Selective chlorination with sulfuryl chloride

Many other glycosides have been subjected to selective chlorination with sulfuryl chloride. Methyl /3-L-arabinopyranoside afforded methyl 4-chloro-4-deoxy-a-D-xylopyranoside 2,3-di(chlorosulfate) in 29% yield, whereas the a-L anomer gave357 methyl 3,4-dichloro-3,4-dideoxy-/3-i)-ribopyranoside 2-(chlorosulfate) (30%). Methyl /3-d-ribopyranoside was converted into methyl 3,4-dichloro-3,4-dideoxy-a-L-arabinopyranoside through the action of pyridine hydrochloride on its 2,3,4-tri(chlorosulfate).358 Methyl a-D-lyxopyranoside gave only the 2,3,4-tri(chlorosulfate),353 as would be expected from the disposition of its hydroxyl groups, similar to that in the rhamno- and manno-pyranosides. Methyl a-D-altropyranoside was transformed into the 6-chloro-6-deoxy 2,3,4-tri(chlorosulfate) derivative in 80% yield.353... 

Similarly, when the selective O-pivaloylation of trehalose was investigated by Richardson, Hough, and Cortes-Garcia, a number of useful derivatives were also obtained in quantities adequate to be of preparative value. Thus when 12 equivalents of pivaloyl chloride were employed for this esterification at — 20 °C, and the reactants were thereafter stored at room temperature for three days, a 61% yield of the 2,2 3,3, 4, 6,6 -heptapivalate was obtained, and following invertive chlorination with sulfuryl chloride, a displacement with different nucleophiles gave access to C-4-modified trehaloses, one example of which is shown in Scheme 17. 

The organic chemistry of sulfuryl chloride involves its use in chlorination and sulfonation (172,175,196,197). As a chlorinating agent, sulfuryl chloride is often mote selective than elemental chlorine. The use of sulfuryl chloride as a chlorinating agent often allows mote convenient handling and measurement as well as better temperature control because of the lower heat of reaction as compared with chlorine. Sulfuryl chloride sometimes affords better selectivity than chlorine in chlorination of active methylene compounds (198—200) ... 

A selective introduction of a chlorine atom at C-6 could be achieved (65) by treating 11 (and the / -anomer) with sulfuryl chloride in pyridine at — 70°C. followed by treatment of the resulting tetrachlorosulfate (83) with one mole of pyridine hydrochloride which gave 84. Heating of 84 with pyridine hydrochloride in chloroform resulted in further substitution by chloride to give 78 after dechlorosulfation. The above illustrated transformations support the proposed mechanism (65) for... 

SCHEME 27. Ballard, Fairclough, Hough, and Richardson s study of the selective low-temperature chlorination of sucrose with sulfuryl chloride (1973). 

The selective replacement of hydroxyl groups in carbohydrates by chlorine has been achieved by the use of sulfuryl chloride.1,74,87,88 The reaction of sulfuryl chloride with maltose89,90 and methyl /3-maltoside24 has been studied. Treatment of maltose with sulfuryl chloride, initially for 2 h at — 70° and then processing at room temperature, gave, after methyl glycosidation and dechlorosulfation, a low yield... 

Partially proton-exchanged Na faujasite X, in turn, is the best catalyst for selective monochlorination with tert-butyl hypochlorite.258 NaX, NaY, and NaKL zeolites used in the chlorination of toluene with sulfuryl chloride undergo rapid deactivation because of the accumulation of polychlorinated toluenes in the pores of the catalysts and dealumination.259, 260 Direct electrophilic fluorination of aromatics can be effected by using Selectfluor in the presence of triflic acid.261 Electrophilic fluorination may also be carried out by R2NF and R3N+FA reagents.262 Elemental fluorine may also act as a powerful electrophile in acidic media (sulfuric acid, trifluoroacetic acid, or formic acid), but monosubstituted aromatics give isomeric mixtures.263-265... 

Searching for other 6-membered "diazido malonyl N-heterocycles" we have selected the pyridazine derivative 25 and diazido barbituric acids 32 as model systems, since they are available easily and in large quantities. Compound 25 is obtained in the usual way by chlorination of 23 with sulfuryl chloride and exchange of the halogen atoms with sodium azide. 

Comparison of the chlorination of fatty esters with chlorine versus sulfuryl chloride has revealed that the former is more selective to halogenation of the co-2 position while the latter results in a mixture of co-2 and co-3 chlorinated esters850. 

Selective chlorination of sucrose, by which three of sucrose s hydroxyl groups are substituted with chlorine atoms, produces sucralose (l,6-dichloro-l,6-dideoxy- S-D-fructofuranosyl-(24>l)-4-chloro-4-deoxy-a-galactopyranoside) sweetener sold as Splenda [49]. Sucralose is approximately 650 times sweeter than sucrose and can be used in baking. Its synthesis involves treatment of a partially acetylated sucrose with sulfuryl chloride the initially formed chlorosulfate esters act as leaving groups and undergo nucleophilic displacement by chlorine [20]. Sucralose was first approved for use in Canada in 1991 as of 2006, it has been approved in over 60 countries. 

Zeolites have been used to enhance the / r i-selectivity of chlorination reactions. For example, anisole has been chlorinated using sulfuryl chloride and ZF520 zeolite under reflux conditions [10]. A yield of 81% was achieved with a para to ortho product ratio of 74 26. Smith et al. reported complete conversion of alkylbenzenes using tertiary-butyl hypochlorite and HNaX zeolite at room temperature with para to ortho ratios of greater than 90 10 [11]. Molecular chlorine in the liquid phase with KL zeolite as the catalyst has been reported to give excellent para selectivity and good yields for deactivated benzenes [12]. 

Kharasch et al. [48] had proposed a mechanism for the sulfochlorination with sulfuryl chloride in the presence of pyridine, simply assuming the dissociation of SOjClj into chlorine and sulfur dioxide, but the different secondary/primary selectivity with respect to that of the SOj—Clj mixture [41] suggests three more possible steps [42] ... 

Sulfuryl chloride, selective introduction of chlorine at C-6 with. . 181... 

The use of sulfuryl chloride for free radical chlorination of aliphatic carboxylic acids gives mixtures of positional isomers.7 However, with the cyclobutane ring, the attack is much more selective. The present method provides a procedure for free radical halogenation of a cyclobutane ring. 

Alkanes can be simultaneously chlorinated and chlorosulfonated. This commercially useful reaction has been applied to polyethylene (201—203). Aromatics can be chlorinated on the ring, and in the presence of a free-radical initiator alkylaromatic compounds can be chlorinated selectively in the side chain Ring chlorination can be selective. A patent shows chlorination of 2,5-di- to 2,4,5-trichlorophenoxyacetic acid free of the toxic tetrachlorodibenzodioxins (204). With alkenes, depending on conditions, the chlorination can be additive or substitutive. The addition of sulfuryl chloride can occur to form a 2-chloroalkanesulfonyl chloride (205). 

The support originally used for solid-phase synthesis was partially chloromethy-lated cross-linked polystyrene, which was prepared by chloromethylation of cross-linked polystyrene with chloromethyl methyl ether and tin(IV) chloride [1-3] or zinc chloride [4] (Figure 6.1). Haloalkylations of this type are usually only used for the functionalization of supports, and not for selective transformation of support-bound intermediates. Because of the mutagenicity of a-haloethers, other methods have been developed for the preparation of chloromethyl polystyrene. These include the chlorination of methoxymethyl polystyrene (Figure 6.1 [5]), the use of a mixture of dimethoxymethane, sulfuryl chloride, and chlorosulfonic acid instead of chloromethyl methyl ether [6], the chlorination of hydroxymethyl polystyrene [7], and the chlorination of cross-linked 4-methylstyrene-styrene copolymer with sodium hypochlorite [8], sulfuryl chloride [8], or cobalt(III) acetate/lithium chloride [9] (Figure 6.1, Table 6.1). 

The use of sulfuryl chloride instead of chlorine as a chlorinating agent eliminates the danger of explosion. It reacts readily with paraffins in a manner similar to that of chlorine. With unsaturated compounds, it forms the chlorine derivatives. It is also used for the chlorination of aromatic compounds but does not react readily in the absence of a catalyst. Halogen carriers are used as catalysts. In the presence of organic peroxides, sulfuryl chloride selectively chlorinates the side chain. Several reviews on the use of sulfuryl chloride as a chlorinating agent are available 18, 22, 66. ... 

Scheme 11.4 illustrates some representative halogenation reactions. The reaction in Entry 1 was conducted by slow addition of bromine to excess 2-methylpentane at 60°C, with irradiation from a tungsten light bulb. The reaction in Entry 2 is a typical benzylic bromination, carried out at 125°C with irradiation from a sun lamp. Entries 3 and 4 are examples of NBS bromination using benzoyl peroxide as the initiator. Entry 3 is interesting in that none of the allylic isomer 2-bromo-3-heptene is found. Entries 5 and 6 are examples of chlorination by f-butyl hypochlorite in which the f-butoxy radical is the chain carrier. Note that in Entry 6, both the primary and secondary allylic products are formed. The reaction in Entry 7 uses sulfuryl chloride as the halogenation reagent. Note that in contrast to chlorination with CI2 (see p. 1021), the reaction shows selectivity for the benzylic position. 

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