From Epichlorohydrin

Epoxy Resins. Epoxy resins (qv) or polyether resins are thermosets used as the binder for terrazzo dooring. The epoxy resin often is made from epichlorohydrin and bisphenol A. An excess of epichlorohydrin is used to assure that the intermediate product contains terminal epoxide groups. 

Bepridil (59) blocks the slow calcium channel and serves as an antianginal agent and a vasodilator. In its synthesis, alcohol (derived from epichlorohydrin) is converted to the corresponding chloride with thionyl chloride and displaced with the sodium salt of ]i-benzylaniline to give bepridil (59) °... 

A mixture of 16.3 g of (2-chloro-5-methylphenyl)glycidic ether (from epichlorohydrin and 2-chloro-5-methylphenol) and 6.2 g of t-butylamine in 50 ml of ethanol is heated at reflux for 6 hours. The solvent is removed, the residue Is washed with water and then extracted with benzene. The dried extract is evaporated to give 1-t-butylamino-3-(2-chloro-5-methylphen-oxy)-2-propanol. Treatment of the free base in benzene solution with dry hydrogen chloride yields the hydrochloride salt. 

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... 

In an extension, we recently reported the formation of cyclic carbonates respectively from epichlorohydrin (Scheme 2.13) and styrene oxide, with carbon dioxide under catalysis by KI in the presence of a crown ether [48],... 

Scheme 2.13 Preparation of the carbonate from epichlorohydrin inthe MBR.

The epoxy polymers are basically poly ethers. One type of epoxy polymer (or epoxy resins) are prepared from epichlorohydrin and bisphenol-A. The reaction is carried out with excess of epichlorohydrin. The various reactions for the preparation of an epoxy polymer are given in the following discussion. 

The original preparation of y-crotonolactone by Lespieau involved a five-step sequence from epichlorohydrin and sodium cyanide. A recent detailed study of this procedure reported an overall yield of 25% for the lactone. Glattfeld used a shorter route from glycerol chlorohydrin and sodium cyanide hydrolysis and distillation of the intermediate dihydroxy acid yielded y-cro-tonolactone in 23% yield and -hydroxy-y-butyrolactone in 28% yield. The formation of y-crotonolactone in 15% yield has also been reported from pyrolysis of 2,5-diacetoxy-2,5-dihydrofuran at 480-500 . ... 

Epoxy resins are really polyethers but are named epoxies because of the presence of epoxide groups in the starting material. They were initially synthesized from epichlorohydrin and bisphenol A in the 1940s. General properties are listed in Table 4.9. 

Polyethers are prepared by the ring opening polymerization of three, four, five, seven, and higher member cyclic ethers. Polyalkylene oxides from ethylene or propylene oxide and from epichlorohydrin are the most common commercial materials. They seem to be the most reactive alkylene oxides and can be polymerized by cationic, anionic, and coordinated nucleophilic mechanisms. For example, ethylene oxide is polymerized by an alkaline catalyst to generate a living polymer in Figure 1.1. Upon addition of a second alkylene oxide monomer, it is possible to produce a block copolymer (Fig. 1.2). 

Epoxy Resins or Epoxies. The commercially available materials of this glass are usually derived from epichlorohydrin and bis phenol A (See under Epon Resins). Before curing they are viscous liquids or clear, brittle solids... 

Stephenson has developed a convenient procedure for preparing J-chloro-3-phenoxy-2-propanols from epichlorohydrin nnd phenols, which is economical of reagents and minimizes the formation of undesirable side-products (Eq. 600). He has also greatly extended the applicability of hydrogen chloride transfer for the preparation of epoxides. ... 

Rozenberg et al. (24) have also studied the kinetics of polymerization of THF initiated by triethyl oxonium tetrafluoroborate. They generated their catalyst in situ from epichlorohydrin and the boron trifluoride-ether cofnplex and carried out their polymerizations in bulk and in... 

B romopheny Itri oz ene(called Bromphenyltri azen in Ger), Brfrom gasoline), mp 36.5°(dec) on standing at RT it transforms into a compd melting at 39° hut when recrystd(from eth + petr etl ) it again melts at 36.5° its Cu salt, CuCgHsN3Br, crysts(from epichlorohydrin), expl in a flame or in contact with coned HNO. These... 

In another development, the statin side chain en route to Atorvastatin (Lipitor , Pfizer) is synthesized via the key intermediate alkyl 3-hydroxy-4-cyanobutyrate (Figure 13.17). Instead of the currently practiced six-step route, a much more concise three-step route starts from epichlorohydrin via Cl chain length enhancement by both nucleophilic substitution of chloride and nucleophilic ring opening of the epoxide with cyanide to yield symmetric dicyanoisopropanol. Nitrilase action desymmetrizes the dinitrile intermediate with the creation of a chiral center in C3 to yield (R)-3-hydroxy-4-cyanobutyrate, which is esterified to the key intermediate ethyl (R)-3-hydroxy-4-cyanobutyrate. 

Another major group of epoxy monomers derived from epichlorohydrin is that comprising monomers synthesized with an aromatic amine, such as aniline (DGA), para-aminophenol (TGpAP) and methylene dianiline (TGMDA) - (Table 2.1 e, f, and g). The reaction of epichlorohydrin with an alcohol is more difficult. Liquid monomers based on butanediol, neo-pentylglycol, and polypropylene oxide (molar mass in the range of 500 g mol-1), are the most common. 

The other approach starts from epichlorohydrin and involves a classical resolution of the amide. The wrong amide is also converted to the desired isomer by a dehydration-rehydration sequence that uses hydrolases (Scheme 31.23).238-239 A biological variation is to hydrolyze the 4-butyrobetaine as the stcrcodi I fcrcn liating step.240-241... 

English investigators reported [60] the synthesis of the title alcohol from epichlorohydrine and sodium acetylide in liquid ammonia. The synthesis is easily performable on a large scale and gives a useful intermediate. The relatively low yield is explained by the occurrence of a number of other processes, the principal one of which is probably the base-catalysed cyclization of Z-HC=CCH=CHCH2ONa to 2-methylfuran, which can be swept along with the ammonia vapour. When the synthesis is carried out with lithium acetylide, a mixture of comparable amounts of - and Z-pentenynol is obtained in a higher yield [61]. Apparently, the Z-lithium alcoholate cyclises less readily. 

The coordination polymerisation and copolymerisation of heterocyclic monomers have been restricted in industry to a much smaller volume than the polymerisation and copolymerisation of hydrocarbon monomers polyether elastomers from epichlorohydrin and ethylene oxide or propylene oxide, and allyl glycidyl ether as the vulcanisable monomeric unit, are produced on a larger scale [4-7],... 

Figure 10-14 Hydrolysis products formed from epichlorohydrin.

The complexation properties of various poly(diaza-crown ether)s have been studied either in water, or in organic solvents, according to their solubilities. Polymers prepared from epichlorohydrine (Epic) or diepoxyoctane (Epico) are water soluble. The structures of the repeating units of these polymers are depicted in Table 9. 

Finding out the mechanism of this process is not idle curiosity as a group of drugs used to combat high blood pressure and heart disease, such as propranolol, are made from epichlorohydrin and it is essential to know which enantiomer to use to get the right enantiomer of the drug. In fact, the more extended mechanism shown in black is correct. This is an example of determination of mechanism by using enantiomers. 

TNAZ was first synthesized in 1983 and has a strained four-membered ring backbone with both C-nitro and nitramine (N—N02) functionalities. There are various routes that yield TNAZ all of which consist of several reaction steps. One possible synthesis of TNAZ is shown in Figure 1.6. It starts from epichlorohydrine and lBu-amine. As far as the author of this book is aware, there has been no wide-spread use for TNAZ so far. 

Name B by IUPAC rules. Show the three components that comprise B. The synthesis of B involves a ring-opening reaction of the epoxide epichlorohydrin. Use this information to propose a synthesis of B from epichlorohydrin and any alcohol or phenol. 

Triethyloxonium tetrafluoroborate was first prepared by Meerwein from epichlorohydrin and BF3-Et20 complex. This is still the most convenient method for preparation of triethyloxonium tetrafluoroborates and hexachloroantimonates [23]. 

The first synthesis of thiete 1,1-dioxide 248 was achieved by elimination of hydrogen chloride from 3-chlorothietane 1,1-dioxide. The overall synthesis from epichlorohydrin (chloromethyloxiran) has been improved in several details. 3-Bromothietane 1,1-dioxide ha.s been obtained by direct bromination of thietane hl-dioxide " and the 3-chloro-derivative has been obtained similarly. " ... 

Schrade cited the first commercial attempt to prepare resins from epichlorohydrin. 

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