The metabolic N-oxidation, N-acetylation and N-deacetylation of the carcinogen benzidine and its N-acetylated metabolites were examined in vitro with rat and mouse liver subcellular fractions. N-acetylbenzidine and N,N-diacetylbenzidine was found to occur with NADPH-, NADH-fortified microsomes, although total oxidation at both nitrogens of N-acetylbenzidine was substantially faster than the N-oxidation of N,N'-diacetylbenzidine (four times for the mouse and 48 times for the rat). In both species, N-oxidation of N-acetylbenzidine to the arylhydroxylamine, N'-hydroxy-N-acetylbenzidine (N'-OH-ABZ), was somewhat faster than the formation of the arylhydroxamic acid, N-hydroxy-N-acetylbenzidine (N-OH-ABZ). N-Acetylation of benzidine and N-acetylbenzidine by liver cytosol was ... efficient for both species (0.7-2.9 nmol/min/mg cytosolic protein), and these rates were found to be 3-10 times faster than their corresponding rates of N-oxidation. N-Deacetylation of N-acetylbenzidine and N,N'-diacetylbenzidine by mouse liver microsomes occurred at a rate that was comparable with N-acetylation; while N-deacetylation by rat liver microsomes was relatively slow, only 1-2% of the rate of N-acetylation. In the case of N-hydroxylated derivatives, N-OH-N-acetylbenzidine and N'-OH-N"-acetylbenzidine hepatic cytosolic N-acetylation by both rats and mice to form N-OH-N,N'-diacetylbenzidine was quite rapid (0.5-1.9 nmol/min/mg cytosol protein). Hepatic microsomal deacetylation of N-OH-N,N'-diacetylbenzidine also occurred with both species and was 2-4 times the rate of N-acetylation. These studies indicate that a significant concentration of potentially electrophilic monoacetylated N-oxidized metabolites may accumulate within the liver cell, and that they may serve as intermediates in the synthesis of the highly toxic metabolite, N-OH-N,N'-diacetylbenzidine. A major metabolic pathway for the formation of N-OH-N,N'-diacetylbenzidine is proposed as: Benzidine-N-acetylbenzidine-N'OH-N-acetylbenzidine-N-OH-N,N'diacetylbenzidine. The activation of N-OH-N,N'diacetylbenzidine by cytosolic N,O-acyltransferase and N'-OH-N-acetylbenzidine by cytosolic sulfotransferase and O-acetyltransferase (acetyl CoA-dependent binding to DNA) were also examined. N-OH-N,N'-diacetylbenzidine N,O-acyltransferase and N'-OH-N-acetylbenzidine O-acetyltransferase were found to be significant pathways for rat and mouse liver, respectively. In addition, the DNA adduct formed from N-OH-N,N'-diacetylbenzidine in the presence of partially-purified rat hepatic N,O-acyltransferase was shown to be N'-(deoxyguanosin-8-yl) N-acetylbenzidine, which is identical to that formed in rat liver in vivo and in the direct
(14)C-labeled benzidine was incubated with Salmonella typhimurium strains TA-98 or TA-98/1,8-DNP6 for up to 24 hours. ... Metabolites were studied by thin layer chromatography and high pressure liquid chromatography. Benzidine metabolized by TA-98 to two major products: N-acetylbenzidine and N,N'-diacetylbenzidine. Unidentified polar metabolites amounting to 8% of the total (14)C activity were also found. Incubation with TA-98/1,8-DNP6 did not produce N-acetylbenzidine or N,N'-diacetyl benzidine; however, the same polar metabolites as produced by TA-98 were observed. The sensitivity of TA-98/1,8-DNP6 to mutagenesis by benzidine, N-acetylbenzidine and N,N'-diacetylbenzidine was investigated with metabolic activation by hamster liver S9 mix. All three compounds showed mutagenic activity; however, ... TA-98/1,8-DNP6 was less sensitive than TA-98. Salmonella strain TA-98/1,8-DNP6 is deficient in this acetylation activity and resistant to benzidine mutagenesis. Endogenous bacterial metabolism may play a role in benzidine mutagenesis.
The azo reduction and acetylation in vitro and the mutagenic activation in vivo of three azo dyes were studied. In the presence of rat-liver 9000 g supernatant, benzidine was released from direct black 38 and direct brown 95, whereas hardly any benzidine was produced during incubation of direct blue 6. Incubation of benzidine with isolated rat hepatocytes resulted in the appearance of diacetylbenzidine. No diacetylbenzidine was formed during incubation of benzidine with rat-liver 9000 g supernatant unless ... acetyl coenzyme A was added to the incubation medium. Isolated rat hepatocytes were capable to produce diacetylbenzidine from direct black 38, direct blue 6 or direct brown 95 without supplementation with acetyl coenzyme A. ... Rat liver has a considerable capacity to reduce azo compounds. nevertheless, for some compounds, like direct black 38, extrahepatic enzymes, most likely present in the intestinal flora, may also play a substantial role in the azo cleavage.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
没有关于人类的数据。动物中有充分的致癌性证据。总体评估：2B组：该物质可能对人类有致癌性。
No data are available in humans. Sufficient evidence of carcinogenicity in animals. OVERALL EVALUATION: Group 2B: The agent is possibly carcinogenic to humans.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌物分类
国际癌症研究机构致癌物：N,N'-二乙酰联苯胺
IARC Carcinogenic Agent:N,N'-Diacetylbenzidine
来源:International Agency for Research on Cancer (IARC)
毒理性
致癌物分类
国际癌症研究机构（IARC）致癌物分类：2B组：可能对人类致癌
IARC Carcinogenic Classes:Group 2B: Possibly carcinogenic to humans
来源:International Agency for Research on Cancer (IARC)
IARC Monographs:Volume 16: (1978) Some Aromatic Amines and Related Nitro Compounds – Hair Dyes, Colouring Agents and Miscellaneous Industrial Chemicals
来源:International Agency for Research on Cancer (IARC)
毒理性
暴露途径
该物质可以通过吸入其气溶胶和经口摄入而被人体吸收，达到有害的量。
The substance can be absorbed into the body in hazardous amounts by inhalation of its aerosol and by ingestion.
来源:ILO-WHO International Chemical Safety Cards (ICSCs)
N,N'-DIACETYLBENZIDINE WAS A METABOLITE PRESENT IN THE URINE OF MALE SPRAGUE-DAWLEY RATS FOLLOWING 4 IP INJECTIONS OF 50 MG 4,4'-DINITROBIPHENYL & OF MALE GUINEA-PIGS FOLLOWING 4 IP INJECTIONS OF 35 MG.
The average environmental exposure levels of four of the workers /in a dye manufacturing facility/ were 4.3, 5.2, 11.7, and 17.4 mg total particulate/cu m. The corresponding urinary concentrations of benzidine average 52, 11, 10, and 112 ppb, respectively /SRP: from the precursor during manufacturing/. /Benzidine-based dyes/
The major route of excretion in rats after a single oral admin of 0.5-50 mg/kg radiolabeled benzidine appeared to be via the feces ... . At the lowest dose studied, 74% of the radiolabel was excreted in the feces during the first 3 days after exposure, as opposed to only 17% in the urine. With incr dose the percentage of radiolabel excreted in the feces decr, while that in the urine incr. At the low and mid-level doses (0.5 and 5.0 mg/kg), the major radiolabeled cmpd were identified as 3-hydroxy-N,N'-diacetylbenzidine glucuronide (39 and 37%), N,N'-diacetylbenzidine (13 and 17%), N-hydroxy-N,N'-diacetylbenzidine glucuronide (4 and 5%), N-acetylbenzidine (3 and 4%), and free benzidine (2%). As the dose was incr (50 mg/kg), the percentage of N-hydroxy-N,N'-diacetylglucuronide incr substantially (to 24%), largely at the expense of N,N'-diacetylbenzidine (reduced to 4%). No radioactivity was detected in expired air.
Urinary excretion of benzidine and its metabolites was found to occur in humans during workshift exposure, which was determined to be primarily dermal, although inhalation may also have been a contributory route ... . Mean concn of urinary cmpd detected after exposure in the spring were: benzidine (0.28 mg/l), N-acetylbenzidine (0.27 mg/l), N,N'-diacetylbenzidine (0.52 mg/l), and conjugated 3-hydroxybenzidine (3.9 mg/l) ... . When determined during hot, humid weather, these values incr 1.5- to 5-fold, presumably due to enhanced dermal contact and subsequent absorption. Fecal excretion was not determined.
Pd(OAc)<sub>2</sub>/PPh<sub>3</sub>-Catalyzed Desulfonylative Homocoupling of Arylsulfonyl Chlorides
作者：Qiao Zhao、Liangshun Chen、Hongyue Lang、Shengying Wu、Limin Wang
DOI：10.1002/cjoc.201400868
日期：2015.5
The Pd‐catalyzed homodimerization with respect to arylsulfonylchlorides as an efficient method for the synthesis of biaryls has been developed. This desulfonylative reaction which was performed at reflux in 1,4‐dioxane for 4 h under air afforded the desired products in good to excellent yields.
the assignment of the absolute configuration of chiral 2‐alkyl‐substituted carboxylicacids and primary amines by [α]D measurements has been developed. The method requires the conversion of the chiralacids or amines into the corresponding 4,4′‐disubstituted biphenylamides or biphenylazepines, respectively. In these derivatives a central‐to‐axial chirality transfer induces a preferred torsion in the biphenyl
Iterative double cyclization reaction by S<sub>RN</sub>1 mechanism. A theoretical interpretation of the regiochemical outcome of diazaheterocycles
作者：Lucas E. Peisino、Gloria P. Camargo Solorzano、María E. Budén、A. B. Pierini
DOI：10.1039/c5ra04563k
日期：——
In this report, we present a synthetic and mechanistic study of novel iterative double cyclization intramolecular SRN1 reactions from diamides bearing two aryliodide moieties. This cyclization affords aromatic diazaheterocyclic compounds in good yields. Two synthetic strategies were employed for their preparation: intramolecular SRN1 and Homolytic Aromatic Substitution. The mechanism is non-trivial
Reactions of Tosylhydrazide Derivatives Having Olefinic Groups
作者：Tadashi Sato、Itomi Homma
DOI：10.1246/bcsj.44.1885
日期：1971.7
85% aqueous acetic acid, a smooth decomposition was induced and β-tosylketones (4) were obtained in fair yields. Tosylhydrazones, devoid of an olefinic group in the specified position, failed to undergo the present reaction. When allyl halides (17) were reacted with the anion of tosylhydrazide in DMSO, substitution occurred on the N-1 of tosylhydrazide, unlike as in the case of the reaction of chlorides
A novel symmetrical bis-benzimidazole was designed as DNA minor groove binder. Molecular modeling study showed that it could dock into the minor groove of DNA. Several derivatives were synthesized and confirmed by IR, MS, and 1H NMR. All these novel compounds were screened for cytotoxic activity on SKOV-3, HeLa, and BGC-823 cell lines in vitro. Some compounds showed IC50s in the single-digit micromolar
一种新型的对称双苯并咪唑被设计为DNA小沟结合剂。分子建模研究表明，它可以插入DNA的小沟中。合成了几种衍生物，并通过IR，MS和1 H NMR确认。所有这些新化合物中筛选出细胞毒活性在SKOV-3，HeLa和BGC-823细胞系在体外。一些化合物对数种肿瘤细胞系的细胞毒性显示在数微摩尔范围内的IC 50 s。
