Bromo compounds

All natural organobromocompounds are of marine origin and have been found especially in algae. The genus Laurencia has provided a series of brominated acetylenic cyclic ethers and bromosesquiterpenes, two of which, aplysin and aplysinol, were isolated earlier from the sea hare, Aplysia kurodai. Reviews by Scheuer 160) and Premuzic (752) may be consulted and also the more recent papers 87, 93, 102, 103, 107, 128, 129, 130). A brominated bicyclic diterpenoid, aplysin-20, with unusual stereochemical features has been also isolated from Aplysia kurodai 186), and more recently unique brominated and chlorinated monoter-penes have been obtained from A. californica 85) 86). Two of them were also found as components of an extract of the alga Plocamium coccineum 

C-Brst 700-500 Strong, of medium width absent in bromoaromaties 

Other 1080-1000 Strong, narrow or of medium width bromoaromaties 

C-I St C-I 8 650-450 300-50 Strong, two or more bands Of medium strength and width  

79 C6H7+ C5HsN+- Br+ aromatics with H-containing substituents pyridines, pyrroles bromo compounds (together with isotope signal for SlBr) 

80 C6H8+- C5H40+- HBr+ C5H6N+ cyclohexenes, polycyclic alicyclics cyclopentenones bromo compounds pyrroles, pyridines 

81 C6H9+ C5H5O+ cyclohexanes, cyclohexenyls, dienes furans, pyrans 

83 C6H11 + C5H7O+ alkenes, alicyclics, monosubstituted alkanes cycloalkanones 

85 C6H13- C5H9O+ CCIF2+ alkanes alkanones, alkanals, tetrahydropyrans, fatty acid derivatives chlorofluoroalkanes (with isotope signal at m/z 87) 

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On adding i drop of bromine water to catechol, a deep red coloration is produced immediately. On gradually adding bromine water to a solution of hydroquinone, a deep red coloration is produced, followed by the separation of deep green crystals which then dissolve giving a yellow solution, i- and 2-Naphthol will decolorise hromine water, but usually no precipitate of the bromo compound can be obtained. 

The test is not verv satisfactory with those phenols which arc Insoluble in water, owing to the difficulty of distinguishing the bromo compound from the original phenol. 

In the preparation of bromo compounds by the Sandmeyer reaction, the amine is generally diazotised in sulphuric acid solution (or in hydrobromic acid solution), and the resulting aryldiazonium sulphate (or bromide) is treated with a solution of cuprous bromide in excess of hydrobromic acid the addition... 

An alternative procedure, more suitable for the preparation of somewhat larger quantities of the bromo derivative, is the following. Dissolve 10 g, of the compovmd in 10-15 ml. of glacial acetic acid, cautiously add 3-4 ml. of hquid bromine, and allow the mixture to stand for 15-20 minutes. Pour into 50-100 ml. of water, filter off the bromo compound at the pump, and wash with a httle cold water. Recrystallise from dilute alcohol. 

That aqueous layer that was saved can be removed of most of its water by vacuum distillation, allowed to cool slightly then extracted with hot toluene. When the toluene cools, a few hundred more grams of catechol will crystallize out but will be contaminated with some heavy red bromo compounds. The crystals are filtered and vacuum distilled such that the pyrocatechol will distill over first, leaving the higher boiling bromo compounds behind. Yield is about 80% or 600g of catechol. 

The preparation of the bromobenzodioxole or bromobenzene is going to be the same no matter which one is used and no matter which precursor the chemist wishes to make. This means that this first part needs to be done correctly. This first part of preparation that Strike is talking about is the creation of a Grignard reagent out of the bromo compound starting material [125,131-134]. Mr. Grignard earned a Nobel prize for this in 1912 so you can bet that it s a pretty good procedure. 

Bromination occurs on the 5-positton of the ring the bromo compound... 

As a further electrophilic substitution the bromination of selenazoles has been investigated. This is not as complicated as nitration. Bromination was carried out in several solvents and with various amounts of bromine. In spite of the great variation in conditions, monobromo derivatives containing the bromine atom in the 5-position are always formed. This could be established, for example, by the bromination of the 2-amino-4-p-nitrophenylselenazole (Scheme 34) and its 2-benzamino compound (98). The 2-benzamido bromo compound gives the same bromo... 

The synthesis of sulfides (172) can be carried out by condensing 2-mercaptothiazoles and the required o-bromo compounds in basic solution at room temperature (488). 

Alkali metal and other iodides are effective catalysts in reactions involving aUphatic chloro and bromo compounds, such as the preparation of cyclopropane from 1,3-dichloropropane andmetaUic 2inc (141). 

Organic compounds of bromine usually resemble their chlorine analogues but have higher densities and lower vapor pressures. The bromo compounds are more reactive toward alkaUes and metals brominated solvents should generally be kept from contact with active metals such as aluminum. On the other hand, they present less fire hazard one bromine atom per molecule reduces flammabiUty about as much as two chlorine atoms. 

A thiocyanato group can be introduced by treatment of the corresponding chloro or bromo compounds with ammonium, sodium or potassium thiocyanate. In polychloro compounds only one halogen is replaced. 

Bromination of 1,2-benzisoxazoles gave primarily the 5-bromo derivative, although other isomers have also been reported (67AHC(8)277). Bromination of 5-methoxy-3-methyl-l,2-benzisoxazole at room temperature gave a mixture of the 4- and 6-bromo compounds, while at elevated temperatures a 4,6-dibromo compound was produced (Scheme 27) <79IJC(B)371). 

Methyl-2,l-benzisoxazole and its 6-methoxy derivative are both readily brominated at the 3-methyl group with NBS (79TL4687, 74RTC139). The 4-methoxy isomer gives only the 7-bromo compound unless excess of the reagent is used, when 7-bromo-3-(bromomethyl)-2,l-benzisoxazole is obtained in 52% yield (74RTC139). However, there is... 

Other direct methods for the sulfonation of the higher fatty acids are by the use of sulfur trioxide vapor or by the use of chlorosulfonic acid. Indirect methods are also available for the preparation of a-sulfo fatty acids and their salts from an a-bromo fatty acid made by the Hell-Volhard-Zelinsky reaction. The bromo compound may be converted directly to the sodium salt of a sulfonic acid through the Strecker reaction or may be converted to the mercaptan and oxidized to the sulfonate. Sulfonation of the lower fatty acids has been studied by Backer and co-workers. ... 

Liebbrandt have prepared arecaidine by bromination of methyl jV-methylpiperidine-3-carboxyIate, scission of hydrogen bromide from the resulting bromo-compound (VI) and hydrolysis of the resulting arecoline, but Preobrachenski and Fischer were unable to confirm this observation. 

This synthesis came shortly after one by Prelog, Kohlberg, Cerkovnikov, Rezek and Piantanida (1937) based on a series of reactions which, with modifications and extensions. Prelog and his colleagues have applied to the syntheses of bridged heterocyclic nuclei, of which this is an example. 4-Hydroxymethyltetrahydropyran (VI R =. OH) is converted via the bromo-compound (VI R = Br) and the nitrile (VI R = CN) into tetrahydropyran-4-acetic acid of which the ethyl ester (VII) is reduced to 4-()3-hydroxyethyl)-tetrahydropyTan (VIII). This is converted by fuming hydrobromic acid into 3-(2-bromoethyl)-l 5-dibromopentane (IX) which with ammonia in methyl alcohol yields quinuclidine (V). 

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 ... 

It has already been mentioned that monobromination of 5a-3-ketones gives 2a-bromo compounds (18). Further bromination occurs under acidic or distinctly basic conditions (the reaction is not satisfactory in weakly basic... 

Bromination of 5j5-3-ketones yields the equatorial 4 -bromo compounds (22) as the thermodynamic or kinetic products,although the presence of a considerable amount of 2-bromo isomer has been reported in bromination with phenyltrimethylammonium bromide-perbromide. This is in keeping with other evidence that enolization of 5j5-3-ketones is not specifically directed to C-4. Cleaner results would probably be obtained via thermodynamic enol acelylation. ... 

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... 

A" -3-ketones from 4-bromo compounds in the 5j5-series. Frequently it is necessary to prepare A -B-ketones from starting materials with the 5a stereochemistry, and this has to be done indirectly. (See sections Ill-C and VI-B for conversion of 5jS-3-ketones into A -3-ketones.) The Syntex group has devised a method of doing this via the thermodynamically stable 2a,4a-di-bromo derivatives. 

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 ... 

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). ... 

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