ALKYL IODIDES: NEOPENTYL

HEXAMETHYLPHOSPHORAMIDE 1-BENZYLINDOLE, 54, 60 ALKYL IODIDES NEOPENTYL IODIDE, IODOCYCLOHEXANE, 51,... 

Alkyl chlorides, from alcohols, benzyl diloride, and triphenyl phosphite, 51,47 ALKYL IODIDES NEOPENTYL IODIDE, lODOCYCLOHEX-ANE,51,44... 

ControUed-potential oxidations of a number of primary, secondary, and tertiary alkyl bromides at platinum electrodes in acetonitrile have been investigated [10]. For compounds such as 2-bromopropane, 2-bromobutane, tert-butyl bromide, and neopentyl bromide, a single Ai-alkylacetamide is produced. On the other hand, for 1-bromobutane, 1-bromopentane, 1-bromohexane, 1-bromo-3-methylbutane, and 3-bromohexane, a mixture of amides arises. It was proposed that one electron is removed from each molecule of starting material and that the resulting cation radical (RBr+ ) decomposes to yield a carbocation (R" "). Once formed, the carbocation can react (either directly or after rearrangement) with acetonitrile eventually to form an Al-alkylacetamide, as described above for alkyl iodides. In later work, Becker [11] studied the oxidation of 1-bromoalkanes ranging from methyl to heptyl bromide. He observed that, as the carbon-chain length is increased, the coulombic yield of amides decreases as the number of different amides increases. 

A general method fen the synthesis of alkyl iodides is the reaction of tosylates or methanesulfonates with sodium iodide in acetone or magnesium iodide in diethyl ether (equation 30). The reaction is not always a clean Sn2 process. Stereoselectively deuterated neopentyl tosylate, for example, gives with Nal in HMPA only low yields (34%) of the racemic iodide (equation 31). This is in contrast to analogous reactions with bromide and chloride (see Sections 1.7.3.2 and 1.7.2.2), where better yields with complete inversion are observed. 

Garst, J. F., Hart, P. W. Evidence against alkyl dimer formation through Sn2 processes in Wurtz reactions of alkyl iodides with sodium in 1,2-dimethoxyethane. Bineopentyl from neopentyl iodide. J. Chem. Soc., Chem. Common. 1975, 215-216. 

Landauer and Rydon describe the preparation of the reagent and its use for the conversion of alcohols to alkyl iodides. Kornblum and Iffland found neopentyl... 

With the exception of iodomethane (CH3I) and neopentyl iodide ((CH3)3CCH2l) all the reactions of 0( P) with the alkyl iodides were found to produce as major product an alkene. An example is shown for 1-iodobutane in Figure 9. Hypoiodous acid (HOI), the probable coproduct in each case, was also identified via its known infrared absorptions at 3620 and 1070 cm (Bames et al., 1992). This compound is, however, very short-lived under the conditions of the experiments and was only visible in the infrared spectrum in the initial stages of the reaction (Figure 10) and could therefore not be quantified. For many of the alkenes calibrated reference spectra were available and the yield of the alkene has been determined. Oxygen atoms also react fairly rapidly with alkenes, therefore, the reaction of O atoms with the alkenes has been taken into consideration when calculating the alkene yields from the O + Rl reactions. The yields and the identity of the alkene for the respective O + RI reactions are listed in Table 1. 

In cases where calibrated alkene spectra were not available identification of the alkene was based on the infrared spectra taken from the NIST infrared database. With the exceptions of iodomethane (CH3I) and neopentyl iodide ((CH3)3CCH2l) the yield of the alkene from the various alkyl iodides was substantial in every case and for some compounds approached, within the error limits, unit yield, e.g. iodoethane, 1,3-diodopropane and l-iodo-2-methylbutane. 

Acrylamide 1 was synthesized [4] and telomerized with four different alkyl iodides and allyltributylstannane (Fig. 3). GC and HPLC were used to determine selectiv-ities in the = 1 (2 and 3) and n = 2 products (4-7). For the n = 1 products, both diastereomers separated in all cases. However, for the n = 2 products, only the neopentyl-derived telomers (4a-7a) would separate by GC for all four diastereomers in all of the other telomer mixtures, two of the four diastereomers co-eluted or incompletely separated. The results are summarized in Table 2. 

Another interesting use of TEMPO has been in free-radical substitution of alkyl halides. In this reaction, halides react with tributyltin hydride and TEMPO to yield A-alkoxyamine substitution products [18. This reaction is especially attractive in cases where anionic nucleophiles are sterically prevented from carrying out substitution reactions. An example of this can be seen in Barrett s synthesis of sucrose [18b], in which a stereoselective iodoetherification reaction was used to produce neopentyl alkyl iodide 13 (Scheme 5). Free radical substitution mediated by tributyltin hydride and TEMPO yielded A-alkoxyamine 14. The mechanism [19] involves TEMPO abstraction of hydrogen from tributyltin hydride [20] the stannyl radical then abstracts iodide from the substrate, and a second equivalent of TEMPO traps the resulting carbon radical. 

Direct preparation of an alkyl iodide by reaction (a) neopentyl iodide, (CH3)3CCH2I 957,958 Methyl iodide (1.4 moles), triphenyl phosphite (1 mole), and neopentyl alcohol (1 mole) are heated in a bath for 24 h, whereby, owing to continuing consumption of methyl iodide, the internal temperature rises from 75° to 130°. The crude iodide and the phenol are distilled off in a vacuum and the distillate is washed with ice-cold, dilute NaOH solution, and water until free from phenol. The product contains about 6% of te/7-pentyl iodide,958 to remove which it is shaken for 5 h with three times its volume of water which is then discarded. The organic layer is next shaken with its own volume of O.lN-aqueous AgN03, washed with water, dried, and fractionated. This gives a 53-57% yield of iodide of b.p. 71°/100 mm. 

Lower alkyl iodides are obtained by treating the p-toluenesulfonates with concentrated aqueous potassium iodide (0.2 mole of KI in 10 ml of water) and are distilled off through a column continuously during the reaction. The aryl ester does not react with Nal in acetone. Although neopentyl iodide can be obtained from the p-toluenesulfonate and Nal,986 it is recommended987 that neopentyl bromide (86% yield) and chloride (60% yield) should be prepared by way of triethylneopentyloxysilane ... 

Preparation of Phosphines from Metallated Phosphines. - Alkali metal-free phosphide anions have been shown to be formed under synthetically useful conditions in the equilibria between primary or secondary phosphines with the Schwesinger bases (23). Techniques have been developed for the preparation of alkali metal diphenylphosphide reagents in high purity, as evidenced by P nmr studies. The same paper reports a study of the course of the reactions between potassium diphenylphosphide and a series of aryl-, n-alkyl- and neopentyl-halides. The results provide the first evidence of the involvement of single electron transfer (SET) processes in the reactions of alkyl halides. This pathway is dominant in the case of neopentyl-type iodides, but plays only a minor role in the related reactions of neopentyl-type bromides and chlorides. No evidence was adduced of the involvement of SET processes in the reactions of unhindered... 

Among the halides that react through this process are unactivated aromatic and heteroaromatic halides, vinyl halides, activated alkyl halides [nitroalkyl, nitroallyl, nitro-benzyl and other benzylic halides substituted with electron-withdrawing groups (EWG) as well as the heterocyclic analogues of these benzylic systems] and non-activated alkyl halides that have proved to be unreactive or poorly reactive towards polar mechanisms (bicycloalkyl, neopentyl and cycloalkyl halides and perfluoroalkyl iodides). 

Clearly, both spectra are of the tertiary 2-methylbutyl cation and the neopentyl cation never saw the light of day. The reaction is the same rearrangement that you saw in the substitution reaction of neopentyl iodide, but here the rate of rearrangement can be measured and it is extremely fast. Ncopentyl tosylate reacts to form a cation under these conditions about 104 times as fast as ethyl tosylate, even though both tosylates are primary. This massive rate difference shows that if migration of an alkyl group can allow rearrangement to a more stable carbocation, it will happen, and happen rapidly. 

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