Intramolecular carboxylic group‐assisted cleavage of N‐(2‐hydroxyphenyl)phthalamic acid (7) and N‐(2‐methoxyphenyl)phthalamic acid (8): Absence of intramolecular general acid catalysis due to 2‐OH in 7

Abstract

The values of pseudo first-order rate constants (k obs ) for the cleavage of N-(2-hydroxyphenyl)phthalamic acid (7), obtained at 4.9 × 10 −2 M HCl, 35 • C, and within CH 3 CN content range 2-80% (v/v) in mixed aqueous solvent are smaller than k obs for the cleavage of N-(2-methoxyphenyl)phthalamic acid (8) INTRAMOLECULAR CARBOXYLIC GROUP-ASSISTED CLEAVAGE 747 by nearly 1.5-to 2-fold. These observations show the absence of expected intramolecular general acid catalysis due to 2-OH group in 7. The values of k obs for the cleavage of 7 and 8 decrease by more than 20-fold with the increase in the content of CH 3 CN from 2 to 80-82% (v/v) in mixed aqueous solvent. The kinetic data reveal that in acidic aqueous cleavage of 7, N-cyclization (leading to the formation of imide) and O-cyclization (leading to the formation of phthalic anhydride) vary from ∼10 to 15% and ∼90 to 85%, respectively, with the increase in CH 3 CN content from 2 to 80% (v/v). Similar increase in CH 3 CN content causes increase in N-cyclization from ∼0 to 5% and decrease in O-cyclization from ∼100 to 95% in the acidic aqueous cleavage of 8. Some speculative, yet conceivable, reasons for nearly 10 and 0% N-cyclization in the cleavage of respective 7 and 8 at low content of CH 3 CN have been described.

Kinetic Evidence for Near Irreversible Nonionic Micellar Entrapment ofN-(2′-Methoxyphenyl)phthalimide (1) under the Typical Alkaline Reaction Conditions

“…The values of δ 1 and δ 2 , at 290 nm, are 2480 and 5570 M −1  cm −1 [15], respectively, in aqueous alkaline solvent containing 2% v/v CH 3 CN. The values of δ 1 are independent of [C m E n ] T [13].…”

“…The values of k 2 (at 35°C) are almost zero and 12 × 10 −4  s −1 at 1.0 mM NaOH and 49 mM HCl, respectively [15]. The efficient reactivity of nonionized 2 (i.e., 2H ) towards the formation of PAn is primarily due to intramolecular carboxylic group—assisted cleavage of 2H [15].…”

“…Although the calculated values of k 1 are not very reliable because they are derived from only either two or one data point(s), these values of k 1 appear to be plausible for the reason that the value of k 1 at pH ~3.5, in mixed aqueous solvent containing 2% v/v CH 3 CN, is 67 × 10 −8  s −1 [16]. Under such typical conditions, the value of k 2 is 120 × 10 −5  s −1 and it decreases from 120 × 10 −5 to 6.6 × 10 −5  s −1 with increase in CH 3 CN content from 2 to 82% v/v [15]. …”

Effects of Non-Ionic Micelles on the Rates of Intramolecular General Base-Assisted Nucleophilic Reactions of Piperidine with Ionized Phenyl Salicylate

“…Furthermore, the formation of 3 and 4 in the respective alkaline hydrolyses of 1 and 2 were confirmed by monitoring the disappearance of reactant 3 and 4, generated from acidification of the reaction products of alkaline hydrolyses of 1 and 2, respectively, at respectively 280 nm and 285 nm where the products turned out to be 100% phthalic acid and 2-hydroxyaniline for 3 and phthalic acid and 2-methoxyaniline for 4 [7]. A single kinetic run was also carried out at acidic pH using synthetic 3 (i.e.…”

“…Synthesis of N-(2 0 -hydroxyphenyl)phthalimide (1) and N-(2 0 -methoxyphenyl)phthalimide (2) has been described in an earlier report [7]. All other chemicals used were commercial products of highest available purity.…”