Ring proton exchange

The suggested reaction mechanism involves a nucleophilic attack of the imine nitrogen at the activated triple bond, followed by a proton exchange, to give a benzimidazolinium system which, by intramolecular attack at the carbonyl group, leads to an epoxide that ring opens to the observed product. For the ethyl derivative (R = Et) a tub conformation could be established by X-ray crystallographic analysis.33... 

After what we have seen to date, it surely comes as no great surprise to find that the ratio of o- to p-product obtained from substitution of C6H5Y, where Y is o-/p-directing, is seldom, if ever, the statistical ratio of 2 1. There is found to be very close agreement between calculation and n.m.r. data for the distribution of +ve charge—p-> o- m—around the ring in the cyclohexadienyl cation (57), which is the Wheland intermediate for proton exchange in benzene (cf. p. 133) ... 

The cyclopropanone intermediate (81) undergoes subsequent addition of eOH, followed by ring-opening to yield the more stable of the two possible carbanions (83, benzyl > primary), followed by proton exchange to yield the rearranged carboxylate anion end-product (84). 

Ring protons of 1,2,3-thiadiazoles are known to undergo rapid deuterium exchange under basic conditions. It has been reported that even weak bases such as phenolate can extract the proton at the 5-position of 4-phenyl-l,2,3-thiadiazole <1999J(P1)1473>. 

A fundamentally different approach to the synthesis of 3-pyrrolines is evidenced in the annulation in Eq. 13.50 [58]. Ethyl 2,3-butadienoate 150 reacts with N-sulfony-limine 151 in the presence of triphenylphosphine under very mild conditions to give JV-protected 3-pyrroline 152 in 90% yield. The mechanism that has been postulated is related to that of the Baylis-Hillman reaction. Michael addition of triphenylphosphine to the allenyl ester generates a zwitterion that combines with the imine to give 153 in a non-concerted process. This is followed by ring closure, proton exchange and expulsion of triphenylphosphine to give 152. This annulation is successful only for aromatic or cinnamyl imines [59]. 

Fig. 6.4 Reversible interconversion of amino acid and keto acid. Conjugation of the imine bond in the aldimine with the electron sink of the pyridine ring plus protonation of the pyridine nitrogen as well as the metal ion - all this results in weakening of the C-H bond of the amino acid residue. Thus, also catalyzed is a-proton exchange, racemization of a chiral center at the a-carbon atom and decarboxylation of the appropriate amino acid. ...

Tautomerism of the proposed pyrrolenin-2-one nucleus of V-2, resulting in proton exchange at C3 and C5 of the five membered ring. Ri, R2, and R3 as in figure 9. 

The presence of a protonated cyclopropyl ring distinguishes the two norbomyl ions and one mi t hope to characterize a stabilized ion by its proton exchange behaviour. To do this one would have to investigate the exchange behaviour of protonated alkylcyclopropanes and tertiary and secondary cations in an acid sufficiently strong to stabilize all species for some time. 

The chelate formation in lithium complexes 17 or 20 contributes to stabilization. Enhancement of kinetic acidity arises from the formation of pre-complexes 16 and 19, respectively. Here, already a dipole is induced and, in addition, proton exchange can proceed intramolecularly via a five- or six-membered ring. Despite these favourable features, the acidity of alkyl carbamates 15 is lower than those of the 1-proton in butane n-BuLi does not lead to deprotonation. In order to suppress carbonyl attack, a branched amino residue NR2 such as diisopropylamino (in Cb) or 2,2,4,4-tetramethyl-l,3-oxazolidin-3-yl (in Cby) is essential. A study on the carbenoid nature of compounds 17 was undertaken by Boche and coworkers. ... 

Ring protons of 1,2,3-thiadiazoles are known to undergo rapid deuterium exchange under basic conditions, yet to date there have been no published estimates or experiments to determine the pA of these protons. Few attempts have even been made to metalate and alkylate this heterocycle. One study <85S945> found that metalation of 5-phenyl-1,2,3-thiadiazole (25) with methyllithium gives 4-lithio-5-phenyl-l,2,3-thiadiazole, which is stable and reacts with aldehydes and ketones in high yields (Equation (11)). Also, treatment of 4-phenyl-1,2,3-thiadiazole with lithium diisopropylamide, in the presence of TMS-Cl, affords 4-phenyl-5-trimethylsilyl-1,2,3-thiadiazole. 

Thiadiazole is a planar, thermally stable, and weakly basic aromatic ring system. Aromatic forms of the 1,2,5-thiadiazole nucleus are generally stable to concentrated mineral acids and are only slightly sensitive to base. Base-catalyzed deuterium exchange of the ring protons can be effected... 

It is well-known that many ILs are not really inert solvents, but can be quite reactive. Dialkylimidazolium salts in particular are prone to deprotonation in the 2-position [69-71]. In addition to this, exchange with D2O was found for all three imidazolium ring protons for halide salts [29,32], but not for BF4 and PF5 anions [32]. Our own work demonstrates that highly pure, neat... 

---