Primary alkyl halide

Alkylation (Section 22.12) Amines act as nucleophiles toward alkyl halides. Primary amines yield secondary amines, secondary amines yield tertiary amines, and tertiary amines yield quaternary ammonium salts. 

Aromatic ring. Must be at least as reactive as a halobenzene. Alkyl halide. Primary alkyl halides undergo carbocation rearrangement. 

Alcohols react with hydrogen halides (HX) to give alkyl halides. Primary alcohols undergo Sn2 reactions with HX. Primary alcohols with branching on the P-carbon give rearranged products. The temperature must be kept low to avoid the formation of E2 product. 

The nitrile route would involve an Sn2 displacement of bromide by cyanide, a highly unlikely step when the alkyl halide is tertiary. The Grignard route, on the other hand, works well for all alkyl halides—primary, secondary, and tertiary. 

The E2 reaction is the most effective for the synthesis of alkenes from alkyl halides and can be used on primary, secondary, and tertiary alkyl halides. The El reaction is not so useful from a synthetic point of view and occurs in competition with the SN1 reaction of tertiary alkyl halides. Primary and secondary alkyl halides do not generally react by this mechanism. 

In the presence of HMPA, Sml2 is a useful reagent for the reduction of alkyl halides. Primary, secondary and tertiary alkyl halides and alkenyl... 

Alkyl halides. Primary, secondary, and allylic alcohols are converted into halides by a Mitsunobu reaction (5, 728) with an added zinc halide. Yields are generally >70%, and are highest with zinc chloride. No other metal salts were found to be useful. 

Some alkyl halides (primary I, Br, Cl and secondary Br) are reduced by NaBH4 under phase-transfer conditions, as shown in equation (4). This reaction is carried out by the addition of a concentrated aqueous solution of NaBH4 to a stirred solution of substrate and catalyst in a suitable solvent, such as toluene. Yields are nearly quantitative in most cases, although an excess of sodium borohydride is required. 

H Hydrocarbon 1 H Alkyl halide. Primary H Primarr alcohol... 

The best results are obtained with the use of alkali metal hydrides (NaH, KH) in THF, DME, or DMF. The reaction works well in THF or DME with activated halides such as ethyl bromoac-etate, ten-butyl bromoacetate, - ethyl 2-bromobutyratc, ethyl T-broniobulyrale.- (iodom-ethyl)trimethylstannane, " (iodomethyl)trimethylsilane, benzoyl bromide,- benzyl bro-mide, - farnesyl bromide,- " alkyl 4-bromocrotonates, l-(bromomethyl)naphtalene,- andN-bromomethylphthalimide but gives poor results with primary alkyl halides.- Primary and secondary alkyl halides, bromides and iodides (Scheme 8.16), react satisfactorily in dMF or DMSO, although bulky electrophiles give poor results. In DMSO the expected product is frequently contaminated by the dialkylation product. ... 

Alkyl halides. Primary alci>h, Me2N=C(Cl)SPh]CI, to the chloride in ccondary hydroxyl groups. In the preseno... 

Alkyl halides. Primary alcohols are converted by this reagent, Mc2N=C(Cl)SPhlCl, to the chlorides in excellent yields without affecting unprotected secondary hydroxyl groups. In the presence of Bu4NBr, the bromides are obtained. 

Typically, the organic substrate in these reactions is an alkyl halide. Primary alkyl halides will generally give 100% substitution products, but tertiary and cyclohexyl halides usually undergo 100% elimination, with secondary halides producing a mixture of the two. Studies of the chloride and bromide displacements of (7 )-2-octyl methanesulfonate have shown that phase transfer displacements proceed with almost complete inversion of stereochemistry at the carbon centre, indicating an Sn2 mechanistic pathway [17]. 

Dehydrohalogenation of alkyl halides in the presence of strong base (E2) is often accompanied by the formation of substitution (Sn2) products. The extent of the competitive substitution reaction depends on the structure of the alkyl halide. Primary alkyl halides give predominantly substitution products (the corresponding ether), secondary alkyl halides give predominantly elimination products, and tertiary alkyl halides give exclusively elimination products. For example, the reaction of 2-bromopropane with sodium ethoxide proceeds as follows ... 

Substitution Reactions. The scope of substitution reactions possible with TMSA has been expanded beyond activated alkyl halides. Primary and secondary alkyl halides, phosphates, or tosy-lates are converted to the corresponding alkyl azides in 91-100% yields via reaction with TMSA induced by the fluoride anion (eq 12).2 .25... 

The Williamson synthesis usually involves the use of the sodium salt of the alcohol and an alkyl halide. Primary halides give the best... 

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