(Stranger)
10-12-03 22:15
No 464342
(Rated as: excellent)
This is very useful to go from substituted chloromethyl compounds, to the easily reduced acetonitriles. What SWIM liked was that it didn't use any DMF, as most acetonitrile syntheses describe, and the yields are usually higher.
From JOC, vol. 25, pp.877 (1960):
Reaction of primary and secondary chlorides with NaCN in DMSO occurs rapidly and efficiently to result in an improved general method for preparing nitriles. Advantages are also realized in conversion of primary and secondary bromides to their corresponding nitriles...
It is now reported that typical primary chloroalkanes react rapidly and exothermically with sodium cyanide in partial solution in dimethyl sulfoxide to give the corresponding nitriles in excellent yields. The nitriles are conveniently isolated from the reaction mixture by dilution with water followed by suitable extraction. At the preferred reaction temperatures of 120-140 C the conversion of primary chlorides to nitriles may usually be completed in one half to two hours... Secondary chloro compounds react relatively slowly (ca. three hours) to give the corresponding nitriles in moderate yields (65-70%).
Experimental
Reaction of 1-chlorobutane and sodium or potassium cyanide. Valeronitrile. 1-Chlorobutane (93 g., 1 mole) was added in 10-15 min. to a rapidly stirred partially-soluble mixture of sodium cyanide (53 g., 1.08 moles, Reagent) in dimethyl sulfoxide (250 ml., technical; ) at 80 C. The temperature of the mixture rose rapidly and was kept at 140 +- 5 C by cooling with water when necessary. During the reaction the mixture became more fluid, and the insoluble salts more crystalline. After the 1-chlorobutane had been added, the temperature dropped rapidly, and the reaction was apparently complete. The brown reaction mixture was cooled, diluted with water to a volume of ca. 1000 ml., and extracted with ether (3 X 150 ml.). The pale yellow ether extracts were washed with 6N HCl (to hydrolyze the small amount of noxious isocyanide) and water, and dried over CaCl2. After removal of ether, the residue was rectified over P2O5 to give forerun (6.0 ml.), b.p. 110-138 C (747 mm.), and valeronitrile (77g., 0.93 mole, 93%), b.p. 138-139 C (747 mm.)
Now for the good stuff, from JOC, vol. 29, pp.2860 (1964):
2,5-Dimethoxybenzyl Chloride, yield 60%... see Post 384897 (Rhodium: "Chloromethylation of p-dimethoxybenzene - 61%!", Methods Discourse)
2,5-Dimethoxyacetonitrile, m.p. 52-53 C, was obtained in 98% yield from the reaction of the dimethoxybenzyl chloride with NaCN in DMSO according to the procedure of Friedman and Schechter above. Yields of 30% were obtained by the earlier procedure using aqueous ethanol.
A good read for solvent effects of DMSO, read JOC, vol. 29 pp. 3262 (1964) - it is informative.
(Stranger)
10-13-03 07:15
No 464342
(Rated as: excellent)
This is very useful to go from substituted chloromethyl compounds, to the easily reduced acetonitriles. What SWIM liked was that it didn't use any DMF, as most acetonitrile syntheses describe, and the yields are usually higher.
From JOC, vol. 25, pp.877 (1960):
Reaction of primary and secondary chlorides with NaCN in DMSO occurs rapidly and efficiently to result in an improved general method for preparing nitriles. Advantages are also realized in conversion of primary and secondary bromides to their corresponding nitriles...
It is now reported that typical primary chloroalkanes react rapidly and exothermically with sodium cyanide in partial solution in dimethyl sulfoxide to give the corresponding nitriles in excellent yields. The nitriles are conveniently isolated from the reaction mixture by dilution with water followed by suitable extraction. At the preferred reaction temperatures of 120-140 C the conversion of primary chlorides to nitriles may usually be completed in one half to two hours... Secondary chloro compounds react relatively slowly (ca. three hours) to give the corresponding nitriles in moderate yields (65-70%).
Experimental
Reaction of 1-chlorobutane and sodium or potassium cyanide. Valeronitrile. 1-Chlorobutane (93 g., 1 mole) was added in 10-15 min. to a rapidly stirred partially-soluble mixture of sodium cyanide (53 g., 1.08 moles, Reagent) in dimethyl sulfoxide (250 ml., technical; ) at 80 C. The temperature of the mixture rose rapidly and was kept at 140 +- 5 C by cooling with water when necessary. During the reaction the mixture became more fluid, and the insoluble salts more crystalline. After the 1-chlorobutane had been added, the temperature dropped rapidly, and the reaction was apparently complete. The brown reaction mixture was cooled, diluted with water to a volume of ca. 1000 ml., and extracted with ether (3 X 150 ml.). The pale yellow ether extracts were washed with 6N HCl (to hydrolyze the small amount of noxious isocyanide) and water, and dried over CaCl2. After removal of ether, the residue was rectified over P2O5 to give forerun (6.0 ml.), b.p. 110-138 C (747 mm.), and valeronitrile (77g., 0.93 mole, 93%), b.p. 138-139 C (747 mm.)
Now for the good stuff, from JOC, vol. 29, pp.2860 (1964):
2,5-Dimethoxybenzyl Chloride, yield 60%... see Post 384897 (Rhodium: "Chloromethylation of p-dimethoxybenzene - 61%!", Methods Discourse)
2,5-Dimethoxyacetonitrile, m.p. 52-53 C, was obtained in 98% yield from the reaction of the dimethoxybenzyl chloride with NaCN in DMSO according to the procedure of Friedman and Schechter above. Yields of 30% were obtained by the earlier procedure using aqueous ethanol.
A good read for solvent effects of DMSO, read JOC, vol. 29 pp. 3262 (1964) - it is informative.
(Chief Bee)
10-13-04 20:33
No 535685
(Rated as: excellent)
Full text of the above articles:
Preparation of Nitriles from Halides and Sodium Cyanide. An Advantageous Nucleophilic Displacement in Dimethyl Sulfoxide
L. Friedman, H. Shechter
J. Org. Chem. 25, 877-879 (1960) (../rhodium/pdf /halide2nitri
Abstract
Reaction of primary and secondary chlorides with sodium cyanide in dimethyl sulfoxide occurs rapidly and efficiently to result in an improved general method for preparing nitriles. Advantages are also realized in conversion of primary and secondary bromides to their corresponding nitriles. Use of dimethyl sulfoxide allows preparative displacement of halides of the neophyl and neopentyl types by cyanide ion without rearrangement. Typical procedures which illustrate the various experimental methods are described.
____ ___ __ _
The Mechanism of Dimethyl Sulfoxide Catalysis in Nucleophilic Displacement
Charles A. Kingsbury
J. Org. Chem. 29, 3262-3270 (1964) (../rhodium/pdf /nucleophilic
Abstract
Kinetic data on nucleophilic aromatic substitution in several systems are reported which have bearing on the mechanism of catalysis by dimethyl sulfoxide and other dipolar aprotic solvents. Significant rate increases occur even at low dimethyl sulfoxide concentrations where desolvation of the nucleophile is not an important effect. The rate increase per mole of dimethyl sulfoxide is due to changes in ΔH*; changes in ΔS* are slight. Using substituted phenoxide molecules as nucleophiles, dimethyl sulfoxide concentration has little effect on ρ of a Hammett ρ-σ plot, although striking rate increases occur. Dimethyl sulfoxide catalysis is independent of the charge the nucleophile bears. The rate increase per mole of dimethyl sulfoxide is relatively independent of nucleophile or solvent system. The mechanism of dimethyl sulfoxide catalysis is thought to involve polarization of the substrate by a random dimethyl sulfoxide molecule and rapid nucleophilic attack upon this species. The change in solvent structure is thought to allow more rapid reaction rates where hydrogen-bond acceptors are present.
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