scholarly journals Amide hydrolysis of 2-bromo-4,5-dimethylacetanilide

10.1039/sp933 ◽  
2020 ◽  
Author(s):  
Steven Kennedy ◽  
Yongyu Ou
Keyword(s):  
Amide Hydrolysis ◽  
Hydrolysis Of

A comparison of the mechanisms of hydrolysis of benzimidates, esters, and amides in sulfuric acid media

2005 ◽  
Vol 83 (9) ◽  
pp. 1391-1399 ◽  
Author(s):  
Robin A Cox
Keyword(s):  
Sulfuric Acid ◽  
Isotope Effects ◽  
Ester Hydrolysis ◽  
Water Molecules ◽  
Acid Media ◽  
Tetrahedral Intermediate ◽  
Amide Hydrolysis ◽  
Solvent Isotope ◽  
Reaction Media ◽  
Hydrolysis Of

The mechanisms given in textbooks for both ester and amide hydrolysis in acid media are in need of revision. To illustrate this, benzimidates were chosen as model compounds for oxygen protonated benzamides. In aqueous sulfuric acid media they hydrolyze either by a mechanism involving attack of two water molecules at the carbonyl carbon to give a neutral tetrahedral intermediate directly, as in ester hydrolysis, or by an SN2 attack of two water molecules at the alkyl group of the alkoxy oxygen to form the corresponding amide, or by both mechanisms, depending on the structure of the benzimidate. The major line of evidence leading to these conclusions is the behavior of the excess acidity plots resulting from the rate constants obtained for the hydrolyses as functions of acid concentration and temperature. The first of these mechanisms is in fact very similar to one found for the hydrolysis of benzamides, as inferred from: (1) similar excess acidity plot behaviour; and (2) the observed solvent isotope effects for amide hydrolysis, which are fully consistent with the involvement of two water molecules, but not with one or with three (or more). This mechanism starts out as essentially the same one as that found for ester hydrolysis under the same conditions. Differences arise because the neutral tetrahedral intermediate, formed directly as a result of the protonated substrate being attacked by two water molecules (not one), possesses an easily protonated nitrogen in the amide and benzimidate cases, explaining both the lack of 18O exchange observed for amide hydrolysis and the irreversibility of the reaction. Protonated tetrahedral intermediates are too unstable to exist in the reaction media; in fact, protonation of an sp3 hybridized oxygen to put a full positive charge on it is extremely difficult. (This means that individual protonated alcohol or ether species are unlikely to exist in these media either.) Thus, the reaction of the intermediate going to product or exchanged reactant is a general-acid-catalyzed process for esters. For amide hydrolysis, the situation is complicated by the fact that another, different, mechanism takes over in more strongly acidic media, according to the excess acidity plots. Some possibilities for this are given.Key words: esters, amides, benzimidates, hydrolysis, excess acidity, mechanism, acid media.

Micellar catalysis of organic reactions. 22. A comparison of the basic hydrolysis of benzodiazepinones in the presence of reactive counterion micelles and vesicles

1988 ◽  
Vol 66 (7) ◽  
pp. 1566-1570 ◽  
Author(s):  
Trevor J. Broxton ◽  
Xenia Sango ◽  
Sallyanne Wright
Keyword(s):  
Surfactant Concentration ◽  
Biological Membranes ◽  
Micellar Catalysis ◽  
Organic Reactions ◽  
Conductivity Measurements ◽  
Amide Hydrolysis ◽  
Rate Of Hydrolysis ◽  
Basic Hydrolysis ◽  
Hydrolysis Of ◽  
Good Agreement

The basic hydrolysis of diazepam and several N-alkyl nitrazepam derivatives has been studied in the presence of reactive counterion micelles of cetyltrimethylammonium hydroxide (CTAOH) and vesicles of didodecyldimethylammonium hydroxide (DDAOH). In both surfactants, the rate of hydrolysis of all compounds was found to be dependent on the hydroxide concentration at constant surfactant concentration and this was interpreted as evidence for initial amide hydrolysis. The hydrolysis in CTAOH was inhibited by added salts in the order Br− < NO3− < SO42−. At concentrations above 3 mM surfactant, the rate of hydrolysis of each compound was similar in CTAOH and in DDAOH. At lower concentrations of CTAOH, however, the rate of hydrolysis was significantly lower than that in DDAOH. On the basis of this evidence, it was concluded that the cmc of CTAOH was between 2–3 mM, which is in good agreement with the value of 1.8 mM obtained by Zana from conductivity measurements. For diazepam, a mechanistic change is indicated on transfer from water to either micelles or vesicles and since vesicles are considered good models of biological membranes, this suggests that conclusions concerning the bioavailability of diazepam should not be based on studies in water but rather on studies in either micelles or vesicles.

scholarly journals Lipoamidase activity in normal and mutagenized pancreatic cholesterol esterase (bile salt-stimulated lipase)

1993 ◽  
Vol 291 (1) ◽  
pp. 65-69 ◽  
Author(s):  
D Y Hui ◽  
K Hayakawa ◽  
J Oizumi
Keyword(s):  
Enzyme Activity ◽  
Gastrointestinal Tract ◽  
Recombinant Protein ◽  
Human Milk ◽  
Bile Salt ◽  
Enzyme Kinetics ◽  
Cholesterol Esterase ◽  
Amide Hydrolysis ◽  
Ester Linkage ◽  
Hydrolysis Of

Purified human milk lipoamidase was digested with endoproteinase Lys-C and the digested peptides were subjected to gasphase microsequence analysis. The sequencing of three isolated peptides of human milk lipoamidase revealed the identity of this protein with human milk bile salt-stimulated lipase (pancreatic cholesterol esterase). The identity of the cholesterol esterase with lipoamidase was confirmed by expressing a recombinant form of rat pancreatic cholesterol esterase and testing for lipoamidase activity of the recombinant protein. The results showed that the recombinant cholesterol esterase displayed both lipolytic and lipoamidase activities and was capable of hydrolysing triacetin and lipoyl-4-aminobenzoate (LPAB). The mechanisms of the esterase and amidase activities of the enzyme were further tested by determining enzyme activity in a mutagenized cholesterol esterase with a His435-->Gln435 substitution. This mutation has been shown previously to abolish enzyme activity against esterase substrates [DiPersio, Fontaine and Hui (1991) J. Biol. Chem. 266, 4033-4036]. We showed that the mutagenized protein was effective in hydrolysing the amidase substrate LPAB and displayed similar enzyme kinetics to those of the native enzyme. These data indicate that the mechanism for the cholesterol esterase hydrolysis of lipoamides is different from that of the hydrolysis of substrates with an ester linkage. The presence of an enzyme in the gastrointestinal tract capable of both ester and amide hydrolysis suggests an important role for this protein in the digestion and absorption processes.

scholarly journals A Novel Amidase (Half-Amidase) for Half-Amide Hydrolysis Involved in the Bacterial Metabolism of Cyclic Imides

2000 ◽  
Vol 66 (5) ◽  
pp. 1947-1952 ◽  
Author(s):  
Chee-Leong Soong ◽  
Jun Ogawa ◽  
Sakayu Shimizu
Keyword(s):  
Catalytic Efficiency ◽  
High Specificity ◽  
Bacterial Metabolism ◽  
Second Step ◽  
Cyclic Imide ◽  
Sulfhydryl Reagents ◽  
Succinamic Acid ◽  
Amide Hydrolysis ◽  
Cyclic Imides ◽  
Hydrolysis Of

ABSTRACT A novel amidase involved in bacterial cyclic imide metabolism was purified from Blastobacter sp. strain A17p-4. The enzyme physiologically functions in the second step of cyclic imide degradation, i.e., the hydrolysis of monoamidated dicarboxylates (half-amides) to dicarboxylates and ammonia. Enzyme production was enhanced by cyclic imides such as succinimide and glutarimide but not by amide compounds which are conventional substrates and inducers of known amidases. The purified amidase showed high catalytic efficiency toward half-amides such as succinamic acid (Km = 6.2 mM; k cat = 5.76 s−1) and glutaramic acid (Km = 2.8 mM;k cat = 2.23 s−1). However, the substrates of known amidases such as short-chain (C2 to C4) aliphatic amides, long-chain (above C16) aliphatic amides, amino acid amides, aliphatic diamides, α-keto acid amides, N-carbamoyl amino acids, and aliphatic ureides were not substrates for the enzyme. Based on its high specificity toward half-amides, the enzyme was named half-amidase. This half-amidase exists as a monomer with an M r of 48,000 and was strongly inhibited by heavy metal ions and sulfhydryl reagents.

Transition state activity coefficients in the acid-catalyzed hydrolysis of amides

1977 ◽  
Vol 55 (16) ◽  
pp. 3050-3057 ◽  
Author(s):  
Tomasz A. Modro ◽  
Keith Yates ◽  
Françoise Beaufays
Keyword(s):  
Transition State ◽  
Bond Cleavage ◽  
Protonated Form ◽  
State Activity ◽  
Alkyl Derivatives ◽  
Amide Hydrolysis ◽  
Conjugate Acid ◽  
Acid Catalyzed ◽  
Hydrolysis Of ◽  
Nitrogen Bond

The transition-state activity coefficient [Formula: see text] approach has been applied to the acid-catalyzed hydrolysis of benzamide and its N-alkyl derivatives. For all systems (with the exception of the N-tert-butyl derivative which reacts via carbon–nitrogen bond cleavage) a uniform type of medium dependence of [Formula: see text] is observed. The reaction shows a pronounced destabilization of S≠ over the whole region of acidity studied, practically identical to that found for the AAc-2 type of ester hydrolysis. This is interpreted in terms of an AoT2 mechanism of amide hydrolysis, that is the rate-determining formation of the oxonium-type tetrahedral intermediate from the O-protonated form of substrate conjugate acid.

scholarly journals A Novel Reaction Mediated by Human Aldehyde Oxidase: Amide Hydrolysis of GDC-0834

2015 ◽  
Vol 43 (6) ◽  
pp. 908-915 ◽  
Author(s):  
Jasleen K. Sodhi ◽  
Susan Wong ◽  
Donald S. Kirkpatrick ◽  
Lichuan Liu ◽  
S. Cyrus Khojasteh ◽  
...  
Keyword(s):  
Aldehyde Oxidase ◽  
Amide Hydrolysis ◽  
Hydrolysis Of

SOLVENT AND SUBSTITUENT EFFECTS ON THE INTRAMOLECULAR AMIDE HYDROLYSIS OF N-METHYLMALEAMIC ACID

2009 ◽  
Vol 08 (06) ◽  
pp. 1217-1226 ◽  
Author(s):  
JUN CAI ◽  
ZHIJIAN WU
Keyword(s):  
Reaction Mechanism ◽  
Gas Phase ◽  
Reaction Mechanisms ◽  
Substituent Effects ◽  
Phase Reaction ◽  
Gas Phase Reaction ◽  
Amide Hydrolysis ◽  
Reaction Barriers ◽  
Hydrolysis Of ◽  
Concerted Reaction

Intramolecular amide hydrolysis of N-methylmaleamic acid is revisited at the B3LYP/6-311G(2df, p)//B3LYP/6-31G(d, p) + ZVPE level, including solvent effects at the CPCM-B3LYP/6-311G(2df, p)//Onsager-B3LYP/6-31G(d, p) + ZPVE level. The concerted reaction mechanism is energetically favorable over stepwise reaction mechanisms in both the gas phase and solution. The calculated reaction barriers are significantly lower in solution than in the gas phase. In addition, it is concluded that the substituents of the four N-methylmaleamic acid derivatives considered herein have a significant effect on the gas-phase reaction barriers but a smaller, or little, effect on the barriers in solution.

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