Synthesis of o-sulfamidotriazobenzenes from 1,1'-sulfonylbis(benzotriazole).

Easily accessible 1,1'-sulfonylbis(benzotriazole) (Bt2SO2, 1) reacts with secondary amines at room temperature to afford (i) the corresponding o-sulfamidotriazobenzenes 2a-d (53-75%) via concurrent substitution of the first and ring opening of the second benzotriazolyl group and (ii) N-sulfonylbenzotriazoles 3b,c,e,f (7-73%). 1-(Morpholine-4-sulfonyl)-1H-benzotriazole 3c reacts with piperidine, pyrolidine, and N-methylpiperazine under microwave irradiation (120 W) at 120 degrees C for 10 min to give the unsymmetrical sulfamides 4a-c (80-90%).

Alkyl, unsaturated, (hetero)aryl, and N-protected alpha-amino ketones by acylation of organometallic reagents.

Stable and easily accessible N-acylbenzotriazoles, derived from a variety of aliphatic, unsaturated, (hetero)aromatic, and N-protected alpha-amino carboxylic acids, were reacted with Grignard and heteroaryllithium reagents to afford corresponding ketones in good to excellent yields.

An epidemic of a "new" haemorrhagic disease in infants attributable to talcum powder contaminated with warfarin in Ho-Chi-Minh Ville (Vietnam).

In August 1981, pediatric hospitals in Ho-Chi-Minh Ville (Saigon) began to report numerous cases of a haemorrhagic syndrome in infants. A collaborative study with a French epidemilogist began on September 24, 1981, with the aim of finding the cause of this "new" haemorrhagic disease. After having excluded the hypothesis of a viral or bacterial infection, a retrospective study, using questionnaires with 83 items, concerning products of hygiene and nutrition and living conditions, was undertaken. This epidemiological investigation showed this phenomenon was caused by an anticoagulant contained in talcum powder. Analysis of the talcum powders found warfarin; the concentrations ranged between 1.7% and 6.5%. This dramatic episode (741 cases with 177 deaths) ended when the contaminated talc was withdrawn from circulation. The hypothesis of accidental contamination or use of warfarin in lieu of a perfuming agent must be rejected. Accidental addition of a rat-killer seems highly improbable and the possibility of intentional and malevolent adulteration is now under study. An experimental study of hemostasis in two baboons was carried out, using dermal application of the contaminated talc powder. The intoxicated animal died on the 5th day with severe vitamin K deficiency. This accident together with the animal study, shows the transcutaneous uptake of the anticoagulant, which could be of considerable importance in toxicology and in pharmacokinetics.

Epidemic of haemorrhagic disease in Vietnamese infants caused by warfarin-contaminated talcs.

In August, 1981, paediatric hospitals in Ho Chi Minh City (formerly Saigon), Vietnam, began to report cases of a haemorrhagic syndrome in infants. The cause of this haemorrhagic phenomenon was identified as talcum powder contaminated with the anticoagulant warfarin. Analysis of talcum powders revealed warfarin in concentrations between 1.7% and 6.5%. 741 cases were detected and 177 patients died. The possibility of accidental contamination or substitution of a perfuming agent by warfarin can be rejected. In an experiment with two baboons, the animal exposed to the contaminated talc died five days later from haemorrhage. The accident and the animal study demonstrate the significant transcutaneous uptake of the anticoagulant.