Nitriles ester exchange

Two patents describe an interesting process for the synthesis of 3,4-unsatu-rated nitriles by ester-nitrile exchange ... 

Tiazofurine (142) is an antimetabolite with antineoplastic activity. It preferentially affects leukemic lymphocytes over normal cells due to selective activation by formation of its adenine dinucleotide by transformed cells. Of the syntheses available, one starts by conversion of iniidate 138 to methyl 2,5-anhydroallonothioate (139). Next, condensation with ethyl 2-amino-2-cyanoac-etate leads to the thioamide which undergoes thiol addition to the nitrile function to produce the amminothiazolecarboxyester system of 140 directly. Sodium nitrite in aqueous hypophosphorus acid eliminates the superfluous amino group via the diazonium transformation to give 141. This synthesis of tiazofurine (142) concludes by ester amide exchange in methanolic ammonia [48]. 

Monomer Purification. All polymers were prepared from either column purified or distilled monomers. The acrylate and methacrylate esters, styrene, and vinyl nitrile type monomers were purified by passing them through Rohm and Haas Amberlyst exchange resins (salt forms), while the diene monomers were either distilled directly from cylinders and condensed in a dry ice trap or alternatively caustic washed to remove the inhibitor. 

The synthesis is straightforward. The nitrile 53 is alkylated and treated directly with acidic ethanol to give the ester 54 so that the new ester 55 can be made by ester exchange. The reduction of the benzene ring is the last step.10... 

Owing to the emphasis in our treatment on criteria rather than on individual reactions, the various arguments that a specific reaction series followed the addition-elimination route were spread among the different sections. It is worthwhile to summarize that the use of stereochemical, isotope exchange, kinetics and element effects show that the a-arylsulphonyl-j8-haloethylenes (Modena et al.), the j3-halo-a-nitro-styrenes (Modena et al.,) the a-aroyl-/ -haloethylenes (Montanari et al.) and the /3-halocrotonic esters and nitriles (Theron, 1967) systems react with thioanions via this route. Use of some of these criteria together show its operation for other reaction systems. 

The electrosynthesis of /Miydroxy esters (220), 2,3-epoxy esters (221) and /Miydroxy nitriles (222) was achieved under nickel-catalyzed conditions, obviating Reformatsky reaction 70(equation 112-114). The reaction proceeds in excellent yield when a sacrificial zinc rod is used as the anode. A mechanism has been proposed which involves reduction of a Ni(II) complex to a Ni(0) complex, oxidative addition of the a-chloroester to the Ni(0) complex, and a zinc (II)/Ni(II) exchange, leading to an organozinc reagent, in analogy to the Reformatsky reactions. 

The iminothiazocine 583 was synthesized from the ethyl ester 580 by Michael addition to acrylonitrile in DMF to give the nitrile 581 which, treated with EtOH saturated with HC1, gave the iminoether 582. Cyclization of 582 upon treatment with Amberlyst A-21 ion exchange resin gave the 1,5-thiazocine 583 (Scheme 115). 

Most alkyl carbanions undergo facile pyramidal inversion. Cyclopropyl anions are an exception, presumably because the transition state, with a planar trigonal carbon, is more strained than the ground state. The configurational stability of cyclopropyl anions is of value in the synthesis of deuterated cyclopropanes by the Haller-Bauer reaction (see Section II.B). An interesting dilemma arises when a cyclopropyl anion is stabilized by a n-electron acceptor substituent such as a nitrile or an ester. Will the anion then retain its pyramidal equilibrium geometry for the strain reasons alluded to above, or will it become planar in order to maximize overlap of the filled orbital on carbon with the n orbital of the substituent Walborsky and coworkers addressed this question in a series of experiments in which rates of H/D exchange and racemization were compared for an optically active cyclopropane exposed to a base in a deuterated hydroxylic solvent. The outcome can be illustrated with the particular example of 1,1-diphenylcyclopropane-2-... 

Generation of ArMgl. Direct formation of ArMgl containing ester, amide, nitrile groups is impractical. A practical alternative is by exchange process (with i-PrMgBr or i-Pr Mg in THF at -25° to -40°). 

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