Acid-base chemistry of singlet carbenes Flashcards
What is the key carbene acid-base reaction?
Deprotonation of a carbocation/protonation of a carbene. Conjugate acid of singlet carbene = carbocation.
Why is carbene pKa important?
Helpful to understand substituent effects and carbene generation in situ. Conjugate acids of carbenes typically weak carbon acids with pKas > 14 (difficult to measure).
How can we determine pKa of carbenes?
Bracketing indicator method in DMSO/MeCN/THF: indirect probing by measurement of Keq (of acid-base equilibrium between carbene and indicator), limited by range of a suitable indicator of known pKa.
Kinetic method in aqueous solution: indirect determination of Ka by access of rate constants for forward and reverse directions of acid dissociation of equilibrium. pKa = - log (kH2O/kH3O+)
What is a standard method to determine pKa in aqueous range?
Spectrophotometric titrations.
How do NHC ring heteroatoms affect pKa?
Additional heteroatoms lead to a decrease in pKa. Electron-withdrawing ring heteroatoms destabilise the positive conjugate acid, product NHC is favoured as a neutral species.
How do N-aryl vs N-alkyl substituents affect pKa?
Generally, N-aryl substituents decrease pKa by electron-withdrawing field/inductive effect. Destablises conjugate acid relative to neutral carbenes.
N-alkyl substituents increase pKa. Linear have very small effect. Branched increase pKa by about 2 units. This is due to donating effects of alkyl chains.
What is benzylation?
Addition of benzene group.
What is annulation?
Fused ring formation, e.g. benzannulation.
How do benzylation and annulation affect pKa?
Benzannulation big example: coplanarity with NHC leads to resonance stabilisation of carbene negative charge, increases carbene stability decreasing pKa.
How does ring size affect pKa?
Ring size dictates NHC internal angle, enforced increases in NCN angle. Singlet carbenes stabilised by larger external angles with more s character. Larger internal angles (larger ring sizes) destabilising. Leads to increase in pKa.
How does linker length affect pKa?
Linkers show no evidence of cooperativity, however cationic substituent effect seen. Magnitude decreases with distance - inductive effect.
How does aromaticity affect pKa?
Similar pKas of aromatic and non-aromatic species, due to retention of aromaticity/non-aromaticity. Overall effects concealed.
What is a “normal” carbene?
Indicates carbene formation in between the heteroatoms. e.g. triazolium, thiazolium, imidazolium and imidazoliniums, etc.
What is an “abnormal” carbene?
Mesoionic carbenes, cannot draw a formally neutral structure.
Rank effects on pKa from most important to least.
Normal vs abnormal carbenes > ring size ~ No. of heteroatoms»_space; N-aryl substituents»_space; benzannulation ~ linker length > branched N-alkyl substituents»_space; linear N-alkyl substiuents, aromaticity.
