Alkyl hypohalites, reactions

This alkoxyfluorination leads to alkoxy fluoro and difluoro compounds. The product distribution depends on the reaction conditions. Similarly, fluoro halides are obtained in addition to alkoxy halides using a combination of boron trifluoride and alkyl hypohalite.50... 

Other alkyl hypohalites usually add to carbon-carbon multiple bonds in a free-radical process.155-158 Ionic additions may be promoted by oxygen, BF3, or B(OMe)3.156-160 While the BF3-catalyzed reaction of alkyl hypochlorites and hypo-bromites gives mainly halofluorides,159 haloethers are formed in good yields but nonstereoselectively under other ionic conditions.156-158 160 In contrast, tert-BuOI reacts with alkenes in the presence of a catalytic amount of BF3 to produce 2-iodoethers.161 Since the addition is stereoselective, this suggests the participation of a symmetric iodonium ion intermediate without the involvement of carbocationic intermediates. 

The photolysis of alkyl hypohalites, especially alkyl hypoiodites [29], can be used in a manner similar to the organic nitrites for functionalization of an unactivated carbon atom. Scheme 25 outlines a general scheme for remote functionalization by the hypoiodite reaction. Readers requiring more information on this subject are advised to refer to review articles [2c, 16, 20],... 

Suginome, H., Reaction and Synthetic Application of Oxygen centered Radicals Photochemically Generated from Alkyl Hypohalites. In Horspool, W. M., Lenci, F. (eds), CRC Handbook of Organic Photochemistry and Photobiology, 2nd edn, CRC Press LLC, Boca Raton, FL, 2004, Chapter 109, pp. 1 16. 

The mechanism by which hypohalites oxidize alcohols probably involves initial formation of an alkyl hypohalite (Eq. 16.16). This product arises from reaction of the alcohol with the hypohalous acid that is in equilibrium with hypohalite ion in aqueous medium (Eq. 16.15). Base-promoted E2 elimination of the elements of H-X from the alkyl hypochlorite leads directly to either an aldehyde or ketone. The advantage of using hypohalite as an oxidant is immediately obvious upon examining Equation 16.16. The inorganic by-product derived from the oxidant is a halide salt that can be safely flushed down the drain. Reactions that do not produce toxic by-products are environmentally friendly and are now commonly referred to as "Green Chemistry." (See the Historical Highlight at the end of this chapter.)... 

Methyl and ethyl hypochlorites, the first alkyl hypohalites known, were prepared by Sandmeyer in 1885. Chattaway and Backeberg of Oxford subsequently reported the preparation of alkyl hypochlorites such as propyl, isopropyl, and f-butyl hypochlorites in 1923 and observed that although the primary and secondary hypochlorites are very unstable and decompose rapidly at room temperature, the tertiary hypochlorites, such as f-butyl hypochlorite, prepared by the reaction of chlorine, sodium hydroxide, and... 

Since this early work, studies from the late 1950s until the 1960s by Walling, Green, Kochi and their collaborators using t-alkyl hypohalites disclosed some fundamental characteristics of the principal radical chain reactions, such as intermolecular hydrogen abstraction and P-scission of intermediate alkoxyl radicals in hypohalite photolysis. This work was summarized in a review article by Kochi."... 

The reaction is applicable to the preparation of amines from amides of aliphatic aromatic, aryl-aliphatic and heterocyclic acids. A further example is given in Section IV,170 in connexion with the preparation of anthranilic acid from phthal-imide. It may be mentioned that for aliphatic monoamides containing more than eight carbon atoms aqueous alkaline hypohalite gives poor yields of the amines. Good results are obtained by treatment of the amide (C > 8) in methanol with sodium methoxide and bromine, followed by hydrolysis of the resulting N-alkyl methyl carbamate ... 

Ghlorohydrination with er -All l Hypohalites. Olefins react with ethyl hypochlorite [624-85-1] to form the corresponding chlorohydrin (49). In 1938 both Shell Development Co. (50) and Arthur D. Litde, Inc. (51) patented the preparation of chlorohydrins by the reactions of olefins with tertiary alkyl hypochlorites. Examples with ethylene and propylene in the Shell patent reported chlorohydrin yields of greater than 95% with tert-huty hypochlorite [507-40-4]. 

The first step is not a free-radical process, and its actual mechanism is not known.451 25 is an acyl hypohalite and is presumed to be an intermediate, though it has never been isolated from the reaction mixture. Among the evidence for the mechanism is that optical activity at R is lost (except when a neighboring bromine atom is present, see p. 682) if R is neopentyl, there is no rearrangement, which would certainly happen with a carbocation and the side products, notably RR, are consistent with a free-radical mechanism. There is evidence that the Simonini reaction involves the same mechanism as the Hunsdiecker reaction but that the alkyl halide formed then reacts with excess RCOOAg (0-24) to give the ester.452 See also 9-13. 

Boron trifluoride and boron trifluoride-diethyl ether complex can be used as a source of fluoride ions in the presence of hypobromites and hypochlorites, e.g. methyl hypobromitc, tert-butyl hypobromite, methyl hypochlorite in carbon tetrachloride at 25 C. The addition of bromine monofluoride" and chlorine monofluoride" to various alkenes is accompanied by the formation of the corresponding alkoxybromides and alkoxychlorides which hinder the isolation of the halofluorinated products.57 jV-Bromo- and A -chloro-substiluted alkyl- and arylamines. -amides, and -imides, A -chloro-A,-methylamine, A -bromo-A -methylamine, A -chloro-A, /V-dimethylamine, A-bromo-A.A-dimethylamine, ACV-dichloro-A -methylamine, V,fV-dibromo-,V-mcthylaminc, A -bromosuccinimide, -V-chlorosuccinimide, Af-bromoacct-amide, A.A -dichlorourethane, can be used in the reaction instead of the hypohalites. The reactions with various alkenes conducted in dichloromethane at room temperature in the presence of boron trifluoride-diethyl ether complex produce bromofluoro and chlorofluoro addition products in 40-80 % yield. However, the reactions are complicated by the addition of A -halo-succinimides and Af.A-dichlorourcthane to the C = C bonds.58... 

Acyl hypohalites are usually prepared in situ by reaction of a metal salt of die carboxylic acid widi a halogen (equation 3). Classically the silver salt is used, but problems associated widi die preparation of dry silver carboxylates, as well as the more obvious economic factor, have led to the development of methods using mercury and thallium salts. Evidently, those functional groups which react readily widi halogens are not compatible with this approach. A major limitation of the acyl hypohalites is the readiness with which they transfer halogen atoms to alkyl radicals this property essend ly limits their use to decarboxylative halogenation reactions. 

This is a good method of synthesising symmetrical alkanes. The Kolbe reaction is usually performed using the potassium or sodium salt of the carboxylic acid. If the silver salt is reacted with bromine, then decarboxylation occurs again, but this time the alkyl bromide is formed. This reaction is called the Hunsdiecker reaction. The first step involves the formation of an acyl hypohalite, RC02X. 

Disulfides, such as the diallyl disulfide shown in Rgure 8.24, can be obtained by the reaction of sodium disulfide (NaiSi), itself prepared by the dissolution of an equivalent of sulfur in a concenctrated sodium sulfide (Na2S) solution, with the corresponding alkyl halide. Reduction of the disulfide (e.g., with zinc dust in acetic acid) results in cleavage of the sulfur-sulfur bond and thiol formation (Scheme 8.105). Alternatively, as might be expected, thiols are rather easily oxidized (e.g., by hypohalites [NaOCl]) and the products are disulfides (Equation 8.60). 

The photolysis of a tertiary hypohalite (readily prepared from the corresponding alcohol) generates alkoxy radical, which abstracts hydrogen from 5-carbon to produce an alkyl radical. The resulting alkyl radical abstracts halogen atom from a second molecule of the hypohalite to give 5-haloalcohol, which is cyclized in presence of a base to form a tetrahydrofuran derivative [9]. These reactions are very similar to the Barton reaction and proceed through a six-membered cyclic transition... 

In contrast to the intramolecular hydrogen abstraction mentioned above, fragmentation, another principal reaction of alkoxyl radicals, was seldom used in organic synthesis until the 1970s. An analysis of the numerous examples reported in the past and our own results concerning the photochemistry of alkyl nitrites and hypohalites indicated that the direction of 3-fragmentation in unsymmetrical substrates is the outcome of an interplay of multiple factors, such as the relative thermodynamic stability of the resultant radicals, ring strain, and stereoelectronic factors. 

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