Alcohols cyanohydrins

Toda, F., Matsuda, S., and Tanaka, K. (1991) Efficient Resolution of Secondary Alcohols, Cyanohydrins, and Glycerol Acetates by Complexation with the Host Derived from Tartaric Acid, Tetrahedron Asymm., 2, 983-986. 

The reactions of enolized keto carboxylic esters with ammonia and amines are described on page 507, and those of a-amino alcohols, cyanohydrins, and a-hydroxy sulfonic acids on pages 516-520. 

ABSTRACT. Novel optical resolutions of guest compounds by inclusion complex formation with optically active host compound are reviewed Tertiary acetylenic alcohols, cyanohydrins, and secondary alcohols were resolved by complexation with alkaloids such as brucine or sparteine. Cycloalkanones, 2,3 -epoxycyclohexanones, and some other neutral compounds were resolved by complex formation with optically active diacetylenic diol. Mutual optical resolution of bis-g-naphthol and sulfoxides by complex formation was also reviewed. 

Miscellaneous Reactions. Sodium bisulfite adds to acetaldehyde to form a white crystalline addition compound, insoluble in ethyl alcohol and ether. This bisulfite addition compound is frequendy used to isolate and purify acetaldehyde, which may be regenerated with dilute acid. Hydrocyanic acid adds to acetaldehyde in the presence of an alkaU catalyst to form cyanohydrin the cyanohydrin may also be prepared from sodium cyanide and the bisulfite addition compound. Acrylonittile [107-13-1] (qv) can be made from acetaldehyde and hydrocyanic acid by heating the cyanohydrin that is formed to 600—700°C (77). Alanine [302-72-7] can be prepared by the reaction of an ammonium salt and an alkaU metal cyanide with acetaldehyde this is a general method for the preparation of a-amino acids called the Strecker amino acids synthesis. Grignard reagents add readily to acetaldehyde, the final product being a secondary alcohol. Thioacetaldehyde [2765-04-0] is formed by reaction of acetaldehyde with hydrogen sulfide thioacetaldehyde polymerizes readily to the trimer. 

ACH = acetone cyanohydrin C-4 = tert-butyl alcohol- isobutylene C-2 = ethylene. ... 

The handling of toxic materials and disposal of ammonium bisulfate have led to the development of alternative methods to produce this acid and the methyl ester. There are two technologies for production from isobutylene now available ammoxidation to methyl methacrylate (the Sohio process), which is then solvolyzed, similar to acetone cyanohydrin, to methyl methacrylate and direct oxidation of isobutylene in two stages via methacrolein [78-85-3] to methacryhc acid, which is then esterified (125). Since direct oxidation avoids the need for HCN and NH, and thus toxic wastes, all new plants have elected to use this technology. Two plants, Oxirane and Rohm and Haas (126), came on-stream in the early 1980s. The Oxirane plant uses the coproduct tert-huty alcohol direcdy rather than dehydrating it first to isobutylene (see Methacrylic acid). 

Formaldehyde Cyanohydrin. This cyanohydrin, also known as glycolonitrile [107-16-4], is a colorless Hquid with a cyanide odor. It is soluble in water, alcohol, and diethyl ether. Equimolar amounts of 37% formaldehyde and aqueous hydrogen cyanide mixed with a sodium hydroxide catalyst at 2°C for one hour give formaldehyde cyanohydrin in 79.5% yield (22). 

Acetaldehyde Cyanohydrin. This cyanohydrin, commonly known as lactonitnle, is soluble in water and alcohol, but insoluble in diethyl ether and carbon disulfide. Lactonitnle is used chiefly to manufacture lactic acid and its derivatives, primarily ethyl lactate. Lactonitnle [78-97-7] is manufactured from equimolar amounts of acetaldehyde and hydrogen cyanide containing 1.5% of 20% NaOH at —10 20 ° C. The product is stabili2ed with sulfuric acid (28). Sulfuric acid hydroly2es the nitrile to give a mixture of lactic acid [598-82-3] and ammonium bisulfate. 

Acetone Cyanohydrin. This cyanohydrin, also known as a-hydroxyisobutyronitnle and 2-methyUactonitrile [75-86-5], is very soluble in water, diethyl ether, and alcohol, but only slightly soluble in carbon disulfide or petroleum ether. Acetone cyanohydrin is the most important commercial cyanohydrin as it offers the principal commercial route to methacrylic acid and its derivatives, mainly methyl methacrylate [80-62-6] (see Methacrylic acid AND derivatives). The principal U.S. manufacturers are Rohm and Haas Co., Du Pont, CyRo Industries, and BP Chemicals. Production of acetone cyanohydrin in 1989 was 582,000 metric tons (30). 

Benzaldehyde Cyanohydrin. This cyanohydrin, also known as mandelonitrile [532-28-5] is a yellow, oily Hquid, insoluble in water, but soluble in alcohol and diethyl ether. Mandelonitrile is a component of the glycoside amygdalin [29883-15-6] a precursor of laetdle [1332-94-7] found in the leaves and seeds on most Prunus species (plum, peach, apricot, etc). In 1832, mandelonitrile was the first cyanohydrin to be synthesized. 

Cyanohydrin Synthesis. Another synthetically useful enzyme that catalyzes carbon—carbon bond formation is oxynitnlase (EC 4.1.2.10). This enzyme catalyzes the addition of cyanides to various aldehydes that may come either in the form of hydrogen cyanide or acetone cyanohydrin (152—158) (Fig. 7). The reaction constitutes a convenient route for the preparation of a-hydroxy acids and P-amino alcohols. Acetone cyanohydrin [75-86-5] can also be used as the cyanide carrier, and is considered to be superior since it does not involve hazardous gaseous HCN and also virtually eliminates the spontaneous nonenzymatic reaction. (R)-oxynitrilase accepts aromatic (97a,b), straight- (97c,e), and branched-chain aUphatic aldehydes, converting them to (R)-cyanohydrins in very good yields and high enantiomeric purity (Table 10). 

Silylated cyanohydrins have also been prepared via silylation of cyanohydrins themselves and by the addition of hydrogen cyanide to silyl enol ethers. Silylated cyanohydrins have proved to be quite useful in a variety of synthetic transformations, including the regiospecific protection of p-quinones, as intermediates in an efficient synthesis of a-aminomethyl alcohols, and for the preparation of ketone cyanohydrins themselves.The silylated cyanohydrins of heteroaromatic aldehydes have found extensive use as... 

The use of acetone cyanohydrin (in an exchange reaction) instead of alcoholic hydrogen cyanide affords even higher yields of 17-cyanohydrins and the former reagent has the added advantage of reacting quantitatively and essentially selectively with the 17-ketone of androst-4-ene-3,17-dione. Sodium hydroxide promotes the exchange reaction in some cases. 

Cyanoandrost-5-ene-3jS,17-diol 3-Acetate Acetic acid (385 ml) is added during a 40 min period at 10° to a stirred mixture of 60 g of 3) -liydroxy-androst-5-en-17-one acetate and 360 g of potassium cyanide in 2 liters of alcohol. The mixture is stirred for 1 hr at 10° and then for 2 hr at room temperature. After dilution with water the precipitated product is collected by filtration, washed with 3 liters of 2 % acetic acid and dried at room temperature. The yield of epimeric cyanohydrins (mp 124° dec [ajj, —93°) is essentially quantitative. 

The requisite starting cyanohydrin is readily prepared from a 20-keto-pregnane substitution at C-21 has no effect on the success of this step. However, the stability of the cyanohydrin is markedly dependent on other features of the molecule thus a 3-acetate confers greater stability than the free alcohol, and a 3-ketone is so unstable that subsequent dehydration with phosphorus oxychloride gives poor yields of the A -unsaturated nitrile. 

Class 6 Poisons such as acetone cyanohydrin, acetonitrile, acrylonitrile, allyl alcohol, allyl chloride, airiline, epiclilorohydrin, lead alkyls, organophosphorus compounds. 

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. ... 

TV-aluminum imines are another example of masked inline derivatives of ammonia. They are easily synthesized by partial reduction of nitriles with diisobutylaluminum hydride (D1BAL-H)6. Addition of lithium organic reagents to /V-aluminum iniines 7 derived from O-protected cyanohydrins 6 provides a-amino alcohols 8a and 8b in moderate yields and low to good diastereo-selectivities n 12. 

Neopentyl alcohol, 40, 76 Nickel catalyst for hydrogenation of resorcinol, 41, 56, 57 Nitramines from amines and acetone cyanohydrin nitrate, 43, 84 Nitration, of amines to nitramines by acetone cyanohydrin nitrate, 43, 83... 

Amino alcohols, which have a broad spectrum of biological activities, can be categorized as adrenahne-like with one chiral center at C-1 or as ephedrine-like with two chiral centers at C-1 and C-2 (Scheme 7). Although a variety of methods have been developed for the stereoselective preparation of 1,2-amino alcohols, " in most cases it is easier and more efficient to prepare these important compounds stereoselectively starting from chiral cyanohydrins (Scheme... 

Similar reactions were undertaken by Choi et al. in the presence of a new family of A -sulfonylated p-amino alcohols possessing two stereocentres as the chiral ligands. In using the chiral sulfonylated p-amino alcohol ligand depicted in Scheme 10.41, the asymmetric addition of McsSiCN to a wide range of aldehydes afforded the corresponding cyanohydrins in both excellent yields and enantioselectivities of up to 96% ee. 

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