Hydrolysis cyanohydrins

S (2)-hydroxy-3-butenenitrile from acrolein and HCN trans hydrocyanation using, for instance, acetone cyanohydrin Hydrolysis of nitriles to amides, e.g. acrylonitrile to acrylamide Isomerization of glucose to fructose Esterifications and transesterifications Interesterify positions 1 and 3 of natural glycerides Oxidation of glucose to gluconic acid, glycolic acid to glyoxalic acid... 

Periodic shaking (once every 3 min) Is sufficient to effect cyanohydrin hydrolysis. 

Commonly available nitrilases hydrolyze cyanohydrins with modest to excellent selectivity for the (R)-enantiomer. The formation of amide coproducts, once thought to be an insignificant side-reaciion, varies erratically in cyanohydrin hydrolysis between minute and copious, depending on the enzyme and the steric character of the nitrile. 

Figure 1 Strecker and related systems complex network of equilibrium reactions from aqueous solutions of cyanide, ammonia, and aldehyde, 1. Pathways for exiting the equilibrated network correspond to (a) cyanohydrin hydrolysis, (b) aminonitrile hydrolysis, and (c) Biicherer-Bergs reaction. Adducts 6 and 7 and other hydrolysis products can be formed at high concentrations of reactants.

The 11-deoxyprostaglandins, a group not found in nature, have been synthesised by workers at the Ayerst Laboratories [115, 148-151]. 11-Deoxy-PGFy (LXXI) has been prepared starting from the enone (LXXII), obtained by the action of sulphuric acid on the monobromo derivative of the condensation product of ethyl 2-cyclopentanone carboxylate and (o-bromoethylheptanoate [115, 148, 149]. Reaction of (LXXII) with acetone cyanohydrin, hydrolysis of the ester-nitrile to the dicarboxylic acid and reaction with methanol and />-toluenesulphonic acid gave the mono ester (LXXIII) of which the acid chloride was converted with heptyne and aluminium chloride into the chlorovinylketone (LXXIV). The sequence was then completed by replacement of chloro with methoxyl, ester hydrolysis and borohydride reduction to the unsaturated ketone (LXXV) followed by borohydride reduction of the side chain carbonyl group. 

Nitriles can be used in reactions other than displacement The Boc-protected aldehyde derived from alanine (known as N-Boc alinal, 1.161) was condensed with potassium cyanide to give a cyanohydrin. Hydrolysis of the cyano group to give an acid and removal of the N-Boc group gave 3-amino-2-hydroxybutanoic acid, 1.162.9 ... 

U8 C, (-l-)-or (-)- m.p. 133X. Occurs combined in the glucoside amygdalin. Prepared by hydrolysis of mandelonitrile (ben-zaldehyde cyanohydrin). It is administered in large doses in the treatment of urinary infections. 

Converting aldehydes and ketones to cyanohydrins is of synthetic value for two reasons (1) a new carbon-carbon bond is formed and (2) the cyano group in the prod uct can be converted to a carboxylic acid function (CO2H) by hydrolysis (to be discussed in Section 19 12) or to an amine of the type CH2NH2 by reduction (to be discussed m Section 22 9)... 

Nitrile groups m cyanohydrins are hydrolyzed under conditions similar to those of alkyl cyanides Cyanohydrin formation followed by hydrolysis provides a route to the preparation of a hydroxy carboxylic acids... 

Acrylics. Acetone is converted via the intermediate acetone cyanohydrin to the monomer methyl methacrylate (MMA) [80-62-6]. The MMA is polymerized to poly(methyl methacrylate) (PMMA) to make the familiar clear acryUc sheet. PMMA is also used in mol ding and extmsion powders. Hydrolysis of acetone cyanohydrin gives methacrylic acid (MAA), a monomer which goes direcdy into acryUc latexes, carboxylated styrene—butadiene polymers, or ethylene—MAA ionomers. As part of the methacrylic stmcture, acetone is found in the following major end use products acryUc sheet mol ding resins, impact modifiers and processing aids, acryUc film, ABS and polyester resin modifiers, surface coatings, acryUc lacquers, emulsion polymers, petroleum chemicals, and various copolymers (see METHACRYLIC ACID AND DERIVATIVES METHACRYLIC POLYMERS). 

Preparation. The general preparation of y acids is by the hydrolysis of an a-halo acid or by the acid hydrolysis of the cyanohydrins of an aldehyde or a ketone. 

Diels-Alder reaction of 2-bromoacrolein and 5-[(ben2yloxy)meth5i]cyclopentadiene in the presence of 5 mol % of the catalyst (35) afforded the adduct (36) in 83—85% yield, 95 5 exo/endo ratio, and greater than 96 4 enantioselectivity. Treatment of the aldehyde (36) with aqueous hydroxylamine, led to oxime formation and bromide solvolysis. Tosylation and elimination to the cyanohydrin followed by basic hydrolysis gave (24). 

Enantioselective addition of hydrogen cyanide to hydroxypivaldehyde (25), catalyzed by (lf)-oxynittilase, afforded (R)-cyanohydrin (26) in good optical yield. Acid-catalyzed hydrolysis followed by cyclization resulted in (R)-pantolactone in 98% ee and 95% yield after one recrystallization (56). 

Nitrile Group. Hydrolysis of the nitrile group proceeds through the amide to the corresponding carboxyUc acid. Because cyanohydrins are unstable at high pH, this hydrolysis must be cataly2ed by acids. In cases where amide hydrolysis is slower than nitrile hydrolysis, the amide may be isolated. 

Thus acid hydrolysis of acetophenone cyanohydrin [20102-12-9] (R = CgH, R = CH3) yields the corresponding amide which can be isolated. Further hydrolysis, usually with sodium hydroxide, gives atrolactic acid [575-30-0] in a 30% overall yield (1). 

Hydroxy-4-methylthiobutyric acid [583-91 -5] the hydroxy analogue of the amino acid methionine, is manufactured by acid hydrolysis of 3-methylthiopropionaldehyde cyanohydrin [17773-41-0] which is produced by the reaction of methyl mercaptan with acrolein (qv). 

The mixture of D and L optical forms of this hydroxy analogue of methionine is converted to the calcium salt which is used in animal feed supplements. Cyanohydrins react with ammonium carbonate to form hydantoins (2), which yield amino acids upon hydrolysis. Commercial DL-methionine [59-57-8] is produced by hydrolysis of the hydantoin of 3-meth5ithiopropionaldehyde [3268-49-3]. 

Direct reaction of formaldehyde cyanohydrin and ethylenediamine in the presence of a sulfuric acid catalyst gives ethylenediarninetetraacetonitrile [5766-67-6], hydrolysis of which leads to ethylenediarninetetraacetic acid [60-00-4] (EDTA), a widely used sequestering agent (26). 

The first commercial process for manufacture of acryHc acid (qv) and acrylates involved hydrolysis of ethylene cyanohydrin in aqueous sulfuric acid. 

The ethoxyethyl cyanohydrin was prepared (NaCN, HCl, THF, 0°, 75% yield, followed by EtOCH=CH2, HCl, 50% yield) to convert an aldehyde ultimately to a protected ketone. It was cleaved by hydrolysis (0.01 N HCl, MeOH, 25°, followed by NaOH, 0°, 85% yield). ... 

The tetrahydropyranyl cyanohydrin was prepared from a steroid cyanohydrin (di-hydropyran, TsOH, reflux, 1.5 h) and cleaved by hydrolysis (cat, coned. HCl, acetone, reflux, 15 min, followed by aq. pyridine, reflux, 1 h)."... 

The cyanohydrin is then treated with 98% sulphuric acid in a cooled hydrolysis kettle to yield methacrylamide sulphate (Figure 15.3)... 

Cyanides are dangerously toxic materials that can cause instantaneous death. They occur in a number of industrial situations but are commonly associated with plating operations, and sludges and baths from such sources. Cyanide is extremely soluble and many cyanide compounds, when mixed with acid, release deadly hydrogen cyanide gas. Cyanide is sometimes formed during the combustion of various nitrile, cyanohydrin, and methacrylate compounds. Cyanides (CN ) are commonly treated by chlorine oxidation to the less toxic cyanate (CNO ) form, then acid hydrolyzed to COj and N. Obviously, care should be taken that the cyanide oxidation is complete prior to acid hydrolysis of the cyanate. 

Merck and Maeder have patented the manufacture of arecaidine by loss of water from l-methyl-4-hydroxypiperidine-3-carboxylic acid. A method of producing the latter has been describd by Mannich and Veit and has been developed by Ugriumov for the production of arecaidine and arecoline. With the same objective, Dankova, Sidorova and Preobrachenski use what is substantially McElvain s process,but start by converting ethylene oxide, via the chlorohydrin and the cyanohydrin, into -chloropropionic acid. The ethyl ester of this with methylamine in benzene at 140° furnishes methylbis(2-carbethoxyethyl) amine (I) which on refluxing with sodium or sodium Moamyloxide in xylene yields l-methyl-3-carbethoxy-4-piperidone (II). The latter is reduced by sodium amalgam in dilute hydrochloric acid at 0° to l-methyl-3-carbethoxy-4-hydroxypiperidine (III) which on dehydration, and hydrolysis, yields arecaidine (IV R = H), convertible by methylation into arecoline (IV R = CH3). 

Hydroxy-20-cyanohydrins can be oxidized to 3-ketones in good yield with chromic acid, and the osmate ester of the unsaturated nitrile is also stable to this oxidant. " After hydrolysis of the osmate ester, the new 17-hydroxy-20-cyanohydrin which is presumably formed cannot be isolated, but loses hydrogen cyanide during the hydrolysis, and only the 17a-hydroxy-20-ketone is obtained. 

One of the earliest preparations of this ring system starts with displacement of the hydroxyl of benzaldehyde cyanohydrin (125) by urea. Treatment of the product (126) with hydrochloric acid leads to addition of the remaining urea nitrogen to the nitrile. There is thus obtained, after hydrolysis of the imine (127), the hydantoin (128). Alkylation by means of ethyl iodide affords ethotoin (129)... 

In a departure from the prototype molecule, the benzylpiperi-done is first converted to the corresponding aminonitrile (a derivative closely akin to a cyanohydrin) by treatment with aniline hydrochloride and potassium cyanide (126). Acid hydrolysis of the nitrile affords the corresponding amide (127). Treatment with formamide followed by reduction affords the spiro oxazinone... 

Reaction of the carbonyl group of pi perl done with cyanide and aniline leads to formation of a cyanohydrin-like function known as an oc-aminonitrile (37) hydrolysis under... 

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