Cyanohydrin route

Selected physical properties of various methacrylate esters, amides, and derivatives are given in Tables 1—4. Tables 3 and 4 describe more commercially available methacrylic acid derivatives. A2eotrope data for MMA are shown in Table 5 (8). The solubiUty of MMA in water at 25°C is 1.5%. Water solubiUty of longer alkyl methacrylates ranges from slight to insoluble. Some functionalized esters such as 2-dimethylaniinoethyl methacrylate are miscible and/or hydrolyze. The solubiUty of 2-hydroxypropyl methacrylate in water at 25°C is 13%. Vapor—Hquid equiUbrium (VLE) data have been pubHshed on methanol, methyl methacrylate, and methacrylic acid pairs (9), as have solubiUty data for this ternary system (10). VLE data are also available for methyl methacrylate, methacrylic acid, methyl a-hydroxyisobutyrate, methanol, and water, which are the critical components obtained in the commercially important acetone cyanohydrin route to methyl methacrylate (11). 

A different approach involving cyanohydrin formation from the 3-keto sugar was also explored in the D-Fru series (Scheme 17). A mixture of epimeric cyanohydrins was quantitatively formed by reaction with sodium cyanide in methanol, albeit without stereoselectivity. Chromatographic separation of (R)- and (A)-isomers was straightforward and the former epimer was selected to exemplify the two-step transformation into an OZT. Reduction of this nitrile by lithium aluminum hydride led to the corresponding aminoalcohol, which was further condensed with thiophosgene to afford the (3i )-spiro-OZT in ca. 30% overall yield. Despite its shorter pathway, the cyanohydrin route to the OZT was not exploited further, mainly because of the disappointing yields in the last two steps. 

The production of MMA has long been accomplished by the old standby acetone cyanohydrin route. (5 Figure 19—4.) Acetone reacts with hydrogen... 

Several alternate routes to MMA eliminate ammonium bisulfate byproduct—really a coproduct since its 1.5 tons for every 10 tons of MMA produced. They also do not involve HCN, always a safety problem in the plants and sometimes an unreliable market. Although these routes are more efficient and economical, American producers have stuck to the acetone cyanohydrin route. The plants are fully amortized and by staying with the old technology, producers can avoid the large capital investments associated with a new plant. 

Acetone-cyanohydrin route Acetone -.68 52 days/weeks 1/750 3.2... 

The competitiveness of the oxidation of isobutene compared to the conventional acetone cyanohydrin route (Equation 33) is not only related to its performance and better environmental standards but has to contend with the demands of other users for isobutene, particularly for MTBE and ETBE production. In fact the predominant methacrylic acid process is still the hydrolysis of acetone cyanohydrin however, the change of mood on the use of MTBE in gasoline blends in the USA, could signal a future shift of isobutene availability making it a more attractive feedstock for methacrylic acid production. 

The configuration of Willstatter s a -cocaine has now been shown to be 3j8-benzoyloxy-3a-methoxycarbonyltropane by adopting the method of oxazine formation of the nor derivative of a -ecgonine methyl ester. This latter had been obtained from tropinone by the cyanohydrin route. Obviously the cyanide ion attacks the ketone from the a-direotion in contrast with metalloorganic compounds, which carry out nucleophilic attack from the nonhindered jS-position (130). 

Indanone-3-Carboxylate/Cyanohydrin Route to Benzazepine 6 (Route B)... 

The further route to spiromesifen 8a is similar to the above shown spirodiclo-fen 7f synthesis (Scheme 28.4.3). Acylation of the cyclopentyl hydroxyester 17 (synthesized from cyclopentanone via the classical cyanohydrin route in three steps) with mesitylacetyl chloride 18 leads to the intermediate 19, which is cyclized to the tetronic acid 20 using, e.g., potassium tert-butylate in N,N-dimethylformamide (DMF). 

The construction of the sulphuric acid recovery unit was forced on ICI once the decision to continue with the acetone cyanohydrin route was made. Huge resources in financial and personnel terms were directed to... 

Ketone trimethylsilyl enol ethers have been employed in an improvement to the cyanohydrin route for the generation of aminomethyl groups (Scheme 76) this modification increases the generality of cyanohydrin formation. 

This process avoids the by-product ammonium sulfate formed from the acetone cyanohydrin route. 

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... 

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... 

The outstanding chemical property of cyanohydrins is the ready conversion to a-hydroxy acids and derivatives, especially a-amino and a,P-unsaturated acids. Because cyanohydrins are primarily used as chemical intermediates, data on production and prices are not usually pubUshed. The industrial significance of cyanohydrins is waning as more direct and efficient routes to the desired products are developed. Acetone cyanohydrin is the world s most prominent industrial cyanohydrin because it offers the main route to methyl methacrylate manufacture. 

Direct combination of hydrogen cyanide and a carbonyl compound is the commercial and most common route to cyanohydrins. 

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). 

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. 

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). 

Other Derivatives. Ethylene carbonate, made from the reaction of ethylene oxide and carbon dioxide, is used as a solvent. Acrylonitrile (qv) can be made from ethylene oxide via ethylene cyanohydrin however, this route has been entirely supplanted by more economic processes. Urethane intermediates can be produced using both ethylene oxide and propylene oxide in their stmctures (281) (see Urethane polymers). 

In contrast to 2-amino acids, only a few non-racemic 2-hydroxy acids are found in nature. Hydrolysis of non-racemic cyanohydrins offers an interesting general route to (R)- as well as (5 )-2-hydroxy carboxylic acids. 

Exposure to inorganic cyanide, its salts, or cyanohydrins by any route produces similar respiratory effects in animals. 

Addition of HCN to acetone to form the cyanohydrin is still the main route to methyl methacrylate. Hydrocyanins can be converted to amino acids as well. The nitrile group can be easily converted to amines, carboxylic acids, amides, etc. Addition to aldehydes and activated alkenes can be done with simple base, but addition to unactivated alkenes requires a transition metal catalyst. The methods of HCN addition have been discussed by Brown [2],... 

Unlike the direct nitration of amines under acidic conditions, nucleophilic nitration is an excellent route to both primary and secondary nitramines. In these reactions the amine or the conjugate base of the amine is used to attack a source of NO2. This source may be a nitrogen oxide, nitronium salt, cyanohydrin nitrate, alkyl nitrate ester or any other similar source of nitronium ion. 

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