Thorpe reactions conditions

It has been established that Thorpe reactions proceed efficiently under solvent-free conditions. For example, when a mixture of acetonitrile (71) and powdered Bu OK was kept at room temperature overnight, a 1 1 mixture of (E)- and (Z)-... 

The intramolecular Thorpe reaction can also be carried out under solvent-free conditions. When a mixture of powdered adiponitrile (80) and Bu OK was kept at room temperature for 3 h, cyclization product 81 was obtained as a... 

Nucleofuges, other than the chlorine atom, can be involved in these reactions. For example, 1,2-bipyridinium chloride 25 reacts with ethyl thioglycolate with elimination of pyridine to form sulfide 26, whose isomerization to thienopyridine 27 occurs under conditions of the Thorpe reaction (1998T5775). 

Butyllithium was freshly titrated by the method of Gilman.2 Excess strong base, either butyllithium or lithium diisopropylamide (LDA), (exceeding 1 equiv per diphenylacetonitrile) should be avoided since the resulting Thorpe-Ziegler cyclization product is susceptible to fragmentation under the reaction conditions to afford 1,1-dicyano-4,4-diphenylbutane. 

Azelaonitrile [N=C-(CH2)7-C=N] converts to cyclic ketone at about 30% yield according to the Thorpe-Ziegler reaction, while 5-t-butyl- and a,a -dimethyl-azelaonitriles [N=C-C(CH3)2-(CH2)6-C=N] convert to the corresponding cyclic ketone at 89% and nearly exclusively, respectively, under the same reaction condition. 

B.iv. Nitrile Enolates. Nitrile enolates are formed by reaction of a nitrile with LDA or another suitable base. Both alkylation 30 and condensation reactions with aldehydes 3 or ketones are known. 32 in addition to alkyl halides and carbonyl derivatives, condensation can occur with another nitrile. The base-catalyzed condensation of two nitriles to give a cyano-ketone, via an intermediate cyano enolate, is known as the Thorpe reaction. 33.109e Reaction of butanenitrile with sodium ethoxide gave a nitrile enolate, which reacted with a second molecule of butanenitrile at the electrophilic cyano carbon to give 206. Hydrolysis gave an intermediate imine-nitrile (207), which is in equilibrium with the enamine form (208, sec. 9.6.A). Hydrolysis led to the final product of the Thorpe reaction, an a-cyano ketone, 209. 33 Mixed condensations are possible when LDA and kinetic conditions are used to generate the a-lithionitrile (a mixed Thorpe reaction). When pentanenitrile was treated with LDA and condensed with benzonitrile, 2-cyano-l-phenyl-1-pentanone was the isolated product after acid hydrolysis. Nitrile enolates can also be alkylated with a variety of alkyl halides. 34... 

Another clever approach by Masamune et al. is an asymmetric aldol reaction of the ketene silyl acetal 32. This reaction is effectively promoted by 20 mol % of chiral borane complexes 33, prepared from BH3 -THF and a,a-disubstituted glycine tosylamide 34, undo-reaction conditions in which aldehydes are slowly added to the reaction mixture (Scheme 8B1.20, Table 8B1.12). The catalysts and the reaction conditions have been designed according to the proposed catalytic cycle shown in Scheme 8B1.21. Thus, the use of a geminally disubstituted catalyst accelerates the ring closure of intermediate 35 as expected from the Thorpe-Ingold effect, and the slow addition of the aldehyde reduces the accumulation of 35, which might catalyze the aldol reaction with low enantioselectivity. Extremely... 

Dunn JA, Ahmed MU, Murtiashaw MH, Richardson JM, Walla MD, Thorpe SR and Baynes JW (1990) Reaction of ascorbate with lysine and protein under autoxidizing conditions formation of N-(carboxymethyl)lysine by reaction between lysine and products of autoxidation of ascorbate. Biochemistry 29, 10964-10970. 

Transformations of 2-alkylthio-l,4-dihydropyridines 17 under conditions of Thorpe isomerization were considered. These compounds are easily formed by alkylation of pyridinethiones 18 or the corresponding thiolates 19 and can be used in reactions without preliminary isolation. Cyclization afforded both 4,7-di-hydrothieno[2,3-6]pyridines 20 (1992KFZ40, 1996KGS553, 1997KGS666,... 

Compounds 2 and 3 react with sodium hydride in THF to give the products of a Thorpe-Ziegler reaction. The procedure under more conventional conditions (KOH/DMF) results in a mixture of closo- and tV/o8-carboranyl-thieno-pyridines and -pyrimidines (Scheme 3) ... 

The original Thorpe conditions involved a catalytic amount of base, as the mechanism would imply. Later workers found that in certain reactions equivalent amounts of base were required or that catalytic and equivalent amounts of base gave different products. As shown in Scheme 84, the Michael dimer (177) is the major product when adiponitrile (175) is cyclized with a trace of sodium f-butoxide in f-butyl alcohol, whereas an equivalent of this base in toluene gave the monomer (176). 

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