Base Hydrolysis

Base hydrolysis Hydrolysis is a chemical reaction during which one or more water molecules are split into hydrogen and hydroxide ions which may go on to participate in further reactions. [1][2] It is the type of reaction that is used to break down certain polymers, especially those made by step-growth polymerization. Such polymer degradation is usually catalysed by either acid i.e concentrated sulphuric acid [H2SO4] or alkali i.e. sodium hydroxide [NaOH] attack, often increasing with their strength or pH. Hydrolysis is distinct from hydration, where hydrated molecule does not "lyse" (break into two new compounds). It should not be confused with hydrogenolysis, a reaction of hydrogen.

Hydrolysis may be acidic and basic: Acid hydrolys: The type of hydrolysis carried out in the presence of an acid is called acid hydrolysis.

Base hydrolysis: The type of hydrolysis carried out in the presence of a base is called base hydrolysis.

Basic hydrolysis of Esters: Reaction under BASIC conditions: •

The mechanism shown below leads to acyl-oxygen cleavage (see step2).

•

The mechanism is supported by experiments using chiral alcohols.

•

This reaction is known as "saponification" because it is the basis of making soap from glycerol triesters in fats.

•

The mechanism is an example of the reactive system type.

18

O labeled compounds and esters of

MECHANISM OF THE BASE HYDROLYSIS OF ESTERS Step1 The hydroxide nucleophiles attacks at the electrophilic C ofthe ester C=O, breaking the bond and creating the tetrahedral intermediate. Step2: The intermediate collapses, reforming the C=O results in the loss of the leaving group the alkoxide, RO-, leading to the carboxylic acid. Step3 An acid / base reaction. A very rapid equilibrium where the alkoxide,RO- functions as a base deprotonating the carboxylic acid, RCO2H, (an acidic work up would allow the carboxylic acid to be obtained from the reaction).

Base Hydrolysis of Bis(acetylacetonato)nitridotechnetium(V)1, 2: Base hydrolysis of bis(acetylacetonato)nitridotechnetium(V), [TcN(acac) 2], was investigated in an aqueous3acetonitrile solution. The reaction kinetics was monitored by UV-visible spectroscopy. The base hydrolysis involves substitution of water molecules for coordinated acetylacetone (this stage is independent of the concentration of hydroxide ion), followed by slow decomposition of the intermediate complex by an attack of the hydroxide ion. The respective rate constants were determined at 25oC.

Base-Catalysed Hydrolysis: The CB Mechanism As mentioned earlier the rates of substitution of octahedral complexes are not sensitive to the nature of the entering group-with one exception. In basic media Co(III) complexes having ligands of the type NH3, RNH2, R2NH are sensitive to the nature of the entering group. The base catalysed reactions are generally much more rapid than anation or hydrolyses in acid solution. The agreed mechanism, involves the removal of a proton from the amine ligand. This step is generally very fast, (105 faster), and represents rapid pre-equilibrium to the rate determining loss of leaving group.

If, however, K is quite small (it is in th erange 0.01-0.2 for Pt(IV) complexes) so that K[OH] << 1,, the rate law would reduce to that experimental observed.

Theoretical Study of Base-Catalyzed Amide Hydrolysis: Gas- and Aqueous-Phase Hydrolysis of Formamide: Base-catalyzed hydrolysis of formamide in the gas phase and in aqueous solution has been studied using a combination of quantum chemical and statistical mechanical methods. A three-step procedure has been applied which comprises the determination of a gas-phase reaction path by high-level ab initio calculations, the calibration of empirical solute−solvent potentials, and classical Monte Carlo simulations of the solute immersed in a bath of solvent molecules. These simulations yield the solvent effect as a potential of mean force along the predetermined reaction coordinate. Each of the three consecutive steps of base-catalyzed hydrolysis has been analyzed in detail: the formation of a tetrahedral intermediate, its conformational isomerization, and the subsequent breakdown to products. The reaction is very exothermic in the gas phase and involves only moderate barriers for the latter two steps. Aqueous solvent, however, induces a significant barrier .

toward formation of the intermediate. On the other hand, it also facilitates conformational isomerization and produces a more product-like transition state for the breakdown step. Solvent effects, as expressed by differences in free energy of solvation, are found to reflect variations in the solute's charge distribution and arereadily explained by the analysis of hydrogen bond patterns. The calculated free energy profile is in satisfactory agreement with available experimental data for the solution-phase reaction.

Base-mediated hydrolytic cleavage with chain migration of 1chloromethyl-tetrahydropyrano[3,4-b]indoles: an unusual pathway to 2-succinoyl tryptophols: An unusual hydrolytic cleavage with 1,2-alkyl chain migration of 1-chloromethyl-tetrahydropyrano[3,4-b]indoles by heating with a limited amount of water and base in DMF is reported. A mechanism for the formation of 1,2-alkyl chain migration products, 2-succinoyl tryptophols, and the ring-expansion products, dihydro-oxepine fused indoles, is reported. No comparable 1,2-chain migration from a structurally related 1-chloromethyl-isochroman is observed.

Graphical abstract: Full-size image

Catalytic hydrolysis of carboxylic acid esters by Cu(II) and Zn(II) complexes containing a tetracoordinate macrocyclic Schiff base ligand in Brij35 micellar solution The macrocyclic Schiff base complexes of Cu(II) and Zn(II) in Brij35 micellar solution are investigated kinetically for the catalytic hydrolysis of p-nitrophenyl acetate (PNPA) and pnitrophenyl picolinate (PNPP) at 30 °C. The results indicate that different mechanisms are operative for the two complexes in the hydrolysis of PNPA and PNPP. The Cu(II) complex can only catalyze the hydrolysis of PNPP by the mechanism which involves the nucleophilic attack of external hydroxide ion on the carbonyl, while the Zn(II) complex can accelerate the hydrolysis of both PNPP and PNPA, by way of the intramolecular nucleophilic attack of zinc-bound hydroxide ion on carbonyl for PNPP and the less effective intermolecular nucleophilic attack of zinc-bound hydroxide ion on carbonyl for PNPA, respectively. The catalytic activity of Zn(II) complex is close to or even higher than that of Cu(II) complex. The reason is discussed in details.

Graphical Abstract: The kinetics and mechanisms for the hydrolysis of two carboxylic esters in Brij35 micellar solution catalyzed by macrocyclic Schiff base complex of Cu(II) and Zn(II) are reported. The differences in mechanisms are highlighted.

Base catalysed substitution reactions of octahedral cobalt(III) complexes: Mechanism switching by changing the leaving group The rates of base catalysed hydrolysis of six asym-[Co(dmptacn)X]n+ and six asym[Co(dmpmetacn)X]n+ complexes have been studied to explore the role of the leaving group and the formal charge on these complex ions in determining the effective site of deprotonation, at one of the four distinct α-CH2 pyridyl sites or at an NH centre. The work corroborates the new pseudo-aminate mechanism established for the chloro derivatives. Deuterium exchange and proton NMR experiments have shown that the site of deprotonation is leaving group dependent, the first time this long-standing speculative idea has been proven. This work has also shown that the effect of improving the leaving group can override rate limiting deprotonation to the point where NH deprotonation, via the normal SN1CB mechanism, operates rather than the rate limiting pseudo-aminate mechanism. The steric course of substitution has been determined and the reaction via NH deprotonation, enforced by employing an exceptionally good leaving group such as the triflate ion, has uncovered a non-retentive pathway leading to the previously unknown (and unstable) sym isomeric product. The steric course of substitution is shown to be mechanism dependent. For reaction via α-CH2 deprotonation, which of the two arms is utilised proved quite leaving group dependent, although the specific proton on a particular ‘arm’ was always the same, consistent with the requirements of this new mechanism.

Graphical abstract The [Co(pentaamine)X]n+ complexes studied bear at least one N-coordinated –CH2-pyridine group. The mechanism for base catalysed hydrolysis can be switched from the classic SN1CB to the pseudo-aminate mechanism, which involves rate limiting deprotonation, by simply changing the leaving group.

On the Origin of the Regioselective Hydrolysis of a Naphthoquinone Diacetate: A Molecular Orbital Study A seletividade observada (Nunes, R.L.; Bieber, L.W.; Longo, R.L. J. Nat. Prod. 1999 62, 1600) na reação de hidrólise do diacetato de 2,5-dimetil-1,4-naftoidroquinona em condições reacionais brandas, meio básico, e que favoreceahidrólise do grupo 4acetato, foi investigada utilizando métodos de ab initio e semi-empíricos. Em fase gasosa (sistemas isolados) estes métodos não forneceram resultados consistentes com a seletividade observada. Com a inclusão dos efeitos do solvente (água) através do modelo de solvatação discreta no método semi-empírico AM1, foi possível estabelecer a estabilidade relativa dos intermediários tetraédricos e dos seus respectivos estados de transição como sendo a responsável pela seletividade observada. A origem da estabilidade relativa, e portanto, da seletividade está relacionada com as interação repulsivas entre o grupo substituinte 2-metil no anel do naftaleno e a metila do grupo 4-acetado, assim como o impedimento destes grupos à hidratação do grupamento iônico dos intermediários tetraédricos. The regioselectivity found in the mild basic hydrolysis of the 2,5-dimethyl-1,4naphthohydroquinone diacetate (Nunes, R.L.; Bieber, L.W.; Longo, R.L. J. Nat. Prod. 1999, 62, 1600) has been studied with ab initio and semiempirical molecular orbital methods. In the gas phase (isolated systems), these methods were not able to provide results that could explain the observed selectivity. However, when the solvent effects were included in the AM1 method using the discrete solvation model it was possible to establish that this selectivity is due to the relative stability of the tetrahedral

intermediates and their transitions states. The origin of this relative stability and thus of the observed selectivity is due to the repulsive interactions between the 2-methyl substituent in the naphthalene ring and the methyl group in the 4-acetate substituent, as well as their hindrance towards the hydration of the ionic group in the tetrahedral intermediates.

INTRODUCTION: Base-promoted ester hydrolysis (saponification) has been used by the Phoenicians to make soap over 2000 years ago1. Nowadays this reaction is employed in organic synthesis mainly for protecting/deprotecting hydroxyl groups. This reaction is also widely used in introductory organic chemistry laboratories in undergraduate courses. Despite this reaction being so old and useful some of its aspects are still elusive. For instance, during the synthesis of the natural product Mansonone F 2 a remarkable regioselectivity has been found for the base-promoted hydrolysis of the 2,5-dimethyl-1,4-naphthohydroquinone diacetate intermediate. As shown in Scheme 1, the hydrolysis of (1) in mild basic aqueous/methanol media yielded the monoacetates in 84% yield in a proportion of 80:20 of the isomers (2):(3), according to an 1H-NMR analysis2.

This selectivity had already been observed in the hydrolysis of other methyl-1,4naphthohydroquinone diacetates3,4 as well as been applied in the synthesis of natural products4. However, no attempt has been made to explain this selectivity, despite of its potential application in organic synthesis. Attempts to rationalize this selectivity based upon the relative stability of the products using resonance stabilization of enolate ions were unsuccessful.2 Consequently, quantitative theoretical approaches were used to study this reaction, namely, ab initio and semiempirical molecular orbital (MO) methods. The computational modeling of this reaction is not trivial if the solvent effects have to be considered, because several groups of the reactants or intermediates

are polar and/or ionic, and the solvent is highly polar (water/methanol). Thus, the specific interactions, namely, hydrogen bonds have to be described accurately. In addition, apolar methyl groups are present, so that their hydrophobic interactions also have to be considered properly. The reaction mechanisms for the hydrolysis of carboxylic esters can be classified, according to Ingold5, as BAC1 and BAC2 for acyl cleavage and BAL1 and BAL2 for alkyl cleavage. In basic aqueous/organic media the BAC2 is the predominant mechanism and involves a tetrahedral intermediate originated from the attack of the carbonyl group by the hydroxyl ion6,7. Spectroscopic detection, 18O labeling and isolation procedures, as well as thermodynamic and kinetic data have provided compelling evidence for the existence of this intermediate7,8. In the gas phase, nucleophilic attacks to carboxylic esters take a different course, with the BAL2 mechanism being the observed one6. However, when the nucleophile is solvated, even by a single solvent molecule, the BAC2 mechanism is also observed6. Thus, the proper description of the solvent effects is essential to model this selectivity and to understand its origin.