Sodium acetate bromide

A solution of 16jS-methyl-l la,17a,21-trihydroxy-5j5-pregnane-3,20-dione 21-acetate (52), 45 g, in dioxane (297 ml) is cooled to 15° and treated over a 5 min period with a solution of bromine (34.2 g) in dioxane (594 ml) precooled to 18°. After 2 min a solution of sodium acetate (60 g) in water (600 ml) is added and the mixture poured into ice water (8 liters). The precipitate is filtered off, washed to neutrality with water, and dried to give the crude dibromide (53), 55.7 g mp 125-126° (dec.) [aJu 58°. A mixture of dibromide (53), 55.5 g, lithium bromide (27.8 g), lithium carbonate (27.8 g) and DMF (1.11 liters) is refluxed under rapid stirring for 6 hr. The mixture is concentrated under vacuum to about 250 ml, poured into ice water (8 liters) containing hydrochloric acid (250 ml), and extracted with methylene dichloride. The extracts are washed to neutrality with water and evaporated to dryness. The residue is dissolved in acetone, evaporated to dryness under reduced pressure, redissolved in acetone and crystallized by the additon of hexane. This gives the dienone (54) 24.4 g, mp 236-239°. 

Robertson et al.261 measured rates of bromination of some aromatic hydrocarbons in acetic acid containing sodium acetate (to eliminate protonation of the aromatic by liberated hydrogen bromide) and lithium bromide (to reduce the rate to a measurable velocity ) at 25 °C, the second-order rate coefficients for 3-nitro-N,N-dimethylaniline and anisole being 14.2 and 0.016 respectively the former compound was thus stated to be about 1012 times as reactive as benzene (though no measurement of the latter rate coefficient, inferred to be 1.33 xlO-11, could be found in the literature) and this large rate spread gives one further indication of the unreactive nature of the electrophile. Other rates relative to benzene were ... 

This work was initiated for the purpose of evaluating the feasibility of synthesizing hexyl acetate (ROAc) fi-om n-hexyl bromide (RBr) and sodium acetate (NaOAc) by a novel PTC technique. In this new technique, the solid-liquid reaction was catalyzed by a catalyst-rich liquid phase in a batch reactor. Because there a solid phase and two liquid phases coexist, it is called as a SLL-PTC system [3]. Actually, this liquid phase is the third liquid phase in the tri-liquid PTC system. It might be formed when the phase-transfer catalyst is insoluble or slightly soluble in both aqueous and organic phases. Both aqueous and organic reactants can easily transfer to this phase where the intrinsic reaction occurs [4, 5]. 

A yellowish precipitate was obtained from the chloride and hydrazinium chlorides when basified with sodium acetate. It had N—Hg bonds and was perhaps CIHgNHNHHgCl. It exploded on heating or shock. A similar compound resulted from the bromides. 

Xu et al. have obtained similar results with n-butyl bromide using TBAB (10 mol%) and alumina (4 1 ivjxv) as the catalyst [13]. Benzyl acetate was also conveniently prepared from sodium acetate and benzyl halide by use of microwave irradiation and PTC in synergy [14]. 

This procedure is the same as that described in (2) except that the iodine water is replaced by bromine water, and the buffer contains added sodium bromide, [i.e, sodium bromide-acetic acid-sodium acetate instead of the acetic acid-sodium acetate buffer used in method (2)]. 

Synthetic approaches to representatives of this ring system have been discussed in CHEC-II(1996) <1996CHEC-II(8)496>. Research activity in this area has been considerably extended during the past years. Thus, the basic starting material is a 6,6-disubstituted tetrahydro[l,2,4,5]tetrazin-3-thione 52, which has been converted in three different ways reaction with phenacyl bromides led to 3,3-disubstituted 3,4-dihydro-6-phenyl-2//-thiazolo[3,2-4]-[l,2,4,5]tetrazines 53, reaction of 52 with 1,2-dibromoethane gave 3,4,6,7-tetrahydro-2//-thiazolo[3,2-7][l,2,4,5]tetra-zines 54, whereas transformation of 52 with chloroacetic acid in the presence of sodium acetate yields substituted 3,4-di hydro-1-2//-thiazolo[3,2- 1 [ 1,2,4,5]tctrazin-6(7//)-oncs 55 <2001IJB584> (Scheme 17). Details are shown in Table 2. 

An unexpected formation of a biguanide occurred 754) in the reaction of trans-l-amino-2-hydroxycyclohexane (LI) with cyanogen bromide in the presence of sodium acetate. In addition to the expected trans-2-amino-3a,4,5,6,7,7a-hexahydro-benzoxazole (LII), traces of its trimer having the biguanide structure (LIII) were obtained. 

The synthesis of valsartan (2) by Novartis/Ciba-Geigy chemists is highlighted in Scheme 9.5. Biphenylbenzyl bromide 18 is converted to biphenyl acetate 19 in the presence of sodium acetate in acetic acid. Hydrolysis of 19 followed by Swern oxidation delivered the biphenyl aldehyde 20, which underwent reductive amination with (L)-valine methyl ester (21) to give biphenyl amino acid 22. Acylation of 22 with penta-noyl chloride (23) afforded biphenyl nitrile 24, which is reacted with tributyltin azide to form the tetrazole followed by ester hydrolysis and acidihcation to provide valsartan (2). [See Biihlmayer et al. (1994, 1995).]... 

Sulfonation (66JOC565) or nitration (74JOC1157) of the acridizinium (benzo[Z ]quin-olizinium) ion (3) occurs at position 10 (Scheme 31). When acridizinium bromide is dissolved in liquid bromine and allowed to stand for 15 h the perbromide salt of 7,8,9,10-tetrabromo-7,8,9,10-tetrahydroacridizinium ion is formed and this is easily converted to the simple bromide by the action of acetone. If the tetrabromo salt is refluxed in xylene, it is reconverted to acridizinium bromide (3) in good yield. Treatment of the tetrabromide with sodium acetate gives 10-bromoacridinium bromide (Scheme 32). 

The presence of at least one electron-withdrawing group in the furan ring makes monobromination a much more viable process. Considerable study has been made of the bromination of 2-acylfurans, especially in the presence of Lewis acid catalysts. A kinetic study of the bromination of 2-formylfuran in aqueous medium showed that the reaction is first order in each reactant and pH-independent, and influenced by bromide ion concentration (83MI1). In contrast to the analogous acylthiophenes and acylselenophenes, 2-acetylfuran was hydrolyzed when treated with bromine in the presence of sodium acetate (81SC29). 

The sodium acetate dissolves as the mixture reaches reflux temperature, but a small amount of solid (perhaps sodium bromide) remains undissolved throughout the heating. 

When the cobalt salt of carboxylic acid and bromide ion are dissolved in acetic acid, a cobalt bromide complex is formed instantaneously. For cobalt dibromide a pronounced induction period was observed, but adding sodium acetate eliminates entirely the induction period, suggesting that cobalt monobromide is responsible for the catalysis. 

The use of mixtures of sodium hydroxide and benzyltrimethylammonium chloride or tetrabutylammonium bromide failed to enhance the DPGE alkylation of HEC by the in situ formation of the corresponding quaternary ammonium hydroxide phase transfer catalyst. These quaternary ammonium halides are too soluble in aqueous /-butyl alcohol and are preferentially extracted into the organic phase. Mixtures of benzyltrimethylammonium hydroxide and sodium acetate were also ineffective in enhancing the DPGE alkylation of HEC for the same reason, namely preferential solubility of benzyltrimethylammonium acetate in the organic phase. 

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