Dakin-West Reaction Research Articles

KAl (SO4)2.12H2O or KHSO4: Efficient and Inexpensive Catalysts for the One-Pot Synthesis of β-Acetamido Ketones by Dakin–West Reaction

Aromatic aldehydes were reacted in a vessel with enolizable ketones, acetonitrile, and acetyl chloride at ambient temperature in the presence of KAl(SO4)2.12H2O to furnish the corresponding β-acetamido ketones in excellent yields. KHSO4 has also been used as another catalyst for this reaction at room temperature. Key features of this methodology are operational simplicity, mild reaction conditions, and excellent yields.

Efficient Synthesis of β-Acetamido Ketones Catalyzed by Cobalt Sulfate Heptahydrate Under Ultrasound Irradiation

Ultrasound-promoted synthesis of β-acetamido ketones catalyzed by cobalt sulfate heptahydrate via one-pot multi-component reaction coupling of aromatic aldehyde, acetophenone and acetyl chloride in acetonitrile was carried out in excellent yields at 25-28 °C, providing an efficient synthesis of these compounds. The use of ultrasound increased the rate of reactions compared with reactions under reflux condition. Keywords: β-Acetamido ketones, cobalt, sulfate, heptahydrate, condensation, synthesis, ultrasound irradiation, MCRs, multi-component reaction, Dakin-West reaction, aromatic aldehyde, cobalt sulfate heptahydrate

On the mechanism of the Dakin–West reaction

The mechanism of the Dakin-West reaction has been thoroughly investigated by monitoring the reaction using ESI-MS/MS techniques in combination with M06-2X/6-311++G(d,p) calculations. Several of the key intermediates in the previously proposed "azlactone" mechanism have been experimentally detected and characterized. In particular, interception of the mixed anhydrides involved in the early and late stages of the mechanistic scheme, as well as of the cyclic acyl-oxazolone intermediate, supports the original pathway suggested by Dakin and West. All intermediates and transition structures involved in several competing mechanisms have been calculated. The theoretical calculations support the experimental results and corroborate the proposed "azlactone" mechanism. The pathway involving the cyclic oxazolone ("azlactone") intermediate represents an energy barrier more than 3 kcal mol(-1) lower than for the competing aldol-type mechanism, thus ruling out this alternative mechanism. The DFT calculations explain the observed ESI-MS data and assess those intermediates which the experiments cannot fully elucidate.

N-(1,3-Diaryl-3-oxopropyl)amides as a new template for xanthine oxidase inhibitors

A series of forty two N-(1,3-diaryl-3-oxopropyl)amides were synthesized via an efficient, modified Dakin–West reaction and were evaluated for in vitro xanthine oxidase inhibitory activity for the first time. Structure–activity relationship analyses have been presented. Selected active xanthine oxidase inhibitors (3r, 3s, and 3zh) were assessed in vivo to study their anti-hyperuricemic effect in potassium oxonate induced hyperuricemic mice model. Compound 3s emerged as the most potent xanthine oxidase inhibitor (IC50=2.45μM) as well as the most potent anti-hyperuricemic agent. The basis of significant inhibition of xanthine oxidase by 3s was rationalized by its molecular docking into catalytic site of xanthine oxidase.

Synthesis and antidiabetic activity of β-acetamido ketones

This paper reports the use of trifluoroacetic acid as a catalyst in the Dakin–West reaction for the synthesis of β-acetamido ketones. The method has several advantages such as requiring only mild conditions and a low concentration of catalyst. Screening of 19 β-acetamido ketones for antidiabetic activity in vitro showed that their activity as peroxisome proliferator-activated receptor (PPAR) agonists and as dipeptidyl peptidase 4 (DPP-IV) inhibitors was fairly weak.

One-pot synthesis of β-acetamido-β-arylpropiophenone employing trifluoroacetic acid as an efficient catalyst

Trifluoroacetic acid as an efficient catalyst promoting the Dakin–West reaction at ambient temperature is reported for the first time in this paper. A few efficacious auxiliary catalysts were also developed for the Dakin–West reaction. A variety of substituted aryl aldehydes and aryl ketones were found to be applicable to the preparation of some new β-acetamido-β-arylpropiophenones. This procedure has several advantages such as high yields, short reaction time, and smaller amount (0.30 mol%) of catalyst.

ChemInform Abstract: Unusual Ring Expansion Observed During the Dakin-West Reaction of Tetrahydroisoquinoline-1-carboxylic Acids Using Trifluoroacetic Anhydride: An Expedient Synthesis of 3-Benzazepine Derivatives Bearing a Trifluoromethyl Group.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: The Dakin—West Reaction of N‐Acylprolines (I) in the Presence of Inorganic Bases: Unexpected Formation of Enol Esters (III).

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

The Dakin-West Reaction of N-Acylprolines in the Presence of Inorganic Bases: Unexpected Formation of Enol Esters

A novel transformation of N-acylprolines (1) to enol esters (2) was realized by utilizing chlorodifluoroacetic or trifluoroacetic anhydrides in the presence of inorganic bases, in which probable intermediates were mesoionic 1,3-oxazolium-5-olates. The structure of the enol ester (2a) was determined by single crystal X-ray analysis.

Efficient synthesis of ( R)-3-amino-1,1,1-trifluoropropan-2-ol via a Dakin–West reaction followed by enantioselective reduction

An efficient, chromatography-free asymmetric synthesis of ( R)-3-amino-1,1,1-trifluoropropan-2-ol was developed for large scale production of a cholesterol ester transfer protein (CETP) inhibitor. The synthesis features a new efficient route to a β-amino trifluoromethylketone involving a modified Dakin–West reaction followed by an asymmetric hydrogenation or an enzymatic reduction of the resulting ketone to the alcohol.

Reduction in post-prandial hyperglycemic excursion through α-glucosidase inhibition by β-acetamido carbonyl compounds

A series of β-acetamido carbonyl compounds ( S 1– S 7) were prepared using Dakin-West reaction from different substituted aldehyde and acetophenone in the presence of lanthanum triflate as a solid catalyst. All the compounds were tested for their α-glucosidase inhibitory potential against rat intestinal α-glucosidase. The most potent rat intestinal α-glucosidase inhibitors S 5 and S 7 were tested for their antihyperglycemic activity following carbohydrate tolerance test. Both the compounds displayed antihyperglycemic activity equivalent to the standard drug acarbose.

Acid catalysis of different supported heteropoly acids for a one-pot synthesis of β-acetamido ketones

The production of β-acetamido ketones from aldehydes, ketones and acetyl chloride in acetonitrile over supported heteropoly acids has been examined. This study reports the use of heteropoly acids (HPAs) supported on metal oxides (SiO 2, Al 2O 3, K 10 and KSF montmorillonite) and activated carbon as efficient and reusable catalysts, and their comparison with other catalysts in Dakin–West reaction. Dodecatungstophosphoric acid supported on KSF and γ-Al 2O 3 shows the best results and reusability.

A modified and green Dakin–West reaction: An efficient and convenient method for a one-pot synthesis of β-acetamido carbonyl compounds

An efficient and improved procedure for the synthesis of β-acetamido carbonyl compounds is developed in the presence of trimethylsilyl chloride by a heteropolyacid catalyzed three-component coupling protocol.

Heteropoly Acids as Solid Green Broensted Acids for a One‐Pot Synthesis of β‐Acetamido Ketones by Dakin—West Reaction.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Heteropoly acids as solid green Brønsted acids for a one-pot synthesis of β-acetamido ketones by Dakin–West reaction

An efficient improved procedure for the synthesis of β-acetamido ketones has been developed by a heteropoly acid (HPA) catalyzed three-component coupling protocol. The present methodology offers several advantages such as excellent yields, simple procedure, short reaction times, and mild conditions.

The silica supported H 3PW 12O 40 (a heteropoly acid) as an efficient and reusable catalyst for a one-pot synthesis of β-acetamido ketones by Dakin–West reaction

Heteropoly acid H 3PW 12O 40 (PW) supported on silica (PW/SiO 2) has been used as an effective catalytic system for a four-component coupling process for the synthesis of β-acetamido ketones by Dakin–West reaction. The present methodology offers several advantages, such as high yields, short reaction times, mild condition and a recyclable catalyst with a very easy work up.

A Modified Procedure for the Dakin—West Reaction: An Efficient and Convenient Method for a One‐Pot Synthesis of β‐Acetamido Ketones Using Silica Sulfuric Acid as Catalyst.

A one-pot, four-component condensation of an aryl aldehyde, an aryl ketone, acetyl chloride and acetonitrile in the presence of silica sulfuric acid as an active, inexpensive, recoverable and recyclable catalyst is disclosed for the synthesis of β-acetamido ketones.

Synthesis of 2-(aminocarbonylmethylthio)-1 H-imidazoles as novel Capravirine analogues

Different analogues of Capravirine (AG-1549) or S-1153 were prepared by synthesis of 2-(5-benzyl-4-isopropyl-1-methyl-2,3-dihydro-1 H-imidazol-2-ylthio)acetamide ( 3a– c), ethyl [5-benzyl-1-(ethoxymethyl)-4-ethyl-1 H-imidazol-2-ylthio]acetate ( 10), 2-[5-alkyl-4-substituted 1-(pyridin-4-ylmethyl)-1 H-imidazol-2-ylthio]acetamides ( 12a– f), and 2-[5-benzyl-1-(benzyloxymethyl)-4-isopropyl-1 H-imidazol-2-ylthio]acetamides ( 14a– l) from their corresponding amino acids through a sequence of reactions: Dakin–West reaction, hydrolysis, condensation with thiocyanate derivatives, alkylation with 2-iodoacetamide and ethyl chloroacetate, and coupling with 4-pyridylmethyl chloride, ethoxymethyl chloride and benzyloxymethyl chloride. All the synthesized compounds were screened for their activity against HIV-1 (wild type) and some of them (especially Capravirine like structures) were found active.

A modified procedure for the Dakin–West reaction: an efficient and convenient method for a one-pot synthesis of β-acetamido ketones using silica sulfuric acid as catalyst

A one-pot, four-component condensation of an aryl aldehyde, an aryl ketone, acetyl chloride and acetonitrile in the presence of silica sulfuric acid as an active, inexpensive, recoverable and recyclable catalyst is disclosed for the synthesis of β-acetamido ketones.

The Conversion of Carboxylic Acids to Ketones: A Repeated Discovery

This article describes the history of the reaction converting carboxylic acids to ketones. The reaction has been rediscovered several times, yet has actually been known for centuries. The best known version of the process is the Dakin–West reaction (1928), which applies to α-amino acids and also involves the simultaneous conversion of the amine group to amido functionality. Unlike other examples, this particular reaction has attracted a reasonable amount of attention and it appears to be better known than the conversion of simple carboxylic acids to ketones. However, this reaction was described as long ago as 1612, when Beguin published an account of it in his book, Tyrocinium Chymicum. Since then, many chemists have rediscovered the reaction, apparently independently. One of the earliest modern accounts was by W. H. Perkin, Sr., in 1886, who made various simple ketones by refluxing the appropriate carboxylic acids with base. However, this work has been largely ignored, including by his son, W. H. Perkin,...