Dehydrobromination, base

Vinyl Bromide. Vinyl bromide [593-60-2] is prepared by the base-promoted dehydrobromination of ethylene dibromide [106-93 ]. It is used as a comonomer in the production of acrylic fibers. 

Until recently, pyridine-type bases have been commonly used to produce conjugated enones from 2-halo ketones yields are usually poor °° and these reactions are frequently accompanied by rearrangement, reduction and salt formation. Thus, Warnhoff found that dehydrobromination of (28) with 2,4-lutidine gave a mixture of (29), (30) and (31) in the ratio 55 25 20. Collidine gave a ratio of 38 25 37, whereas pyridine gave mainly the salt (32). 

Pyridine base eliminations of a-bromo ketones cannot be recommended for general use because of the side reactions already discussed. The semi-carbazone-pyruvic acid method should be employed if strict absence of isomerization is required in the dehydrobromination of 2- or 4-bromo-3-ke-tones. This procedure is not applicable for the preparation of -3-ketones,... 

The direct dehydrobromination of 16-bromo-17-ketones is not a viable route to A -17-ketones (see, for example, ref. 49, 69, 119). However, these compounds can be prepared via the bromo ketals which provide unsaturated ketones on treatment with strong bases followed by acid hydrolysis." ... 

Eberle and Schaub (93EUP571326) describe the synthesis of a large series of 3-hydroxy-2-(2-methyl-4-prop-l-ynyl-2//-pyrazol-3-yl)acrylic acid methyl esters 26 and methoxyimino-(2-methyl-4-prop-l-ynyl-2//-pyrazol-3-yl)acetic acid methyl esters 27 by dehydrohalogenation of the corresponding chloroolefins 25 under the action of bases. In this case, the functional groups in position 5 of the pyrazole ring undergo dehydrobromination (Scheme 34). 

Base catalyzed dehydrobromination of a-bromoketones is frequently employed in steroidal systems as a means to obtain a,/9-unsaturated ketones (12). An example of this reaction employing lithium carbonate as the base is also given. 

Assume that you are carrying out the base-induced dehydrobromination of 3-bromo-3-methylpentane (Section 11.7) to yield an alkene. How could you use 1R spectroscopy to tell which of two possible elimination products is formed ... 

The pharmacologically active and commercially important 5//-dibenz[/>,/]azepines 40 are available by base-catalyzed dehydrobromination of their 5-acyl- 10-bromo-l 0.11-dihydro derivatives 38,118 followed by hydrolysis of the isolable tV-acyl compounds 39 29.119-121... 

Reduction of the 5A/-2-benzazepin-5-one 5, prepared by base-catalyzed (triethylamine) dehydrobromination of4-bromo-8-chloro-l-(2-chlorophenyl)-3//-2-benzazepin-5(4//)-one, with lithium aluminum hydride at — 78 C yields a mixture of the 5//-azepin-5-ol 6 and the dihydrobenz-azepinone 7.78 Attempts to prepare the 5-bromo derivative from the alcohol 6 failed. 

Kinetic measurements were performed on a Hitachi 150-20 UV/VIS spectrophotometer. Dehydrobrominations were studied in DMF solution using cyclohexyl amine (CHA) as the base. Applied CHA concentrations were 2, 2.5, 3, 3.5, 4 and 5 10 3 mole.dm-3, initial concentration of 1 was 5 10 5 mole.dm-3 in every case (pseudo-first-order conditions). Ionic strength was adjusted to lO l mole.dm 3 with potassium nitrate. Kinetic curves / D(t) / were recorded at fix wavelength, X = 290 ran and the temperature was maintained at 30, 35.5, 40°C. Stock solutions were made daily for la and freshly for every measurement of Ih. The reaction was started by injection of solution of 1 to the thermostated solution of CHA. 

The accessibility of ethyl-substituted stabilizer precursors suggests benzylic bromination with N-bromosuccinimide followed by base-catalyzed dehydrobromination. Tertiary amines were found to be particularly effective in the syntheses described in this paper. 

Monodehydrohalogenation of allylic halides is another classical method for diene synthesis24. This method is complementary to double dehydrohalogenation as both the 1,2-dihalides and allylic halides are readily accessed from alkenes. The commonly employed protocol for diene synthesis, particularly for cyclic 1,3-dienes, is through the allylic monobromination of the alkene with A-bromosuccinimide or related reagents followed by dehydrobromination with hindered bases such as DBN or DBU (equation l)25. 

Dehydrobromination of 219 with DBU gave rise to allyl propargyl ethers 220, which underwent a base-catalyzed isomerization-[4 +2]-cycloaddition sequence to afford tricyclic enol ethers 221 [179]. 

Table 9.1). The rate of dehydrobromination from the intermediate bromoalkenes follows the pattern 2-bromoalkenes > Z-l-bromoalkenes > E- -bromoalkenes the corresponding chloro derivatives react more slowly. For optimum yield, the reaction temperature should be <100°C to reduce decomposition of the catalyst, and the concentration of base should be kept low to prevent isomerization of the resulting alkynes. [3-Elimination of HBr from 1,2-dibromo-1 -phenylethane can be controlled to yield 1-bromo-l-phenylethene in 83% yield [15]. The addition of alcohols and diols have a co-catalytic effect on the elimination reaction, as the alkoxide anions are transferred more effectively than the hydroxide ions into the organic phase [13]. 

The bromination-dehydrobromination route is in many cases preferable [Scheme 2 80JCS(P1)2081], using bromine, N-bromosuceinimide (NBS), or phenyltrimethylammonium tribromide (PTAB). The resulting mono-bromo, geminal, or vicinal dibromo and tribromo derivatives (e.g., 5a,b) are often preferentially dehydrobrominated by Jones method [73JCS(P1)968] using lithium salts in dimethylformamide (DMF). Bases such as triethyla-mine, sodium methoxide, and l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) were also used. 

Base-catalyzed cyclization of A -benzoyl-a-chloroacetamide is a classical method used to prepare 2-phenyl-4(5//)-oxazolone. Extension of this methodology to the A -aroylcinnamides 35 afforded a series of 5-arylidene analogues 37 albeit in unstated yield (Scheme 6.12). " Thus, acylation of the sodium salt of a benzamide with a cinnamoyl chloride gave the imides 35 that were converted to 36 via a bromination-dehydrobromination sequence. Cyclization to 37 was affected with sodium hydride in 1,2-dimethoxyethane (DME). The authors noted that catalytic reduction of 37 afforded the 5-(arylidene)oxazolidine from which 37 could be regenerated in the presence of air. 

A base-catalyzed, elimination reaction was a key step in a synthesis of D-ribose from L-glutamic acid.188 In that work, L-glutamic acid was converted, by a series of reactions, into 5-0-benzyl-2,3-dideoxy-D-glycero-pentofuranose (157) from compound 157, a mixture of glycosides was obtained which, on treatment with bromine and calcium carbonate, gave the monobromo derivative 158 as a mixture of diastereoisomers. Base-catalyzed dehydrobromination of 158 afforded the unsaturated derivative 159. Hydroxylation of 159 with potassium permanganate or with osmium tetraoxide gave a mixture of methyl 5-0-benzyl-/3-D-ribofuranoside and methyl 5-O-benzyl-a-D-lyxofuranoside. 

Dehydrobromination with a base such as collidine then establishes the 1,4-diene function to yield fluoroprednisolone acetate (19-3) [13]. 

Despite careful control of reaction conditions the base-catalyzed dehydrobromination of the dibromoepisulfide indicated in equation (73) was consistently found to yield only benzene... 

Dehydrobromination of bromotrifluoropropene affords the more expensive trifluoropropyne [237], which was metallated in situ and trapped with an aldehyde in the TIT group s [238]synthesis of 2,6-dideoxy-6,6,6-trifluorosugars (Eq. 77). Allylic alcohols derived from adducts of this type have been transformed into trifluoromethyl lactones via [3,3] -Claisen rearrangements and subsequent iodolactonisation [239]. Relatively weak bases such as hydroxide anion can be used to perform the dehydrobromination and when the alkyne is generated in the presence of nucleophilic species, addition usually follows. Trifluoromethyl enol ethers were prepared (stereoselectively) in this way (Eq. 78) the key intermediate is presumably a transient vinyl carbanion which protonates before defluorination can occur [240]. Palladium(II)-catalysed alkenylation or aryla-tion then proceeds [241]. 

Treatment of MFA (1) with cyanogen bromide [6] opened ring G to yield the bromo derivative 3 [7]. Attempts to dehydrobrominate 3 in one step via a base-catalyzed elimination with DBU/CH3CN, KOH/MeOH, or terr-BuOK/DMSO were unsuccessful. However, the required methylene entity could be introduced by converting 3 first to a selenide, then oxidation with periodate, followed by thermolysis in benzene to provide compound 4. Hydrolysis of the cyano group with NaOH in ethylene glycol [8] produced 5 (50% yield). Osmium catalyzed oxidation of 5 in the presence of 4-methylmorpholine A-oxide (NMO) gave a diol, which was cleaved to an aldehyde upon treatment with periodate. Treatment of the aldehyde with sodium cyanoborohydride resulted in an intramolecular reductive animation to yield the desired product PHB (6). 

In an attempt to prepare di-zerz-butylbenzocyclobutadiene by base-catalyzed dehydrobromination of 100, a mixture of oxygen-containing substances was obtained in some experiments a compound could be isolated... 

Furanones have been prepared by treatment of y-ketoacids with acetic anhydride. Furanones have also been formed by hydrolysis and dehydrobromination of j8,y-dibromoacids (B-50MI31200). The furan-3(2//)-one system (164) has been prepared by intramolecular cyclization of the diazoketones (163) (74TL3073). Some natural 3(2//)-furanones are known furaneol (166), occurring in strawberries and pineapples, is obtained by acid or base treatment of the dihydroxydiketone (165) (73JOC123). 

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