Alkyl chlorides, bromides and iodides

Cuprous iodide catalyzes the reaction of various alkyl chlorides, bromides, and iodides in hexamethylphosphoric triamide (HMPT), to give the complexed product RaSnXj, which can then be further alkylated with a Grignard reagent, or can be hydrolyzed to the oxide and converted into various other compounds, R2SnY2 (43). This promises to be a useful laboratory method, e.g.,... 

In general, higher alkyl chlorides, bromides, and iodides are all liquids and tend to have boiling points near those of alkanes of similar molecular weights. 

This microwave-accelerated double alkylation reaction was applicable to a variety of aniline derivatives and dihalides, furnishing N-aryl azacycloalkanes in good to excellent yields [89]. The reaction was applicable to alkyl chlorides, bromides and iodides and was extended to include hydrazines [90]. This improved synthetic methodology provided a simple and straightforward one-pot approach to the synthesis of a variety of heterocycles such as substituted azetidines, pyrrolidines, piperidines, azepanes, N-substituted-2,3-dihydro-Iff-isoindoles, 4,5-dihydro-pyrazoles, pyrazolidines, and 1,2-dihydro-phthalazines [91]. The mild reaction conditions tolerated a variety of functional groups such as hydroxyls, carbonyls, and esters. 

The method is an extension of the well-known Grignard synthesis in ethers to the use of nonsolvating media, and is a development of procedures previously reported.2-6 A version of it has been employed with straight-chain primary alkyl chlorides, bromides, and iodides from C2 to Cu,5-7 and in solvents (or an excess of the halide) which permit reaction temperatures above 120°, with simple aryl halides such as chlorobenzene and 1-chloro-naphthalene. Branched-chain primary, secondary, and tertiary alkyl halides, allyl, vinyl, and benzyl halides either fail to react or give extensive side reactions. Better results are reported to be obtained in such cases with the use of catalytic quantities of a mixture of an alkoxide and an ether such as diethyl ether or tetrahydrofuran in a hydrocarbon medium, but the products are not, of course, completely unsolvated.4... 

Oxidative metabolism of alkyl chlorides, bromides and iodides is initiated primarily by insertion of an oxygen atom into an a-C—H bond. The geminal halohydrin product rapidly loses hydrogen halide to form a carbonyl compound (an aldehyde, ketone, acid chloride or carbonyl chloride, depending on substrate structure). 

Aliphatic halides react easily with disodium ditelluride to yield dialkyl ditellurium compounds. Although a systematic investigation of this reaction has not yet been carried out, primary alkyl chlorides, bromides and iodides, and secondary alkyl bromides produce the corresponding dialkyl ditellurium derivatives in good yields. 

Alkyl chlorides, bromides, and iodides undergo metal insertion reactions with Li, Mg, and Zn, just as aryl and alkenyl halides do. The reaction is more facile for heavier halogens. 

Vogel, A.I. Physical Properties and Chemical Constitution. Part VIII. Alkyl Chlorides, Bromides and Iodides Journal of the Chemical Society (1943) 636-647... 

Alkyl chlorides, bromides and iodides can be formed by the reaction of alcohols with p-toluenesulfonyl chloride (or tosyl chloride, abbreviated as TsCl) in the presence of a nitrogen base (e.g. triethylamine or pyridine). The OH group is converted into a tosylate (abbreviated as ROTs), which can be displaced on reaction with CF, BF or I-. The stable tosylate anion is an excellent leaving group (SN1 or SN2 mechanism depending on the nature of the alkyl group, R). 

There are no data on Grignard reactions that suggest mechanistic differences among typical alkyl chlorides, bromide, and iodides or among typical primary, secondary, and tertiary halides. All react at similar rales, with chlorides being somewhat slower than bromides and iodides, and all give similar distributions of products of r and c. 

Alkyl chlorides, -bromides, and -iodides can be converted to tri- or tetrasulfanes by treatment with elemental sulfur at 20 °C in the presence of KOH and traces of water methyl-, ethyl-, isopropyl-, and allylpolysulfanes have been prepared in this manner. Sometimes hydrazine is added to reduce Sg to polysulfide anions. ... 

Another very interesting point in connection with the reactions of the alkyl chlorides, bromides and iodides, is the fact that the iodides show a tendency to give a larger yield of olefin than do the chlorides in the presence of alkali [A. Lieben and A. Rossi, Lieb. Ann. 158, 164 (1871)]. This is the opposite to what would have been supposed from the behavior of the halides in the presence of catalysts such as aluminium chloride. Furthermore, the chlorides yield ether more readily than do the corresponding bromides or iodides [M. Wildermann, Z. phys. Chem. 8, 661 (1891) and S. Brussow, Ibid. 34, 129 (1900)]. 

It should be noted here that iron can catalyze the cross-coupling of arylmagnesium reagents with alkyl chloride, bromides and iodides even in the absence of supporting ligands. Thus, Bedford revealed that iron nanoparticles , produced by the reduction of FeCls with organomagnesium compounds in the presence of polyethylene glycol (PEG 14000), can catalyze the arylation of cyclohexyl chloride in 77% yield (Equation 5.33) [40]. 

In alkyl chlorides, bromides, and iodides the carbon-halogen bonds (C—X) are weaker than either the C-C or the C-H bonds. During irradiation mostly carbon—halogen dissociation occurs forming alkyl radical and X or X (Spinks and Woods 1990). Reaction (O 23.90) is due to the high electron affinity of Cl, Br, and I atoms, 3.61, 3.36, and 3.06 eV, respectively. 

Methods reported this year for the reduction of alkyl halides to alkanes include the potassium-dicyclohexyl-18-crown-6 reduction of alkyl fluorides, sodium borohydride reduction of alkyl chlorides, bromides, and iodides (or sulphonate esters) under liquid-liquid phase-transfer conditions, and the selective reduction of tertiary alkyl, benzyl, and allyl halides with the borate (61). Continuing... 

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,... 

The Hunsdiecker Reaction. The classical Hunsdiecker reaction is somewhat restricted due to the relatively harsh conditions required. In the Barton version, alkyl radicals generated from O-acyl thiohydroxamates, under either thermal or photolytic conditions, are efficiently trapped either by CI3C-X (X=C1 or Br CbC is the chain carrier) or by IodoformThe method is applicable to sensitive substrates for which the classical methods are unsuitable. thus allowing the preparation of a wide range of alkyl chlorides, bromides, and iodides by the one-carbon degradation of a carboxylic acid. Similar reactions of aromatic acid derivatives tend to require an additional radical initiator (e.g. Azo-bisisobutyronitrile), if high yields (55-85%) are to be obtained. ... 

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