Bromination of acetic acid

Bromoacetic acid can be prepared by the bromination of acetic acid in the presence of acetic anhydride and a trace of pyridine (55), by the HeU-VoUiard-Zelinsky bromination cataly2ed by phosphoms, and by direct bromination of acetic acid at high temperatures or with hydrogen chloride as catalyst. Other methods of preparation include treatment of chloroacetic acid with hydrobromic acid at elevated temperatures (56), oxidation of ethylene bromide with Aiming nitric acid, hydrolysis of dibromovinyl ether, and air oxidation of bromoacetylene in ethanol. 

Bromoacetic acid has been prepared by direct bromination of acetic acid at elevated temperatures and pressures,2-3-4 or with dry hydrogen chloride as a catalyst 6 and with red phosphorus as a catalyst with the formation of bromoacetyl bromide.6-7-8-9-19 Bromoacetic acid has also been prepared from chloroacetic acid and hydrogen bromide at elevated temperatures 6 by oxidation of ethylene bromide with fuming nitric acid 7 by oxidation of an alcoholic solution of bromoacetylene by air 8 and from ethyl a,/3-dibromovinyl ether by hydrolysis.9 Acetic acid has been converted into bromoacetyl bromide by action of bromine in the presence of red phosphorus, and ethyl bromoacetate has been... 

The purpose of this review has been to illustrate and document the kinds of information about non-aqueous solvent systems which have been obtained by vibrational spectroscopy. We have seen that these include insight into intermolecular forces and structure of the pure solvents, the nature of the solvation shell around ions and their solvation numbers, the identification of ion pairs and complexes, measurement of mass law constants and their dependence on the polarity of the solvent, the detection and characterisation of the hydrogen bond and measurement of acid and base strengths. Little kinetic data have so far been obtained by Raman spectroscopy but recent progress in the study of ultra-fast proton transfer and the detection of associated ions of type [Br , (Bra)] during the bromination of acetic acid presage considerable advance in this area in the future. ... 

Scheme 9.104. (Scheme 8.49 repeated). A variety of possibilities to account for the formation of a-bromoacetic acid (bromoethanoic acid) by bromination of acetic acid (ethanoic add) with bromine (Br ) in the presence of red phosphorus (P). 

Bromination of fatty acids in the a-position can be effected quite readily in the presence of phosphorus trichloride, red phosphorus or pyridine as catalysts or halogen carriers with acetic acid, the addition of acetic anhydride (to ensure the absence of water) improves the yield and facilitates the bromination. Examples are —... 

The preparation and spectroscopic properties (infrared, ultraviolet, NMR) of iV-alkoxycarbonyl-N -(2-thiazolyl)thioureas (268) have been studied by the Nagano group (78, 264). These compounds react with bromine in acetic acid or chloroform to give 2--alkoxycarbonylimino-thiazolo[3,2-h]thiadiazolines (Scheme 162), whose structures were established by mass spectroscopy, infrared, NMR, and reactivity patterns (481). 

Bromination in acetic acid has been the more widely studied reaction, and s ubstitution occurs readily at the 5 -position of the thiazole nucleus (247). For instance, itis possible tostudy the influenceof groups X and R on thereactivnty of the 5-position towards Br" (Scheme 6) (249). 

The most important of the halogenated derivatives of acetic acid is chloroacetic acid. Fluorine, chlorine, bromine, and iodine derivatives are all known, as are mixed halogenated acids. For a discussion of the fluorine derivatives see Fluorine compounds, organic. 

Acetaldehyde can be used as an oxidation-promoter in place of bromine. The absence of bromine means that titanium metallurgy is not required. Eastman Chemical Co. has used such a process, with cobalt as the only catalyst metal. In that process, acetaldehyde is converted to acetic acid at the rate of 0.55—1.1 kg/kg of terephthahc acid produced. The acetic acid is recycled as the solvent and can be isolated as a by-product. Reaction temperatures can be low, 120—140°C, and residence times tend to be high, with values of two hours or more (55). Recovery of dry terephthahc acid follows steps similar to those in the Amoco process. Eastman has abandoned this process in favor of a bromine promoter (56). Another oxidation promoter which has been used is paraldehyde (57), employed by Toray Industries. This leads to the coproduction of acetic acid. 2-Butanone has been used by Mobil Chemical Co. (58). 

Eigure 3 is a flow diagram which gives an example of the commercial practice of the Dynamit Nobel process (73). -Xylene, air, and catalyst are fed continuously to the oxidation reactor where they are joined with recycle methyl -toluate. Typically, the catalyst is a cobalt salt, but cobalt and manganese are also used in combination. Titanium or other expensive metallurgy is not required because bromine and acetic acid are not used. The oxidation reactor is maintained at 140—180°C and 500—800 kPa (5—8 atm). The heat of reaction is removed by vaporization of water and excess -xylene these are condensed, water is separated, and -xylene is returned continuously (72,74). Cooling coils can also be used (70). 

Cinnolin-4(lF/)-one and its 6-chloro, 6-bromo, 6-nitro and 8-nitro derivatives react with sulfuryl chloride or bromine in acetic acid to give the corresponding 3-halo derivatives in about 20% yields. lodination of 8-hydroxycinnolin-4(lF/)-one with a mixture of potassium iodide and potassium iodate gives the 5,7-diiodo derivative the 6,8-diiodo derivative is formed from 5-hydroxycinnolin-4(lF/)-one. 

As might be expected from a consideration of electronic effects, an amino substituent activates pyrazines, quinoxalines and phenazines to electrophilic attack, usually at positions ortho and para to the amino group thus, bromination of 2-aminopyrazine with bromine in acetic acid yields 2-amino-3,5-dibromopyrazine (Scheme 29). 

The electrophilic substitution of thiophene is much easier than that of benzene thus, thiophene is protonated in aqueous sulphuric acid about 10 times more rapidly than benzene, and it is brominated by molecular bromine in acetic acid about 10 times more rapidly than benzene. Benzene in turn is between 10 and lo times more reactive than an uncharged pyridine ring to electrophilic substitution. 

Treatment of pyrrole, 1-methyl-, 1-benzyl- and 1-phenyl-pyrrole with one mole of A -bromosuccinimide in THF results in the regiospecific formation of 2-bromopyrroles. Chlorination with IV-chlorosuccinimide is less selective (8UOC2221). Bromination of pyrrole with bromine in acetic acid gives 2,3,4,5-tetrabromopyrrole and iodination with iodine in aqueous potassium iodide yields the corresponding tetraiodo compound. 

Halogens react with benzo[6]furan by an addition-elimination mechanism to give 2- and 3-substituted products (76JCS(P2)266). Treatment of benzo[6]thiophene with chlorine or bromine in acetic acid gives predominantly 3-substituted products (71JCS(B)79). 2,2,3,3,4,5,6,7-Octachloro-2,3-dihydrobenzothiophene is obtained when benzo[6]thio-phene is treated with chlorine in the presence of 1 mole of iodine (80JOC2l5l). 

The 2-thienylthiourea (245) on oxidation with bromine in acetic acid gave the thieno[3,2-djthiazole (247). It has been suggested that the intermediate electrophilic sulfenyl bromide adds to the 2,3-bond of the thiophene ring to form (246) when then loses HBr to give (247) (71AJC1229, 78JHC81). Pyrazolo(3,4- /]thiazoles are formed in a similar fashion (76GEP2429195). 

Bromine in chloroform and bromine in acetic acid are the reagents used most often to brominate pyrazole. When nitric acid is used as a solvent, both bromine and chlorine transform pyrazoles into pyrazolones (Scheme 24). Thus 3-methyl-l-(2,4-dinitrophe-nyOpyrazole is brominated at the 4-position (309). The product reacts with chlorine and nitric acid to give the pyrazolone (310). The same product results from the action of bromine and nitric acid on (311). The electrophilic attack of halogen at C-4 is followed by the nucleophilic attack of water at C-5 and subsequent oxidation by nitric acid. 

Acetoxy-17a-hydroxy-5a-pregnane-3,l 1,20-trione (40) is brominated in acetic acid under equilibrating conditions to give a solution of the 2a,4a-di-bromo compound (41). This is reduced by chromous chloride without further treatment, to the 4a-bromo compound (42). The recrystallized bromo compound (42) is then dehydrobrominated via the semicarbazone (43) which is converted without isolation into cortisone acetate (44) by treatment with pyruvic acid ... 

Bromohydrm acetates are formed by the oxidation of the vinyl group in perfluoroalkylethylenes with bromine in acetic acid [34] (equation 26)... 

Procedures have been worked out which increased the yield of 2-bromothiophene to 78% on direct bromination in acetic acid-ether mixtures and to 67% in carbon tetraehlorided With the mild brominating agent, dioxane dibromide, quantitative yields of 2-bromothiophene are obtained. A very convenient procedure for the iodination of thiophenes consists of the acid-catalyzed (HzSOi) reaction with iodine and HIO3, giving 2-iodothiophene in 75% yieldd In contrast to the HgO method, all the iodine is utilized. 

To the best of our knowledge, the hrst paper which mentioned an A-(l-haloalkyl)pyridinium compound appeared 66 years ago in the Chemische Berichte (Krohnke 33CB1386). Tlie author described the reaction of phenacyl pyridinium derivatives 1 with bromine in acetic acid to give the halides 2 (36CB2006 37CB864). Tire addition of bromine to the double bonds of A-vinylpyridinium salts 3 and 4 giving the adducts 5 and 6 has also been reported (51CB399) (Scheme 1). 

The bromination of 5,8-dimethoxyquinoxaline in methanol gives a mixture of 6-bromo and 6,7-dibromo compounds/ Treatment of 2-methylquinoxaline with bromine in acetic acid yields a mixture of 27% of 2 bromomethyl- and 37% of 2-dibromomethyl-quinoxaline." Thus in the absence of powerfully activating groups, side-chain rather than nuclear substitution takes place. 

One of a variety of syntheses of the antipsychotic agent bro-foxine (50) begins with a Grignard reaction on methyl anthra-nilate. The resulting product ( ) is reacted with phosgene in pyridine and the synthesis is completed by bromination in acetic acid to give brofoxine. 

It forms a characteristic dibromide, CjjHjgBrjO, by the action of bromine in acetic acid, melting at 69° to 70° (optically active form) or 96° to 97° (racemic variety). Dihydrocarvoxime melts at 89° (active variety) or 115° to 116° (racemic variety). 

A particularly common cr-substitution reaction in the laboratory is the halogenation of aldehydes and ketones at their a- positions by reaction with Cl2, Br2, or I2 in acidic solution. Bromine in acetic acid solvent is often used. 

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