Cycloalkyl bromide

Evidence for a free radical pathway in the foregoing cycloalkyl bromide reactions was secured by San Filippo and coworkers, who found that cis and iraws-4-r-butylcydohexyl bromide afford nearly identical product mixtures with MesSnLi, MesSnNa and MesSnK under a given set of conditions (Table 7)45. Of the various combinations examined, that of di-bromide and Me3SnLi appeared to be most favorable to S/v2 displacement. 

Several perfluoroalkyl and cycloalkyl bromides were tested for potential as oxygen carriers, blood substitutes, radiopaque agents, for other medical applications or as intermediates. Their LD50 toxicity data are listed in Table 14 (for additional information, see also ref 2). 

An effect of the ring-size in addition to that observed in the elimination taking place in the reduction of vicinal dibromides, has been observed for medium-sized ring compounds which carry the electro-active group either in the side-chain or directly attached to the ring. The half-wave potentials of cycloalkyl bromides can be correlated with the half-wave potentials of cyclic ketones and their derivatives (Fig. 29). The observed relation indicates that the relative effect of ring-size on the reactivity is similar in all the reaction series compared. 

Fig. 29. Dependence of half-wave potentials of cyclanones (1) their betainyl hydra-zones (3) and l-piperidinomethyl-2-cycloalkanones (2) on half-wave potentials of cycloalkyl bromides. Full points deviate...

Shifts of half-wave potentials towards more positive values in the presence of bulky groups can be explained in some cases also by changes in the mechanism of the electrode process. The most thoroughly studied example is the reduction of alkyl and cycloalkyl bromides (141). Departures of the half-wave potentials from predicted values for a-branched alkyl bromides, increasing in the sequence Et < — Pr nucleophilic substitutions. Hence a similar explanation, i.e. varying participation of SnI and 5N2-like... 

Reduction of aikyl halides. Allylic and benzylic chlorides and bromides are reduced by the reagent almost instantaneously at 25° (S 2 displacement). Simple primary halides are completely reduced in 2 min. Even neopentyl bromide is reduced to neopentane (96% yield) in 3 hr. under reflux. Secondary cycloalkyl bromides are reduced at 25° in 24 hr. Even CAro-2-bromonorbomane (I) can be reduced quantitatively. The... 

In alkyl and cycloalkyl bromides a complicating factor in the spectrum (Figures 12 and 13) is the presence of appreciable spin-orbit interaction which raises the degeneracy of... 

Olefins and allylic alcohols from alkyl or cycloalkyl bromides and from epoxides (general procedures The i-alkyl or cycloalkyl bromide is treated with sodium phenyl tellurolate (1 equiv from diphenyl ditelluride and NaBH, see Section 3.1.3.2). The crude telluride is purified by SiOj chromatography (elution with hexane) and converted into the corresponding dibromide by addition of bromine (1 equiv) in CCI4, at 0°C. Epoxides are converted into j8-hydroxylalkyl and )3-hydroxycycloalkyl phenyl tellurium dibromide by a similar procedure, except that the intermediate tellurides are chromatographed on SiOj using hexane/EtOAc (5 1) as the eluent. 

The data of Friswell et al. [51] for the reactions of the cycloalkyl bromides with sodium at 520°K can be compared with the competitive method data [35, 37] for the reaction of cycloalkyl chlorides with potassium at the same temperature (see Table 4). 

Diethylaminosulphur trifluroide converts cyclo-octanol into a mixture of cyclooctyl fluoride (70%) and ds-cyclo-octene (30%). Kinetic data suggests that there is considerable C—Br bond breaking in the transition state for abstraction of bromine from cycloalkyl bromides by phenyl radicals, and that anchimeric assistance by an adjacent bromine atom to bromine abstraction depends upon the accessibility of a trans-periplanar alignment of leaving and neighbouring groups. ... 

Hydroxy group of 8-hyd oxy-2-cycloalkyl-2,3,4,6,ll,lla-hexahydro-l//-pyrazino[l,2-i]isoquinoline-l,4-diones was alkylated with allyl bromide, 2-(bromodifluoromethyl)pyridines, l-(bromodifluoromethyl)- and l-(bro-momethyl)benzenes, halomethyl derivatives of different heterocycles (pyridine, pyrazine, pyrazole, pyrrole, thiazole, thiophene) in the presence of CS2CO3 or K2CO3 (98MIP7). Hydroxy group of 8-hydroxy-2-cyclopentyl-... 

The utility of SCFs for PTC was demonstrated for several model organic reactions - the nucleophilic displacement of benzyl chloride with bromide ion (26) and cyanide ion (27), which were chosen as model reversible and irreversible Sn2 reactions. The next two reactions reported were the alkylation and cycloalkylation of phenylacetonitrile (28,29). Catalyst solubility in the SCF was very limited, yet the rate of reaction increased linearly with the amount of catalyst present. Figure 5 shows data for the cyanide displacement of benzyl bromide, and the data followed pseudo-first order, irreversible kinetics. The catalyst amounts ranged from 0.06 (solubility limit) to 10% of the limiting reactant, benzyl chloride. 

The enthalpies of formation of the cycloalkylmagnesium bromides that have been determined by reaction calorimetry are listed in Table 3. As with other functionalized cycloalkanes and the cycloalkanes themselves, there is no regularity to these values with respect to carbon number as there are for their acyclic analogs because of the influence of ring strain on the enthalpies. Unfortunately, there are no enthalpies of formation for the bromocycloalkanes with which to compare these values there are, however, enthalpies of formation for liquid phase cycloalkanes. Figure 3 is a plot of the enthalpies of formation for the cycloalkyl-MgBr vs. those for cycloalkyl-H. There is a linear relationship with... 

The experimental enthalpies of protonation and the formal enthalpies of protonation, RMgBr —RH, are fairly constant for structurally similar species (R = cycloalkyl, primary alkyl) and would be expected to be constant also for the primary cycloalkyhnethyl-magnesium bromides. For the two examples just discussed, the formal enthalpies of protonation that are calculated using the derived enthalpies of formation for the cyclopropyl-and cyclobutylmethyhnagnesium bromides are 262 and 235 kJmoU, respectively. The mean value is thus 248 kJmoU, which is very close to that expected for the formal protonation of other primary R groups. 

Cycloalkyl and secondary alkyl bromides react with N02 BF4 in pyridinium poly(hydrogen fluoride) solution to yield /J-fluorinated compounds in moderate to good yields. In the case of the cyclic starting materials like 1-bromocyclohexane only trans-substituted products are formed (see Table 22). 

Reduction of aryl and alkyl halides. This reaction can be conducted in generally good yield with LiAlHi by a free-radical process initiated by irradiation of di-t-butyl peroxide. The order of reactivity of aryl halides is Arl > ArBr > ArCI > ArF. Alkyl and cycloalkyl halides are reduced efficiently, but vinyl bromides are reduced in only modest yield. 

With dibromoalkanes, the diethyl l,l-cycloalkyl-l-(ethoxycarbonyl)methylphosphonates are readily obtained by two successive alkylations in fair to good yields using NaH in THF-DMSO (Scheme 8.17), ° K2CO3 in MeCN-DMSO, NaOH (50%)/benzyl tributylammonium bromide or EtONa/EtOH, EtiO. By contrast, reaction of the potassium salt of diethyl 1-(ethoxycarbonyl)methylphosphonate with 1,3-dibromopropane leads to the formation of 1,2-oxaphosphorinane, resulting from alkylation at the methylene carbon and at phosphorus. ... 

Suitable substrates include alkyl, hen/.yl. ally I. cycloalkyl, vinyl, and aryl iodides, bromides, and... 

The replacement of OH on carbon adjacent to phosphorus by Br or I using allyl bromide or Mel in the presence of carbonyldiimidazole, has been reported. The electrolysis of diisopropyl (trichloromethyl)phosphonate in DMF containing the alkyl halide RX with a carbon cathode and magnesium anode affords diisopropyl (l,l-dichloroalkyl)phosphonates (132) interestingly, the corresponding diethyl esters may be reduced further. A similar reaction leading to (l-chloro-l-cycloalkyl)phosphonic diesters (133) has already been referred to. ... 

TABLE V. ORGANIC DERIVATIVES OF HALIDES A) Alkyl and cycloalkyl halides 2. Bromides a) Liquids (Listed in order of increasing atmospheric b.p.) ... 

In addition, during the course of recent mechanistic studies, new methodology for the functionalization of saturated hydrocarbons based on Gif-type protocol has been invented. These reactions are of interest as mechanistic probes and also from the point of view of synthetic utility. Thus, cycloalkanes are transformed with vaiying efficiency into mono-substituted cycloalkyl derivatives (chlorides, bromides, azides, cyanides, thiocyanates, dicycloalkyl sulfides, or nitroalkanes) by conducting iron or copper catalyzed reactions in the presence of alkali metal salts (scheme). 

Perfluoro- and polyfluoro-alkyl and -cycloalkyl chlorides, bromides, and iodides are encountered so often as starting materials, derivatives, solvents, products in mechanistic studies, by-products, etc., that it is impracticable to provide a comprehensive coverage of the relevant literature in one section. Readers with a particular interest in fluorocarbon halides are thus advised to browse widely through this volume. Additionally, some of the information collected on chloro- (including environmental effects), bromochloro-, and iodo-compounds has been relegated to appendices (pp. 43, 45, and 46). 

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