Benzyltrimethylammonium tribromide

The results were compared with the bromination with bromine. It was apparent that bromine gave /jora-bromides exclusively except 2-allylphenol. As the reaction of 2-allylphenol with bromine gave the mixture of many products (bromine adduct as main product, some ring bromides as by-products, etc.), 2-allylphenol was treated with benzyltrimethylammonium tribromide (BTMA Br3) which was already developed as mild and easy bromine (ref. 10). 

Our recent studies on effective bromination and oxidation using benzyltrimethylammonium tribromide (BTMA Br3), stable solid, are described. Those involve electrophilic bromination of aromatic compounds such as phenols, aromatic amines, aromatic ethers, acetanilides, arenes, and thiophene, a-bromination of arenes and acetophenones, and also bromo-addition to alkenes by the use of BTMA Br3. Furthermore, oxidation of alcohols, ethers, 1,4-benzenediols, hindered phenols, primary amines, hydrazo compounds, sulfides, and thiols, haloform reaction of methylketones, N-bromination of amides, Hofmann degradation of amides, and preparation of acylureas and carbamates by the use of BTMA Br3 are also presented. 

OXIDATION WITH BENZYLTRIMETHYLAMMONIUM TRIBROMIDE Oxidation of alcohols and ethers... 

Treatment with sodium hypochlorite or hypobromite converts primary amines into N-halo- or N,N-dihaloamines. Secondary amines can be converted to N-halo secondary amines. Similar reactions can be carried out on unsubstituted and N-substituted amides and on sulfonamides. With unsubstituted amides the N-halo-gen product is seldom isolated but usually rearranges (see 18-13) however, N-halo-N-alkyl amides and N-halo imides are quite stable. The important reagent NBS is made in this manner. N-Halogenation has also been accomplished with other reagents, (e.g., sodium bromite NaBr02) benzyltrimethylammonium tribromide (PhCH2NMe3 Br3"), and NCS. The mechanisms of these reactions involve attack by a positive halogen and are probably similar to those of 12-47 and 12-49.N-Fluorination can be accomplished by direct treatment of amines °° or... 

Halogenation can be run under milder conditions using more active quaternary ammonium polyhalides such as pyridinium tribromide. The reaction between thiophene and benzyltrimethylammonium tribromide in acetic acid-ZnCl2 provided 2,5-dibromothiophene [6]. Chloro- and iodo-substituted thiophene derivatives may be prepared in the same manner. In comparison, bromination of thiophene employing 2 equivalents of NBS in chloroform gave 2,5-dibromothiophene in 56% yield [7]. 

Benzyl salicylate, 22 16 25 184 physical properties of, 22 13t Benzyl sulfone pyrolysis, 21 141 Benzyltrimethylammonium tribromide, bromination reagent, 4 344 Bepadin, molecular formula and structure, 5 97t, 118t Bepridil, 5 104... 

Benzyltrimethylammonium tribromide has been used for the A -bromination of amides in good yield [54]. Under basic conditions, Hofmann rearrangement to amines is also possible (see Section 9.3). 

Benzene-l,4-diols are oxidized to quinones by benzyltrimethylammonium tribromide under mild conditions in almost quantitative yields [6]. With an excess of the tribromide further reaction produces the 2-bromo-l, 4-quinones. This oxidation is in contrast to the analogous reaction of phenols, which produces bromophenols (see Section 2.3). Hindered 4-methyl-phenols are oxidized to the corresponding benzyl alcohols, benzaldehydes, bromomethyl derivatives and 4-bromo-4-methylcyclo-hexa-2,5-dien-l-ones [7]. Benzylic alcohols are oxidized under neutral or basic conditions to yield the corresponding aldehydes (>70%) oxidation with an excess of the reagent produces the benzoic acids (>90%) [8],... 

A primary kinetic isotope effect (kn/ko = 6.03 at 298 K) was observed for the oxidation of formic and oxalic acids by benzyltrimethylammonium tribromide (BTMAB) to carbon dioxide. The kinetics of oxidation of pyridoxine to pyridoxal by broma-mine-T and bromamine-B ° and caffeine by bromamine-B have been investigated. 

The use of bromine adsorbed on alumina gave 85% bromination of 2-methylthiophene with no obvious benzylic halogenation. After a 1-min stirring at room temperature, an 80 20 mixture of 5-bromo and 3,5-dibromo products was obtained (92SC1095). Benzyltrimethylammonium tribromide converted 3-methylthiophene into its 2,5-dibromo derivative (91BCJ2566). 

The oxidation of a-hydroxy acids by benzyltrimethylammonium tribromide (BTMAB) to the corresponding carbonyl compounds shows a substantial solvent isotope effect, A (H20)/A (D20) = 3.57, but no KIE for a-deuteromandelic acid.133 The oxidation of glucose by hypobromous acid is first order in glucose and the acid.134 [l,l-2H2]Ethanol shows a substantial kinetic isotope effect when oxidized by hexamethylenetetramine-bromine (HABR) in acetic acid to aldehyde.135 Kinetics of the oxidation of aliphatic aldehydes by hexamethylenetetramine-bromine have been studied by the same group.136 Dioxoane dibromide oxidizes y-tocopherol to 5-bromomethyl-y-tocopherylquinone, which spontaneously cyclizes to 5-formyl-y-tocopherol.137... 

H2O2 in methanol. Aryl methyl ketones can be dibrominated (ArCOCHa ArCOCHBr2) in high yields with benzyltrimethylammonium tribromide. Active methylene compounds are chlorinated with NCS and Mg(C104)2. " Similar chlorination in the presence of a chiral copper catalyst led to cx-chlorination with modest enantioselectivity. 

Kajigaeshi, S., Kakinami, T. Bromination and oxidation with benzyltrimethylammonium tribromide. Ind. Chem. Library 1995, 7, 29-48. 

The use of benzyltrimethylammonium tribromide is particularly effective for the synthesis of aromatic and heteroaromatic carboxylic acids as shown in Table 1. 

Benzyltrimethylammonium tribromide (6.04 g, 15.5 mmol) was added to a solution of acetophenone (0.60 g, 5 mmol) and NaOH (1.2 g, 30 mmol) in water (50 mL), and the mixture was stirred at room temperature for 20 min. The orange color of the solution immediately faded and bromoform formed during the period. To the mixture was added 5% aq. solution of NaHSC>3 (10 mL) and bromoform was filtered off. The filtrate was made acidic with 6 N HC1 and was extracted with ether (40 mL x 4). The ether layer was dried over MgS04, filtered and evaporated at reduced pressure to give benzoic acid yield 0.58 g (95%) mp 122-123 °C. 

The Hugerschoff reaction is a classical method to convert arylthioureas into aminobenzothiazoles under oxidative conditions. It was discovered by Hugerschoff in the early 1900s, who found that an arylthiourea can be cyclized with liquid bromine in chloroform to form a 2-aminobenzothiazole. Solvents such as carbon tetrachloride and carbon disulfide can also be used. This transformation is aided by thiophilic bromine or its equivalent and requires an intramolecular aromatic elecb ophilic substitution reaction of the aryl ring to the thiocarbonyl group of thiourea. Attempts have been made to avoid the use of bromine due to the handling concerns it poses. For example, Jordan and coworkers have used benzyltrimethylammonium tribromide. ... 

A formal synthesis of ehartelline A (143) was reported by Weinreb and eoworkers and it is depicted in Scheme 13 [72]. The synthesis was started by taking 5-nitroisatin 148, which was transformed into y0-laetam produet 149 and then converted into amine 150. Now, three contiguous bromines were installed by the treatment of benzyltrimethylammonium tribromide... 

A soln. of acetanilide in 5 2 methylene chloride/methanol treated with benzyltrimethylammonium chlorobromate(l-) at room temp., and stirred for 20 min - 4-bromoacetanilide. Y 97%. Tetrabutylammonium and benzyltrimethylammonium tribromide were also effective in the presence of methanol, but reaction times were longer (cf. Synth. Meth. 42,471). F.e. incl. dibromination of amino- or hydroxy-subst. acetanilides s. S. Kajigaeshi et al.. Bull. Chem. Soc. Japan 61, 2681-3 (1988). 

Benzyltrimethylammonium tribromide j sodium hydroxide Modified Hofmann degradation under mild conditions... 

B. Brominating agents Pyridinium hydrotribromide (pyridinium hydrobromide perbromide) Dioxane-bromine complex A-Bromosuccinimide 2,4,4,6-Tetrabromocyclohexadienone Benzyltrimethylammonium tribromide Substitute for bromine when increased selectivity or mild reaction conditions are required Same as for pyridinium hydrotribromide Substitute for bromine when low Br concentration is required Selective bromination of polyolefins and cyclization induced by Br+ Selective bromination of alkenes and carbonyl compounds... 

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