Experimental and computational studies of the regioselective protection of hydantoins using anhydride

Kruger, Hendrik G.; Mdluli, Phumlane Selby; Power, Trevor D.; Raasch, Terrence; Singh, Amith

doi:10.1016/j.theochem.2006.03.037

Cited by 16 publications

(9 citation statements)

References 16 publications

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“…Alcoholysis of acid anhydrides [(RCO) 2 O] and acyl chlorides (RCOCl) are also used to obtain esters, with the latter more commonly studied . Applications of (RCO) 2 O and RCOCl in regioselective protection of compounds with multifunctional groups are also well established …”

Section: Introductionmentioning

confidence: 99%

DFT study of the acid‐catalyzed esterification reaction mechanism of methanol with carboxylic acid and its halide derivatives

Lawal

Govender

Maguire

et al. 2017

Int J of Quantum Chemistry

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Extensive experimental studies have been dedicated to the esterification mechanisms from carboxylic acids and acid halides. However, attention on the theoretical aspect of the mechanism has been scarcely addressed. Herein, the acid-catalyzed esterification mechanism of methanol with acetic acid and its halide derivatives is described using density functional theoretical method and solvation model based on density. The mechanistic investigation involved formation of cyclic prereaction and 6-membered ring transition structures, which favors the esterification process and product formation. A good comparison with experimental data from literature for the esterification reaction of acetic acid with methanol was achieved through this in silico approach. Density Functional Theory-based quantum descriptors were applied to provide a better understanding on the reactivity, selectivity, and stability of this reaction. This theoretical results provide a crucial guide to study classical acid-catalyzed reaction mechanisms and applying a reasonable theoretical model to study similar organic reactions. In addition, it can be applied to larger systems such as enzymatic mechanism. K E Y W O R D S acetic acid (HOAc), acetyl halides (XAc), Density Functional Theory (DFT), esterification reaction 1 | I N TR ODU C TI ON Esters remained important intermediates in the chemical industry due to their widespread pharmaceutical applications and biodiesel production.Dating back to the 1890s, the Fischer esterification [1] reaction has remained a crucial process through which esters are formed via dehydrative coupling of carboxylic acids (RCOOH) with alcohol (ROH) in the presence of inorganic liquid acids. [2][3][4] Among studies on kinetics and mechanism of acid-catalyzed RCOOH esterification, methyl acetate (MeOAc) formation from acetic acid (HOAc) and methanol (MeOH) using homogeneous and heterogeneous acid catalysts are abundant. [4][5][6] R€ onnback et al. [2] had earlier hypothesized the nature of the acid-catalyzed esterification of HOAc with MeOH as a stepwise model involving 7 transition structures and 3 intermediates in acidic solution. This experimental study [2] was novel and serves as a basis for subsequent investigations.The overall reaction process is presented as:The production of MeOAc from HOAc and MeOH has been kinetically mediated by homogeneous [2,[6][7][8][9][10][11] or heterogeneous catalysts, [5,6,[12][13][14][15] with more research being performed on the latter due to increased reusability, [16] high selectivity, [17] and less product contamination. [6,16,18] The synthesis and kinetics via microwave, membrane, batch, and microchannel reactors have also been addressed. [12,13,19,20] Most recent experimental investigations (from 2011) have reported free energy of activation for this process with values ranging from 7.7 to 15.1 kcal mol 21[4-6,15,21-26] in Int J Quantum Chem. 2018;118:e25497.

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Section: Introductionmentioning

confidence: 99%

DFT study of the acid‐catalyzed esterification reaction mechanism of methanol with carboxylic acid and its halide derivatives

Lawal

Govender

Maguire

et al. 2017

Int J of Quantum Chemistry

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“…Hydantoins are biologically active molecules widely used in medicine as antiepileptic, antischisto somal, antiarythmic, antibacterial and tuberculostatic drugs [1,2]. It is also an effective medication for the treatment of metastatic prostate cancer.…”

Section: Introductionmentioning

confidence: 99%

FTIR spectroscopic and quantum chemical studies on hydantoin

2012

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In this study the geometry optimization of monomeric and dimeric forms (D1, D2, and D3) of hydantoin molecule were done using DFT method employing 6-31++G(d, p) basis set. Harmonic and anharmonic wavenumbers and infrared intensities were computed at the same theory level. Experimental IR spectrum was recorded in the region 400-4000 cm -1 . It has also been characterized by 1 H and 13 C NMR spectrum. The hydrogen bond (HB) interaction of hydantoin was analyzed via dimers of hydantoin. Detailed vibrational wavenumber shifts and all vibrational mode analyses were reported. Total energy distributions (TED, %) calculations were done to characterize the fundamentals.

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“…The Boc-protection of N-1 and N-3 positions of the hydantoin core was described by Kruger. 82,83 Mono or bis-N-acylation reactions were studied and compared for 5-methylhydantoin, 5,5-dimethylhydantoin, and the cage-like molecule trishomocubane hydantoin (Figure 6), highlighting the essential role of steric hindrance of C-5 position in the regioselectivity of the Boc-protection and the competitive 84 Although substitution at the N-3 position can enhance the pharmaceutical activity of hydantoins, this same position can as well be deprotected. The ruthenium-catalyzed deprotection of N-3 allylic hydantoin was reported, 85 along with other examples of amide-like moieties that are lactams, imides, or oxazolidinones.…”

Section: Alkylation/acylation At N-1 Positionmentioning

confidence: 99%

Recent Advances in the Synthesis of Hydantoins: The State of the Art of a Valuable Scaffold

et al. 2017

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The review highlights the hydantoin syntheses presented from the point of view of the preparation methods. Novel synthetic routes to various hydantoin structures, the advances brought to the classical methods in the aim of producing more sustainable and environmentally friendly procedures for the preparation of these biomolecules, and a critical comparison of the different synthetic approaches developed in the last twelve years are also described. The review is composed of 95 schemes, 8 figures and 528 references for the last 12 years and includes the description of the hydantoin-based marketed drugs and clinical candidates.

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Experimental and computational studies of the regioselective protection of hydantoins using anhydride

Cited by 16 publications

References 16 publications

DFT study of the acid‐catalyzed esterification reaction mechanism of methanol with carboxylic acid and its halide derivatives

DFT study of the acid‐catalyzed esterification reaction mechanism of methanol with carboxylic acid and its halide derivatives

FTIR spectroscopic and quantum chemical studies on hydantoin

Recent Advances in the Synthesis of Hydantoins: The State of the Art of a Valuable Scaffold

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