Alkyl bromide alkylation

Me3Si)3SiH and Ph4Si2H2 systems initiated by AIBN or Et3B also reduce alkyl iodides, alkyl bromides, alkyl xanthates, and alkyl selenides to the corresponding reduction products as shown in eq. 2.12. 

The yields and the ratios of the products depends on the scale at which the reactions arc carried out, on the molar ratios of the reactants, and on the nature of the alkyl halide. The yields of alkyl vinyl telluriums are two-times higher for reactions using 0.01 mol of alkyl halide than for reactions using 0.1 mol alkyl halide. The yields of alkyl vinyl telluriums were substantially increased by using a 10 1 molar ratio of tellurium/alkyl halide. The yields decrease in the sequence alkyl bromide alkyl iodide alkyl chloride. Primary and secondary alkyl bromides are equally reactive, tert.-Butyl bromide failed to give tert.-butyl vinyl tellurium2,3. 

Phosphorylation of alkyl bromides. Alkyl bromides react with 1 in refluxing DME to form an alkyl di-f-butyl phosphate, which is converted by TFA in benzene to a monoalkyl phosphate, usually isolated as the anilinium salt. ... 

Nal. Triphenyldibromophosphorane (Ph3PBr2) cleaves dialkyl ethers to give 2 moles of alkyl bromide. Alkyl aryl ethers can also be cleaved with Lil to give alkyl iodides and salts of phenols in a reaction similar to 10-51. Allyl aryl... 

Use Analytical chemistry, solvent for ore minerals, manufacture of inorganic and some alkyl bromides, alkylation catalyst. 

One of the reasons that the Staudinger reduction is such a powerful synthetic tool is the fact that azides can be introduced into a molecule fairly easily.1-2 In fact, some of the improvements to the Staudinger reduction over the years have included many one-pot protocols converting alkyl bromides, alkyl chlorides, alcohols, and acetates to azides followed by the in situ reduction to the corresponding amines using the Staudinger reaction. 

Reduction. This hydride reduces alkyl iodides to the alkane in quantitative yield at 25° (24 hours) alkyl bromides, alkyl chlorides, and aryl iodides are relatively inert under these conditions. It reduces enones predominantly by 1,2-addition. It reduces 4-t-butylcyclohexanone quantitatively the ratio of cis- to trans-alcohol is 83 17. When magnesium hydride is used for this reduction more of the trans-alcohol is obtained, the ratio being 24 76. 

Table 1 Electrophiles and organoboron reagents for Suzuki reactions of alkyl bromides, alkyl chlorides, and alkyl tosylates...

Alkyl bromides Alkyl chlorides 252,254,262-266 254,263,266-268 Arylalkythiocarbonamides 244,246,250, Dithioamides of dicarboxylic acids 284... 

On keeping the resin in contact with an aqueous phase, such as a solution of sodium cyanide, and an organic phase, such as an alkyl bromide, alkyl cyanides were formed by nucleophilic substitution (Scheme 13-6). The basic difference between the common heterogeneous catalytic reaction and the one being discussed is that in the latter, the catalyst and each pair of reactants are located in separate phases. 

Nucleophilic Substitutions.—Many of the nucleophilic substitutions covered by equation (1) can be catalysed as effectively in liquid-liquid two-phase systems by crown and cryptand compounds as by quaternary ions. Alkyl substitution on the basic crown skeleton of (28), as in (31), was found to increase the efficiency of catalysis for the conversion of alkyl mesylates to halides, presumably by ensuring partitioning of the crown-salt complex between the phases. A similar observation has been made using alkyl-substituted crown (32) and aza-crown compounds (33) as catalysts in two-phase reactions, for example between iodide, cyanide or thiocyanate aniohs and an alkyl bromide. Alkyl substitution in the macrobicyclic cryptands (34) has the same effect on Sn processes, and in all the above cases systems can be devised with catalytic efficiency comparable to or greater than that achieved by quaternary ion PTC. 

The Alkyl Halides. Ethyl bromide and iodide (see below) are typical alkyl halides. Compounds of this class are of very great importance in synthetic work, owing to the reactivity of the halogen atom. This is illustrated by the following reactions ... 

Alkyl and aryl iodides usually react with magnesium more rapidly than the corresponding bromides, and the bromides very much more rapidly than the chlorides. Aryl (as distinct from alkyl) chlorides have usually only a slow reaction with magnesium and are therefore very rarely used. With alkyl and aryl iodides in particular, however, a side reaction often occurs with the formation of a hydrocarbon and magnesium iodide ... 

Methyl iodide ethyl bromide ethyl iodide, higher alkyl halides, chloroform, iodoform, carbon tetrachloride, chlorobenzene, bromobenzene, iodobenzene, benzyl chloride (and nuclear substituted derivatives)... 

Alkyl fluorides may be prepared in moderate yield by interaction of an alkyl bromide with anhydrous potassium fluoride in the presence of dry ethylene glycol as a solvent for the inorganic fluoride, for example ... 

Mix 40 g. (51 ml.) of isopropyl alcohol with 460 g. (310 ml.) of constant boiling point hydrobromic acid in a 500 ml. distilling flask, attach a double surface (or long Liebig) condenser and distil slowly (1-2 drops per second) until about half of the liquid has passed over. Separate the lower alkyl bromide layer (70 g.), and redistil the aqueous layer when a further 7 g. of the crude bromide will be obtained (1). Shake the crude bromide in a separatory funnel successively with an equal volume of concentrated hydrochloric acid (2), water, 5 per cent, sodium bicarbonate solution, and water, and dry with anhydrous calcium chloride. Distil from a 100 ml. flask the isopropyl bromide passes over constantly at 59°. The yield is 66 g. 

Owing to the comparatively negligible difference in the cost of bromine and the equivalent quantity of constat boiling point hydrobromio acid, there is little to be gained—apart from the instructional value—in preparing the hydrobromio acid from bromine in the preparation of alkyl bromides. 

S-Alkyl-iso-thiuronium picrates. Alkyl bromides or iodides react with thiourea in alcoholic solution to produce S-alkyl-iso-thiuronium salts, which yield picrates of sharp melting point ... 

Place a mixture of 0-5 g. of finely powdered thiourea, 0-5 g. of the alkyl halide and 5 ml. of alcohol in a test-tube or small flask equipped with a reflux condenser. Reflux the mixture for a j)eriod depending upon the nature of the halide primary alkyl bromides and iodides, 10-20 minutes (according to the molecular weight) secondary alkyl bromides or iodides, 2-3 hours alkyl chlorides, 3-5 hours polymethy lene dibromides or di-iodides, 20-50 minutes. Then add 0 5 g. of picric acid, boil until a clear solution is obtained, and cool. If no precipitate is obtained, add a few drops of water. RecrystaUise the resulting S-alkyl-iso-thiuronium picrate from alcohol. 

Where R and R are identical, the dialkylmalonic ester may be prepared in one operation by treating 1 mol of ethyl malonate with 2 mots each of sodium ethoxide and the alkyl halide (usually bromide or iodide). 

A better method involves the interaction of an alkyl bromide and thiourea to form an alkyl tso-thiourea, followed by hydrolysis of the latter with sodium hydroxide solution, for example ... 

Pure dialkylanilines may be prepared by refluxing the monoalkylaniline (1 mol) with an alkyl bromide (2 mols) for 20-30 hours the solid product is treated with excess of sodium hydroxide solution, the organic layer separated, dried and distilled. The excess of alkyl bromide paases over first, followed by the dialkylaniline. Di-n-propylaniline, b.p. 242-243°, and di-n-butylaniline b.p. 269-270°, are thus readily prepared. 

Higher alkyl ethers are prepared by treating the sodium derivative of the phaiol (made by adding the phenol to a solution of sodium ethoxide in ethyl alcohol) with the alkyl iodide or bromide (Williamson synthesis), for example ... 

A solution of sodamide in liquid ammonia (essentially the amide NHj ion) is a very powerful alkylation catalyst, enabling condensations to be carried out with ease and in good yield which are otherwise either impossible or proceed with difficulty and are accompanied by considerable by-products. Thus 3-alkylpjTidines, otherwise inaccessible, are easily prepared from 3-picoline (see 3-n-amylpyridine in Section V,20). Also benzyl cyanide (I) and cyclohexyX bromide give a- r/ohexylphenylacetonitrile (II) ... 

It is of interest to note that by substituting alkyl bromides for cyciohexyl bromide the corresponding a-phenyl-a-alkyl-acetonitriles are obtained, which may be hydrolysed to the a-phenylaliphatic acids thus with ethyl iodide a-phenyl-lwt3Tonitrile is produced, hydrolysed by ethanoUo potassium hydroxide to a-phenylbutyric acid. 

Many organolithium compounds may be prepared by the interaction of lithium with an alkyl chloride or bromide or with an aryl bromide in dry ethereal solution In a nitrogen atmosphere ... 

Other alkylbenzenes may be prepared similarly by using the appropriate primary or secondary alkyl bromide. 

Alkylbenzenes are also obtained (but in somewhat lower yield) from phenyl-sodium and alkyl bromides. Thus ethylbenzene is produced from phenyl-sodium and ethyl bromide ... 

Further development How would you make TM 413 using the alkyl bromide you have just made This molecule is obviously on the way to a steroid and you can read more about it in Helv. Chim. Acta.. 1947, 3 1422 and J. Amer. Chem. Soc.. 1942, 974. 

Alkvl Azides from Alkyl Bromides and Sodium Azide General procedure for the synthesis of alkyl azides. In a typical experiment, benzyl bromide (360 mg, 2.1 mmol) in petroleum ether (3 mL) and sodium azide (180 mg, 2.76 mmol) in water (3 mL) are admixed in a round-bottomed flask. To this stirred solution, pillared clay (100 mg) is added and the reaction mixture is refluxed with constant stirring at 90-100 C until all the starting material is consumed, as obsen/ed by thin layer chromatographv using pure hexane as solvent. The reaction is quenched with water and the product extracted into ether. The ether extracts are washed with water and the organic layer dried over sodium sulfate. The removal of solvent under reduced pressure affords the pure alkyl azides as confirmed by the spectral analysis. ... 

The lithiation of allene can also be carried out with ethyllithium or butyl-lithium in diethyl ether (prepared from the alkyl bromides), using THF as a cosolvent. The salt suspension which is initially present when the solution of alkyllithium is cooled to -50°C or lower has disappeared almost completely when the reaction between allene and alkyllithium is finished. 

The alkylations proceeded much more slowly, when ethyl- or butyllithium in diethyl ether, prepared from the alkyl bromides, had been used for the metallation of allene, in spite of the presence of THF and HMPT as co-solvents. 

Alkylation of the dilithiated sulfide can be performed by adding at -10°C 0.12 mol of an alkyl bromide, allowing the temperature to rise to 20-30°C and hydrolyzing the reaction mixture after stirring for an additional 45 min at about 25°C. 

Note 1. Butyl- or ethyllithium in diethyl ether, prepared from the alkyl bromide, contains LiBr, which may react with chlorine to form bromine, so that RCeC-Br will also be formed. 

Lithium l,3-dithian-2-ides (p. 6, 8) may be alkylated with alkyl bromides or iodides. Steric hindrance is usually of little importance and the resulting ketone can be easily liberated by hydrolysis (D. Seebach, 1969). 

Anions of allylic thioethers may also be alkylated with alkyl bromides in high yield. The thioether groups can subsequently be removed by hydrogenolysis (F.W. Sum, 1979). 

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