4- butyl bromide hydrolysis reaction

In substitution reactions, a new covalent bond is formed and an old one is broken, as in the hydrolysis of tertiary-butyl bromide ... 

Penfluridol Penfluridol, 4-(4-chloro-3-trifluoromethylphenyl)-l-[4,4-Z M-(p-fluorophenyl) butyl]-4-piperidinol (6.6.12), is synthesized implementing a Grignard reaction between l-carbomethoxypiperidin-4-one and 4-chloro-3-trifluoromethylphenylmagnesium bromide, giving l-carbomethoxy-(4-chloro-3-trifluoromethylphenyl)-4-piperidinol (6.6.10). Upon alkaline hydrolysis of the carbomethoxy group, it turns into (4-chloro-3-trifluo-romethylphenyl)-4-piperidinol (6.6.11), the alkylation of which with l,l-( ti(4-fluo-rophenyl)butyl bromide (6.6.3) gives penfluridol (6.6.12) [67-69],... 

Cationic and anionic mechanisms involve species that have either positive or negative charges, respectively (heterolytic reactions). An example of a reaction that proceeds via a cationic mechanism is the hydrolysis of t-butyl bromide (Scheme 2). 

Reaction XXXVUI. (a) Action of Aqueous and Alcoholic Potassium or Sodium Cyanide on Aliphatic Halogen Compounds, and Hydrolysis of the Nitriles so formed. (B., 14, 1965 15, 2318.)—The preparation and hydrolysis of nitriles are dealt with on p. 151 and p. 239 respectively. In many cases, however, it is unnecessary to isolate the nitrile it can be directly hydrolysed to the corresponding acid on its formation. Among others, the following syntheses have been carried out in this way — i (i.) w-Valeric acid [jpentan acid] from w-butyl bromide (Am. Soc., 42, 310). 

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. 

In contrast, the hydrolysis of tm-butyl bromide (2-bromo-2-methylpropane) occurs in a stepwise manner (reaction 1.1b). In the first slow step, the C-Br bond breaks, with the bromine atom taking both electrons from the bond and leaving as a negatively charged bromide ion. The remainder of the molecule is the positively charged tert-butyl cation (2-methylprop-2-yl cation). This is a highly reactive intermediate, which reacts rapidly with the hydroxide ion to form the corresponding alcohol. 

Hydrolysis of tertiary butyl bromide by alkali resulting in the formation of tertiary butyl alcohol is an example for S l reaction. 

In their studies of reaction kinetics, Hughes and Ingold observed that the hydrolysis of ferf-butyl bromide follows a first-order rate law ... 

The structure of the carboxylated derivative of the addition product tvas proven from a mixed melting point determination with an authentic sample. K6-brich and Stober [21] reinvestigated this reaction in tetrahydrofuran (THF) at -80 to 20 °C and isolated a,a-diphenylheptanoic acid in 98% yield protonation and alkylation of the intermediate 1,1-diphenylhexyllithium with water and n-butyl bromide formed 1,1-diphenylhexane and 5,5-diphenyldecane in 99% and 97% yields, respectively. However, Evans and George [22] have reported that further reversible addition can occur when a large molar excess (6.4-fold) of 1,1-diphenylethylene is reacted with -butyllithium in benzene at 30 °C as shown in Scheme 1. The amount of 1,1,3,3-tetraphenyloctane isolated after hydrolysis was much less than the amount of 1,1-diphenylhexane therefore it was concluded that the second equilibrium step in Scheme 1 strongly favors the monoadduct. No 1,1,3,3-tetraphenyloctane was detected when only a 1.8-fold excess of DPE was used [22, 23]. From the kinetics of the reaction it was concluded that the addition of n-butyllithium to DPE is irreversible [23]. 

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. 

Marchand and co-workers reported a synthetic route to TNAZ (18) involving a novel electrophilic addition of NO+ NO2 across the highly strained C(3)-N bond of 3-(bromomethyl)-l-azabicyclo[1.1.0]butane (21), the latter prepared as a nonisolatable intermediate from the reaction of the bromide salt of tris(bromomethyl)methylamine (20) with aqueous sodium hydroxide under reduced pressure. The product of this reaction, A-nitroso-3-bromomethyl-3-nitroazetidine (22), is formed in 10% yield but is also accompanied by A-nitroso-3-bromomethyl-3-hydroxyazetidine as a by-product. Isolation of (22) from this mixture, followed by treatment with a solution of nitric acid in trifluoroacetic anhydride, leads to nitrolysis of the ferf-butyl group and yields (23). Treatment of (23) with sodium bicarbonate and sodium iodide in DMSO leads to hydrolysis of the bromomethyl group and the formation of (24). The synthesis of TNAZ (18) is completed by deformylation of (24), followed by oxidative nitration, both processes achieved in one pot with an alkaline solution of sodium nitrite, potassium ferricyanide and sodium persulfate. This route to TNAZ gives a low overall yield and is not suitable for large scale manufacture. 

---