AMINATION OF ARYL SULFAMATE ESTERS - A CONVENIENT GENERAL-SYNTHESIS OF ALIPHATIC SULFAMIDES
AMINATION OF ARYL SULFAMATE ESTERS - A CONVENIENT GENERAL-SYNTHESIS OF ALIPHATIC SULFAMIDES
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DOI：
10.1021/jo01314a034
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发表时间：
1980-01-01
影响因子：
3.6
通讯作者：
DUBOIS, GE
中科院分区：
文献类型：
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作者：
DUBOIS, GE
然而，有趣的是，苯胺的缓慢反应（方案I），需要在42 ℃下68小时以达到94%的转化率（66%产率的5），也产生28%产率的N，N ′-二苯基磺酰胺（7）。1推测，弱亲核性苯胺对4的攻击速率足够低，使得未反应的苯胺促进芳基酯5的碱催化消除为瞬时稳定的N-磺酰胺6，其迅速被苯胺捕获，得到7。这一观察结果，再加上缺乏一个温和的，高产率的制备方法对称和混合磺酰胺，2 - 3，避免使用强烈的亲电试剂，如SO2 Cl 2和PC 1 S，促使我们检查1与胺的反应中的一些细节。我们对1与胺产生磺酰胺的拟议反应有些担忧，因为1的NH质子4的酸性和脂族胺的碱性，如在水性介质中通过pK&测量所建议的，将强制形成盐8（方案II）。没有显著浓度的游离胺，衍生自8的磺酰胺9不能被胺捕获以产生磺酰胺产物。使用大量过量的胺并不代表解决方案，因为如果形成1的二价阴离子，就像1与无机碱反应的情况一样，1将不太可能断裂。因此，我们惊喜地发现，用1当量的苄胺在沸腾的二氧六环中处理1 2小时，导致定量裂解，产生邻苯二酚和N，N ′-二苄基磺酰胺（10）。显然存在足够的游离胺以允许高产率转化。用几种胺处理1的结果总结在表I中。因此，用伯胺、支链伯胺和仲胺进行1的胺化似乎进行得很好。然而，芳香胺的反应比较困难。因此，该反应似乎是制备二烷基磺酰胺的良好的通用方法。然而，芳烷基或二芳基磺酰胺的制备不太有吸引力，因为4与芳胺的反应非常缓慢，而中间体磺胺的反应甚至更缓慢。（2）亲核性大致与碱性平行（March，J.《高等有机化学》，第2版;麦格劳-希尔：纽约，1977，第322-5页和其中的参考文献），并且，例如，由于苯胺的碱度比苄胺的碱度低得多[pff，（苯胺）= 4.63，pK，（苄胺）= 9.33（“Handbook of Chemistry and Physics”，第50版;化学橡胶公司Cleveland，OH，1969，p D115）]，亲核性预期会降低相当的量。
Interestingly, however, the sluggish reaction of aniline (Scheme I), which required 68 h at 42 C for 94% con-version (66% yield of 5), also produced a 28% yield of iV, iV'-diphenylsulfamide (7). 1 Presumably, the rate of attack on 4, by the poorly nucleophilic aniline, is low enough such that unreacted aniline promotes base-cata-lyzed elimination of the aryl ester 5 to the transiently stable N-sulfonylamine 6 which is quickly trapped by an-iline to give 7. This observation, coupled with the absence of a mild, high-yield preparative method for symmetrical and mixed sulfamides, 2 3 which avoids the use of strongly electrophilic agents such as S02C12 and PC1S, prompted us to examine the reactions of 1 with amines in some detail. We viewed the proposed reaction of 1 with amines to produce sulfamides with some apprehension since the acidity of the NH proton4 of 1 and the basicity of aliphatic amines, as suggested by pK& measurements in aqueous media, would mandate the formation of a salt 8 (Scheme II). Without a significant concentration of free amine, the'-sulfonylamine 9, derived from 8, could not be trapped by the amine to yield sulfamide products. The use of the amine in large excess does not represent a solution since the dianion of 1, if formed, as is apparently the case on reaction of 1 with inorganic bases, 1 would be unlikely to fragment. We were thus pleasantly surprised to find that treatment of 1 with 1 equiv of benzylamine in boiling dioxane for 2 h resultedin a quantitative cleavage to produce catechol and N, iV'-dibenzylsulfamide (10). Apparently enough free amine is present to allow a high-yield conversion. The results of treatment of 1 with several amines are summarized in Table I. Thus, animation of 1 appears to proceed well with primary amines, branched primary amines, and secondary amines. Aromatic amines react only with difficulty, how-ever. This reaction therefore appears to be a good general method for preparation of dialkylsulfamides. Preparation of arylalkyl-or diarylsulfamides is less attractive, however, due to a very slow reaction of 4 with aromatic amines and an even more sluggish reaction of the intermediate sulfa-(2) Nucleophilicity roughly parallels basicity (March, J.“Advanced Organic Chemistry”, 2nd ed.; McGraw-Hill: New York, 1977, pp 322-5 and references therein) and, eg, since aniline’s basicity is much lower than that of benzylamine [pff,(aniline)= 4.63, pK,(benzylamine)= 9.33 (“Handbook of Chemistry and Physics”, 50th ed.; The Chemical Rubber Co.; Cleveland, OH, 1969, p D115)], the nucleophilicity is expected to be lower by a comparable amount.