Chlorination intramolecular

The haloalkane dehalogenase DhlA mechanism takes place in two consecutive Sn2 steps. In the first, the carboxylate moiety of the aspartate Aspl24, acting as a nucleophile on the carbon atom of DCE, displaces chloride anion which leads to formation of the enzyme-substrate intermediate (Equation 11.86). That intermediate is hydrolyzed by water in the subsequent step. The experimentally determined chlorine kinetic isotope effect for 1-chlorobutane, the slow substrate, is k(35Cl)/k(37Cl) = 1.0066 0.0004 and should correspond to the intrinsic isotope effect for the dehalogenation step. While the reported experimental value for DCE hydrolysis is smaller, it becomes practically the same when corrected for the intramolecular chlorine kinetic isotope effect (a consequence of the two identical chlorine labels in DCE). 

Pattison, D. I. and Davies, M. J. (2006). Evidence for rapid inter- and intramolecular chlorine transfer reactions of histamine and carnosine chloramines Implications for the prevention of hypochlorous-acid-mediated damage. Biochemistry 45, 8152-8162. 

Such normal free-radical substitution processes might be geometrically directed to otherwise unremarkable positions in substrates, as the benzophenone reactions had been. Consequently, in our first example, we found that intramolecular chlorination could be directed by attachment of a PhICl2 group to the steroid [156], i.e., compound 82 directed chlorination exclusively to C-14 (83), while 84 directed halogenation exclusively to C-9 (85). As shown in Scheme 1.1, an intramolecular hydrogen abstraction by... 

Intramolecular chlorine isotope effects have been determined in metastable ion decompositions induced by El of carbon tetrachloride, silicon tetrachloride, hexachloroethane and hexachlorosilane [687]. In all cases, the isotope effects were normal, i.e. losses involving the lighter isotope Cl were favoured. The loss of a chlorine atom from (CCl3) and from (SiCl4) showed isotope effects greater than 1.50. Other... 

We have largely been describing reactions on steroid substrates, which are conforma-tionally rigid and permit selective functionalizations by appropriate tethered templates. However, when the templates are linked to flexible chains, the results can be used to learn about the conformational preferences of such flexible chains. In one study [56], we examined the positional selectivities of insertion reactions into flexible chains by attached benzophenone units, a process we had also examined earlier [31], and compared the results with those from the intramolecular chlorination of such flexible chains by attached aryliodine dichlorides. The results were complementary. In another study [57] we used long-chain alkyl esters of nicotinic acid in radical relay chlorination, and saw some interesting selectivities reflecting conformational preferences in these nominally flexible cases. 

Deformylflustrabromine (235) can also be converted to flustramine C (236) on treatment with ferf-BuOCl (1 equiv.) in the presence of NEts in THE at —78°C. Here, it was possible to identify the first intermediate 243 of the reaction sequence, which was N-chlorinated in the side chain (Scheme 47). The reaction could proceed with intramolecular chlorination of the indole 3-position affording chloroin-dolenine 244. Alternatively, azetidine 245 could be formed by nucleophilic attack... 

Walling, C. and Padwa, A., Intramolecular chlorination with long chain hypochlorites, /. Am. Chem. Soc., 83, 2207, 1961. 

In principle, the direct hydride addition or catalytic hydrogenation, which did not give chlorins, was replaced by an electrocyclic intramolecular addition which is much easier with the above system. Complete regioselectivity was also achieved since electrocyclization did not occur with the resonance-stabilized ring C. 

A similar intramolecular oxidation, but for the methyl groups C-18 and C-19 was introduced by D.H.R. Barton (1979). Axial hydroxyl groups are converted to esters of nitrous or hypochlorous acid and irradiated. Oxyl radicals are liberated and selectively attack the neighboring axial methyl groups. Reactions of the methylene radicals formed with nitrosyl or chlorine radicals yield oximes or chlorides. 

In the case of carbon tetrachloride, the radical intermediate undergoes two competing reactions intramolecular hydrogen abstraction is competitive with abstraction of a chlorine atom from carbon tetrachloride ... 

To establish the nature of the chlorine migration (intramolecular or intermolec-ular), rearrangement of 54 was carried out in the presence of 4-(phenylethynyl)-1,3-dimethylpyrazole 55 (molar ratio of 54 55 = 2). About 40% of the chlorine migrates to the 5 position of the acceptor molecule 55 (Scheme 107). 

The mechanism for the transformation of 5 to 4 was not addressed. However, it seems plausible that samarium diiodide accomplishes a reduction of the carbon-chlorine bond to give a transient, resonance-stabilized carbon radical which then adds to a Smni-activated ketone carbonyl or combines with a ketyl radical. Although some intramolecular samarium(n)-promoted Barbier reactions do appear to proceed through the intermediacy of an organo-samarium intermediate (i.e. a Smm carbanion),10 ibis probable that a -elimination pathway would lead to a rapid destruction of intermediate 5 if such a species were formed in this reaction. Nevertheless, the facile transformation of intermediate 5 to 4, attended by the formation of the strained four-membered ring of paeoniflorigenin, constitutes a very elegant example of an intramolecular samarium-mediated Barbier reaction. 

As for chlorins and bacteriochlorins, reactions at the chromophore periphery of porphyrins can be used to prepare isobacteriochlorins. The lack of regioselectivity in these reactions necessitates the use of highly symmetric porphyrins as starting materials. In some cases, intramolecular reactions have been used to solve the problems of regioselectivity. 

There are no proven examples of 1,2-hydrogen atom shifts this can be understood in terms of the stereoelectronie requirements on the process. The same limitations are not imposed on heavier atoms (e.g. chlorine). The postulate309 that ethyl branches in reduced PVC are all derived from cbloroethyl branches formed by sequential 1,5-intramolecular hydrogen atom transfers as described for PE (Section 4,4.3.1) has been questioned.,6,6 It has been shown that many of these ethyl branches are derived from dichloroethyl groups. The latter are formed by sequential 1,2-chlorine atom shifts which follow a head addition (Section 4.3.1.2). 

Among the halogens, fluorine does not undergo rearrangement, and what evidence there is suggests that the rearrangement of chlorine is an intramolecular process (1,2 shift) whereas that of bromine appears to take place by both inter-and intramolecular routes. Less is known about iodine migration. 

An interesting way to control the stereoselectivity of metathesis-reactions is by intramolecular H-bonding between the chlorine ligands at the Ru-centre and an OH-moiety in the substrate [167]. With this concept and enantiomerically enriched allylic alcohols as substrates, the use of an achiral Ru-NHC complex can result in high diastereoselectivities like in the ROCM of 111-112 (Scheme 3.18). If non-H-bonding substrates are used, the selectivity not only decreases but proceeds in the opposite sense (product 113 and 114). 

Nitrogen mustards such as 23 decompose to yield aziridinium ions 24 (Scheme 8.14). " As in the case of sulfur mustards, the reaction involves rate-limiting intramolecular displacement of p-chlorine by nitrogen. The resulting aziridinium ions... 

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