Iron-catalyzed synthesis of cinnarizine

Shakhmaev, R. N.; Сунагатуллина, А. Ш.; Зорин, В. В.

doi:10.1134/s1070428015010169

Cited by 12 publications

(5 citation statements)

References 14 publications

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“…In this regard, recent studies by Shakhmaev and co‐workers demonstrated the effect of substoichiometric amounts of NMP on C(sp 2 )−C(sp 2 ) allyl–aryl cross‐couplings using Fe(acac) 3 (1 mol %; Scheme ) . This method was applied to short syntheses of allylamine pharmaceuticals, such as naftifine (antifungal), cinnarizine (antihistamine), and flunarizine (calcium antagonist) . It is likely that the amino group of the substrate acts as a ligand to iron in these couplings …”

Section: Development Of Sustainable Methodsmentioning

confidence: 99%

Iron‐Catalyzed Cross‐Couplings in the Synthesis of Pharmaceuticals: In Pursuit of Sustainability

2018

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The scarcity of precious metals has led to the development of sustainable strategies for metal-catalyzed cross-coupling reactions. The establishment of new catalytic methods using iron is attractive owing to the low cost, abundance, ready availability, and very low toxicity of iron. In the last few years, sustainable methods for iron-catalyzed cross-couplings have entered the critical area of pharmaceutical research. Most notably, iron is one of the very few metals that have been successfully field-tested as highly effective base-metal catalysts in practical, kilogram-scale industrial cross-couplings. In this Minireview, we critically discuss the strategic benefits of using iron catalysts as green and sustainable alternatives to precious metals in cross-coupling applications for the synthesis of pharmaceuticals. The Minireview provides an essential introduction to the fundamental aspects of practical iron catalysis, highlights areas for improvement, and identifies new fields to be explored.

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Section: Development Of Sustainable Methodsmentioning

confidence: 99%

Iron‐Catalyzed Cross‐Couplings in the Synthesis of Pharmaceuticals: In Pursuit of Sustainability

2018

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Section: Letters To the Editormentioning

confidence: 99%

“…It is known that available iron(III) salts are effective catalysts in cross-coupling reactions of Grignard reagents with vinyl [9--12] and allyl halides [13,14]. Fe(acac) 3 the most commonly used in the synthesis of natural compounds [15,16] and drugs [17][18][19][20] is advantageously characterized by low hygroscopicity, good solubility, and ease of handling [21].The reaction of (E)-1,3-dichloropropene la with 3 equiv of PhMgBr in tetrahydrofuran in the presence of 3 mol % of Fe(acac) 3 afforded a mixture of (E)-and (Z)-isomers of 1,3-diphenylpropene 2a and 2b (E : Z = 92 : 8) in a 52% yield. The introduction of the most frequently used ligands like N,N,N,N-tetramethylethylenediamine (TMEDA) [22] or N-methylpyrrolidone (NMP) [10], the replacement of THF by diethyl ether and the use of FeCl 3 as the catalyst did not substantially increase the yield of the reaction product.…”

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confidence: 99%

A Simple Synthesis of 1,3-Diphenylpropene

et al. 2018

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Abstract-A simple approach to the synthesis of 1,3-diphenylpropene isomers was developed based on Fe(acac) 3 -catalyzed cross-coupling of (E)-and (Z)-1,3-dichloropropenes with phenylmagnesium bromide.Keywords: 1,3-diphenylpropene, cross-coupling, Fe-catalyzed cross-coupling, Fe(acac) 3 ISSN 1070-3632, Russian Journal of General Chemistry, 2018, Vol. 88, No. 2, pp. 342-344. © Pleiades Publishing, Ltd., 2018. Original Russian Text © R.N. Shakhmaev, A.Sh. Sunagatullina, A.N. Vasilyeva, V.V. Zorin, 2018, published in Zhurnal Obshchei Khimii, 2018 1,3-Diphenylpropene isomers are used in organic synthesis as the starting substrates and model compounds [1][2][3][4]. The specific reactivity of 1,3-diphenylpropene is due to the presence of methylene group, being simultaneously in the allyl and benzyl positions. (E)-1,3-Diphenylpropene is usually obtained by treating a not easily accessible phenylacetaldehyde with a KOH alcohol solution [5,6], while the synthesis of less thermodynamically stable (Z)-isomer with an acceptable stereochemical purity is very problematic [7,8]. LETTERS TO THE EDITORWe investigated the possibility of obtaining 1,3-diphenylpropene 2 by Fe(acac) 3 -catalyzed crosscoupling of 1,3-dichloropropene 1 with phenylmagnesium bromide. It is known that available iron(III) salts are effective catalysts in cross-coupling reactions of Grignard reagents with vinyl [9--12] and allyl halides [13,14]. Fe(acac) 3 the most commonly used in the synthesis of natural compounds [15,16] and drugs [17][18][19][20] is advantageously characterized by low hygroscopicity, good solubility, and ease of handling [21].The reaction of (E)-1,3-dichloropropene la with 3 equiv of PhMgBr in tetrahydrofuran in the presence of 3 mol % of Fe(acac) 3 afforded a mixture of (E)-and (Z)-isomers of 1,3-diphenylpropene 2a and 2b (E : Z = 92 : 8) in a 52% yield. The introduction of the most frequently used ligands like N,N,N,N-tetramethylethylenediamine (TMEDA) [22] or N-methylpyrrolidone (NMP) [10], the replacement of THF by diethyl ether and the use of FeCl 3 as the catalyst did not substantially increase the yield of the reaction product. However, a decrease in the reaction temperature to -35°C results in an increase in the yield of 1,3-diphenylpropene to 80% with the same isomeric composition.The cross-coupling with (Z)-1,3-dichloropropene under similar conditions resulted in an isomeric mixture of 1,3-diphenylpropene (E : Z = 55 : 45) with 72% yield, while at room temperature the reaction direction shifted toward the formation of (E)-isomer (E : Z = 76 : 24). (E)-and (Z)-isomers of 1,3-diphenylpropene and diphenyl formed by homocoupling reaction were separated by column chromatography (Scheme 1).Structure and purity of the obtained compounds was confirmed by high-performance GLC analysis, NMR spectroscopy and chromato-mass spectrometry. A reliable evidence of the stereochemical configuration of isomers 2a and 2b was the values of spin-spin coupling constant of vinyl hydrogen atoms (J = 15.6 and 11.3 Hz), characteristic of the E-and Z-con...

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“…, toremifene and cinnarizine. 8,9 HCAL has been utilized to produce HIV protease inhibitors. 10 HCOL is not only a spice but also an important intermediate towards phenprobamate.…”

Section: Introductionmentioning

confidence: 99%

“…[2][3][4][5][6][7] COL and its derivatives are preferred products since they are key inter-mediates of important medicines e.g., toremifene and cinnarizine. 8,9 HCAL has been utilized to produce HIV protease inhibitors. 10 HCOL is not only a spice but also an important intermediate towards phenprobamate.…”

Section: Introductionmentioning

confidence: 99%