Chemistry of the Diazeniumdiolates: Z E Isomerism
详细信息 查看全文
- 作者：Yan-Ni Wang ; D. Scott Bohle ; Challice L. Bonifant ; Gwendolyn N. Chmurny ; Jack R. Collins ; Keith M. Davies ; Jeffrey Deschamps ; Judith L. Flippen-Anderson ; Larry K. Keefer ; John R. Klose ; Joseph E. Saav
- 刊名：Journal of the American Chemical Society
- 出版年：2005
- 出版时间：April 20, 2005
- 年：2005
- 卷：127
- 期：15
- 页码：5388 - 5395
- 全文大小：328K
- 年卷期：v.127,no.15(April 20, 2005)
- ISSN：1520-5126
文摘
Here, we explore the chemistry of the previously undocumented E form of diazeniumdiolateshaving the structure R1R2NN(O)=NOR3. Reported crystallographic studies have uniformly revealed the Zconfiguration, and our attempts to observe a Z 
E conversion through thermal equilibration or photochemicalmeans have, until now, consistently failed to reveal a significant amount of a second conformer. As atypical example, the NMR spectrum of trimethyl derivative Me2NN(O)=NOMe revealed no evidence for asecond configuration. Electronic structure calculations attribute this finding to a prohibitively highinterconversion barrier of ~40 kcal/mol. A similar result was obtained when we considered the case of R1= Me = R3 and R2 = H at the same levels of theory. However, when MeHNN(O)=NOMe was ionized bydissociating the N-H bond, the barrier was calculated to be lower by approximately 20 kcal/mol, with theE form of the anion being favored over Z. This circumstance suggested that an E isomer might be isolableif a Z anion were formed and given sufficient time to assume the E configuration, then quenched by reactionwith an electrophile to trap and neutralize the E form and restore the putatively high interconversion barrier.Consistent with this prediction, basifying iPrHNN(O)=NOCH2CH2Br rapidly led to a six-memberedheterocycle that was crystallographically characterized as containing the -N(O)=NO- functional group inthe E configuration. The results suggest an approach for generating pairs of Z and E diazeniumdiolates forsystematic comparison of the rates at which the individual isomers release bioactive NO and of otherphysicochemical determinants of their biomedical utility.
E conversion through thermal equilibration or photochemicalmeans have, until now, consistently failed to reveal a significant amount of a second conformer. As atypical example, the NMR spectrum of trimethyl derivative Me2NN(O)=NOMe revealed no evidence for asecond configuration. Electronic structure calculations attribute this finding to a prohibitively highinterconversion barrier of ~40 kcal/mol. A similar result was obtained when we considered the case of R1= Me = R3 and R2 = H at the same levels of theory. However, when MeHNN(O)=NOMe was ionized bydissociating the N-H bond, the barrier was calculated to be lower by approximately 20 kcal/mol, with theE form of the anion being favored over Z. This circumstance suggested that an E isomer might be isolableif a Z anion were formed and given sufficient time to assume the E configuration, then quenched by reactionwith an electrophile to trap and neutralize the E form and restore the putatively high interconversion barrier.Consistent with this prediction, basifying iPrHNN(O)=NOCH2CH2Br rapidly led to a six-memberedheterocycle that was crystallographically characterized as containing the -N(O)=NO- functional group inthe E configuration. The results suggest an approach for generating pairs of Z and E diazeniumdiolates forsystematic comparison of the rates at which the individual isomers release bioactive NO and of otherphysicochemical determinants of their biomedical utility.