Chlorination with tert-butyl hypochlorite

The addition of cyclopropanone to a large variety of primary amines, including amines with a primary, secondary or tertiary alkyl substituent, afforded the corresponding labile, but isolable, hydroxyamines 24. These amines are a suitable source of the )S-lactams 25 via a synthetic procedure which involves Af-chlorination with tert-butyl hypochlorite and subsequent treatment with silver salts. ... 

Our own earlier work on the chlorination of toluene had been subject to similar constraints. In this case, chlorination with ferf-butyl hypochlorite had proved to be advantageous. In the presence of silica gel as catalyst the yield of chlorotoluenes was quantitative but the regioselectivity was more or less statistical (ref. 8). However, the use of proton-exchanged zeolite X allowed the production of chlorotoluenes with a para-selectivity of more than 90 % (Fig. 4) (ref. 9). No HCl is generated in this process since the by-product is tert-butanol, and there is no inhibition of the catalyst. Indeed, the catalyst can be reused if necessary. 

Chlorination of yohimbine (74) at the (3 position of the indole moiety with tert-butyl hypochlorite and treatment of the resulting chloride (539) with base in... 

The final, critical oxidative spirocyclization of the 2,3-disubstituted indole to the spiro oxindole was effected by treatment of 124 with tert-butyl hypochlorite in pyridine to provide the labile 125 [Fig. (34)]. The Pinacol-type rearrangement was conducted by treating compound 125 with p-toluenesulfonic acid in THF/water. It is assumed that the chlorination of 124 proceeds from the least hindered face of the indole, to give the a-chloroindolene 125. The hydration of the imine functionality must also occur from the same a-face that is syn to the relatively large chlorine atom furnishing the syn-chlorohydrin 126, that subsequently rearranges stereospecifically to the desired spiro oxindole 127. 

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... 

The method of N-chlorination of amino acid esters 40 and AT-acylamino acid esters with tert-butyl hypochlorite and subsequent elimination of hydrogen chloride is of general use in the preparation of DHA derivatives 41/42 122-1241 (Scheme 15). 

Compared with chlorination, hydrogen abstraction reactions of alkoxy radicals are relatively insensitive to solvent effects [160, 222, 223]. The results of the AIBN-initiated radical chain chlorination of 2,3-dimethylbutane with tert-butyl hypochlorite indicate a solvent effect on tert-butoxy radical reactions of much smaller magnitude, but greater selectivity in aromatic solvents [222, 223], The reduced solvent effect for this hydrogen abstraction reaction has been attributed to steric effects. Due to the bulky... 

The same 8-chloroadenosine (5) is also obtained with tetrabutylammonium iodotetrachloride (TBAIClJ or with tert-butyl hypochlorite (r-BuOCl) in dimethylformamide. Analogous chlorination of -methyladenosine, to give 6, and A. A -dimethyladenosine is also possible with the latter reagent. ... 

Chlorination of toluene with tert-butyl hypochlorite in the presence of silica gel gave a mixture of chlorotoluenes in which the ortho isomer predominated. Rutming this reaction using a large pore zeolite, H-X, gave p-chlorotoluene in... 

Similarly, thermal isomerization of the [7,7- H2] isotopomer gave [3,7- H2]cyclonona-l,3,6-triene, and the [5,5,9,9- H4.] isotopomer gave [5,5,9,9- H4]cyclonona-l,3,6-triene. In contrast to these thermal ring expansions, chlorination of 1,5-bishomocycloheptadiene with tert-butyl hypochlorite yielded unrearranged, bridgehead chlorides, Silver(I) trifluoroacetate cleaved only one cyclopropane unit, without ring expansion, to afford 4-(methoxymethyl)bi-cyclo[5.1,0]octa-2,4-diene. ... 

To try to obviate some of the problems involved in dealing with dias-tereoisomers, the same sequence was carried out with dihydrocorynan-theine (362). Treatment of demethyldihydrocorynantheine (363) with cyanogen bromide in ethanol-chloroform gave only the 3-(f )-ethoxy derivative 364, albeit in only 25% yield. Upon reaction with tert-butyl hypochlorite the 3-(7 )-16-deformy]-l 6-chlorinated compound 365 was... 

The amine hydrogens of polyfluorinated anilines can be replaced with chlorine by using tert-butyl hypochlorite [65,66]... 

The sulfur analogue of the Hauser ortho-substitution rearrangement provides access to an arylacet-ic NSAID. Reaction of the aminobenzophenone 176 with ethyl methylthioacetate and tert-butyl hypochlorite gives the intermediate 178. The reaction probably proceeds by way of formation of the S-chlorinated sulfonium derivative 177 displacement on sulfur will lead to the salt 178. Treatment with triethylamine leads initially to the betaine 179. Electrocyelic rearrangement of that transient intermediate leads, after rearomatization, to the homoanthranilic acid 180. Internal ester-amine interchange leads then to indolone 181 [45]. The thiomethyl group is then removed with Raney niekel. Saponifieation of intermediate 182 affords bromfenac (183) [46J. 

Dichlorourethane and tert-butyl hypochlorite (TBH) were even more reactive in the presence of silica, chlorination of toluene with TBH being complete in just one hour at ambient temperature with 3.8g of BDH silica for a 5 mmol reaction in 10 ml of tetrachloromethane solvent Intrigued by these observations, we decided to undertake a more systematic investigation of the potential of solid catalysts for organic synthesis. 

Chlorination of steroid ketones has been studied in only a few cases. The reaction with elementary chlorine [iS ] is generally similar to bromination, but other sources of electrophilic chlorine have also been used. These include sulphuryl chloride, pyridine hydrochloride perchloride, and tert-butyl hypochlorite [J57]. 

ClSiMes. Other A -bromo amides have also been used. Allylic chlorination has been carried out, with A -chlorosuccinimide, tert-butyl hypochlorite, or with NaC10/CeCl3 7 H20. With any reagent an initiator is needed this is usually AIBN (1), a peroxide, such as di-tert-butyl peroxide or benzoyl peroxide or, less often, uv light. 

Photochlorination of cyclopropane gave chlorocyclopropane (la) and 1,3-dichloro-propane. The latter was the major product at low temperature. Photochlorination with tert-h Ay hypochlorite gave mostly chlorocyclopropane (la). Methylcyclopropane reacted with chlorine to give predominantly l-chloro-2-methylcyclopropane (lb), but small amounts of acyclic products such as 2-chlorobutane, 1,3-dichlorobutane, and 1,3-dichloro-2-methyl-propane were also obtained. With ferr-butyl hypochlorite 4-chlorobut-l-ene was isolated as the only acyclic product. Photochlorination of 1,1-dimethylcyclopropane in trichloro-fluoromethane atO°C gave the chloromethylcyclopropane derivative 2 in 67% yield after immediate workup. 

For addition of HOC1 the olefins are stirred with 0.125-0.5 m-HOCl at 10°. The yields of chlorohydrin from 1-alkenes of higher molecular weight are considerably increased by addition of pyridine and sulfuric acid (initial pH 6-6.5)278. Chlorohydrins of higher molecular weight are also, accessible by reaction of alkyl hypochlorites with the olefin in an aqueous medium tert-butyl hypochlorite (a yellow oil, b.p. 77-78°/760 mm) is suitable for this purpose it is obtained by passage of chlorine into tert-butyl alcohol in aqueous sodium hydroxide at 0-20°. 

This reaction was initially reported by Gassman in 1972. It is a multistep preparation of 6>rf/z6>-alkylated anilines by sequential treatment of the anilines with tert-huXyX hypochlorite, dialkylsulfide, and triethylamine followed by Raney nickel desulfurization. Therefore, it is known as the Gassman reaction. Although it is a multistep process, it is actually a one-pot reaction. In addition, this reaction can be adapted to prepare anilines with vinyl, formyl, and benzyl groups at the 6>rf/z<9-position. Furthermore, para-substituted anilines can be prepared as well via a modified process by which A-f-butyl-A-chloro anilines, generated from the chlorination of anilines fi om tert-b xiy hypochlorite, are treated with silver salt and a nucleophile such as methanol. ... 

The preparation of chloromethyldisilanes has been accomplished with chlorine (ultraviolet light) (2), sulfuryl chloride (peroxides) (2), and tert-butyl hypochlorite (ultraviolet light) (77). The preparation and reactions of... 

Preparation from 3-hydroxyacetophenone by chlorination of its ethylene ketal using two equivalents of tert-butyl hypochlorite. Hydrolysis of the obtained dichloroketal with dilute hydrochloric acid in tetrahydrofuran gave essentially 2,4-dichloro-3-hydroxyacetophenone [1859]. Also obtained (by-product) by reaction of tert-butyl hypochlorite on 3-hydroxyacetophenone in chloroform at 15°, in subdued light (9%) [1859],... 

Preparation from 3-hydroxyacetophenone by chlorination of its 2,3-butylene ketal or its ethylene ketal using tert-butyl hypochlorite. The hydrolysis of these chloroketals with concentrated hydrochloric add in tetrahydrofuran-water mixture gave 3-hydroxy-4-chloroacetophenone (94% and 48% yields, respectively) [1859]. 

It would be advantageous to develop a chlorodecarboxylation reaction that only required catalytic amounts of the heavy metal. To address this issue, a method that was catalytic with respect to the silver salt was devised (Scheme 7.28) [49]. The key to the chemistry was the use of tert-butyl hypochlorite as the chlorine source. The redesigned reactions proceeded under very mild conditions using only 5% of a silver complex. Primary, secondary, and tertiary alcohols as well as bulky substrates were all successfully chlorinated using this approach. 

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... 

Butyl hypochlorite, warning, 44, 26 N-chlorination of amines with, 41, 82 M-Butyl isocyanide, 41,14 tert-Butyl isocyanide, 41,14 n-Butylmagnesium bromide, 41, 61 reaction with rec-butyl crotonate, 41, 61... 

Aqueous sodium hypochlorite is another low-priced oxidant. Very efficient oxidative systems were developed which contain a meso-tetraarylporphyrinato-Mn(III) complex salt as the metal catalyst and a QX as the carrier of hypochlorite from the water phase to the organic environment. These reactions are of interest also as cytochrome P-450 models. Early experiments were concerned with epoxidations of alkenes, oxidations of benzyl alcohol and benzyl ether to benzaldehyde, and chlorination of cyclohexane at room temperature or 0°C. A certain difficulty arose from the fact that the porphyrins were not really stable under the reaction conditions. Several research groups published extensively on optimization, factors governing catalytic efficiency, and stability of the catalysts. Most importantly, axial ligands on the Mn porphyrin (e.g., substituted imidazoles, 4-substituted pyridines and their N-oxides), 2 increases rates and selectivities. This can be demonstrated most impressively with pyridine ligands directly tethered to the porphyrin [72]. Secondly, 2,4- and 2,4,6-trihalo- or 3,5-di-tert-butyl-substituted tetraarylporphyrins are more... 

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