Epichlorohydrin nucleophile reactions

Epoxide 34 can be prepared by nucleophilic reaction of mPEG with the oxirane ring of epichlorohydrin in the presence of BFj.Et O complex. The intermediate alcohol product is then dehalogenated with sodium aluminate to afford the required mPEG reagent 34 [170]. 

Virtually all of the organo derivatives of CA are produced by reactions characteristic of a cycHc imide, wherein isocyanurate nitrogen (frequendy as the anion) nucleophilically attacks a positively polarized carbon of the second reactant. Cyanuric acid and ethylene oxide react neady quantitatively at 100°C to form tris(2-hydroxyethyl)isocyanurate [839-90-7] (THEIC) (48—52). Substitution of propylene oxide yields the hydroxypropyl analogue (48,49). At elevated temperatures (- 200° C). CA and alkylene oxides react in inert solvent to give A/-hydroxyalkyloxazohdones in approximately 70% yield (53). Alternatively, THEIC can be prepared by reaction of CA and 2-chloroethanol in aqueous caustic (52). THEIC can react further via its hydroxyl fiinctionahty to form esters, ethers, urethanes, phosphites, etc (54). Reaction of CA with epichlorohydrin in alkaline dioxane solution gives... 

Substitution of an additional nitrogen atom onto the three-carbon side chain also serves to suppress tranquilizing activity at the expense of antispasmodic activity. Reaction of phenothia zine with epichlorohydrin by means of sodium hydride gives the epoxide 121. It should be noted that, even if initial attack in this reaction is on the epoxide, the alkoxide ion that would result from this nucleophilic addition can readily displace the adjacent chlorine to give the observed product. Opening of the oxirane with dimethylamine proceeds at the terminal position to afford the amino alcohol, 122. The amino alcohol is then converted to the halide (123). A displacement reaction with dimethylamine gives aminopromazine (124). ... 

The early literature of epoxide chemistry contains several accounts of the reaction of hydrogen cyanide with epichlorohydrin, 11-1T1 epibromohydrin,10 ethyl glycidyl ether,J- and related substance Attack by the nucleophilic aperies, CN- ion in this case, occurs uniquely at the site furthest from the polar atom,. e. at the terminal epoxidi-carbon atom (Eq. 787), An important contribution was made by... 

Exercise 29-14 The terminal carbon of the epoxide ring of epichlorohydrin generally is quite a bit more reactive toward nucleophilic agents than is the carbon bonded to chlorine. Work out a mechanism for the following reaction that takes account of this fact (review Section 15-11D) ... 

The effect of the anion on the copolymerization rate is controversial. Hilt et al.41 established for different sodium halides the following order of efficiency F < Cl < Br < J . This order was interpreted on the basis of the increase in nucleophilicity or polarizability of the anions. Sfluparek and Mleziva 43) observed that the reaction rate of the benzoate anion was about twice as high as that of the bromide anion in the copolymerization of epichlorohydrine with phthalic anhydride. On the other hand, Luston and Manasek56) did not detect any effect of the anion size on the copolymerization rate initiated by tetramethylammonium and tetrabutylammonium halides. 

Propranolol, a drug that is used to lower blood pressure, is prepared from the epoxide epichlorohydrin. First, the oxygen of 1-naphthol displaces the chlorine of epichlorohydrin in an SN2 reaction. Then the epoxide ring is opened by the nucleophilic nitrogen of isopropylamine in another SN2 reaction to form propranolol. 

Epoxy resins, which are used as adhesives, are also thermoset polymers that form by cross-linking when the two components of the resin are mixed. One component is a low-molecular-mass linear polymer formed by the reaction of the conjugate base of bisphenol A with epichlorohydrin. The nucleophilic oxygens of the phenolate dianion can either displace the chlorine or open the epoxide ring of epichlorohydrin. A slight excess of epichlorohydrin is used to keep these polymer chains short and to ensure that the linear molecules have epoxide groups at their ends. 

The interaction of perfluoro-2-methylpent-2-ene and epichlorohydrin in the presence of CsF or triethylamine in aprotic solvents forms tetrahydrofuran 49. The reaction occurs by cleavage of the epoxide ring under the action of the fluoride ion generating an O-nucleophilic center, which reacts at the multiple bond of the perfluoroolefin. Further cyclization the new terminal double bond gives the final reaction product. 

Though this reaction looks like a simple SN2 displacement by the naphthyloxide anion on the primary alkyl chloride, there is, in fact, a reasonable alternative—the opening of the epoxide at tire less hindered primary centre followed by closure of the epoxide the other way round. The electrophile is called epichlorohydrin and has two reasonable sites for nucleophilic attack. 

Reaction with epichlorohydrin (the chloroepoxide shown below) followed by amine displacement puts in one of the side chains and nucleophilic substitution with morpholine on the ring completes the synthesis. 

A subtle method of controlling the reaction so that it can be made to run at will is to use bisphenol A as the diol and epichlorohydrin js the epoxide. Epichlorohydrin reacts with nucleophiles at the epoxide end, but the released alkoxide ion immediately closes down at the other end to give a new epoxide. 

Epichlorohydrin elastomers may be chemically modified by nucleophilic substitution reactions at the side-chain chloromethyl group. Numerous substituted products have found applications as flame retardants, flocculating agents, selectively permeable membranes, photosensi ti ve materials, etc. 

The most widely used epoxy resins and adhesives are based on a prepolymer made from bisphenol A and epichlorohydrin. On treatment with base under carefully controlled conditions, bisphenol A is converted into its anion, which acts as a nucleophile in an S142 reaction with epichlorohydrin. Each epichlorohydrin molecule can react with two molecules of bisphenol A, once by S 2 displacement of chloride ion and once by opening of the epoxide ring. At the same time, each bisphenol A molecule can react with two epichlorohydrins, leading to a long polymer chain. Each end of a prepolymer chain has an unreacted epoxy group, and each chain has numerous secondary alcohol groups. 

Epibromohydrins and epichlorohydrins can be used as alternatives for 1,2-dihalides. The reaction of these compounds with suitable nucleophiles gives substituted hydroxymethylcyclop-ropanes (Table 8). Particular attention should be given to the use of 2-lithium bis(alkyl-... 

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