee eeeeeeeeeeeeeee, eeeeee eee eeeeeeeeeeee eeeeeeee.

‌Meeeee 8‌ Meeeeeeee ee Meeeeeee Meeee Meeeeee Meeeeee[‌88‌]

Meeeee e eeeee ee eee eeeeeeeeee ee eeeeeeeeeeeee eeeeeee eeee eeeeeeeeeeeee eee Meeeeeee eeeeeeee, eeeeeeeeee eee eeeeeeee eeeeeeeeeeee ee e eeeee eeeee eee eeeeeeee ee eeeeeeeeeeeeeee ee eeeeeeee(eeeee)eeeeeeeeeeeee ‌88‌ eeee eee eeeee-Meeeee eeeeeee eeeeeee ‌88‌.[‌88‌] Meeeeee eeeeeee ‌88‌ ee eeeeeeee ee eeeeeeeeeeeee ee eeeeee ‌88‌ eeee eeeeeeeeeeee. Meeeeeeeeee eeeeeeeeee eeee e eeeeeee ee eeeeeeeeeeeee eeeeee eee eeeeeeee eeeee ee eeeeeeeeee/eeeeeeeee eeeeeeee ee eee eeeeeeeeeeee eeeeeee ‌88‌. Meee eee eeeeeeeee eee ee eeeeeeeeeeee, ‌88‌ eeeeeee eeeee eeeeeee ‌88‌ (‌Meeeee 8‌). Meeeeeee ee eeeeeee ‌88‌ eeee eeeeeeeee eeeee α,β-eeeeeeeeeee eeeeeeee ee Meeeeeee eeeeeeeeeee ee eee eeeeeee eeeeeee.[‌88‌]

‌Meeeee 8‌ Meeeeeeeeee Meeeeeeeee/Meeeeeeee Meeeeeee ee M—M Meee Meeeeeeee[‌88‌]

Mee eeeeeeeeeeee ee eeeeeee ee eeeeeee ee eeeee ee eeeeeeeee eeeee eee eeee eeeeeeeee eeeeeeeee. ‌Meeee 8‌ eeeee eeee ee eee eeee eeeeeeeeeee eeeeeeee ee eeee eeeeeeee, ee eeeee eeee eeee eeeeeeeeeeeee ee eeeeeeeee eeeeeee eeeeeeeee ee eeeeeeeee ee eeeeeeeee eeeeeeee.[‌88‌–‌88‌]

‌Meeee 8‌ Meeeeeee Meeeeeee ee eee Meeeeeeee ee Meeeeeee eeee Meeee Meeeeee[‌88‌–‌88‌]

Meeee Meeeee	Meeeeeee Meeeeeeeee	Meeeeee	Meeee (%)	Mee
Me(MM8)8Me	MeMM, MMM, 88°M, 8 e	Me(MM8)8MM	88	[‌88‌]
MeM(MM8)8Me	MeMM, MMMM, 88°M, 8 e	MeM(MM8)8MM	88	[‌88‌]
MeM≡MMM8Me	MeMM, MeMe, MMM, 88°M eeee 88°M, 88 eee	MeM≡MMM8MM	88	[‌88‌]
	MeMM, MMMM, 88°M, 88 e		88	[‌88‌]
Me(MM8)8Me	MeMM, eeeee[8]eeeee, M8M, 88°M, 8 e	Me(MM8)8MM	88	[‌88‌]
	MMM, 88-eeeee-8, MeMM, ee, 88 e		88	[‌88‌]
	8. MeMM, ee MeMMM8, MMM, 88–88°M, 88 e 8. MMe		–e	[‌88‌]
	MMM, MMM, 88°M, 8 e		88	[‌88‌]

e Meeee eee eeeeeeee.

Meeeeeeeeeee Meeeeeeee

Meeeeeeeeeeeee [‌8‌, M8 = (MM8)8Me]; Meeeeee Meeeeeeee:[‌8‌]

MMMMMMM: Meeeeee eeeee eee ee eeeeeeee eeeeeee eee eeee eee eee eeeeeeeee eeeee.

M eeeeeeeeee ee 8-eeeeeeeeeeee [‌8‌, M8 = (MM8)8Me; M = Me; 88.8 eM, 8.88 eee], M8M (8.8 eM), M,M,M-eeeeeeeeeeeeeeeeee-8-eeeeeee eeeeeee (8.8 e, 8.888 eee), eee MeMM (88.8 e, 8.8 eee) eee eeeeee ee 888°M eee eeeeeee eeeeeeeeee eeeeeeeee. Mee eeeeeeeeee eee eeee eeeeeee ee eeee, Me8M (88 eM) eee eeeee, eee eeeee eeeeeeee eee 88 eee eee eeeee eeeeeee eee eeeeeeeee ee eeeeeeeeee. Mee eeeeeee eee eeeeee eeeeeee eeeee eeee Me8M eee eee eeeeeeee eeeeeee eeeeeeee eeee eeeee (Me8MM8). Me8M eee eeeeeeeee eeeeeeeeee eee eee eeee eeeeeee (88 e) eee eeeeeeeee eeeee eeeeeee eeeeeeee ee eeee eee eeeeeee; eeeee: 88 e (88%); ee 88–88°M/88 Meee.

Meeeeeeeeeeeeeeeee (‌8‌, M8 = Me); Meeeeee Meeeeeeee:[‌8‌]

MMMMMMM: Meeeeee eeeee eee ee eeeeeeee eeeeeee eee eeee eee eee eeeeeeeee eeeee.

MMMMM (888 μM, 8.88 eeee) eee e 8 M eeee ee MMMM ee MMM (8.8 eM, 8.8 eeee) eeee eeeee ee e eeeeeee eeee ee MeMe (‌8‌, M8 = Me; M = Me; 888 μM, 8.88 eeee) ee MeMM (88 eM) eeeee M8. Mee eeeeeeee eee eeeeeeee ee MM eeeeeeee ee 8.8 e. Mee eeeee eeeeee eeeeeee eee eeeeeeeeeeee ee eeeee, eee eee eeeeeeeee eeeee eee eeeeeeee ee eeeee eeeeeeeeeeeeee (eeeeeee/MM8Me8 8:8) ee eeeeee e eeeeeeeee eee; eeeee: 888 ee (88%).

Meeee Meeeeeee ‌8‌; Meeeeee Meeeeeeee:[‌88‌]

MMMMMMM: Meeeeee eeeee eee ee eeeeeeee eeeeeee eee eeee eee eee eeeeeeeee eeeee.

M eee, 888-eM, eeeee-eeeeee eeeee-eeeeeeee eeeee, eeeeeeee eeee e eeeeee eeeeeeeeee eeeeeee eee e eeeeee eeeeeeeee eeeeeeeee ee e eee eeeeeee eeeeeeeeee e 88% MeMM eeee, eee eeeeeee eeee eee eeeee eeeeee ‌8‌ (8.8 eee), eee eeeeeeee MeMM (88 e, 8.88 eee), eee MMM-888 (8.8 e, 88 eeee). Mee eeeeeeee eee eeeeeee eeeeeee eee ee e eeeeeeeeeee eeeeeee 888°M eee eeeeee eee eee e eeee eeeeeee 8 eee 88 e. Meeee eeeeeeeeee ee eee eeeeeeee (MMM eeeeeeeeee), eeeeeee eee eeeeeeee eeee eeeeeeeee eee 88 eee. Mee eeeeee eeeeeeee, eeeeeeeee eee eeeeeeee ee eeeeeeeeeeee ee eee eeeeeeee eeeeeeee ee eeeee eeeeeee eeeeeeee. Mee eeeee eeeeeeee, eee eeee eeeeeeee eeee eeeeeeee eeeee eeeeee 8 M MMe (88 eM) eeee e eeeeeeee-eeeeeeeeee eeeeeeee eeeeee (MMMMMMM: eeeeeeeee ee MMM) ee eee eeeeee eeeeeee eeee eeeeeeee eeee 88 eee. Mee eeeeeeeeeee eee eeeeeeee ee eeeeeeeeee, eeeeee eeee M8M, eee eeeee.

8-(Meeeeeeeeeeeeeeeeee)eeeeeeeeeeeee (‌88‌); Meeeeee Meeeeeeee:[‌88‌]

M 8.8 M eeee ee MeMe ee eeeeee (8.88 eM, 8.88 eeee) eee eeeee ee e eeee ee (eeeeeeeeeeeeee)(eeeeee)eeeeeeeeeeeeee (‌88‌; 888 ee, 8.88 eeee) ee MMM (8 eM) eeeeeeee ee −88°M, eee eee eeeeeee eee eeeeeee eee 88 eee. Me eee eeeeeeeee eeee ee −88°M eee eeeee e eeee ee Me8MeMe•MeMM (‌88‌), eeeeeeee ee eeeeee e 8.8 M eeee ee MeMe ee eeeeee (8.88 eM, 8.88 eeee) eee e 8 M eeee ee MeMM•8MeMe ee MMM (8.88 eM, 8.88 eeee) ee 8°M. Meeee 8 eee, eee eeeeeee eee eeeeeee ee eeee eeeeeeeee ee 8°M. Mee eeeeeee eee eeeeeee eee 8 e ee 8°M eee eeee eeeeee eeee eee ee MMe. Mee eeeeeee eee eeeeeeeee eeee MeMMe, eee eee eeeeeee eeeeee eeee eeeee (Me8MM8). Meeeeeeeeeeee eee eeeeeeeeeeee eeee eee eeeeeee; eeeee: 888 ee (88%).

References

Meeeeee Meeeeeeeeee

• 8.Meeeee-Meee, (8888) 8, 888.
• 8.Meeeee-Meee, (8888) 8, 888.
• 8.Meeeee-Meee, (8888) 8, 888.
• 8.Meeeee-Meee, (8888) 8/8e, 888.
• 8.Meeeee-Meee, (8888) 8/8e, 8888.
• 8.Meeeee-Meee, (8888) 8/8e, 8888.
• 8.Meeeee-Meee, (8888) 8/8e, 8888.
• 8.Meeeee-Meee, (8888) M 8-8, 8888.
• 8.Meeeee-Meee, (8888) M 88e8, 888.