Epichlorohydrine process

The old, non-catalytic route (called the epichlorohydrine process) follows a three-step synthesis ... 

Figure 2.2.9 Scheme of the glycerol to epichlorohydrin process (GTE, Dow Chemical Company) [46]. 

Glycerin by the Epichlorohydrin Process. In the ECH process, synthetic glycerin is produced in three successive operations, the end products of which are allyl chloride, ECH, and finished glycerin, respectively. Glycerin is formed by the hydrolysis of ECH with 10 percent caustic. Crude glycerin is separated from this reaction mass by multiple-effect evaporation to remove salt and most of the water. A final vacuum distillation yields a 99+ percent product. 

In industrial practices, epichlorohydrin is produced by direct chlorohydrox-ylation of allyl chloride in chlorine and water (10-13). Alternatively, a new epichlorohydrin process has been developed and commercialized by Showa Denko (14) in Japan in 1985. It involves the chlorination of allyl alcohol as the precursor and is claimed to be more efficient in chlorine usage. 

The difference between a catalytic and a stoichiometric reaction is illustrated by the selective oxidation of ethylene to ethylene epoxide, where we compare the silver-catalyzed ethylene epoxidation with the stoichiometric epichlorohydrine process. Ethylene epoxide (oxirane) has industrial importance as a starter material for the production of ethylene glycol (antifreeze) and many other products (poly ethers, polyurethanes). 

In the stoichiometric epichlorohydrine process, ethylene epoxide is produced in three steps ... 

Cationic monomers are used to enhance adsorption on waste soHds and faciHtate flocculation (31). One of the first used in water treatment processes (10) is obtained by the cyclization of dimethyldiallylammonium chloride in 60—70 wt % aqueous solution (43) (see Water). Another cationic water-soluble polymer, poly(dimethylarnine-fi9-epichlorohydrin) (11), prepared by the step-growth... 

The boric and sulfuric acids are recycled to a HBF solution by reaction with CaF2. As a strong acid, fluoroboric acid is frequently used as an acid catalyst, eg, in synthesizing mixed polyol esters (29). This process provides an inexpensive route to confectioner s hard-butter compositions which are substitutes for cocoa butter in chocolate candies (see Chocolate and cocoa). Epichlorohydrin is polymerized in the presence of HBF for eventual conversion to polyglycidyl ethers (30) (see Chlorohydrins). A more concentrated solution, 61—71% HBF, catalyzes the addition of CO and water to olefins under pressure to form neo acids (31) (see Carboxylic acids). 

In this process, the fine powder of lithium phosphate used as catalyst is dispersed, and propylene oxide is fed at 300°C to the reactor, and the product, ahyl alcohol, together with unreacted propylene oxide is removed by distihation (25). By-products such as acetone and propionaldehyde, which are isomers of propylene oxide, are formed, but the conversion of propylene oxide is 40% and the selectivity to ahyl alcohol reaches more than 90% (25). However, ahyl alcohol obtained by this process contains approximately 0.6% of propanol. Until 1984, ah ahyl alcohol manufacturers were using this process. Since 1985 Showa Denko K.K. has produced ahyl alcohol industriahy by a new process which they developed (6,7). This process, which was developed partiy for the purpose of producing epichlorohydrin via ahyl alcohol as the intermediate, has the potential to be the main process for production of ahyl alcohol. The reaction scheme is as fohows ... 

For many years ethylene chlorohydrin was manufactured on a large iadustrial scale as a precursor to ethylene oxide, but this process has been almost completely displaced by the direct oxidation of ethylene to ethylene oxide over silver catalysts. However, siace other commercially important epoxides such as propylene oxide and epichlorohydrin cannot be made by direct oxidation of the parent olefin, chlorohydrin iatermediates are stiU important ia the manufacture of these products. 

Epichlorohydrin Elastomers without AGE. Polymerization on a commercial scale is done as either a solution or slurry process at 40—130°C in an aromatic, ahphatic, or ether solvent. Typical solvents are toluene, benzene, heptane, and diethyl ether. Trialkylaluniinum-water and triaLkylaluminum—water—acetylacetone catalysts are employed. A cationic, coordination mechanism is proposed for chain propagation. The product is isolated by steam coagulation. Polymerization is done as a continuous process in which the solvent, catalyst, and monomer are fed to a back-mixed reactor. Pinal product composition of ECH—EO is determined by careful control of the unreacted, or background, monomer in the reactor. In the manufacture of copolymers, the relative reactivity ratios must be considered. The reactivity ratio of EO to ECH has been estimated to be approximately 7 (35—37). 

AH of the polyether elastomers, like other vulcanizable elastomers, can be compounded with processing aids, fillers, plasticizers, stabilizers, and vulcanizing agents to make useful mbber products. A typical compounding recipe for epichlorohydrin elastomer is as follows ... 

Taffy Process. Bisphenol A reacts direcdy with epichlorohydrin in the presence of a stoichiometric amount of caustic. The molecular weight of the product is governed by the ratio of epichlorohydrin—bisphenol A. 

Epichlorohydrin zero TT Stomach problems reproductive difficulties increased risk of cancer Discharge from industrial chemical factories added to water during treatment process... 

Jacobsen (1999) has carried out carbomethoxylation of asymmetric epoxides. Thus, the carbomethoxylation of (R)-propylene oxide with CO and methanol yields 92% of (3R)-hydroxybutanoic acid in greater than 99% ee. Similarly, the reaction of (/ )-epichlorohydrin gives 96% of 4-chloro-(3R)-hydroxybutanoic acid in greater than 99% ee. The catalyst consists of dicobalt octacarbonyl and 3-hydroxy pyridine. A continuous process for making enantiomeric 1-chloro-2-propanol has been suggested. With a suitable catalyst propylene reacts with O2, water, cupric and lithium chloride to give 78% of (S)-l-chloro-2-propanol in 94% ee. 

A summary of the industrial-scale process development for the nitrilase-catalyzed [93] route to ethyl (/ )-4-cyano-3-hydroxy-butyrate, an intermediate in the synthesis of Atorvastatin (Pfizer Lipitor) from epichlorohydrin via 3-hydroxyglutaronitrile (3-HGN) was recently reported (Figure 8.15) [94], The reaction conditions were further optimized to operate at 3 m (330 gL ) substrate, pH 7.5 and 27 °C. Under these conditions, 100% conversion and product ee of 99% was obtained in 16 h reaction time with a crude enzyme loading of 6% (based on total protein, 0.1 U mg-1). It is noted that at pH < 6.0 the reaction stalled at <50% conversion and at alkaline pH a slowing in reaction rate was observed. Since the starting material is of low cost and the nitrilase can be effectively expressed in the Pfenex (Pseudomonas) expression system at low cost, introduction of the critical stereogenic center... 

The majority of plasticiser consumption is in CR and NBR. Plasticisers are also technically important in chlorosulphonated polyethylene, hydrogenated nitrile, ethyl acrylate copolymer, epichlorohydrin copolymer and ethylene-acrylic terpolymer. At around 10 kt/annum (Europe), total consumption of plasticisers is on a much smaller scale than the process oils used in hydrocarbon rubbers. Typical addition levels are below 20 phr. 

Numerous biocatalytic routes to this challenging intermediate have been reported. " For example. Fox et al. have recently developed an efficient regioselective cyanation starting from low-cost epichlorohydrin (Scheme 1.26). Initial experiments found that halohydrin dehydrogenase from Agrobacterium radiobacter expressed in E. coli produced the desired product, but inefficiently. To meet the projected cost requirements for economic viability, the product needed to be produced at 100 g L with complete conversion and a 4000-fold increase in volumetric productivity. The biocatalyst needed to function under neutral conditions to avoid by-product formation, which causes downstream processing issues. 

Breslow et al. (13) have prepared an insolubilized cyclodextrin resin by crosslinking with epichlorohydrin. The resin was used for the chlorination of anisole via a three-step process. The column was loaded with anisole, that is, the available cycloclextrin cavities were filled with anisole. Aqueous HOCl was passed through and the product, 99% / -chloroanisole, was eluted with tetrahydrofuran. 

Reactions catalyzed by enzymes or enzyme systems exhibit far greater specificities than more conventional organic reactions. Among these specificities which enzymatic reactions possess, stereospecificity is one of the most excellent. To overcome the disadvantage of a conventional synthetic process, i.e., the troublesome resolution of a racemic mixture, microbial transformation with enzymes possessing stereospecificities has been appHed to the asymmetric synthesis of optically active substances [1-10]. C3- and C4-synthetic units (synthons, building blocks), such as epichlorohydrin (EP), 2,3-dichloro-l-propanol (2,3-DCP), glycidol (GLD), 3-chloro-l,2-propanediol (3-CPD), 4-chloro-... 

To overcome this issue Kureshy et al. [55, 56] reported dimeric form of Jacobsen s catalysts 3, 4. They used the concept of solubility modification by altering the molecular weight of the catalyst so that in a post catalytic work-up procedure the catalyst is precipitated, filtered and used for subsequent catalytic runs. The complexes 3, 4 (0.2 mol % of Co(lll)-salen unit) (Figure 2) were effectively used for HKR of racemic epoxides, e.g., styrene oxide, epichlorohydrin, 1,2-epoxypropane, 1,2-epoxyhexane, 1,2-epoxyoctane, and 1,2-epoxydodecane to achieve corresponding epoxides and 1,2-diols in high optical purity and isolated yields. In this process, once the catalytic reaction is complete the product epoxides were collected by reduced pressure distillation. Addition of diethylether to the residue precipitated the catalyst which was removed by filtration. However, the recovered catalyst was required to be reactivated by its treatment with acetic acid in air. The catalysts were reused 4 times with complete retention of its performance. 

As an aside to the manufacture of propylene oxide via the chlorohydrin process let us mention use of this type of chemistry to make epichlorohydrin. 

Approximately 27% of glycerol (glycerin) comes from a synthetic process, the hydrolysis of epichlorohydrin. The remaining 73% is made from fats as a by-product of soap manufacture. 

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