Mohammad Niyaz Khan

Effects of ionic and non-ionic micelles on rate of hydroxide ion-catalyzed hydrolysis of securinine

The effects of micelles of cetyltrimethylammonium bromide (CTABr), tetradecyltrimethylammonium bromide (TTABr), sodium dodecyl sulfate (SDS) and polyoxyethylene 10 lauryl ether (C12E10) on the rates of alkaline hydrolysis of securinine were studied at a constant [−OH] (0.05 M). An increase in the total concentrations of CTABr, TTABr, SDS and C12E10 from 0.0 to 0.2 M causes a decrease in the observed pseudo-first-order rate constants (kobs) by factors of ca 2.5, 3, 7 and 4, respectively. The observed data are explained in terms of pseudophase and pseudophase ion-exchange (PIE) models of micelle. The binding constants, KS, of securinine with SDS, C12E10, CTABr and TTABr micelles are 32.4, 14.8, 22.1, and 9.1 M−1, respectively. The magnitudes of the second-order rate constants, kM, for the reactions in the micellar pseudophase are negligible compared with the corresponding rate constant, kW, for the reaction occurring in the aqueous pseudophase for CTABr, TTABr, SDS and C12E10.

Suggested Improved Method for the Ing‐Manske and Related Reactions for the Second Step of Gabriel Synthesis of Primary Amines

Abstract This work demonstrates an improvement in the Ing‐Manske and related procedures by the increase of pH of the reaction mixture after the complete disappearance of N‐substituted phthalimide. Hydrazinolysis of N‐phenylphthalimide (1a) gave 80% of the desired primary amines after 5.3 h in the absence of added NaOH. The reaction time was reduced to 1.6 h and 1.2 h when 1 eq. and 5 eq. of NaOH were added to the reaction mixture after the complete disappearance of 1a. Hydroxyaminolysis of N‐(4‐ethylphenyl)phthalimide (1b) gave 80% of the desired primary amines after 7.5 h of reaction time (at added [NaOH] = 0). When 10 eq. and 20 eq. of NaOH were added to the reaction mixture after the disappearance of 1b, the reaction time was reduced to 4 h and 2 h, respectively. Methylaminolysis of N‐(2‐ethylphenyl)phthalimide (1c) gave 80% of the desired primary amines after 1.7 h (at added [NaOH] = 0). The reaction time was reduced to 1 h and 0.7 h when 1 eq. and 25 eq. of NaOH were added to the reaction mixture after the complete disappearance of 1c.

Solvolytic stereoselective coupling reaction of p-methoxyphenylmagnesium bromide with substituted allylic chlorides.

Abstract The α- and γ-coupling reactions of a few substituted allylic chlorides with p-methoxyphenylmagnesium bromide were concluded as to involve the formation of an intimate ion-pair intermediate. The solvents used gave substantial effects of both on the regio- and stereo-selectivity of the reaction.

Kinetics and mechanism of aminolysis of phthalimide and N-substituted phthalimides. Evidence for the occurrence of intramolecular general acid-base catalysis in the reactions of ionized phthalimides with primary amines

The kinetics and mechanism of the reactions of propane-1,3-diamine (PDA) and 1,4-diazabicyclo-[2.2.2]octane(DABCO) with phthalimide (PTH), N-hydroxyphthalimide (NHPH), and N-bromopropyl-phthalimide (NBPPH) and 2-methoxyethylamine with NHPH and NBPPH are described. Both ionized and non-ionized PTH are reactive toward PDA while only ionized NHPH showed reactivity toward PDA and 2-methoxyethylamine under the experimental conditions imposed. The presence and absence of or weak nucleophilic reactivity of DABCO toward neutral and ionized imides, respectively, are noted for PTH and NHPH. Significant nucleophilic reactivity of primary amines and the absence or considerably low nucleophilic reactivity of DABCO toward ionized PTH and NHPH are attributed to the occurrence of intramolecular general acid–base (GA–GB) catalysis due to the presence of a mobile proton at the nucleophilic site of the nucleophile. This intramolecular GA–GB catalysis seems to decrease with increased steric requirements of the leaving group. Diffusion-controlled trapping stepwise and preassociation stepwise mechanisms are suggested in the amino-lysis of non-ionized phthalimides and ionized phthalimides, respectively. Intermolecular GA and GB catalysis has been detected in the reactions of PDA and 2-methoxyethylamine with ionized NHPH and 2-methoxylethylamine with NHPH and ionized NHPH, respectively. Specific-base catalysis could be detected in the reactions of 2-methoxyethylamine with ionized NHPH. The reactions of monoprotonated PDA with ionized NHPH reveal few of favourable electrostatic effects.

Effects of anionic micelles on the intramolecular general-base-catalysed hydrazinolysis and hydrolysis of phenyl salicylate. Evidence for a porous cluster micelle

The hydrazinolysis of phenyl salicylate has been studied in the presence and absence of micelles of sodium dodecyl sulphate (SDS) at 30 °C. The nucleophilic reaction of hydrazine with ionized phenyl salicylate (PS–) involves intramolecular general-base catalysis while the probable intramolecular general-acid catalysis could not be detected in the reaction of non-ionized phenyl salicylate (PSH) with hydrazine. Kinetic data for both hydrolysis and hydrazinolysis of phenyl salicylate are explained in terms of the pseudophase model of micelles. The rate constants for hydrolysis and hydrazinolysis of PS– in micellar pseudophase are either insignificant or significantly smaller compared with the corresponding rate constants in aqueous pseudophase. This is attributed largely to considerably low water activity in the specific micellar environment where micellar bound PS– molecules exist. The micellar bound reactants (PSH and PS–) and products (non-ionized and ionized phenol and N-hydrazinylsalicylamide) appear to exist in the micellar environments of different water activity. The rate constants, Kobs′ increase ca. fivefold with increased [NaOH] from 0.001 to 0.040 mol dm–3 at 0.2 mol dm–3 SDS and 0.08 mol dm–3 NH2NH2. This is attributed to an increase in [PS–] with increase in [NaOH]. These observations favour the porous cluster micellar structure. The values of Kobs remain unchanged with increased concentration of 1,4-diazabicyclo[2.2.2]octane from 0.06 to 0.60 mol dm–3 at 0.3 mol dm–3 SDS, 0.05 mol dm–3 NaOH, and 37 °C. This shows that the presence of SDS micelles does not change the reaction mechanism of aqueous pseudophase hydrolysis and aminolysis of PS–.

Intramolecular general base catalysis and the rate-determining step in the nucleophilic cleavage of ionized phenyl salicylate with primary and secondary amines

The nucleophilic second-order rate constants for the reactions of ionized phenyl salicylate (PS–) with primary and secondary amines have revealed Bronsted plots of slopes βnuc1= 0.52 ± 0.06 and βnuc2= 0.27 ± 0.05, respectively. The suggested stepwise reaction mechanism involves the intramolecular proton transfer from cationic nitrogen to the anionic phenolic oxygen to form the monoanionic tetrahedral addition intermediate as the rate-determining step. The low value of βnuc2 is attributed to the extensive of proton transfer in the late transition state while the large value of βnuc1 is ascribed to the proton transfer in the early transition state of the rate-determining step. However, these low and high values of βnuc2 and βnuc1 respectively, are also compatible with the occurrence of respective early and late transition states in the rate-determining step involving concerted intramolecular general base-catalysed nucleophilic attack at the carbonyl carbon of PS–. Significantly large positive deviations from Bronsted plots have been observed for the reactivities of α-nucleophiles toward PS–. Monoprotonated ethane-1,2-diamine is ca. 20-fold more reactive than would be expected from its basicity, and this is attributed to the occurrence of the intramolecular general acid catalysis. The reactions of PS– with hydroxylamine and N-methylhydroxylamine involve ca.70% aminolysis and ⩽30% transesterification while those with tris-(2-hydroxyethyl)amine involve 100% transesterification. The extremely low reactivity of ammonia compared with that of primary amines of similar basicity indicates that it does not belong to a series of homologous primary amines in its nucleophilic reactivity toward PS–.

Intramolecular general acid–base catalysis and the rate-determining steps in the nucleophilic cleavage of maleimide- with primary amines

The kinetics of nucleophilic cleavage of maleimide have been studied at 30 °C under the buffer solutions of 13 primary amines including three diamines and carbonate. Both ionized (S–) and non-ionized (SH) forms of maleimide have been found to exhibit significant reactivity toward amines and carbonate anion. The respective bimolecular rate constants k1 and k2 for the reactions of nucleophiles with non-ionized and ionized forms of maleimide display Bronsted plots with respective slopes of βnuc1= 0.81 ± 0.15 and βnuc2= 0.48 ± 0.19. The significantly different values of βnuc1 and βnuc2, reveal the involvement of different rate-determining steps in the nucleophilic cleavage of non-ionized and ionized maleimide. The high value of βnuc1 is attributed to the expulsion of the leaving group as the rate-determining step while the value of βnuc2 of 0.48 indicates the nucleophilic attack within the encounter complex as the rate-determining step. The values of βnuc1 and βbnuc2 for the nocleophilic reactivity of diamines were found to be 0.52 ± 0.02 and 0.13 ± 0.02, respectively. The value of βnuc1 of 0.52 has been attributed to intramolecular general acid–base-catalysed expulsion of the leaving group as the rate-determining step. The low value of βnuc2(0.13) reveals the nucleophilic attack as the rate-determining step. A pre-association stepwise mechanism is proposed for the reactions of amines with S– while a diffusion-controlled trapping mechanism is favoured for the reactions of amines with SH. The rate constants k1 and k2 for TRIS, 2-amino-2-methylpropane-1,3-diol, ammonia, and carbonate have been found to show significant negative deviations while hydrazine revealed a large positive deviation from Bronsted plots.

N-(2-Methoxy­phen­yl)phthalimide

The phthalimide fused-ring system and the phenylene ring in the title compound, C15H11NO3, are inclined at an angle of 54.2 (1)°.

Effects of Mixed H2O—CH3Cn And H2O—HCONMe2 Solvents on the Rate Of Cleavage Of N-benzylphthalamic Acid

The values of pseudo first-order rate constants, k1, for the O-cyclization and k3 for N-cyclization of N-benzylphthalamic acid 1, obtained at 0.02 M HCl and 35°C, show a respective nonlinear increase from 17.6 × 10−6 to 29.7 × 10−6 s−1 and decrease from 12.5 × 10−7 to 3.75 × 10−7 s−1 with increase in the CH3CN content from 2 to 60% v/v in mixed aqueous solvent. Increase in the CH3CN content from 60 to 90% v/v decreases k1 from 29.7 × 10−6 to 24.4 × 10−6 s−1 and increases k3 from 3.75 × 10−7 to 14.7 × 10−7 s−1. The respective values of k1 and k3 decrease nonlinearly from 16.0 × 10−6 to 3.0 × 10−6 s−1 and 14.0 × 10−7 to ~4.0 × 10−7 s−1 with increase in the content of N,N-dimethylformamide (HCONMe2) from 2 to 80% v/v in mixed aqueous solvents. These results indicate rather mild rate-retarding effects of mixed H2O—CH3CN and H2O—HCONMe2 solvents on the rates of the intramolecular reactions.

Kinetic evidence for the occurrence of 1,3-proton transfer through a proton-switch mechanism in the aminolysis of salicylate esters

The nucleophilic reactions of primary amines (pKa range 5.97–10.85) with ionized methyl salicylate (MS–) show significant solvent isotope (D2O) effects. Ionized phenyl salicylate (PS–) reveals high reactivity towards primary amines (pKa >8.15) and secondary amines (pKa range 6.24–11.32) with essentially no solvent isotope effects. However, the nucleophilic reactions of primary amines of pKa⩽8.15 with PS– do exhibit solvent isotope effects. These observations, coupled with the absence of nucleophilic reactivity of secondary amines towards MS–, are attributed to the occurrence of 1,3-proton transfer in these reactions.