- Preparation method of 4AA
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The invention discloses a preparation method of 4AA. The preparation method comprises the following steps: S1, preparing a first intermediate from benzamide and a formaldehyde aqueous solution; S2, preparing a second intermediate from the first intermediate, thionyl chloride, toluene and n-heptane; S3, preparing a third intermediate from the second intermediate, methyl acetoacetate, sodium methoxide, toluene, diluted hydrochloric acid and isopropanol; S4, preparing a fourth intermediate from the third intermediate, reductase, ethyl acetate, saturated sodium bicarbonate and saturated salt water; S5, preparing a fifth intermediate from the fourth intermediate, imidazole, TBSCL and methylbenzene; S6, preparing a sixth intermediate from the fifth intermediate, ethanolamine, methanol and n-heptane; S7, preparing a seventh intermediate by using the sixth intermediate, a Grignard reagent and n-heptane; and S8, preparing 4AA from the seventh intermediate, ruthenium trichloride, potassium acetate, ethyl acetate, acetic acid and a peracetic acid solution.
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Paragraph 0016; 0018; 0021; 0024
(2021/07/28)
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- Three-component synthesis of amidomethylarenes and -heteroarenes over HΒ zeolite under solvent-free conditions
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A highly efficient and eco-friendly protocol has been described for the synthesis of amidomethylarenes and -heteroarenes via one-pot three-component coupling reaction of amides, aldehydes and (hetero)arenes over a heterogeneous catalyst (Hβ zeolite) in solvent-free conditions. The scope and limitations of this catalytic process are demonstrated with various amides and arenes and the corresponding amidoalkylated arene products were obtained in moderate to excellent yields. The preliminary mechanistic insight (control experiments) suggest that bisamide and/or N-(hydroxymethyl)benzamide are probable intermediates in this reaction. Moreover, the catalyst can be reused without any significant loss of the catalytic activity and only water is produced as by-product.
- Chevella, Durgaiah,Mameda, Naresh,Kodumuri, Srujana,Banothu, Rammurthy,Gajula, Krishna Sai,Kutepov, Boris Ivanovich,Nama, Narender
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- A convenient and clean synthesis of methylenebisamides and carbinolamides over zeolites in aqueous media
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A simple, efficient and environmentally benign protocol for the synthesis of methylenebisamides and carbinolamides in high yields from aromatic amides and formaldehyde in the presence of heterogeneous catalysts (Hβ and NaY zeolites) using water as a solvent is demonstrated. Moreover, the catalyst is recyclable and can be reused without significant loss in its catalytic activity.
- Mameda, Naresh,Marri, Mahender Reddy,Peraka, Swamy,Macharla, Arun Kumar,Kodumuri, Srujana,Chevella, Durgaiah,Naresh, Gutta,Nama, Narender
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- Bi(OTf)3-Catalyzed Multicomponent α-Amidoalkylation Reactions
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A bismuth(III) triflate catalyzed three-component synthesis of α-substituted amides starting from amides, aldehydes, and (hetero)arenes is reported. The reaction has a broad substrate scope, encompassing formaldehyde as well as aryl and alkyl aldehydes. Low catalyst loadings are required, and water is formed as the only side product. The scope and limitation of this method will be discussed.
- Schneider, Angelika E.,Manolikakes, Georg
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p. 6193 - 6212
(2015/06/30)
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- Rate of formation of N-(hydroxymethyl)benzamide derivatives in water as a function of pH and their equilibrium constants
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The third-order rate constants for the pH-dependent formation of the carbinolamides generated from the reaction of formaldehyde and benzamide, 4-chloro, 4-nitro, 4-methyl and 4-methoxybenzamide, are reported. The acid-catalyzed reaction was found to occur via rate-limiting proton transfer, whereas the hydroxide-dependent reaction occurred via a specific-base process. Coupling the rate constants for carbinolamide formation reported herein with the previously established rates for carbinolamide breakdown yielded equilibrium constants for the carbinolamides studied in water.
- Ankem, Ramana V.,Murphy, John L.,Nagorski, Richard W.
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supporting information; scheme or table
p. 6547 - 6549
(2009/04/05)
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- Amidates as leaving groups: Structure/reactivity correlation of the hydroxide-dependent E1cB-like breakdown of carbinolamides in aqueous solution
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(Graph Presented) The kinetic study of the aqueous reaction, between pH 10 and 14, of eight N-(hydroxymethyl)benzamide derivatives in water at 25°C, I = 1.0 M (KCl), has been performed. In all cases, the reaction proceeds via a specific-base-catalyzed deprotonation of the hydroxyl group followed by rate-limiting breakdown of the alkoxide to form aldehyde and amidate (E1cB-like). Such a mechanism was supported by the lack of general buffer catalysis and the first-order dependence of the rate of reaction at low hydroxide concentrations and the transition to zero-order dependence on hydroxide at high concentration. A ρ-value of 0.67 was found for the Hammett correlation between the maximum rate for the hydroxide independent breakdown of the deprotonated carbinolamide (k1) and the substituent on the aromatic ring of the title compounds. Conversely, the substituents on the aromatic ring of the amide portion of the carbinolamide had only a small effect on the Ka of the hydroxyl group indicating that the amide group does not strongly transmit the electronic information of the substituents. These observations led to the conclusion that the major effect of electronic changes on the amide of carbinolamides is reflected in the nucleofugality of the amidate once the alkoxide is formed and not in the pKa of the hydroxyl group of the carbinolamide.
- Tenn III, William J.,Murphy, John L.,Bim-Merle, Jessica K.,Brown, Jason A.,Junia, Adam J.,Price, Malea A.,Nagorski, Richard W.
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p. 6075 - 6083
(2008/02/10)
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- Solvent-free N-hydroxymethylation using formalin over basic alumina
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A convenient and high yield method for N-hydroxymethylation of amines with formalin over basic alumina under solvent-free conditions with microwave heating is described.
- Gupta, Rajive,Paul, Satya,Nanda, Puja
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p. 573 - 574
(2007/10/03)
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- Mechanism of Hydrolysis of Benzamidomethyl Derivatives of Phenols and Its Implications for Prodrug Design
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A series of O-benzamidomethyl derivatives of phenols was synthesized, and their rates of hydrolysis were investigated.The hydrolyses of the compounds follow pseudo-first-order kinetics resulting in quantitative and rapid regeneration of the phenol.The rates of hydrolysis were shown to be dependent on phenol nucleofugicity as well as the pKa of the amide.The mechanism of hydrolysis apparently involves as elimination of the phenol anion from the conjugate base of the amide (E1cB-like).
- Getz, John J.,Prankerd, Richard J.,Sloan, Kenneth B.
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p. 1702 - 1706
(2007/10/02)
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- Acyloxymethyl as a Drug Protecting Group. Kinetics and Mechanism of the Hydrolysis of N-Acyloxymethylbenzamides
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Acyloxymethyl derivatives of secondary and tertiary amides undergo hydrolysis via acid-catalysed, base-catalysed and pH-independent processes.The pH-independent pathway involves rate-limiting iminium ion formation and is characterised by the following: a Hammett ρ value for the substituent in the benzamide moiety of ca. -1.2 for both types of substrate; the absence of general-base or nucleophilic catalysis; a common benzoate ion effect; a solvent deuterium isotope effect, kobsH2O/kobsD2O, of ca. 1.6; Σ(excit.) values of -4 and -12 J k-1 mol-1 for secondary and tertiary substrates respectively; and higher reactivity of the tertiary amides over their secondary counterparts.The acid-catalysed process involves protonation of the substrate followed by iminium ion formation, and is characterised by the following: a Hammett ρ value of ca. -1.5 for the substitutent effect of the benzamide moiety; a solvent deuterium isotope effect of ca. 0.4; a monotonic rise in the pseudo-first-order rate constant kobs with increasing ; ΔS(excit.) values > 0 J K-1 mol-1; higher reactivity of the tertiary substrates over their secondary counterparts; and a value of 0.85 for the Bronsted coefficient, βlg, for the carboxylate nucleofuge.The base-catalysed hydrolysis of tertiary substrates involves normal ester hydrolysis via acyl-oxygen bond cleavage, and is characterised by a Hammett ρ value of +0.38, a solvent deuterium isotope effect, kOH-/kOD-, of 0.85, and a ΔS(excit.) balue of -96 J K-1 mol-1.The corressponding base-catalysed process for the secondary substrates involves imine formation via an E2 elimination reaction.The secondary acyloxymethylamides are some 7 * 104 times more reactive than their tertiary counterparts in the base-catalysed region.Hammett ρ values of +1.1 and +0.6 are obtained for the substituents in the base-catalysed region.Hammett ρ values of +1.1 and +0.6 are obtained for the substituents in the ester and amide moieties, respectively.Buffer catalysis is observed, and the value of ca. 0.5 for the Bronsted β coefficient identifies the amide proton as approximately 50percent transferred to the buffer species in the transition state.Heats of formation, ΔHf, calculated using the AM1 SCF MO package reveal that iminium ion formation is thermodynamically equi-energetic for cyclic and acyclic systems.Iminium ion formation from tertiary substrates is favoured by ca. 25 kJ mol-1 over the corresponding secondary analogues.
- Iley, Jim,Moreira, Rui,Rosa, Eduarda
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p. 563 - 570
(2007/10/02)
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- 1H and 13C NMR Spectra of the Rotational Isomers of N-Hydroxymethylamides and Derivatives
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A series of N-hydroxymethylamides, RCONR'CH2OH, and their O-methyl and O-acetyl derivatives, have been studied by 13C and 1H magnetic resonance spectroscopy.Signals have been assigned to the E- and Z-isomers on the basis of the analysis of the fully coupled spectra, and by comparison of the chemical shifts with those of model compounds.The introduction of the hydroxy, alkoxy or acetoxy groups at the α-position of the N-alkyl moiety causes a significant shift in the equilibrium towards the E-rotamer compared with the unsubstituted N-alkylamide.The predominant effect in determining the E:Z ratio appears to be the steric interaction between the carbonyl oxygen and the α-oxygen in the alkyl moiety; intramolecular hydrogen bonding does not play a significant role in determining the rotamer populations of these molecules.
- Gate, E. N.,Hooper, D. L.,Stevens, M. F. G.,Threadgill, M. D.,Vaughan, K.
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- Kinetics and Mechanism of Reactions of Amides with Formaldehyde
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Kinetics of the reactions of substituted ureas like methylurea, phenylurea, acetamide and benzamide with formaldehyde have been studied, using a TLC method developed for the purpose.The increased reactivity of methylurea towards formaldehyde, as compared to urea, is due to the electron-releasing nature of the methyl group.The reduced reactivity of phenylurea is due to the electron-withdrawing nature of the phenyl group.The reduced reactivity observed in the case of acetamide and benzamide is also explained.
- Nair, B. Raveendran,Francis, Joseph
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p. 159 - 161
(2007/10/02)
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- Preparation of 3-chloromethyl-4-alkyl-nitrobenzene by chloromethylation
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A method for the preparation of 3-chloromethyl derivatives of 4-alkylnitrobenzenes from the corresponding amidomethyl derivatives with phosphorus oxychloride or with phosphorous oxychloride and inert solvents. This process also relates to 3-chloromethyl-4-alkylnitrobenzenes which are useful intermediates for the preparation of certain substituted 2,6-dinitroaniline pre-emergence herbicides.
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