Ethylene oxide reactions with nucleophiles

With Ammonia and Amines. Ethylene oxide reacts with ammonia to form a mixture of mono-, di-, and triethanolamines. Nitrogen is a stronger nucleophile than oxygen (59). A small amount of water is essential for the reaction (60). 

The characteristic ease with which ethylene oxides undi ruu nucleophilic attack or isomerization in tbe presence of Lewie acids made them obvious substrates for tbe org nometallic reagents intro duoed by Grignard 07 around the turn of the century, and subsequently named in his hunor. The earliest disclosure of a reaction between an epoxide and a Grignard reagent, however, bears the name of Blaise,1 who noted the formation of ethylene bromohydrin on troii merit of ethylene oxide with raethylmagneeium bromide. In the years... 

Long-chain molecules with active hydrogen (alcohols, amines, and amides) react as nucleophiles with ethylene oxide usually with a basic catalyst. The product has a hydroxyl group that can react with further ethylene oxide, leading to polyoxyethylene products with a range of molecular weights. The average number of ethylene oxide molecules added depends on the reaction conditions and can be adjusted to alter the solubility and surfactant properties of the product. 

We saw an example of nucleophilic ring opening of epoxides in Section 15 4 where the reaction of Grignard reagents with ethylene oxide was described as a synthetic route to primary alcohols... 

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... 

The reactions are highly exothermic. Under Uquid-phase conditions at about 200°C, the overall heat of reaction is —83.7 to —104.6 kJ/mol (—20 to —25 kcal/mol) ethylene oxide reacting (324). The opening of the oxide ring is considered to occur by an ionic mechanism with a nucleophilic attack on one of the epoxide carbon atoms (325). Both acidic and basic catalysts accelerate the reactions, as does elevated temperature. The reaction kinetics and product distribution have been studied by a number of workers (326,327). 

Polymerization. The reaction of ethylene oxide with a nucleophile introduces the hydroxyethyl group ... 

Many other reactions of ethylene oxide are only of laboratory significance. These iaclude nucleophilic additions of amides, alkaU metal organic compounds, and pyridinyl alcohols (93), and electrophilic reactions with orthoformates, acetals, titanium tetrachloride, sulfenyl chlorides, halo-silanes, and dinitrogen tetroxide (94). 

The nucleophilicity of the organocuprate cluster derives mainly from the filled copper 3d orbital, in combination with the carbon orbital associated with bonding to copper. These orbitals for the TS for reaction with methyl bromide and ethylene oxide are shown in Figure 8.4. 

More traditional carbon nucleophiles can also be used for an alkylative ring-opening strategy, as exemplified by the titanium tetrachloride promoted reaction of trimethylsilyl enol ethers (82) with ethylene oxide, a protocol which provides aldol products (84) in moderate to good yields <00TL763>. While typical lithium enolates of esters and ketones do not react directly with epoxides, aluminum ester enolates (e.g., 86) can be used quite effectively. This methodology is the subject of a recent review <00T1149>. 

Functionalization of these reactive anionic chain ends can be achieved by a variety of methods all based on the general concepts of carbanion chemistry. For example, reaction with C02 or succinnic anhydride leads to the carboxy terminated derivatives [10], while hydroxy-terminated polymers can be easily obtained by reaction with ethylene oxide (Scheme 3) [11]. In select functionalization reactions, such as alkylation with p-vinyl benzyl chloride, the nucleophilicity of the carbanionic species may be necessary and this can be achieved by reaction of the chain end with 1,1-diphenylethene followed by functionalization [12,13]. 

Oxidation is the first step for producing molecules with a very wide range of functional groups because oxygenated compounds are precursors to many other products. For example, alcohols may be converted to ethers, esters, alkenes, and, via nucleophilic substitution, to halogenated or amine products. Ketones and aldehydes may be used in condensation reactions to form new C-C double bonds, epoxides may be ring opened to form diols and polymers, and, finally, carboxylic acids are routinely converted to esters, amides, acid chlorides and acid anhydrides. Oxidation reactions are some of the largest scale industrial processes in synthetic chemistry, and the production of alcohols, ketones, aldehydes, epoxides and carboxylic acids is performed on a mammoth scale. For example, world production of ethylene oxide is estimated at 58 million tonnes, 2 million tonnes of adipic acid are made, mainly as a precursor in the synthesis of nylons, and 8 million tonnes of terephthalic acid are produced each year, mainly for the production of polyethylene terephthalate) [1]. 

Thioetherification of PECH is feasibly performed in DA-solvents as already described in the patent (20J. For example, the highest substitution was obtained by the reaction of P(ECH-EO)(1 1 copolymer of epichloro-hydrin and ethylene oxide) and equimolar thiophenoxide in HMPA at 100°C for 10 h as DS 83% for sodium and 93% for potassium salts. The DS in our nucleophilic substitution was estimated by the elemental analysis as well as the titration of liberated chloride ion with mercuric nitrate (21). In the latter method, reacted medium was pretreated with hydrogen peroxide when the reductive nucleophiles which can react with mercuric ion were used. As described before for PVC, thiolation was also achieved conveniently with iso-thiuronium salt followed by alkaline hydrolysis without the direct use of ill-smelling thiolate. The thiolated PECH obtained are rubbery solids, soluble in toluene, methylene chloride, ethyl methyl ketone and DMF and insoluble in water, acetone, dioxane and methanol. 

The reaction of a -halocarboxylic acids with sodium nitrite has been used to synthesize ni-tromethane, nitroethane and nitropropane, although the reaction fails for higher nitroalkanes. " A number of other reactions have been reported which use nitrite anion as a nucleophile, including (1) reaction of alkyl halides with potassium nitrite in the presence of 18-crown-6, (2) reaction of alkyl halides with nitrite anion bound to amberlite resins, (3) synthesis of 2-nitroethanol from the acid-catalyzed ring opening of ethylene oxide with sodium nitrite, and (4) reaction of primary alkyl chlorides with sodium nitrite in the presence of sodium iodide. ... 

In the example shown, reaction of a Grignard reagent with the epoxide electrophile ethylene oxide proceeds as expected, and after acidification results in formation of an alcohol that is two carbons longer than the original nucleophile. 

In most, but not all, instances substituents are introduced onto the carbazole nitrogen via a carbazol-9-yl anion formed by base N-deprotonation. It seems now that the conditions often used in earlier work to generate the carbazol-9-yl anion were unnecessarily severe and that much milder conditions can be utilized. Anionic carbazole nitrogen, in common with other heteroanionic centers, is about 80 times less nucleophilic than a pK -comparable carbanionic center. The order of reactivity is carbazole > 3-chlorocarbazole > 3,6-dichlorocarbazole > 3-nitrocarbazole in the reaction of the corresponding 9-yl anions with ethylene oxide. This illustrates the relative stabilities of these anions as measured by the acidities of the car-bazoles (see Section II,A,3) the more acidic the carbazole, the more stable and less reactive its anion as a nucleophile. 

Styrene oxide (Eq. 654) illustrates tbe reaction of the aryl substituted class of ethylene oxides -with albylmercaptans a In this ease ring opening allegedly occurs only by attack of tbe nucleophile on the terminal carbon atom, in contrast with the direction of fission obtained with amines (see section IV.4..B.). 

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