Facile solvolysis of a surprisingly twisted tertiary amide

Bloomfield, Aaron J.; Chaudhuri, Sanjay; Mercado, Brandon Q.; Batista, Víctor S.; Crabtree, Robert H.

doi:10.1039/c5nj02449h

Cited by 4 publications

(4 citation statements)

References 40 publications

(63 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the case of R2 A , we were able to form a sufficient number of stable junctions to measure the conductance and I-V characteristics, despite the fact that the bent configuration is energetically favored. 49 Considering the Boltzmann distribution and energy difference between the linear and bent configurations, roughly 4% of R2 A molecules are in their linear configuration in solution at room temperature. In addition, the mechanical force imparted by the gold tip pulling away from the surface may also increase the probability of stable junction formation when the energy difference between the bent and linear configuration is relatively small, as is the case with R2 A .…”

Section: Resultsmentioning

confidence: 99%

Structure–function relationships in single molecule rectification by N-phenylbenzamide derivatives

et al. 2016

Self Cite

View full text Add to dashboard Cite

We examine structure-function relationships in a series of N-phenylbenzamide (NPBA) derivatives by using computational modeling to identify molecular structures that exhibit both rectification and good conductance together with experimental studies of bias-dependent single molecule conductance and rectification behavior using the scanning tunneling microscopy break-junction technique. From a large number of computationally screened molecular diode structures, we have identified NPBA as a promising candidate, relative to the other structures that were screened. We demonstrate experimentally that conductance and rectification are both enhanced by functionalization of the NPBA 4-carboxamido-aniline moiety with electron donating methoxy groups, and are strongly correlated with the energy of the conducting frontier orbital relative to the Fermi level of the gold leads used in break-junction experiments.

show abstract

Section: Resultsmentioning

confidence: 99%

Structure–function relationships in single molecule rectification by N-phenylbenzamide derivatives

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…In contrast to 2° amides, for which the trans conformation is nearly universally favored over the cis conformation (as shown in Figures and ), N -alkyl- N -aryl 3° amides demonstrate the opposite conformational preference. Both experimental and computational results from dozens of independent researchers, together studying hundreds examples of N -alkyl- N -aryl 3° amides have clearly identified that the cis conformation is generally favored over the trans conformation by between 0.5 and 5 kcal/mol. − Multiple studies have even taken advantage of this conformational preference, using 3° amides as cis backbones for chelating ligands and macromolecular architecture, , for preorganization to facilitate synthesis of lactams, , or for restricting rotation. − Okamoto et al synthesized 3° N -pyridyl amides and demonstrated that the conformational preference can switch upon the addition of acid , or in solvents capable of hydrogen bonding …”

Section: Introductionmentioning

confidence: 99%

“…In many cases, especially when the alkyl substituent is a methyl group, it may appear at first glance that purely steric considerations predict the oppositeplacing the bulkier aromatic substituent near the oxygen of the amide and the less bulky methyl group near the larger organic portion (R 1 in Figure 1). In some cases, 7,25 the steric strain between the aromatic substituent and R 1 is sufficiently unfavorable to substantially distort the planarity of the amide itself, weakening the N−C bond of the amide and enhancing the rate of solvolysis 7 or allowing insertion of transition metals into the N−C bond. 25 A few studies over the course of the last 30 years have attempted to provide an explanation for this change in conformational preference.…”

Section: Introductionmentioning

confidence: 99%

Why Do N-Alkylated Anilides Bend Over? The Factors Dictating the Divergent Conformational Preferences of 2° and 3° N-Aryl Amides

Pros

Bloomfield

2019

J. Phys. Chem. A

Self Cite

View full text Add to dashboard Cite

The conformational preferences of 28 sterically and electronically diverse N-aryl amides were determined using density functional theory (DFT), using the B3LYP functional and 6-31G(d) basis set. For each compound, both the cis and trans conformers were optimized, and the difference in ground state energy calculated. For six of the compounds, the potential energy surface was determined as a function of rotation about the N-aryl bond (by 5° increments) for both cis and trans conformers. A natural bond orbital (NBO) deletion strategy was also employed to determine the extent of the contribution of conjugation to the energies of each of the conformers. By comparing these computational results with previously reported experimental data, an explanation for the divergent conformational preferences of 2° N-aryl amides and 3° N-alkyl-N-aryl amides was formulated. This explanation accounts for the observed relationships of both steric and electronic factors determining the geometry of the optimum conformation, and the magnitude of the energetic difference between cis and trans conformers: except under the most extreme scenarios, 2° amides maintain a trans conformation, and the N-bound arene lies in the same plane as the amide unless it has ortho substituents; for 3° N-alkyl-N-aryl amides in which the alkyl and aryl substituents are connected in a small ring, trans conformations are also favored, for most cases other than formamides, and the arene and amide remain in conjugation; and for 3° N-alkyl-N-aryl amides in which the alkyl and aryl substituents are not connected in a small ring, allylic strain between the two N-bound substituents forces the aryl substituent to rotate out of the plane of the amide, and the trans conformation is destabilized with respect to the cis conformation due to repulsion between the π system of the arene and the lone pairs on the oxygen atom of the carbonyl. The cis conformation is increasingly more stable than the trans conformation as electron density is increased on the arene because the more electron-rich arenes adopt a more orthogonal arrangement, increasing the interaction with the carbonyl oxygen, while simultaneously increasing the magnitude of the repulsion due to the increased electron density in the π system. The trans conformation is favored for 2° amides even when the arene is orthogonal to the amide, in nearly all cases, because the C–N–C bond angle can expend at the expense of the C–N–H bond angles, while this is not favorable for 3° amides.

show abstract

“…We calculated the values of r, d, φ1, and φ2 of 2-oxabicyclo[2.2.2]octanes from the X-ray data of compounds 30, 57. The related parameters for bicyclo[2.2.2]octanes 58, 31 59, 32 and 60 33 were calculated from their X-ray data published in the literature. The corresponding parameters for the parasubstituted phenyl ring were calculated from the reported crystal structure of the anticancer drug Imatinib (Figure 2).…”

mentioning

confidence: 99%

An “Ideal” Bioisoster of the para-substituted Phenyl Ring

Mykhailiuk

Levterov

Panasyuk

et al. 2023

Preprint

View full text Add to dashboard Cite

The phenyl ring is a basic structural element in chemistry, and we learn about it already in school. We have developed an “ideal” saturated bioisoster of the para-substituted phenyl ring, - 2 oxabicyclo[2.2.2]octane. Its incorporation into Imatinib drug led to dramatic improvement of all physicochemical properties. This study opens new horizons in science, given the commonplace of the phenyl ring everywhere.

show abstract

Facile solvolysis of a surprisingly twisted tertiary amide

Abstract: A twisted 3° amide is cleaved at the same rate as a methyl ester under alkaline conditions at 22 °C.

Cited by 4 publications

References 40 publications

Structure–function relationships in single molecule rectification by N-phenylbenzamide derivatives

Structure–function relationships in single molecule rectification by N-phenylbenzamide derivatives

Why Do N-Alkylated Anilides Bend Over? The Factors Dictating the Divergent Conformational Preferences of 2° and 3° N-Aryl Amides

An “Ideal” Bioisoster of the para-substituted Phenyl Ring

Contact Info

Product

Resources

About