P-Acetamidobenzenesulfonyl

The first pyrimidine analogues of sulfanilamide were introduced in 1942, some five years after the start of the bacterial chemotherapy revolution. Sulfadiazine (1018 R = R = H) and sulfamerazine (1018 R = Me, R = H) may be made by treatment of pyrimidin-2-amine or its 4-methyl derivative, either with p-acetamidobenzenesulfonyl chloride followed by... 

Compounds containing a CH2 bonded to two Z groups (as defined on p. 464) can be converted to diazo compounds on treatment with tosyl azide in the presence of a base,164 The use of phase transfer catalysis increases the convenience of the method.165 p-Dodecylbenzenesul-fonyl azide,166 methanesulfonyl azide,167 and p-acetamidobenzenesulfonyl azide168 also give the reaction. The reaction, which is called the diazo transfer reaction, can also be applied to other reactive positions, e.g., the 5 position of cyclopentadiene.169 The mechanism is probably as follows ... 

The diazo transfer reaction with sulfonyl azides has been extensively used for the preparation of diazo compounds with two electron-withdrawing groups (equation 1 ).28 Toluenesulfonyl azide (13a)29 is the standard reagent used, but due to problems of safety and ease of product separation, several alternative reagents have been developed recently. n-DodecylbenzenesuIfonyl azide (13b)30 is very effective for the preparation of crystalline diazo compounds, while p-acetamidobenzenesulfonyl azide (13c)31 or naph-thalenesulfonyl azide (13d)30 are particularly useful with fairly nonpolar compounds. Other useful reagents are methanesulfonyl azide (13e)32 and p-carboxybenzenesulfonyl azide (13f).33... 

The report stresses the advantages of p-acetamidobenzenesulfonyl azide, N3S02C6H4NHC0CH3-p,6 for preparation of diazo compounds by diazo-transfer. It is safe, inexpensive, and the sulfonamide by-product is removed by simple trituration with H20. 

Commercially available p-acetamidobenzenesulfonyl azide (Aldrich Chemical Company, Inc.) was preferred over p-dodecylbenzenesulfonyl azide (Danheiser, R. L Miller, R. F. Brisbois, Org. Synth. 1995, 73, 134, Note 9 Ref. 4a), or methanesulfonyl azide4 for reasons of safety, yield, and ease of manipulation. 

The carbocyclic [6-7] core of guanacastepenes was prepared by. D. Trauner et al. using the intramolecular reaction between carbenoids derived from diazo carbonyl compounds and furans. The required diazo carbonyl substrate was synthesized using p-acetamidobenzenesulfonyl azide (p-ABSA) as the diazo-donor component in the Regitz diazo transfer reaction. 

B. Ethyl diazoacetoacetate. A 2-L, round-bottomed flask equipped with a magnetic stirrer is charged with 26.0 g (0.20 mol) of ethyl acetoacetate, 49.0 g, (0.20 mol) of p-acetamidobenzenesulfonyl azide and 1.5 L of acetonitrile. The reaction vessel Is cooled in an ice bath, and 60.6 g (0.60 mol) of triethylamine is added to the stirring mixture In one portion. The reaction mixture is warmed to room temperature and stirred for 12 hr. The solvent Is removed under reduced pressure, and the residue Is triturated with 500 mL of a 1 1 mixture of ether/petroleum ether. The mixture is filtered to remove the sulfonamide by-product, and the filtrate and wash are concentrated under reduced pressure. The crude product is purified by chromatograpy on silica gel (130 g. Note 5) with ether/petroleum ether (1 4) as eluant to yield 28.5 g (91%) of ethyl diazoacetoacetate as a yellow oil (Note 6). 

Benzenesulfonyl azide, 4-(acetylamino)- (9) (2158-14-7) p-Acetamidobenzenesulfonyl chloride Sulfanilyl chloride, N-acetyl- (8) Benzenesulfonyl chloride, 4-(acetylamino)- (9) (121-60-8)... 

Caution These reactions, which involve toxic reagents, should be carried out in an effident hood. Although p-acetamidobenzenesulfonyl azide exhibited no impact sensitivity, proper caution should be exercised with all azide compounds. 

A. p-Acetamidobenzenesulfonyl azide. A 2-L Erlenmeyer flask equipped with a magnetic stirrer is charged with 117.0 g (0.50 mol) of p-acetamidobenzenesulfonyl... 

The following chemicals were obtained from the Aldrich Chemical Company, Inc., and were used without further purification p-acetamidobenzenesulfonyl chloride, 97% acetone, 99.9+%, HPLC grade sodium azide, 99% ethyl acetoacetate, 99% triethylamine, 99% rhodium(ll) acetate dimer phenylacetylene, 98%. The following solvents were obtained from Fisher Scientific and were used without further purification toluene, certified A. C. S. ethyl ether (Solvent grade, Concentrated) petroleum ether, certified A. C. S. Dichloromethane was distilled from calcium hydride. 

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