Ferf-Butyl hypochlorite

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. 

The first compound is an antibiotic isolated from Streptomyces aureus [20], while the second compound is a cytotoxic antibiotic isolated from Dysidea fragilis, a marine sponge [21]. A logical approach to the synthesis of azirines would be an elimination reaction of a suitably M-substituted aziridine. Thus, AT-chlorination of aziridine-2-carboxylic esters was carried out using ferf-butyl hypochlorite (Scheme 8). 

Hydroximoyl halides (4) are conveniently prepared by halogenation of the respective aldoximes (5), for which a number of halogenating agents such as chlorine (38), ferf-butyl hypochlorite, A -chlorosuccinimide (NCS) (39), or A -bromosuccin-imide (NBS) (40) have been employed. A plausible mechanistic course involves Hal addition and proton loss to give an a-halonitroso compound, often observed as a transient blue-green color, as shown for the chloro case (Scheme 6.1). 

The Dervan group discovered that addition of ferf-butyl hypochlorite to a solution of l-amino-2,2,6,6-tetramethylpiperidine and triethylamine in ether at —78 °C produces triethylammonium chloride as an insoluble white precipitate and an intense purple solution. The purple coloration, which is stable for hours at —78 °C, fades in minutes at 0 °C and was assigned to the 1,1-diazene 64. " " " ... 

Radical-chain reaction (Sections 4-4 and 4-5) Br2 is more selective than Cl2 used for preparation of 2-propenyl and arylmethyl halides other reagents include S02CI2 (Section 4-5B), ferf-butyl hypochlorite and W-bromosuccinimide (Section 14-3A). 

Oxidation by chlorine to the arylimidosulfonyl chlorides is sometimes violent, and ferf-butyl hypochlorite is a milder reagent. 

In view of these results, attention was turned to amine 124, whose derivatives could be hoped to react with electrophiles from the opposite face. Indeed, formamide 127 gave (+)-fischerindole I (117) in 47% overall yield after treatment with ferf-butyl hypochlorite and triethylamine followed by addition of silica gel deactivated with triethylamine and subsequent exposure to the Burgess reagent. This transformation presumably takes place by generation of chloroindolenine 128, anti elimination to give 129, tautomerism to 130 and final dehydration (Scheme 30). 

A revised version of this synthesis has been subsequently developed that has a higher overall yield and is more easily scalable [42]. Reasoning that the yield and selectivity problems in the previous route were due to the use of ferf-butyl hypochlorite, the transformation of 11-epz-fischerindole G 132 into (-)-fischerindole I 133 was carried out in excellent yield by exposure of 132 to DDQ in the presence of water, presumably through the intermediate unsaturated imine 136. For the final ring contraction step, it was decided to replace the previously employed chlorohydroxylation by a hitherto unknown fluoro-hydroxylation, expecting that the increased hardness of fluorine over chlorine... 

Some of the nitrogen sources mentioned above (e.g., Chloramine-T and N-bromoacetamide) are commercially available. In other cases, the chloramine salts have to be prepared in situ by treating the amide with ferf-butyl hypochlorite [32] and sodium hydroxide [15]. It has been found that the unstable tert-... 

To prove this hypothesis a suitable substrate, l-diazo-3-methyl-3-[(E)-phenyldiazenyl]butan-2-one (42) was used. Methyl 2-(2-arylhydrazino)-2-methylpropanoate (39) reacting with a bulky Grignard reagent like isopropyl magnesium bromide gives 4,4-dimethyl-2-phenyl-l,2-diazeti-din-3-one 40 (87TL6577). Oxidation with ferf-butyl hypochlorite converts diazetidinone 40 into 2-methyl-2-(phenyldiazenyl)propanoyl chloride 41, which upon treatment with diazomethane affords the desired diazo ketone 42 (Scheme 8) (98ACE2229). 

The efficient oxidative ring-opening of diazetidinone 40 with ferf-butyl hypochlorite forming acid chloride 41 and its conversion into a-diazenyl diazo ketone 42 upon treatment with diazomethane (Scheme 8) was anticipated to be transferable to the five-membered homologue 50. However, 5,5-dimethyl-2-phenylpyrazolidin-3-one (50) (96LA272,... 

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

Just as free-radical halogenation occurs at the carbon of an alkane, via hydrogen abstraction to form the radical, a similar reaction occurs at silicon. When triisopro-pylsilane (iPraSi—H) reacts with ferf-butyl hypochlorite at — 10°C, the product is triisopropylchlorosilane (iPraSi—Cl)... 

The quantitative analysis of thiamine hydrochloride (vitamin Bj), using HPTLC on silica gel plates with two different mobile phases, was elaborated.After TLC separation, vitamin Bj was derivatized by the use of ferf-butyl hypochlorite or potassium hexocyanoferrate (Ill)-sodium hydroxide as reagents. The ferf-butyl... 

Some forty years ago, Regitz et al. reported synthesis of vicinal triketone compounds from 2-diazo 1,3-dioxo-compounds using oxygen-halogen-insertion chemistry provided by ferf-butyl hypochlorite in formic acid. However, no analogous reaction for phosphorus compounds, in particular 2-diazo 1,3-diphos-phono substrates, had been previously described. 

Indeed, we found that diazomethylenebisphosphonate esters in ethyl acetate containing a few equivalents of H20 react at room temperature or below with ferf-butyl hypochlorite to form the corresponding carbonylbisphosphonate es-... 

Livant et al. have reported the sulfurane having two axial oximate (R2C=NO) ligands, as shown in Scheme 24 [60]. This sulfurane 31 was synthesized by the reaction of 2,2 -thiobis(acetopohenone) bis-oxime with ferf-butyl hypochlorite... 

When added to a cold aqueous solution of NaOH and passing chlorine into the mixture it forms ferf-butyl hypochlorite. 

The chromatogram is freed from mobile phase in the drying cupboard (10 min 160 °C) and placed while still hot in the chamber with ferf-butyl hypochlorite vapor for 5 min. After removal of excess reagent (15 min stream of warm air) the chromatogram is sprayed with reagent 2. 

A soln. of 2.2 moles ferf-butyl hypochlorite in dry benzene added dropwise with stirring to cyclohexylamine and benzene at such a rate that the temp, does not exceed 10°, allowed to come to room temp., then stirred 1 hr., the soln. of the resulting N,N-dichlorocyclohexylamine added to a refluxing soln. of K-acetate in abs. ethanol, and refluxing continued 3 hrs. N-chlorocyclohexylideneimine. Y 48-69%. G. H. Alt and W. S. Knowles, Org. Synth. 45, 16 (1965). 

Phthalhydrazide dissolved in boiling aq. NaOH, evaporated to dryness, the resulting Na-salt added with water to a soln. of ferf-butyl hypochlorite in acetone cooled in an acetone-Dry Ice bath, filtered, allowed to warm and to stand overnight at room temp. 3,3 -bis-(l-hydroxy-4(3H)-phthalazinone). Y F. diazaquinones and their reactions s. T. J. Kealy, Am. Soc. 84, 966 (1962). 

N-ferf-Butylphenylacetamide treated with ferf-butyl hypochlorite and a trace of K-ferf-butoxide, the resulting mixture containing N-ferf-butyl-N-chloro-... 

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