Efficient and Chemoselective Access to 3-(Chloromethyl)coumarins via Direct Cyclisation of Unprotected Baylis-Hillman Adducts

Kaye, Perry T.; Musa, Musiliyu A.; Nocanda, Xolani W.

doi:10.1055/s-2003-37655

Cited by 46 publications

(21 citation statements)

References 3 publications

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“…The Baylis-Hillman adducts obtained were cyclized using HCl and AcOH to afford the coumarins 4a-d in very good yields. The Baylis-Hillman adducts 3a-d and 3-chloromethyl(coumarins) 4a-d were characterized and their spectra data are in accordance with literature (Kaye et al, 2003). In an attempt to synthesize a hydroxyurea analogue, 6-chloro-3-(chloromethyl)coumarin (4d) was treated with thiourea in the hope of obtaining a nucleophilic substitution product but rather spectroscopic evidence suggests the formation of chlorocoumarin-3-sulfinic acid 5d (Scheme 1).…”

Section: Synthesis Of Baylis-hillman Adducts and 3-substituted Coumarinssupporting

confidence: 65%

“…White solid, melting point: 108-110 o C (lit. 108-110 o C) (Kaye et al, 2003). IR spectrum: 3194 cm -1 (aliphatic O-H); 1688 cm -1 (vinylic C=O of ester); 1635 cm -1 (olefinic C=C stretching); 1150 cm -1 and 1020 cm -1 (C-O of ester).…”

Section: Tert-butyl-3-hydroxy-3-(2-hydroxyphenyl)-2-methylene Propanomentioning

confidence: 98%

“…In this present study, salicylaldehyde derivatives 1a-d and tert-butyl acrylate 2 (Scheme1) were used as starting materials for the preparation of Baylis-Hillman adducts (3a-d) using literature methods (Kaye et al, 2003). The Baylis-Hillman adducts were further cyclized to 3-(chloromethyl)coumarins 4a-d using acid catalysis (Kaye et al, 2003).…”

Section: Synthesis Of Baylis-hillman Adducts 3a-d and 3-(chloromethylmentioning

confidence: 99%

“…Various Baylis-Hillman adducts 3a-d were synthesized following literature methods (Kaye et al, 2003), using salicylaldehyde derivatives as electrophiles and tert-butyl acrylate as the activated alkene in the presence of diazabicyclo[2.2.2]octane (DABCO). The Baylis-Hillman adducts obtained were cyclized using HCl and AcOH to afford the coumarins 4a-d in very good yields.…”

Section: Synthesis Of Baylis-hillman Adducts and 3-substituted Coumarinsmentioning

confidence: 99%

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Evaluation of Some Salicylaldehyde-derived Baylis-Hillman Adducts and Coumarin Derivatives as Potential Antisickling Compounds

Olomola

Kelani

Cyril-Olutayo

et al. 2018

Annals of Science and Technology

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Some salicylaldehyde-derived Baylis-Hillman adducts and 3-(chloromethyl)coumarins have been synthesised and evaluated in vitro for their antisickling activities. The compounds were screened for inhibitory and reversal activity against mutated haemoglobin (HbSS) in red blood cells at four different concentrations (4 mg/mL, 2 mg/mL, 1 mg/mL and 0.5 mg/mL) as a measure of their antisickling potentials. Among the synthesized compounds, 6-chloro-3-(chloromethyl)coumarin 4d showed the highest inhibitory activity (83.75±1.90%), followed by 6-chlorocoumarin-3-methylsulfinic acid 5d (80.90 ±0.91%) and the least was tert-butyl-3-hydroxy- 3-(2-hydroxyphenyl)-2-methylenepropanoate 3a (33.33±1.86%). The results obtained from the reversal antisickling experiment showed that the percentage of sickle cells able to revert to the normal biconcave shape was dose dependent. Compound 5d had the highest reversal activity (66.49±1.39%) followed by 6-bromo-3- (chloromethyl)coumarin 4c (59.66±2.95) and 4d (55.50±1.95%) at 4 mg/mL. Compound 4c had higher reversal activity than the standard p-hydroxybenzoic acid at 2 mg/mL, 1 mg/mL and at 0.5 mg/mL. The 3-substituted coumarins 4a-d, and 5d had higher inhibitory antisickling activities than their Baylis-Hillman precursors 3a-d. Effect of 4a-d and 5d on the rate of polymerization of sickle cell heamoglobin was further studied spectrophotomerically using hemolysate of HbSS. The considerable inhibitory and reversal activities of these compounds make them good candidates for further antisickling studies.

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Section: Synthesis Of Baylis-hillman Adducts and 3-substituted Coumarinssupporting

confidence: 65%

Section: Tert-butyl-3-hydroxy-3-(2-hydroxyphenyl)-2-methylene Propanomentioning

confidence: 98%

Section: Synthesis Of Baylis-hillman Adducts 3a-d and 3-(chloromethylmentioning

confidence: 99%

Section: Synthesis Of Baylis-hillman Adducts and 3-substituted Coumarinsmentioning

confidence: 99%

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Evaluation of Some Salicylaldehyde-derived Baylis-Hillman Adducts and Coumarin Derivatives as Potential Antisickling Compounds

Olomola

Kelani

Cyril-Olutayo

et al. 2018

Annals of Science and Technology

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“…Besides Perkin condensation, other named reactions such as the Knoevenagel condensation or the von Pechmann reaction are also well known for the synthesis of coumarins. Alternative means to build the coumarin frame are also reported, including, for example, condensation of salicylaldehydes with acetic acid derivatives , the Baylis‐Hillman reaction , or oxidative cyclization of Z ‐cinnamic acids . Pd‐catalyzed reactions were also applied in various ways, for example, Heck‐type coupling , ring closing of aryl alkynoate , or acrylate derivatives through C─H activation.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of 7‐Azido‐3‐Formylcoumarin – A Key Precursor in Bioorthogonally Applicable Fluorogenic Dye Synthesis

Pünkösti

Kele

Herner

2018

Journal of Heterocyclic Chem

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Coumarins represent an important group of natural products and a common part of various drugs and fluorescent dyestuffs. Herein, we present the synthesis of a coumarin that can serve as a key starting material in the design and synthesis of bioorthogonally applicable fluorogenic dyes. The synthesis of 7‐azido‐3‐formylcoumarin started from 7‐diallylaminocoumarin. This allyl protected aminocoumarin is otherwise hard to obtain by conventional methods but was conveniently accessed in good yields by a sequential, Wittig‐reaction–UV isomerization process. This sequential approach was studied in more details and applied for the synthesis of a series of substituted coumarins even in one‐pot.

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Potassium Carbonate‐Catalyzed Reactions of Salicylic Aldehydes with Allenic Ketones and Esters: an Effective Way to Synthesize Functionalized 2H‐Chromenes

Shi¹,

Dai²,

Shi³

et al. 2006

Adv Synth Catal

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Efficient and Chemoselective Access to 3-(Chloromethyl)coumarins via Direct Cyclisation of Unprotected Baylis-Hillman Adducts

Abstract: Reaction of substituted 2-hydroxybenzaldehydes with tbutyl acrylate in the presence of DABCO has been shown to afford isolable Baylis-Hillman adducts, acid-catalysed cyclisation of which affords the corresponding 3-(chloromethyl)coumarins directly and in high yield.

Cited by 46 publications

References 3 publications

Evaluation of Some Salicylaldehyde-derived Baylis-Hillman Adducts and Coumarin Derivatives as Potential Antisickling Compounds

Evaluation of Some Salicylaldehyde-derived Baylis-Hillman Adducts and Coumarin Derivatives as Potential Antisickling Compounds

Synthesis of 7‐Azido‐3‐Formylcoumarin – A Key Precursor in Bioorthogonally Applicable Fluorogenic Dye Synthesis

Potassium Carbonate‐Catalyzed Reactions of Salicylic Aldehydes with Allenic Ketones and Esters: an Effective Way to Synthesize Functionalized 2H‐Chromenes

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