NUCLEOPHILIC AROMATIC-SUBSTITUTION ON ESTER DERIVATIVES OF CARCINOGENIC N-ARYLHYDROXAMIC ACIDS BY ANILINE AND N,N-DIMETHYLANILINE
NUCLEOPHILIC AROMATIC-SUBSTITUTION ON ESTER DERIVATIVES OF CARCINOGENIC N-ARYLHYDROXAMIC ACIDS BY ANILINE AND N,N-DIMETHYLANILINE
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DOI：
10.1021/jo00079a028
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发表时间：
1993-12-31
影响因子：
3.6
通讯作者：
MANITSAS, RK
中科院分区：
文献类型：
--
作者：
NOVAK, M;RANGAPPA, KS;MANITSAS, RK
N-（戊酰氧基）-2-（乙酰氨基）芴（1b）和N-（磺酰基）-4-（乙酰氨基）-联苯（2a）在MeOH中的分解主要通过N-0键裂解生成恶唑（5,6,23）、甲氧基加合物（7,8,24,25,26）和重排产物（10b,11b,28）。次要的酯甲醇分解途径导致n -芳基羟肟酸（9,27）。在0.1 M苯胺(3)的存在下，1b产生了一些加合物（14-18），与先前3与N-（磺酰基）-2-（乙酰氨基）芴（1a）反应得到的加合物（14-18）相同。这在1b分解的速率常数不变的情况下发生。在0.1 m3时，除重排产物10波段11b外，所有1b的溶剂溶解产物都降低到可检测水平以下。对于2a也得到了类似的结果，在3存在的情况下得到30-35，在N，N-二甲基苯胺存在的情况下得到36-38(4)。这些结果与方案V的机制一致，即N-O键异裂导致一个紧密的离子对，该离子对可以进行内部返回以产生重排产物或扩散分离以产生自由离子。游离的氮离子可以被溶剂或加入的亲核试剂捕获。n -乙酰- n -（4-联苯基）nitnitium离子（45）和n -乙酰- n -（2-芴基）nitnitium离子（48）与溶剂反应足够慢，可以与强亲核试剂发生选择性反应。由于1a、1b和2a跨越了常见N-芳基羟肟酸在水中进行N- o键异解的酯衍生物的反应性范围，因此似乎所有致癌酯都将通过S(N)1机制与简单芳香胺发生反应。
Decomposition of N-(pivaloyloxy)-2-(acetylamino)fluorene (1b) and N-(sulfonatooxy)-4-(acetylamino)-biphenyl (2a) in MeOH occurs predominately via N-0 bond cleavage to yield oxazoles (5, 6, 23), methoxy adducts (7,8,24,25,26), and rearrangement products (10b,11b,28). Minor ester methanolysis paths lead to the N-arylhydroxamic acids (9, 27). In the presence of 0.1 M aniline (3), 1b yields a number of adducts (14-18) identical to those previously obtained from the reaction of 3 with N-(sulfonatooxy)-2-(acetylamino)fluorene (1a). This occurs with no change in the rate constant for decomposition of 1b. At 0.1 M 3 all solvolysis products of 1b, except the rearrangement products 10 band 11b, are reduced below detectable levels. Similar results were obtained for 2a, which yields the adducts 30-35 in the presence of 3 and 36-38 in the presence of N,N-dimethylaniline (4). These results are consistent with a mechanism (Scheme V) in which the N-O bond heterolysis leads to a tight ion pair that can undergo internal return to yield the rearrangement products or diffusional separation to yield the free ion. The free nitrenium ion can be trapped by solvent or added nucleophiles. Both the N-acetyl-N-(4-biphenylyl)nitrenium ion (45) and the N-acetyl-N-(2-fluorenyl)nitrenium ion (48) react slowly enough with the solvent to undergo selective reaction with strong nucleophiles. Since 1a, 1b, and 2a span the reactivity range of the ester derivatives of the common N-arylhydroxamic acids which undergo N-O bond heterolysis in H2O, it appears that all of the carcinogenic esters will react with simple aromatic amines via an S(N)1 mechanism.