Triphenylmethyl Isocyanide1


[1600-49-3]  · C20H15N  · Triphenylmethyl Isocyanide  · (MW 269.36)

(cyanide transfer via metal-isonitrile exchange reaction2)

Alternate Names: trityl isocyanide; isocyanotriphenylmethane.

Physical Data: mp 130-133 °C (benzene).3

Solubility: insol water, cold methanol, hexane; sol common organic solvents.

Form Supplied in: white solid.

Analysis of Reagent Purity: IR n = 2130 cm-1; NMR.

Preparative Method: easily prepared in 94% yield from N-triphenylmethylformamide by dehydration with Dimethylchloromethyleneammonium Chloride (Vilsmeier reagent).4

Purification: recrystallization from benzene.

Handling, Storage, and Precautions: can be stored indefinitely at room temperature; quickly adds water in the presence of acids; easily undergoes isocyanide-nitrile rearrangement (60-80 °C in acetonitrile).5 Since some isocyanides are known to be toxic, appropriate precautions are recommended.6

Reactions with Organometallic Reagents.

Addition of organolithium reagents to triphenylmethyl isocyanide leads to the formation of unstable a-metalloaldimines which readily undergo elimination reaction to give nitriles and triphenylmethyllithium (eq 1).7 However, only when t-Butyllithium is used can the nitrile (tertiary) be isolated in high yield (88%). In all other cases, subsequent reaction of the nitrile with the organolithium reagent (used therefore in excess) gives rise to symmetrical ketones upon acid hydrolysis (eq 2). Sequential addition of t-BuLi and another organolithium reagent produces unsymmetrical (t-alkyl-alkyl) ketones in good yields (eq 3). The intermediate ketimine can also be isolated when 2 equiv of t-BuLi are used and the reaction mixture is hydrolyzed with water (eq 4).

Secondary Grignard reagents react readily with triphenylmethyl isocyanide to give secondary nitriles in 70-95% yield. Tertiary and aromatic organomagnesium compounds fail to give synthetically useful reactions. Reaction of primary Grignard reagents gives neither nitriles nor ketones as main products. When n-butylmagnesium bromide is treated with triphenylmethyl isocyanide, 5-amino-4-cyano-4-nonene is isolated in 50-60% yield (eq 5). Reaction of triphenylmethyl isocyanide with organometallic reagents can be stopped at the nitrile stage when organocopper (dialkylcuprate) reagents are used, but low yields mitigate its use as a synthetic tool.7

Synthesis of Masked Acyl Cyanides.

Triphenylmethyl isocyanide reacts readily with 2-Lithio-1,3-dithiane to give the expected nitrile in 83% yield (eq 6).8 The product can subsequently be alkylated with a variety of alkylating reagents in high yields.

1. (a) Isonitrile Chemistry; Ugi, I., Ed.; Academic: New York, 1971. (b) Hoffmann, P.; Marquarding, D.; Kliimann, H.; Ugi, I. In The Chemistry of the Cyano Group; Rappoport, Z., Ed.; Wiley: New York, 1970. (c) Periasamy, M. P.; Walborsky, H. M. OPP 1979, 11, 293. (d) Walborsky, H. M.; Periasamy, M. P. In The Chemistry of Functional Groups; Patai, S.; Rappoport, Z., Eds.; Wiley: New York, 1983; Suppl. C, pp 835-887.
2. Walborsky, H. M.; Niznik, G. E.; Periasamy, M. P. TL 1971, 4965.
3. Alexandrou, N. E. JOC 1965, 30, 1335.
4. Walborsky, H. M.; Niznik, G. E. JOC 1972, 37, 187.
5. (a) Meier, M.; Rüchardt, C. C 1986, 40, 238. (b) Meier, M.; Rüchardt, C.; Müller, B. JOC 1987, 52, 648.
6. Olson, J. S.; Gibson, Q. H. JBC 1972, 247, 1713.
7. Periasamy, M. P.; Walborsky, H. M. JOC 1974, 39, 611.
8. Khatri, H. N.; Walborsky, H. M. JOC 1978, 43, 734.

Harry M. Walborsky & Marek Topolski

Florida State University, Tallahassee, FL, USA

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