Imino cyanation

Chlorosulfonyl isocyanate is an excellent alternative to alkaline cyanates ia the preparation of hydantoias from stericaHy hindered or labile amino nitriles (62). Imino derivatives similar to (18) can also be obtained by addition of sonitnles to imines followed by treatment with a cyanate (63). 

Many organic and inorganic cyanides, cyanates, isocyanates and thiocyanates react with sulfur tetrafluoride at elevated temperatures with the formation of iminosulfur difluorides. Thus, cyanogen bromide, sodium cyanide, and sodium thiocyanate give (trifluoromethyl)imino-sulfur difluoride (1) in 37 -70% yield.202... 

Subsequently, it was shown that the reaction was catalyzed by base (48M(79)106). Dicyandiamide reacts with nitriles (the most valuable method), amidines, cyanamides, ammonia, cyanates, thiocyanates, carboxylic acids and anhydrides to yield 1,3,5-triazines (Table 13). This synthetic route has been reviewed thoroughly several times (59HC(13)1, p. 219,61MI22000, p. 650, 73ZC408). The base-catalyzed reaction of dicyandiamide with alkyl or aryl nitriles (Scheme 65) proceeds via the imino ether anion and the rate determining step is solvent dependent. In DMSO the formation of the imino ether is rate determining, but in 2-methoxyethanol the reaction between the anion and dicyandiamide controls the rate (66T157). 

Supplement to Chapter 28 Cyanation of Carbonyl and Imino Groups... 

Extension of this reaction toward a one-pot asymmetric Mannich-hydrocyanation reaction sequence was also reported by the Barbas group [29]. In this one-pot two-step process proline-catalyzed asymmetric Mannich reaction of unmodified aldehydes with the a-imino glyoxylate was performed first, then diastereoselective in situ cyanation. The resulting /i-cyanohydroxymethyl a-amino acids were obtained with high enantioselectivity (93-99% ee) [29]. Another one-pot two-step reaction developed by Barbas et al. is the Mannich-allylation reaction in which the proline-catalyzed Mannich reaction is combined with an indium-promoted allylation [30], This one-pot synthesis was conducted in aqueous media and is the first example of a direct organocatalytic Mannich reaction in aqueous media [28, 30]. 

Since an important feature of Biicherer-Bergs hydantoin formation is that the process can only work for a-aminonitriles without substituent on the amino group, it follows that one compound of the equilibrium mixture formed from an aldehyde, ammonia, and cyanide is selectively reacted through an irreversible process leaving N-alkylated aminonitriles or imino-dinitriles unreacted. However, the difficulty with this process is that CAAs and hydantoins are poorly reactive towards hydrolysis and need long periods of time to be converted into free AAs. But, CAAs may also have per se a prebi-otic importance in activation pathways towards polypeptides (see Sect. 3.3.7). CAAs can also be synthesized by reaction of free amino acids with cyanic acid/cyanate (a likely prebiotic compound [50]). In the presence of a steady-state concentration of either cyanate or urea in aqueous medium, CAAs are at equilibrium with A A [51]. 

Mori, A. Inoue, S. Cyanation of Carbonyl and Imino Groups. In Comprehensive Asymmetric Catalysis Jacobsen, E. N., Pfaltz, A., Yamamoto,... 

Martin et al report investigations on the kinetics and the mechanism of aryl cyanate formation frx>m cyanogen bromide and phenols in the presence of different tertiary aliphatic amines. According to Vo-winkel," the use of diethyl ether as the solvent at -10 C raises the yields and various patents describe how the amines can be replaced by sodium hydroxide. There are even reports on work in aqueous solution under phase transfer conditions. With all synthetic variants it is crucial to avoid a surplus of the phenolate as only under these conditions can the often quite fast formation of imino carbonates be prevented (equation 28). 

Vachal, P., Jacobsen, E. N. Cyanation of carbonyl and imino groups. Comprehensive Asymmetric Catalysis, Supplement 2004,1, 117-130. 

Amino-5-imino-3-pyrazolidinones have been synthesized by reduction of the corresponding oximes.644,1339 Such amines form ureas and thioureas by reaction with potassium cyanate in acid solution and with phenyl isothiocyanate.644 4-Arylimino-5-imino-3-pyrazolidinones have been prepared by reaction of the 5-imino-3-pyrazolidinones with p-amino-A.-AT-diethylaniline in the presence of silver salts as oxidizing agents (eq. 172).244,519,1255,1538 4-Arylazo-5-imino-3-pyrazolidinones have most frequently been prepared by reaction of 5-imino-3-pyrazoli-dinones with aryldiazonium chlorides, as is usual for the preparation of similar compounds.591,594,920,1087,1255,1339,1539,1649 One such compound has been prepared by the Curtius rearrangement of the corresponding 4-arylazo azide.594... 

The model satisfactorily described the cure behavior for the entire range as experimentally monitored by FTIR, DSC, and torsional braid analysis (TBA). This model satisfactorily explained the cure behavior of both catalyzed and uncatalyzed systems over a wide range of temperature and throughout the curing process. The authors proposing the kinetic model considered the reaction to be triggered by the adventitious water and phenol impurities (whose reactions with the cyanate ester is considered as an equilibrium reaction). Catalysis by the added metal ions, which stabilizes the imino carbonate intermediates by complex-ing, is also considered. The model has considered all possible reaction paths and intermediates as detailed in Sect. 4 and depicted in Scheme 14. Considering the various reactions, expressions could be obtained for the individual apparent empirical rate constants of the second order auto catalytic model in terms of the actual rate constants and equilibrium constants. 

Concerning the cyanating agent, hydrogen cyanide and its alkaline metal salts are frequently used to effect cyanation in the presence of a catalytic or a stoichiometric amount of a base, such as amines, phosphines, and metal alkoxides. Acetone cyanohydrin, which serves as an alternative to hydrogen cyanide, also promotes the cyanation of carbonyl and imino compounds (transhydrocyanation) to yield the corresponding cyanohydrins or aminonitriles along with the formation of acetone. 

Catalysts (25) are the Lewis acid-Lewis base bifunctional catalysts in which Lewis acid-Al(III) moiety activates acyl iminium ion and the Lewis base (oxygen of phosphine oxide) does TMSCN, simultaneously (Scheme 5.7). Halogen atoms at the 6-position enhanced both yields and enantioselectivity in Reissert-type cyanation of the imino part of 26. However, the order for the activation is not parallel to the electronegativity of the halogen atoms and, moreover, the strong electron-withdrawing trifluoromethyl group provided unexpectedly the worst result for the activation [13]. It is not simple to explain this phenomenon only in terms of the increased Lewis acidity of the metal center. Trifluoromethylated BINOL-zirconium catalysts (28) for asymmetric hetero Diels-Alder reaction (Scheme 5.8) [14], trifluoromethylated arylphosphine-palladium catalyst (32) for asymmetric hydrosilylation (Scheme 5.9) [15], and fluorinated BINOL-zinc catalyst (35) for asymmetric phenylation (Scheme 5.10) [16] are known. 

Cycloaddition of 2-(dicyanomethylene)piperidine with iso(thio) cyanates afforded 3-imino-4-cyano-2,3,5,6,7,8-hexahydro-l//-pyrido[l,2-c]pyrimidin-l-ones or -1-thiones (198, = H, X = O or S) (78MI1). When... 

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