Dehydrobromination

Apparatus 1-1 round-bottomed, three-necked flask with a dropping funnel, a mechanical stirrer and a thermometer, combined with a vent, for the addition of bromine and the dehydrobromination to 1-bromocyclooctene 1-1 flask (see Fig. 1) for the preparation of cyclooctyne. 

Axial halide is in proper orientation for anti elimination with respect to axial hydrogens on adjacent carbon atoms Dehydrobromination is rapid... 

Heating butyrolactone with bromine at 160—170°C gives a 70% yield of a-bromobutyrolactone (152). With phosphoms tribromide as catalyst, bromination is accelerated, giving 2,4-dibromobutyric acid, which dehydrobrominates to a-bromobutyrolactone when distilled (153). Chlorination gives a-position monochlorination at 110—130°C and a-dichlorination at 190—200°C (154). 

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. 

Although bromotrifluoroethylene was first prepared (9) by the dehydrobromination of l,2-dibromo-l,l,2-triduoroethane [354-04-17, it is more conveniendy prepared from chlorotriduoroethylene [79-38-9] by the following high yield steps (26) ... 

Chroman-4-one, 3-bromo-2-hydroxy-synthesis, 3, 856 Chroman-4-one, 2-/-butyl- H NMR, 3, 583 Chroman-4-one, 3-/-butyl- H NMR, 3, 583 Chroman-4-one, 2,3-dibromo-dehydrobromination, 3, 828 Chroman-4-one, 3,3-dibromo-dehydrobromination, 3, 828 Chroman-4-one, 2,3-dihalogeno-synthesis, 3, 856 Chroman-4-one, 2,2-dimethyl-mass spectra, 3, 617 Chroman-4-one, 2,2-diphenyl-synthesis, 3, 852 Chroman-4-one, 3-hydroxy-synthesis, 3, 856... 

The procedure described is essentially that of Belleau and Weinberg and represents the only known way of obtaining the title compound. One other quinone acetal, 1,4,9,12-t6traoxadispiro[4.2.4.2]tetradeea-6,13-diene, has been synthesized by a conventional method (reaction of 1,4-cyclohexanedione with ethylene glycol followed by bromination and dehydrobromination ) as well as by an electrochemical method (anodic oxidation of 2,2-(l,4-phenylenedioxy)diethanol ). Quinone acetals have been used as intermediates in the synthesis of 4,4-dimethoxy-2,5-cyclohexadienone,. syw-bishomoquinone, - and compounds related to natural products. ... 

In general bromination of 20-ketones is directed to the introduction of functionality at C-21. However, on occasion 17-bromo compounds are required for dehydrobromination to A -20-ketones, although these are generally obtained in other ways. Kinetic enolization of a 20-ketone gives the A °-enol, whereas the thermodynamic product is the A kjsomer. An interesting enolate trapping reaction has been used recently to prepare 16-methyl-A -20-ketones ... 

Further bromination of the 4 -bromo compound, under thermodynamic or kinetic conditions, yields the 2, 4)S-dibromo compound (23) which apparently contains a little of the 2,2-dibromo isomer. Again, the 2,4-dibromo compound is best obtained directly from the parent ketone with two moles of bromine in acid. " With suitable methods of dehydrobromination (see... 

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). 

An improved method for the preparation of A" -3-ketones from 4-bromo compounds was described by Mattox and Kendall. This procedure involves dehydrobromination of the 2,4-dinitrophenylhydrazone and subsequent cleavage of the hydrazone with pyruvic acid ... 

While the use of substituted hydrazine derivatives is generally recognized to be the most reliable method for dehydrobromination of bromo ketones without rearrangement, this side reaction can be important in some cases. Both the 2-bromo-A" -3-ketone and its 4-bromo isomer give the same A" -diene hydrazone (33), °° which is cleaved to the ketone in very poor yield (however, see ref. 65 for a successful use of the semicarbazide method). 

A successful application of the two methods of dehydrobromination so far discussed, illustrating selective reactions, is described by Magerlein ... 

The semicarbazide method does not affect 17-bromo-20-ketones. is superior to collidine for dehydrobromination of the latter. 

The bromination of 4,5-j -dihydrocortisone acetate in buffered acetic acid does not proceed very cleanly (<70%) and, in an attempt to improve this step in the cortisone synthesis, Holysz ° investigated the use of dimethylformamide (DMF) as a solvent for bromination. Improved yields were obtained (although in retrospect the homogeneity and structural assignments of some products seem questionable.) It was also observed that the combination of certain metal halides, particularly lithium chloride and bromide in hot DMF was specially effective in dehydrobromination of 4-bromodihydrocortisone acetate. Other amide solvents such as dimethylacetamide (DMA) and A-formylpiperidine can be used in place of DMF. It became apparent later that this method of dehydrobromination is also prone to produce isomeric unsaturated ketones. When applied to 2,4-dibromo-3-ketones, a substantial amount of the A -isomer is formed. 

The Joly procedure may be used under milder conditions ( 30 min at 100°) for selective dehydrobromination ... 

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,... 

Dibromo-3-ketones may also be used as substrates for the preparation of A -3-ketones by Joly s method. " Hexamethylphosphoramide has been recommended as a medium suitable for the dehydrobromination of a-bromo ketones to give a, -unsaturated ketones in high yield without rearrange-... 

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 ... 

Addition of bromine to the dienol acetate (49) gives the 6j5-bromo-A -3-ketone (50). Dehydrobromination of the crude bromo compound in DMF with lithium or calcium carbonate gives the title compound (51). ... 

The 7a-bromo-5a-6-ketone (56) is conveniently prepared from a mixture of the 5a- and 5j5-6-ketones (55) under equilibrating conditions. It is formed from the 5a-isomer (55) via the 5a-bromo-compound, and from the 5j -isomer (55) via the 7a-bromo-5i -6-ketone (see section II-A). Dehydrobromination is effected in DMF, and chromatography of the crude product separates the title compound (58) from remaining starting material and isomeric A -6-ketone (57). ... 

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." ... 

Acetoxyandrost-5-en-17-one (59) is converted into the ethylene ketal (60) by treatment with ethylene glycol, triethylorthoformate and p-toluenesulfonic acid. The ketal is brominated with pyridinium bromide perbromide in THF and then treated with sodium iodide to remove bromine from the 5 and 6 positions. This gives the 16a-bromo compound (61) which is hydrolyzed in methanol to the free alcohol (62). Dehydrobromination is effected with potassium Fbutoxide in DMSO to give the -compound (63). Acid catalyzed hydrolysis of the ketal in aqueous acetone gives the title compound (64). ... 

An illustration of the difference in reactivity of a-and / -halides is provided by the ready elimination of 1,4a-dibromo-5a-cholestan-3-one to 4a-bromo-5a-cholest-l-en-3-one in collidine at room temperature. Calcium carbonate in refluxing DMA is necessary to complete the dehydrobromination to the l,4-dien-3-one. ... 

An important application of the allylic bromination-dehydrobromination approach is the formation of the A -diene system e.g. 110) in vitamin D synthesis. Dehydrobromination of the A -7-bromo system in the presence of mercuric chloride gives a high yield of A -diene. ... 

Pregnenolone acetate (111) is brominated to give the intermediate 7-bromo compound (112). This is dehydrobrominated in collidine to yield the title... 

A"" -3-Ketones are more reactive than cross-conjugated A ""-3-ketones. A"" -3,3-CycIoethylenedioxy compounds can be easily prepared by acid-catalyzed reaction with ethylene glycol or by exchange dioxolanation. 3,3-Cycloethylenedioxy-A -dienes can be prepared from 3,3-cycloethy-lenedioxy-A -enes by allylic bromination and dehydrobromination. Acid hydrolysis yields A"" -3-ketosteroids. ... 

The A -double bond can also be introduced in saturated A-nor-2-ketones by bromination-dehydrobromination. This has been used in an alternate preparation of A-norprogesterone" and in a recent synthesis of A-nor-19-nortestosterone. ... 

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