Ethyl bromide, hydrolysis reactions

Primary carbocations are so high m energy that their intermediacy m nucleophilic substitution reactions is unlikely When ethyl bromide undergoes hydrolysis m aqueous formic acid substitution probably takes place by an 8 2 like process m which water is the nucleophile... 

An early application of this reaction to the preparation of barbiturates starts by the condensation of the ketone, I21, with ethyl cyanoacetate by Knoevenagel condensation. Alkylation of the product (122) with ethyl bromide by means of sodium ethoxide affords 123. Condensation of this intermediate with guanidine in the presence of sodium ethoxide gives the diimino analog of a barbiturate (124). Hydrolysis affords vinbarbital (111). > ... 

To ascertain whether tritium could have entered the polyisobutylenes by a process other than the hydrolysis of a carbon-aluminium bond, we tested the reaction of suitable polymers with aluminium bromide. The polyisobutylenes were dissolved in ethyl bromide, and phials of aluminium bromide were crushed into these solutions, which were subsequently kept at 0 °C for ca. 15 minutes, and then hydrolysed in the usual way with tritiated water. The three substances examined in this way were polyisobutylenes of high and low DP, and nonadecane. The polyisobutylenes contain approximately one double bond per molecule. The results in... 

If liquid ethyl bromide is shaken with water at 25 C, no appreciable reaction takes place even after several days. The aciiieous phase will not show a Br test with Ag+, and the original reactants may be recovered unchanged. With -butyl bromide, on the other hand, one finds a fairly vigorous reaction with water at 25°C, accompanied by the liberation of heat, to produce -butyl alcohol and HBr. With bcnzhydryl bromide, (CeH6)2CHBr, the hydrolysis reaction appears to be almost immeasurably fast. Although all of these reactions can be represented stoichiometrically by the same general equation,... 

Problem 14.7 In 80% ethanol at SS", the second-order rate constant for the reaction of ethyl bromide with hydroxide ion is 0.0017 liters/mole/sec. Making use of this rate constant and those in Sec. 14.8 and Problem 14.4, calculate the relative rates of hydrolysis in 0.1 N hydroxide for methyl, ethyl, isopropyl, and rerr-butyl bromides. 

Phenobarbital is prepared by treating benzyl ehloride with sodium eyanide when benzyl eyanide (or a-phenyl acetonitrile) is formed with the elimination of a moleeule of sodium chloride. Benzyl cyanide, first on hydrolysis yields phenyl aeetic acid which on subsequent esterification with ethanol forms the eorresponding ester as ethyl phenyl acetate. This on reaction with diethyl oxalate in the persence of absolute ethanol and sodium metal gives diethyl phenyl oxalo acetate which on distillation at 180°C results into phenyl malonic ester. When it is treated with ethyl bromide and sodium ethoxide, the lonely active hydrogen atom gets replaced with an ethyl group thus forming ethyl phenyl malonic ester. Lastly, this on condensation with urea loses two molecules of ethanol and finally forms the desired compound phenobarbital. 

We have seen a similar trend in the reaction of alcohols with hydrogen halides (Section 4.10), in the acid-catalyzed dehydration of alcohols (Section 5.12), and in the conversion of alkyl halides to alkenes by the El mechanism (Section 5.18). As in these other reactions, the more stable the carbocation, the faster it is formed, and the faster the reaction rate. Methyl and primary carbo-cations are so high in energy that they are unlikely intermediates in nucleophilic substitutions. Although methyl and ethyl bromide undergo hydrolysis under the condirions just described, substitution probably takes place by an Sn2 process in which water is the nucleophile. 

The kinetics of the basic hydrolysis of ethyl / -nitrophenyl ethylphosphonate (190) in the SDS-hexanol-water reverse micellar system has shown that at high pH and low water content the reaction occurs in the surface layer and is adequately described by a pseudo-phase model.The reactivity of ethyl aryl chloromethylphosphonates (191 X = NO2, Br, H, Et, Bu, n-octyl) in the basic hydrolysis reactions in direct micelles of cetyltrimethylammonium bromide depends on both the electronic and the hydrophobic... 

In a completely analogous manner, the methoxy acid (326 R = MeO) was synthesized from the ketone (324 R = MeO). In this case the starting material was obtained from /3-(6-methoxy-l-naphthyl)ethyl bromide (3) (Scheme 1) by treatment with potassium cyanide and hydrolysis to naph-thylpropionic acid and the reaction of the chloride of this acid with dime thy Icadmium, leading to the methoxyketone (324 R = MeO) [417]. 

Now let s draw the forward scheme. Ethyl bromide is converted into ethyl magnesium bromide, which is then treated with acetaldehyde (to give a Grignard reaction), followed by water work-up, to give 2-butanol. Oxidation of 2-butanol with chromic acid gives 2-butanone, which can then be converted into a cyanohydrin upon treatment with KCN and HCl. And finally, hydrolysis of the cyano group gives the desired product ... 

Now let s draw the forward scheme. Hydrolysis of acetonitrile gives acetic acid which is subsequently reduced to ethanol upon treatment with excess LAH, followed by water work-up. Upon treatment with PBrj, ethanol is converted to ethyl bromide which is then converted to ethyl magnesium bromide (a Grignard reagent). A Grignard reaction with acetaldehyde (produced by PCC oxidation of ethanol, as shown), followed by water work-up, produces the desired alcohol, 2-butanol. 

These compounds yield, on hydrolysis, the free acids, which, like all acids containing two carbo.xyl groups attached to the same carbon atom, lose COj on heating. Thus, ethyl malonic acid yields butyric acid. In this way the synthesis of monobasic acids may be readily effected. Malonic ester, moreover, may be used in the preparation of cyclic compounds as well as of tetrabasic and also dibasic acids of the malonic acid series ( Perkin). To give one illustration malonic ester, and ethylene bromide in presence of sodium alcoholate, yield triniethyleiic dicarbo.xylic ester and tetramethylene tetracarbo.xylic ester. The first reaction takes place in two steps,... 

Independently, Antane reported that arylisonipecotic acids were obtained from aryl bromides in a two-step process involving microwave-assisted palladium-catalyzed amination with ethyl isonipecotate followed by ester hydrolysis with KOH (Scheme 91) [96]. Interestingly, toluene, which is the standard solvent for Buchwald-Hartwig aminations under conventional heating, was used as the sole reaction medium, although it is a very weak... 

An effect similar to that of cetyltrimethylammonium bromide micelles can be realized through the use of microgels with trimethylamino side-chain function and this may then allow solid supported microgels to be used in a continuous reaction. Evans et al. (1995) have utilized microgels incorporating 2-tetradecyl dimethyl amino/ethyl methacrylate bromide, which solubilizes aryl laurate esters in an aquous solution and catalyses the alkaline hydrolysis. 

In this series, too, replacement of the N-methyl by a group such as cyclopropylmethyl leads to a compound with reduced abuse potential by virtue of mixed agonist-antagonist action. To accomplish this, reduction of 24 followed by reaction with tertiary butylmagnesium chloride gives the tertiary carbinol 27. The N-methyl group is then removed by the classic von Braun procedure. Thus, reaction with cyanogen bromide leads to the N-cyano derivative (28) hydrolysis affords the secondary amine 29. (One of the more efficient demethylation procedures, such as reaction with ethyl chloroformate would presumably be used today.) Acylation with cyclopropylcarbonyl chloride then leads to the amide 30. Reduction with lithium aluminum hydride (31) followed by demethylation of the phenolic ether affords buprenorphine (32).9... 

Triphenylcarbinol has been obtained by the reaction between phenylmagnesium bromide and benzophenone,1 methyl benzoate, or phosgene 8 by action of phenylsodium upon benzophenone, benzoyl chloride, ethyl chlorocarbonate, or ethyl benzoate 4 by hydrolysis of triphenylchloromethane 5 and by oxidation of tri-phenylmethane.6... 

As a result of the inductive and hyperconjugative effects it is to be expected that tertiary carbonium ions will be more stable than secondary carbonium ions, which in turn will be more stable than primary ions. The stabilization of the corresponding transition states for ionization should be in the same order, since the transition state will somewhat resemble the ion. Thus the first order rate constant for the solvolysis of tert-buty bromide in alkaline 80% aqueous ethanol at 55° is about 4000 times that of isopropyl bromide, while for ethyl and methyl bromides the first order contribution to the hydrolysis rate is imperceptible against the contribution from the bimolecular hydrolysis.217 Formic acid is such a good ionizing solvent that even primary alkyl bromides hydrolyze at a rate nearly independent of water concentration. The relative rates at 100° are tertiary butyl, 108 isopropyl, 44.7 ethyl, 1.71 and methyl, 1.00.218>212 One a-phenyl substituent is about as effective in accelerating the ionization as two a-alkyl groups.212 Thus the reactions of benzyl compounds, like those of secondary alkyl compounds, are of borderline mechanism, while benzhydryl compounds react by the unimolecular ionization mechanism. 

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