<b>Acid-Catalyzed Hydrolysis of Carboxylic Acid Orthoesters</b>

DeWolfe, Robert H.; Jensen, James L.

doi:10.1021/ja00903a046

Cited by 28 publications

(14 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Melting-points (mp) were determined on a System Kofler type WME apparatus and are uncorrected. The term room temperature means [20][21][22][23][24][25][26][27][28][29][30] o C. All products were identified through their spectroscopic data and the melting-points which were confirmed by comparison with those reported in the literature.…”

Section: Chemical Analysismentioning

confidence: 92%

“…of TEOF for 6 h and in absence of Bronsted acids did not afford none product, evidencing the necessity of employment of Bronsted acid to activate the dehydrating form of TEOF (entries 6 and 7, respectively). 30 On the other hand, the reaction carried out in presence of HCl/TEOF during 2 h, afforded the desired DHPM 1b in 84% yield (entry 8). We can compare this result with that in absence of TEOF (74%, cf.…”

Section: Chemistrymentioning

confidence: 99%

See 1 more Smart Citation

Synthesis of dihydropyrimidin-2-one/thione library and cytotoxic activity against the human U138-MG and Rat C6 glioma cell lines

Canto¹,

Bernardi²,

Battastini³

et al. 2011

J. Braz. Chem. Soc.

View full text Add to dashboard Cite

Duas séries de 4-aril-3,4-diidropirimidin-2(1H)-(tio)onas incluindo monastrol (1a), foram sintetizadas por uma metodologia não agressiva ao meio ambiente baseada no uso combinado de ácido cítrico ou ácido oxálico na presença de TEOF (ortoformato de trietila). A atividade como inibidores da proliferação celular da quimioteca de compostos foi avaliada em duas linhagens de gliomas (U138-MG-humana e C6-rato). Os compostos derivados da tiouréia 1f e 1d mostraram atividade citotóxica maior do que a do monastrol. O composto derivado da uréia 2d apresentou a maior atividade citotóxica dentre todos os compostos analisados.Two series of 4-aryl-3,4-dihydropyrimidin-2(1H)-(thio)ones including monastrol (1a), have been synthesized by an environment-friendly methodology based on the combined use of citric acid or oxalic acid and TEOF (triethylorthoformate). The library was evaluated as inhibitor of cell proliferation on two glioma cell lines (human-U138-MG and Rat-C6). The compounds derived from thiourea 1f and 1d were more cytotoxic than monastrol. The compound derived from urea 2d showed the highest cytotoxic activity among the analyzed compounds.Keywords: dihydropyrimidin-2(1H)-ones, Biginelli reaction, triethylorthoformate, TEOF, monastrol, cancer, glioma IntroductionThe 4-aryl-3,4-dihydropyrimidin-2(1H)-ones (DHPMs) are a class of compounds that has a huge interest in the medicinal chemistry community in recent years.Using high throughput screening (HTS) Mayer et al.1 have evaluated a library of 16,330 small molecules that vary in functional groups and charge. These findings have lead to discover a small molecule which they named monastrol, whose acts by inhibiting the motility of the mitotic kinesin Eg5, a motor protein required for spindle bipolarity. This revealed the potential of this compound as antitumor prototype and since that, some SAR (structure activity relationship) studies concerning this interaction have been performed. 9 This set of potentialities linked to the possibility of chemical modulation in all positions of the dihydropirimidinone/thione rings make DHPMs a privileged structure, justifying the great interest in their synthesis.The original three component reaction of DHPMs consisted of a simple one-pot condensation of benzaldehyde 4b, ethyl acetoacetate 5 and urea 6b (Schemes 1 and 2), catalyzed by few drops of hydrochloric acid under refluxing In this context, we have reported the synthesis of a small library of DHPM, including monastrol (1a), using a Lewis acid as catalyst and this series was evaluated against seven human cancer cell lines. 21 The results showed that the oxo-monastrol analogue (2a) just shows cytostatic activity, while monastrol (1a) was cytotoxic against the seven cancer cell lines. We have also found that the 3,4-methylenodioxy derivative (piperastrol, 1c) was approximately 30 times more potent than monastrol (1a) against five of the seven tested cancer cell lines, and it was also more potent than the positive control doxorrubicine against three of the tested cell lines (Figur...

show abstract

Section: Chemical Analysismentioning

confidence: 92%

Section: Chemistrymentioning

confidence: 99%

Synthesis of dihydropyrimidin-2-one/thione library and cytotoxic activity against the human U138-MG and Rat C6 glioma cell lines

Canto¹,

Bernardi²,

Battastini³

et al. 2011

J. Braz. Chem. Soc.

View full text Add to dashboard Cite

show abstract

“…The only detectable catalysis of this reaction in aqueous buffer solutions is by hydronium ion (49-51, 53,134,141, 258, 260). Hydronium ion is more than twice as effective a catalyst in heavy water than in ordinary water (49)(50)(51)141), and the reaction has small positive values for the entropy of activation (81,162) and volume of activation (162).…”

Section: B Kinetics and Mechanism Of Ortho Ester Hydrolysismentioning

confidence: 99%

“…The first examples of general acid catalysis to be discovered were hydrolysis reactions of ortho esters. Hydrolyses of triethyl orthoacetate, triethyl orthopropionate, and tetraethyl orthocarbonate are general acidcatalyzed reactions in water (53), and triethyl orthoformate hydrolysis exhibits general and acid catalysis in aqueous dioxane (81,82). Trimethyl orthobenzoate hydrolysis is a general acid-catalyzed reaction in 70% methanol-30% water (168).…”

Section: B Kinetics and Mechanism Of Ortho Ester Hydrolysismentioning

confidence: 99%

“…Trimethyl orthobenzoate hydrolysis is a general acid-catalyzed reaction in 70% methanol-30% water (168). Hydrogen ion-catalyzed hydrolyses of triethyl orthoacetate and trimethyl and triethyl orthobenzoates have small positive entropies of activation (81,118,158). In aqueous solutions the catalytic coefficient ratio of hydrogen ion in heavy and ordinary water (k D +lk H +) is 1.4 for tetraethyl orthocarbonate hydrolysis (303), almost 2.3 for trimethyl and triethyl orthobenzoate hydrolysis (81,118) and about 2.7 for triethyl orthoformate hydrolysis (57).…”

Section: B Kinetics and Mechanism Of Ortho Ester Hydrolysismentioning

confidence: 99%

See 1 more Smart Citation

Reactions of Ortho Esters Which Result in Carbon-Oxygen and Carbon-Halogen Bond Formation

1970

Carboxylic Ortho Acid Derivatives - Preparation and Synthetic Applications

View full text Add to dashboard Cite

In this chapter are considered reactions of trialkyl orthocarboxylates and tetraalkyl orthocarbonates which result in the formation of new carbonoxygen or carbon-halogen bonds. In most of these reactions the ortho ester (or an alkoxycarbonium ion derived from it) functions as an alkylating agent.Many of these reactions are useful synthetic tools. These include formation and hydrolysis of cyclic ortho ester derivatives of diols and triols (which serve to protect the hydroxyl groups of the polyols, and provide means for their mild monoacylation), alkylation of phenols, enols and acids (to form ethers and esters), and conversion of carbonyl compounds to acetals and ketals. Other reactions, such as the alkylation of halogens by ortho esters, are of only limited synthetic utility, while still others, such as the acidcatalyzed hydrolyses of ortho esters, are of interest primarily because of the light they shed on the mechanisms of reactions of ortho esters with nucleophilic reagents.

show abstract

Mechanism and Catalysis for the Hydrolysis of Acetals, Ketals, and Ortho Esters

Cordes¹

1967

Progress in Physical Organic Chemistry

View full text Add to dashboard Cite

Acid-Catalyzed Hydrolysis of Carboxylic Acid Orthoesters

Cited by 28 publications

References 7 publications

Synthesis of dihydropyrimidin-2-one/thione library and cytotoxic activity against the human U138-MG and Rat C6 glioma cell lines

Synthesis of dihydropyrimidin-2-one/thione library and cytotoxic activity against the human U138-MG and Rat C6 glioma cell lines

Reactions of Ortho Esters Which Result in Carbon-Oxygen and Carbon-Halogen Bond Formation

Mechanism and Catalysis for the Hydrolysis of Acetals, Ketals, and Ortho Esters

Contact Info

Product

Resources

About