Benzylic chlorination

Grafting on the resin was achieved via a nucleophilic substitution of the benzylic chlorine by the deprotonated OH-linker of 52 (Scheme 29) by using a mixture of KO Bu, 18-crown-6 and CsBr. Determining the nitrogen content of solid phase samples by elemental analyses was accomplished, to verify the functionalization of the polymer. This enables calculation of the degree of functionalization. Usually, an occupancy of more than 20 percent of the theoretical sites was achieved. Saponification of the functionalized Merrifield resin P-52 leads to the monoanionic NJ, 0 functionalized solid phase. Subsequent reaction with [ReBrtCOlsJ afforded the polymer mounted tricarbonyl rhenium complex P-52-Re (Scheme 29). 

Benzylic halides are reduced very easily using complex hydrides. In a-chloroethylbenzene lithium aluminium deuteride replaced the benzylic chlorine by deuterium with inversion of configuration (optical purity 79%) [537]. Borane replaced chlorine and bromine in chloro- and bromodiphenylme-thane, chlorine in chlorotriphenylmethane and bromine in benzyl bromide by hydrogen in 90-96% yields. Benzyl chloride, however, was not reduced [5iSj. Benzylic chlorine and bromine in a jy/n-triazine derivative were hydrogeno-lyzed by sodium iodide in acetic acid in 55% and 89% yields, respectively [5i9]. 

The percent of the benzyl chlorines replaced in the reaction was referred to as percent functionalization and was controlled via the reaction time. Figure 3 contains the data of percent functionalization versus time for a number of functionalized membranes. 

Figure 3. The percent of benzyl chlorines replaced in a reaction with trimethyl phosphite as a function of reaction time (measured by weight gain). The reaction time is measured from the time the reaction bath reached 100°C.

Side-chain chlorination of alkylarenes. The reagent effects benzylic chlorination of alkylarenes in CC14 in the presence of AIBN. The co-product is CH,).,NBz1IC12-. 

NaX (13X) zeolite is the catalyst of choice for benzylic chlorinations while zeolites with high Bronsted acidity (ZF520) affected ring chlorination, even though X-ray diffraction studies have later shown that the zeolite lattice collapses under the reaction conditions127. In both instances the mechanism involves active site outside the channel network of the microporous solid. Contradictory to the latter authors, Delude and Laszlo suggest that aluminum-rich zeolites would preferably initiate radical chain reaction via formation of siloxy radicals. Both the reaction medium and substituents on the aromatic substrate have a profound effect on the rate and selectivity of these reactions. Interestingly, the catalyst applied in the radical chlorinations can be easily recycled and reused. The opposite has been observed in the ionic chlorinations where the catalyst has rapidly lost its activity. 

The woik of Tuleen and Stevens on the regioselectivity of chlorination of a series of unsymmetrically substituted dialkyl sulfides with NCS provides clues to Ae directive effects implicit in the mechanisms encompassed by Scheme 3. These observations are collected in Scheme 6 where the preferred site of chlorination in each case is indicated with an arrow, the number over the arrow indicating the majortminor product ratio (minor = 1). In the first example, chlorination of benzyl methyl sulfide (2) produces chlorobenzyl methyl sulfide exclusively. Secondly, chlorination of benzyl ethyl sulfide (3) and benzyl isopropyl sulfide (4) also shows a marked, though not exclusive, preference for the benzylic position. In the latter case the extent of benzylic chlorination can be modulated by ring substitution. The directive effects in these internal competitions for p-methyl and p-chloro substituents are correlated by the Hammett relationship with a value of p = 1.0, which is consistent with a mechanism involving abstraction of the more acidic proton in the chlorosulfonium ion intermediate. Further indications of the im-... 

Scheme 24. A Synthesis of benzyl chlorine-based ATRP macroinitiators from A vinylsilyl- ...

Isotope effect and relative rate studies also suggest an early TS for benzylic chlorination and bromination. The benzylic position is only moderately activated toward uncomplexed chlorine atoms. Relative to ethane, toluene reactivity is increased only by a factor of 3.3. The kinetic isotope effect observed for bromination and chlorination of toluene suggest little rehybridization at the TS. 

Kunz and Kirschning developed a chemically functionalized monolithic material which is based on a glass/polymer composite [28,29] (refer to Sect. 3.1). This material is available in different shapes including rods, disks, and Raschig rings. The polymeric phase of this composite was chemically functionalized (e.g., substitution of the benzylic chlorine by trimethylamine or sulfonation). Rod-shaped objects were first embedded in a solvent-resistant and shrinkable PTFE tube. This was followed by encapsulation with a pressure-resistant fiber-reinforced epoxy resin housing with two standard HPLC fittings, which created... 

Figure 5. Calculated carbon-14 (upper curves) and chlorine-37 (lower curves) isotope effects for displacement on benzyl chlorine by oxygen, chlorine, and sulfur as a function of bond order...

Benzylic chlorination of methylbenzene takes place in the gas phase at 400-600 °C or in the presence of UV light. When an excess of chlorine is used, multiple chlorinations of the side chain occur ... 

We have already seen in this chapter that we can substitute bromine and chlorine for hydrogen atoms on the benzene ring of toluene and other alkylaromatic compounds using electrophilic aromatic substitution reactions. We can also substitute bromine and chlorine for hydrogen atoms on the benzylic carbons of alkyl side chains by radical reactions in the presence of heat, light, or a radical initiator like a peroxide, as we first saw in Chapter 10, (Section 10.9). This is made possible by the special stability of the benzylic radical intermediate (Section 15.12A). For example, benzylic chlorination of toluene takes place in the gas phase at 400-600 °C or in the presence of UV light, as shown here. Multiple substitutions occur with an excess of chlorine. 

The question of ami nation of aromatics by protonated amino radicals has been examined extensively by Minisci and co-workers (16). Benzene is aminated in good yields by a variety of N-chloroamines in acidic solutions, catalyzed by Iron(II) sulfates. With activated aromatics competing chlorination and sulfonation complicates the reactions, but In many cases good yields of the substituted anilines are obtained. In the case of a1kylbenzenes, benzylic chlorination competes with nuclear amlnatlon. The latter is favored by high acid concentrations. Thus, the reaction of toluene with N-chlorodimethyl amine (17) gives 95 percent amination and 6 percent benzylic chlorination in neat H SO., but 100 percent benzylic chlorination In neat acetic acid. The amount of nuclear amination increases with the concentration of H2SO4 in acetic acid. 

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