Bromides, preparation from alcohols

To a mixture of 100 ml of THF and 0.10 mol of the epoxide (note 1) was added 0.5 g Of copper(I) bromide. A solution of phenylmagnesium bromide (prepared from 0.18 mol of bromobenzene, see Chapter II, Exp. 5) in 130 ml of THF was added drop-wise in 20 min at 20-30°C. After an additional 30 min the black reaction mixture was hydrolysed with a solution of 2 g of NaCN or KCN and 20 g of ammonium chloride in 150 ml of water. The aqueous layer was extracted three times with diethyl ether. The combined organic solutions were washed with water and dried over magnesium sulfate. The residue obtained after concentration of the solution in a water-pump vacuum was distilled through a short column, giving the allenic alcohol, b.p. 100°C/0.2 mmHg, n. 1.5705, in 75% yield. 

Both reactants m the Williamson ether synthesis usually originate m alcohol pre cursors Sodium and potassium alkoxides are prepared by reaction of an alcohol with the appropriate metal and alkyl halides are most commonly made from alcohols by reaction with a hydrogen halide (Section 4 7) thionyl chloride (Section 4 13) or phosphorus tri bromide (Section 4 13) Alternatively alkyl p toluenesulfonates may be used m place of alkyl halides alkyl p toluenesulfonates are also prepared from alcohols as their imme diate precursors (Section 8 14)... 

Bromides can be prepared from alcohols in a one-step process. 

Fig (20) Bromide (172), prepared from alcohol (171) on alkylation yields (173) which is converted to (174) without any difficulty. Conversion of (174) to homoallylic bromide (175) is accomplished by the method of Julia. On alkylation followed by cyclization generated the tricyclic alcohol which undergoes dehydration to yield unsaturated ester (177) which is converted to unsaturated lactone (146) by epoxidation and elimination. 

Phenyl selenides are prepared from alcohols and PhSeCN in presence of Bu3P and then brominated by Br2/Et3N to yield the corresponding bromides. Both steps proceed with inversion of configuration resulting in overall retention of configuration at the substituted carbon atom (equation 146)962. 

Iodomercuri-2-methylthiophene, prepared in a similar manner to the bromide, crystallises from alcohol in silvery needles melting at 111° to 112° C. It is readily soluble in cold ethyl acetate or benzene, less so in acetone unless heated. 

Bicyclopropylidene has also been prepared from alcohol 2 via the tosylate instead of the bromide (see Section 5.2.2.3.). ... 

It is evident that if a mixture contains two or more constituents which are members of the same class of compounds or are soluble in the same reagents, separation can not be effected in the way outlined. In such cases fractional distillation or crystallization must be resorted to. A thorough knowledge of the properties of compounds is of great value in the examination of mixtures, and is of service in the purification of compounds. The purification of ethyl bromide prepared from potassium bromide, alcohol, and sulphuric acid, is an example. The bromide prepared in this way may contain ether, which is separated with difficulty from the halide by distillation. When the mixture is shaken with concentrated sulphuric acid, the ether dissolves and the bromide is unaffected. In effecting the separation of compounds it is often necessary to convert them into other substances. Thus, acetone can be separated from many other substances which are soluble in water by converting it into the difficultly soluble addition-product with sodium hydrogen sulphite. 

Chapleur et al. [24] described a concise synthesis of i-glycero-D-tnanno-heptose from readily available aldehyde 23 previously prepared from alcohol 22 (Scheme 2.7). The condensation of aldehyde 23 with commercial vinylmagnesium bromide afforded a single alcohol 40 in 83% yield (Scheme 2.10). The benzylation of allylic alcohol 40 followed by oxidative cleavage of the double bond and reductive workup gave alcohol 41 which was further elaborated into L-glycero-D-manno-heptose 11 in 38% overall yield, after deprotections. 

The conversion of alcohols to iodides with inversion using triphenylphosphine-iodine-imidazole, or triphenylphosphine-2,4,5-tri-iodoimidazole, (4,157) has now been described in detail. The purity and yield of tertiary iodides (or bromides) prepared from the alcohols and aqueous HI (or HBr) at 0 can be improved by addition of lithium or calcium halides it is believed the metal salts retard competing hydrolysis of the tertiary halides. Secondary alkyl bromides have been prepared from the alcohols with retention of configuration via the inverted selenides (Scheme 35). Two other new reagents for the... 

Preparation.— The 2-alkoxydiazaphospholidines (55), mentioned earlier in this Report, have been prepared from alcohols and their facile conversion into alkyl chlorides, bromides, and iodides with inversion of configuration at carbon has been reported (Scheme 34) a one-pot procedure is suggested for the transformation of an alcohol into an alkyl iodide. Tributyldi-iodophosporane, BU3PI2,... 

Owing to the corrosive action of bromine upon corks j-jg 7, l. and rubber stoppers, ground glass joints are recommended in this preparation. The apparatus, depicted in Fig. Ill, 37, 1, is particularly convenient for the preparation of bromides from alcohols. A double surface condenser is fitted into D and a round-bottomed flask is fitted on to the ground glass joint at C R is a three-way stopcock f which permits the removal of the contents of A without disconnecting the apparatus. For preparations of moderate size, A has a capacity of 60 or 100 ml. and a 250 or 500 ml. flask is attached at C. 

Add 4 0 g. (4 0 ml.) of pure anihne dropwise to a cold solution of ethyl magnesium bromide (or iodide) prepared from 1 Og. of magnesium, 5 0 g. (3-5 ml.) of ethyl bromide (or the equivalent quantity of ethyl iodide), and 30 ml. of pure, sodium-dried ether. When the vigorous evolution of ethane has ceased, introduce 0 02 mol of the ester in 10 ml. of anhydrous ether, and warm the mixture on a water bath for 10 minutes cool. Add dilute hydrochloric acid to dissolve the magnesium compounds and excess of aniline. Separate the ethereal layer, dry it with anhydrous magnesium sulphate and evaporate the ether. Recrystallise the residual anihde, which is obtained in almost quantitative yield, from dilute alcohol or other suitable solvent. 

In the flask were placed 0.40 mol of dry, powdered copper(I) cyanide, 9 g of anhydrous lithium bromide (note 1), 50 ml of dry THF and 0.30 mol of l-bromo-2--heptyne (prepared from the corresponding alcohol and PBrs in diethyl ether, see VIII-2, Exp. 10). The mixture was heated until an exothermic reaction started, which occurred at about 80°C. The solid dissolved gradually. The mixture was kept... 

AHylestrenol (37) is prepared from (32), an intermediate in the synthesis of norethindrone. Treatment of (32) with ethanedithiol and catalytic boron trifluoride provides a thioketal. Reduction with sodium in Hquid ammonia results in the desired reductive elimination of the thioketal along with reduction of the 17-keto group. Oxidation of this alcohol with chromic acid in acetone followed by addition of aHyl magnesium bromide, completes the synthesis... 

Adamantylamine is prepared from the corresponding alcohol or bromide by bridgehead cation generation in the presence of acetonitrile (49). Selective hydrolysis of the resultant acetamide to the rigid cycloahphatic amine by acid or base is difficult. 

This ether was prepared from an alcohol and 2-(phenylselenyl)ethyl bromide (AgN03, CH3CN, 20°, 10-15 min, 80-90% yield) it is cleaved by oxidation (H2O2, 1 h ozone or NaI04), followed by acidic hydrolysis of the intermediate vinyl ether (dil. HCl, 65-70% yield). ... 

The p-cyanobenzyl ether, prepared from an alcohol and the benzyl bromide in the presence of sodium, hydride (74% yield), can be cleaved by electrolytic reduction (—2.1 V, 71% yield). It is stable to electrolytic removal ( — 1.4 V) of a tritylone ether [i.e., 9-(9-phenyl-10-oxo)anthiyl ether]. ... 

The M-hexyl bromide may be prepared from redistilled -hexyl alcohol by the red phosphorus-bromine procedure or may be purchased from Eastman Kodak Company. 

Sylvestrene tetrabromide, CjoHjf.Br, is prepared when pure sylvestrene, regenerated from its ihydrochloride and dissolved in acetic acid, is heated with bromine until a permanent yellow colour is produced. Water is added to the reaction product, but not sufficient to precipitate the bromide, and the vessel allowed to stand in a cold place. The bromide separates and can be purihed by recrystallisation from alcohol. It forms mono-symmetric crystals melting at 135° to 136°, and having a specihc rotation -t- 73 7°. 

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