Bases. cyanohydrins

In 2003, Kanerva s group reported the preparation of novel (l )-furyl-benzothiazole-based cyanohydrin acetates from the corresponding furan-... 

A similar methodology was applied by the same group to the preparation of novel phenylfuran-based cyanohydrin esters by using Pseudomonas cepacia lipase and vinyl butanoate as the acylating agent. The results are summarised in Scheme 3.25. 

Paizs, C Tahtinen, P To a, M Majdik, C Irimie, F-D Kanerva, LT. Biocatalyticenantio selective preparation of phenothiazine-based cyanohydrin acetates kinetic and dynamic kinetic resolution. Tetrahedron, 2004, v. 60 (46), 10533-10540. 

Paizs C, Tahtinen P, Tosa M, Majdik C, Irimie F-D, Kanerva LT. Biocatalytic enantioselective preparation of pheno-thiazine-based cyanohydrin acetates kinetic and dynamic kinetic resolution. Tetrahedron 2004 60 10533-10540. 

In the mid 1970s, Ugi and co-workers developed a scheme based on treating reactions by means of matrices - reaction (R-) matrices [16, 17]. The representation of chemical structures by bond and electron (BE-) matrices was presented in Section 2.4. BE-matrices can be constructed not only for single molecules but also for ensembles of them, such as the starting materials of a reaction, e.g., formaldehyde (methanal) and hydrocyanic add as shown with the B E-matrix, B, in Figure 3-12. Figure 3-12 also shows the BE-matrix, E, of the reaction product, the cyanohydrin of formaldehyde. 

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.). 

Out first example is 2-hydroxy-2-methyl-3-octanone. 3-Octanone can be purchased, but it would be difficult to differentiate the two activated methylene groups in alkylation and oxidation reactions. Usual syntheses of acyloins are based upon addition of terminal alkynes to ketones (disconnection 1 see p. 52). For syntheses of unsymmetrical 1,2-difunctional compounds it is often advisable to look also for reactive starting materials, which do already contain the right substitution pattern. In the present case it turns out that 3-hydroxy-3-methyl-2-butanone is an inexpensive commercial product. This molecule dictates disconnection 3. Another practical synthesis starts with acetone cyanohydrin and pentylmagnesium bromide (disconnection 2). Many 1,2-difunctional compounds are accessible via oxidation of C—C multiple bonds. In this case the target molecule may be obtained by simple permanganate oxidation of 2-methyl-2-octene, which may be synthesized by Wittig reaction (disconnection 1). 

In the early versions, ethylene cyanohydrin was obtained from ethylene chlorohydrin and sodium cyanide. In later versions, ethylene oxide (from the dkect catalytic oxidation of ethylene) reacted with hydrogen cyanide in the presence of a base catalyst to give ethylene cyanohydrin. This was hydrolyzed and converted to acryhc acid and by-product ammonium acid sulfate by treatment with about 85% sulfuric acid. 

Processes rendered obsolete by the propylene ammoxidation process (51) include the ethylene cyanohydrin process (52—54) practiced commercially by American Cyanamid and Union Carbide in the United States and by I. G. Farben in Germany. The process involved the production of ethylene cyanohydrin by the base-cataly2ed addition of HCN to ethylene oxide in the liquid phase at about 60°C. A typical base catalyst used in this step was diethylamine. This was followed by liquid-phase or vapor-phase dehydration of the cyanohydrin. The Hquid-phase dehydration was performed at about 200°C using alkah metal or alkaline earth metal salts of organic acids, primarily formates and magnesium carbonate. Vapor-phase dehydration was accomphshed over alumina at about 250°C. 

Until 1982, almost all methyl methacrylate produced woddwide was derived from the acetone cyanohydrin (C-3) process. In 1982, Nippon Shokubai Kagaku Kogyo Company introduced an isobutylene-based (C-4) process, which was quickly followed by Mitsubishi Rayon Company in 1983 (66). Japan Methacryhc Monomer Company, a joint venture of Nippon Shokubai and Sumitomo Chemical Company, introduced a C-4-based plant in 1984 (67). Isobutylene processes are less economically attractive in the United States where isobutylene finds use in the synthesis of methyl /i / butyl ether, a pollution-reducing gasoline additive. BASF began operation of an ethylene-based (C-2) plant in Ludwigshafen, Germany, in 1990, but favorable economics appear to be limited to conditions unique to that site. 

Considerable research is currendy directed toward development of novel technologies that may present economic advantages with respect to the conventional acetone cyanohydrin (ACH) route. Mitsubishi Gas Chemical Co. has developed and patented a modified acetone cyanohydrin-based route... 

Mitsubishi Gas Chemical Company Process. The commercial MMA manufacturing process based on sulfuric acid and acetone cyanohydrin suffers from the large quantities of ammonium sulfate produced. Because ammonium sulfate has only low value as fertili2er, regeneration of sulfuric acid from ammonium sulfate [7783-20-2] is required. Despite the drawbacks of using sulfuric acid, this technology is stiU the most widely practiced... 

A cyanohydrin is an organic compound that contains both a cyanide and a hydroxy group on an aUphatic section of the molecule. Cyanohydrias are usually a-hydroxy nitriles which are the products of base-cataly2ed addition of hydrogen cyanide to the carbonyl group of aldehydes and ketones. The lUPAC name for cyanohydrias is based on the a-hydroxy nitrile name. Common names of cyanohydrias are derived from the aldehyde or ketoae from which they are formed (Table 1). 

Cyanohydrins can be formed by (/) the acid- or base-cataly2ed reaction of hydrogen cyanide with an aldehyde or ketone ... 

Production of cyanohydrins is accompHshed through the base-cataly2ed combination of hydrogen cyanide and the carbonyl compound in a solvent, usually the cyanohydrin itself (17). The reaction is carried out at high dilution of the feeds, at 10—15°C, and pH 6.5—7.5. The product is continuously removed from the reaction 2one, cooled to push the equilibrium toward cyanohydrin formation, and then stabili2ed with mineral acid. Purification is usually effected by distillation. 

Like the formation of a-cyanohydrins, this reaction is catalyzed by bases or cyanide ion, but unlike the a-cyanohydrin case this reaction is not reversible, and under certain conditions it can proceed with violence. Ethylene cyanohydrin can also be prepared by the reaction of ethylene chlorohydrin and alkaH cyanides (39). 

The first U.S. plant for acrylonitrile manufacture used an ethylene cyanohydrin feedstock. This was the primary route for acrylonitrile manufacture until the acetylene-based process began to replace it in 1953 (40). Maximum use of ethylene cyanohydrin to produce acrylonitrile occurred in 1963. Acrylonitrile (qv) has not been produced by this route since 1970. 

In 1896, Emil Fisher found that 2,5-diphenyloxazole hydrochloride was precipitated by passing gaseous hydrogen chloride into an absolute ether solution of benzaldehyde and benzaldehyde cyanohydrin. The oxazole hydrochloride can be converted to the free base by addition of water or by boiling with alcohol. Many different aromatic aldehydes and cyanohydrin combinations have been converted to 2,5-diaryloxazoles 4 by this procedure in 80% yield. ... 

Aldehydes and unhindered ketones undergo a nucleophilic addition reaction with HCN to yield cyanohydrins, RCH(OH)C=N. Studies carried out in the early 1900s by Arthur Eapworth showed that cyanohydrin formation is reversible and base-catalyzed. Reaction occurs slowly when pure HCN is used but rapidly when a small amount of base is added to generate the nucleophilic cyanide ion, CN. Alternatively, a small amount of KCN can be added to HCN to catalyze the reaction. Addition of CN- takes place by a typical nucleophilic addition pathway, yielding a tetrahedral intermediate that is protonated by HCN to give cyanohydrin product plus regenerated CN-. 

When cyclohexanone is heated in the presence of a large amount of acetone cyanohydrin and a small amount of base, cyclohexanone cyanohydrin and acetone are formed. Propose a mechanism. 

The procedure is modified for the reaction of preformed cyanohydrins with chiral amines39. I11 a further variation, Schiff bases of aliphatic aldehydes with optically active 1-arylalkyl-amines are transformed with liquid hydrogen cyanide to the corresponding a-aminonitrilcs, which, after acid hydrolysis, give the /V-aryUilkylamino acids. Hydrogenation then yields the a-amino acids40 41. 

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