Reactivity of some nucleophiles and amino-acid derivatives towards 4-dimethylamino-1-methoxycarbonylpyridinium chloride

Abstract

The kinetics of the reaction of 4-dimethylamino-1 -methoxycarbonylpyridinium chloride (MeOCOPy+NMe,) with water and nucleophiles have been examined as a model reaction of 1 -acyl-4-dimethylaminopyridinium ions with amino-acid residues of proteins.Second-order rate constants determined for a series of 11 L-amino-acids allow the calculation of the relative reactivity of the different functional groups as well as the prediction of the selectivity of the reagent at various pH values (thiol, phenol, and imidazole functions are much more reactive than primary amines).The reagent MeQCOPy+NMe, is particularly insensitive to hydrolysis in the pH range 5-7, a region in which hydrolysis is often competitive with nucleophilic reactions. A Bronsted correlation is observed with primary amines; the slope is (3 = 1, a value which is usually interpreted as a rate-determining breakdown of the tetrahedral intermediate. For thiol and phenol functional groups, the attack is the rate-determining step.A comparison with AclmH+ reactivity shows a similar behaviour for both substrates although MeOCOPy+NMe, is much less reactive.

Modification of Both the Electrophilic Center and Substituents on the Nonleaving Group in Pyridinolysis of O-4-Nitrophenyl Benzoate and Thionobenzoates

“…One of the initial products (i.e., 1-thionobenzoylpyridinium ion or its oxygen analogue) was not isolated but hydrolyzed to yield thiobenzoate (or benzoate for reactions of 1c ). Similar pyridinium intermediates have been reported in pyridinolyses of 2,4-dinitrophenyl methyl thionocarbonate, methyl chloroformate, and acetic anhydride. , Since the pyridinium intermediate in the current reactions does not absorb at 410 nm, where the reactions were monitored, the k N values obtained are the rate constants for formation of the intermediate and 4-nitrophenoxide ion.…”

“…The contrasting reactivity order is consistent with a hard and soft acids and bases (HSAB) analysis since the softer thiocarbonyl group (relative to carbonyl) would exhibit lower reactivity toward hard bases such as OH - , EtO - , ArO - , and alicyclic secondary amines. On the contrary, pyridines have been suggested to be relatively soft nucleophiles compared to isobasic alicyclic secondary amines 16a. Thus, the current result that 2c is more reactive than 1c toward pyridines is also in accordance with the HSAB principle.…”

Effect of Changing Electrophilic Center from CO to CS on Rates and Mechanism: Pyridinolyses of O-2,4-Dinitrophenyl Thionobenzoate and Its Oxygen Analogue

“…The initial product (e.g., 1-thionobenzoyl-4-dimethylaminopyridinium ion or its oxygen analogue) was detected as explained in the Experimental Section but hydrolyzed to yield thiobenzoate (or benzoate for the reaction of 2 ) as shown in Scheme . Similar intermediates have been reported for the pyridinolyses of 5 , 6 , 7 ,14a methyl chloroformate, 14b-d and acetic anhydride 14e. Since the intermediate does not absorb at 420 nm where the reactions were monitored, the k N values obtained are the macroscopic rate constants for the formation of the intermediate and 2,4-dinitrophenoxide ion.…”

“…The contrasting reactivity order might be explained by the hard and soft acids and bases (HSAB) principle; i.e., the soft thiocarbonyl group relative to carbonyl would exhibit higher reactivity toward relatively soft pyridines of low basicity (p K a ≤ 9.12), while the harder nature of the carbonyl group would prefer to bind hard oxyanionic nucleophiles (e.g., OH - , EtO - and phenoxide anions) and relatively hard alicyclic secondary amines . However, the qualitative HSAB principle cannot explain the finding that 3 is more reactive than 4 toward relatively hard primary amines, , while 6 is less reactive than its oxygen analogue toward relatively soft pyridines 14a…”

“…Effect of Amine Nature on Rate. Tertiary amines have generally been reported to be more reactive than secondary and primary amines of similar basicity for ester aminolyses 4a,7e,,14a, as well as for deprotonations of various carbon acids (e.g., phenylnitromethane,25a 4-nitrophenylacetonitrile,25b and 9-carbomethoxyfluorene 25c ) and additions to activated ethylenes (e.g., benzylidene Meldrum's acid 25d and β-methoxy-α-nitrostylbene 25e ). Since solvation energy has been reported to decrease in the order RNH 3 + > R 2 NH 2 + > R 3 NH + , solvent effect has been suggested to be responsible for the reactivity order …”