4-toluenesulfonyl azide

A novel method for preparing amino heterocycles is illustrated by the preparation of 2-amino-5-methylthiophene (159). In this approach vinyl azides act as NH2 equivalents in reaction with aromatic or heteroaromatic lithium derivatives (82TL699). A further variant for the preparation of amino heterocycles is by azide reduction the latter compounds are obtained by reaction of lithio derivatives with p- toluenesulfonyl azide and decomposition of the resulting lithium salt with tetrasodium pyrophosphate (Scheme 66) (82JOC3177). 

A gas ehromatographic analysis on the produet by the submitter, using an 0.3 x 80 cm. column packed with 10% silicone rubber (SE-30) supported on acid-washed, 60-80 mesh Chromasorb P at 80°, exhibited a single peak. The retention times of di-ter(-butyl malonate, di-fert-butyl diazomalonate, and p-toluenesulfonyl azide were 2, 6, and 9 minutes, respectively. The purity of the product obtained by the checkers was estimated from proton magnetic resonance spectra to be ca. 94%, the remainder being di-tert-butyl malonate. 

The diazo transfer reaction between p-toluenesulfonyl azide and active methylene compounds is a useful synthetic method for the preparation of a-diazo carbonyl compounds. However, the reaction of di-tert-butyl malonate and p-toluenesulfonyl azide to form di-tert-butyl diazomalonate proceeded to the extent of only 47% after 4 weeks with the usual procedure." The present procedure, which utilizes a two-phase medium and methyltri-n-octylammonium chloride (Aliquat 336) as phase-transfer catalyst, effects this same diazo transfer in 2 hours and has the additional advantage of avoiding the use of anhydrous solvents. This procedure has been employed for the preparation of diazoacetoacetates, diazoacetates, and diazomalonates (Table I). Ethyl and ten-butyl acetoacetate are converted to the corresponding a-diazoacetoacetates with saturated sodium carbonate as the aqueous phase. When aqueous sodium hydroxide is used with the acetoace-tates, the initially formed a-diazoacetoacetates undergo deacylation to the diazoacetates. Methyl esters are not suitable substrates, since they are too easily saponified under these conditions. 

These reactions were carried out with 0.005 mole of the carbonyl compound and 0.005 mole of p-toluenesulfonyl azide. 

A. p-Toluenesulfonyl azide -8 A solution of 71.5 g. (1.10 moles) of sodium azide (Note 1) in 200 ml. of water is placed in a 2-1. Erlenmeyer flask and diluted with 400 ml. of 90% aqueous ethanol (Note 2). To this solution is added with stirring a warm... 

ACETATE AND ALDEHYDES OR KETONES ETHYL 1-HYDROXYCYCLO-HEXYLACETATE, 53, 66 2- (Hydroxymethylene)cyclohexanone with p-toluenesulfonyl azide to give 2-diazocyclo-hexanone, 51, 86 y-HYDROXY-ct, (3-UNSATURATED ALDEHYDES VIA 1,3-BIS(METHYL-THIO) ALLYLLITHIUM trans-4-HYDROXY-2-HEXENAL, 54, 19... 

Diazocycloalkanones, from a-(hydroxymethylene)ketones with p-toluenesulfonyl azide, 51, 88... 

Toluenesulfinyl azide, 2780 4-Toluenesulfonyl azide, 2781 Trifluoroacetyl azide, 0627... 

NAPHTHALENETHIOL, 51, 759 o-Tolualdehyde, by reduction of o-tolu-nitrile with Raney nickel alloy in formic acid, 51,25 p-Toluenesulfonyl azide, with 2-(hy-... 

Diphenyl phosphorszldate can be replaced with diethyl phosphorazidate in the above procedure. Use of other azides such as p-toluenesulfonyl azide, p-methoxybenzyloxycarbonyl azide, diphenylphosphinic azide, or diphenylthio-phosphinic azide is less satisfactory. No reaction occurs when trimethylsilyl azide, dimethylthiophosphinic azide, or alkaline azides are used, while decomposition of formed trimethylsilyldiazomethane seems to occur when... 

Trimethylsilyldiazomethane, as a stable and safe substitute for hazardous diazomethane, is useful both as a reagent for introducing a Cj-unit and as a C-N-N synthon for the preparation of azoles. Many methods are described in the literature for the preparation of trimethylsilyldiazomethane, including the trimethylsilylation of diazomethane (7-74S), the alkaline decomposition of N-nitroso-N-(trimethylsilylmethyl)amides (25-61%) and the diazo group transfer reaction of trimethylsilylmethyllithium with p-toluenesulfonyl azide (38%). The present modified diazo group transfer method appears to be the most practical, high-yield, and large scale procedure for the preparation of... 

In a 2-1. wide-necked Erlenmeyer flask are mixed 66.2 g. (0.525 mole) of 2-(hydroxymethylene)cyclohexanone (Note 1), 400 ml. of methylene chloride, and 106 g. (1.05 moles) of triethylamine (Note 2). The flask is cooled in an ice-salt bath at —12 to —15°, and 98.0 g. (0.500 mole) of p-toluenesulfonyl azide (Note 3) is added with vigorous mechanical stirring over a period of approximately 1 hour, at such a rate that the temperature of the reaction mixture does not rise above —5°. Stirring is continued for an additional 2 hours as the cooling bath melts. A solution of 30.8 g. (0.55 mole) of potassium hydroxide in 400 ml. of water is added, and the mixture is stirred for 15 minutes at room temperature. The resulting emulsion is placed in a 2-1. separatory funnel, the methylene chloride layer is separated after the emulsion has broken, and the aqueous alcoholic layer is... 

Diazocycloalkanones with five- to twelve-membered rings can be synthesized by the present procedure in good yields (Table I).4 Diazo transfer with deformylation can also be used for the preparation of bicyclic a-diazo ketones.10,11 A related procedure involving reaction of the sodium salt of an a-(hydroxy methylene)-ketone with p-toluenesulfonyl azide in ethanol has been applied to the synthesis of diazoalkyl ketones, a-diazo aldehydes, and a-diazo carboxylic esters.12... 

One of the key steps in building the fused ring involves the reaction of the activated acetoacetate methylene group in that compound with toluenesulfonyl azide to give the diazo intemediate (12-1). Treatment of that product with rhodium acetate leads to a loss of nitrogen with the consequent formation of carbene (12-2) this inserts into the adjacent amide N—H bond to form a five-membered ring and thus the carbapenem (12-3) [15]. The first step in the incorporation of the thioenol function consists in the conversion of the ketone to the enol phosphate derivative... 

A novel azide synthesis using p-toluenesulfonyl azide and amine anions... 

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