Cyanide classical method

Among the classic methods for the extension of the aldose chain by one carbon atom from the reducing end [9J, the Kiliani-Fischer cyanohydrin synthesis [10] is a milestone in carbohydrate chemistry. However after 110 years from discovery and numerous applications [11], including the preparation of carbon and hydrogen isotopically labeled compounds for mechanistic and structural studies [12], there are still several drawbacks that make the method impractical. These are the low and variable degree of selectivity and the harsh reaction conditions that are required to reveal the aldose from either the aldonic acid or directly from the cyanohydrin. Synthetic applications that have appeared in recent times confirmed these limitations. For instance, a quite low selectivity was registered [13] in the addition of the cyanide ion to the D-ga/acfo-hexodialdo-l,5-pyranose derivative 1... 

Oxidation of a,(J-unsaturated aldehydes (2, 261). Woo and Sondheimer6 prepared methyl [18]annulenecarboxylate (2) by the method of Corey et al. (2, 263, ref. 42) by treating [18]annulenecarboxaldehyde (1) in THF and methanol with hydrogen cyanide and manganese dioxide (44% yield). In this case the classical method of oxidation by Jones reagent failed owing to complete destruction of the annulene system. 

Several reviews have been written which cover the history of the Krapcho reaction through 1982.1,4 Further research in this area revealed the application of the decarboxylation method to compounds such as P-ketoesters, malonate esters, a-cyanoester, and a-sulfonylesters. The classical method for decarboxylation of these compounds usually involves acidic or basic hydrolysis, followed by thermal decarboxylation. Unfortunately, compounds containing acid or base sensitive functional groups are not compatible with these methods. Modem Krapcho conditions have replaced cyanide with less toxic halide anions. Additionally, several decarboxylations have occurred in the absence of salt.4... 

There are numerous classical methods such as gravimetric or titrimetric method using AgNOs with different reagents p-dimethylaminobenzylidine, rhodanine or dithizone, and also a mercurimetric or iodimetric for determining cyanide. These methods have been explained by Williams [7]. 

The most general methods for the syntheses of 1,2-difunctional molecules are based on the oxidation of carbon-carbon multiple bonds (p. 117) and the opening of oxiranes by hetero atoms (p. 123fl.). There exist, however, also a few useful reactions in which an a - and a d -synthon or two r -synthons are combined. The classical polar reaction is the addition of cyanide anion to carbonyl groups, which leads to a-hydroxynitriles (cyanohydrins). It is used, for example, in Strecker s synthesis of amino acids and in the homologization of monosaccharides. The ff-hydroxy group of a nitrile can be easily substituted by various nucleophiles, the nitrile can be solvolyzed or reduced. Therefore a large variety of terminal difunctional molecules with one additional carbon atom can be made. Equally versatile are a-methylsulfinyl ketones (H.G. Hauthal, 1971 T. Durst, 1979 O. DeLucchi, 1991), which are available from acid chlorides or esters and the dimsyl anion. Carbanions of these compounds can also be used for the synthesis of 1,4-dicarbonyl compounds (p. 65f.). 

This procedure is representative of a new general method for the preparation of noncyclic acyloins by thiazol ium-catalyzed dimerization of aldehydes in the presence of weak bases (Table I). The advantages of this method over the classical reductive coupling of esters or the modern variation in which the intermediate enediolate is trapped by silylation, are the simplicity of the procedure, the inexpensive materials used, and the purity of the products obtained. For volatile aldehydes such as acetaldehyde and propionaldehyde the reaction Is conducted without solvent in a small, heated autoclave. With the exception of furoin the preparation of benzoins from aromatic aldehydes is best carried out with a different thiazolium catalyst bearing an N-methyl or N-ethyl substituent, instead of the N-benzyl group. Benzoins have usually been prepared by cyanide-catalyzed condensation of aromatic and heterocyclic aldehydes.Unsymnetrical acyloins may be obtained by thiazol1um-catalyzed cross-condensation of two different aldehydes. -1 The thiazolium ion-catalyzed cyclization of 1,5-dialdehydes to cyclic acyloins has been reported. 

Strecker reactions provide one of the most efficient methods for the synthesis of a-amino nitriles, which are useful intermediates in the synthesis of amino acids and nitrogen-containing heterocycles. Although classical Strecker reactions have some limitations, use of trimethylsilyl cyanide (TMSCN) as a cyano anion source provides promising and safer routes to these compounds.133-351 Consequently, we focused our attention on tributyltin cyanide (Bu3SnCN), because Bu3SnCN is stable in water and is also a potential cyano anion source. Indeed, the Strecker-type reactions of aldehydes, amines, and Bu3SnCN proceeded smoothly in water (Eq. 9).1361 It should be noted that no surfactants are required in this reaction. Furthermore, Complete recovery of the toxic tin compounds is also possible in the form of bis(tributyltin) oxide after the reaction is over. Since conversion of bis(tributyltin) oxide to tributyltin cyanide is known in the literature, this procedure provides a solution to the problem associated with toxicity of tin compounds. 

This process is superior to classical hydrocyanation methods using an alkali metal cyanide and to the improved method using potassium cyanide and ammonium chloride with respect to reactivity, stereospeciific.ity, and absence of side reactions. Also, the process is applicable to onjuga.te hydrocyanation of... 

The classical procedure for the reaction involves heating the alkyl halide (usually the chloride or bromide) with sodium or potassium cyanide in metha-nolic or ethanolic solution. The method is clearly of value for the extension of the carbon chain by one carbon atom, since the cyano group may be converted into a carboxyl group by hydrolysis (Section 5.11.2, p. 671) or into an amino-methyl group (—CH2-NH2) by reduction (Section 5.16.1, p. 771), or into a formyl group by controlled reduction to the imine followed by hydrolysis (Section 5.7.4, p. 594). ... 

The automation or semi-automation of a conventional manual method by FIA often results in a decrease in the number and level of interferents. Thus, in the FIA version of the determination of cyanide by the classical reaction with barbituric acid/chloramine T, nitrite and sulphide pose no Interference at concentrations ten times as high as that of the analyte, which is otherwise adversely affected by the presence of both interferents in the manual method [48], The greater tolerance to foreign species in FIA methods can be generally attributed to their kinetic character, so that undesirable side reactions scarcely have the opportunity to develop to an appreciable extent in such a short interval as the residence time. The tolerance to extransous species is even more remarkable in kinetic FIA methods based on the measurement of a reaction rate (stopped-flow). Optimization of FIA systems as regards selectivity is a relatively simple task on account of their enormous versatility. 

Cyanogen iodide may be analyzed by classical wet methods for cyanide and iodide tests, by colorimetry, and by GC and GC/MS. 

The identification and quantitative determination of decomposition products can be carried out by any of the appropriate techniques of classical and modern analytical chemistry. Carbon monoxide, carbon dioxide, water, hydrogen chloride, hydrogen cyanide, sulphur dioxide, and other inorganics are still analyzed by the conventional methods. The organics such as hydrocarbons, alcohols, aldehydes, ketones, etc. are usually separated and determined by gas chromatography. 

Cyanide addition to the lactamic carbonyl group has been described in a reaction in which the cyanide ion acts as a catalyst (Fig. 14).The intermediate acyl cyanide can be attacked by an added nucleophile (allylic, propargylic, benzylic alcohols, aniline, benzylmercaptan). Comparative experiments were carried out using more classical procedures, such as under catalysis by potassium cyanide with stirring at room temperature, and with sodium alkoxides at -78 C. This last method provides the highest yields, up to 95% in most of the cases tested, but the sonochemical method proceeds under less basic conditions. Both methods preserve the integrity of the asymmetric center. 

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