A Facile Method for the Preparation of Pure<i>cis</i>‐2,4‐Pentanediol

Bonner, Lisa A; Frescas, Stewart; Nichols, David E.

doi:10.1081/scc-200026213

Cited by 3 publications

(10 citation statements)

References 8 publications

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“…The pure syn-2 was initially obtained by recrystallization of syn-enriched 2 (dr s/a = 6:1) from isopropanol. 5 This gave syn-2 in 50−55% yield (based on syn-1) with dr s/a = 98:2. However, approximately 40% of the syn-2 remained in the filtrate and was not recovered.…”

Section: ■ Results and Discussionmentioning

confidence: 95%

“…It featured a selective acetalization of syn-1, isolation of the resulting synacetal (syn-2) by recrystallization, and then hydrogenolysis of the acetal protecting group. 5 In syn-2, the two methyl groups reside in equatorial positions in the preferred chair conformation. In contrast, in anti-2 one of the methyl groups is forced into an axial position, where it experiences unfavorable syn-pentane interactions with the acetal substituent (Scheme 3).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…This selective acetalization was indeed observed and was utilized to obtain syn-1. 5 We envisioned that by adapting this reaction we could achieve our desired isolation of both 2,4-pentanediol diastereomers.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…4 Recently, Nichols and co-workers prepared syn-1 by selective formation of the syn-acetal (syn-2) with acetophenone and subsequent hydrogenolysis of the acetal protecting group. 5 None of the previously reported methods are adequate to obtain both syn-1 and anti-1 in high diastereomeric purity and high yield. Herein we report a simple and efficient separation of 2,4-pentanediol diastereomers that features a diastereoselective acetalization and a hydrolytic kinetic resolution of the corresponding acetals 2, which leads to a high yield and high diastereomeric purity of both syn-1 and anti-1 (Scheme 1).…”

Section: ■ Introductionmentioning

confidence: 96%

“…These useful building blocks are often produced as mixtures of syn and anti diastereomers in varying ratios, and separation of the two isomers can be challenging. For example, separation of the syn and anti diastereomers of 2,4-pentanediol ( 1 ) has been a laborious and inefficient task. − Pritchard and Vollmer reported a separation of syn - and anti -2,4-pentanediol diastereomers by formation of the cyclic sulfite ester diastereomers followed by separation via fractional distillation (a difficult operation because of their similar boiling points) and then hydrolysis . Diastereoselective formation of the syn cyclic sulfite ester could be effected in a syn / anti diastereomeric ratio (dr s / a ) of 96:4, but subsequent alkaline hydrolysis of the sulfite ester furnished syn - 1 with only moderate enrichment (dr s / a = 69:31) .…”

Section: Introductionmentioning

confidence: 99%

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Efficient Separation of Diastereomeric Mixtures of syn- and anti-2,4-Pentanediol

Pan

Zhang

et al. 2015

Org. Process Res. Dev.

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A simple and practical process was developed for the efficient separation of diastereomeric syn- and anti-2,4-pentanediol by selective acetalization of a diastereomeric mixture of the 2,4-pentanediols and selective hydrolysis of the corresponding acetals. The process relies upon the reaction rate differences of syn-2,4-pentanediol (syn-diol) and anti 2,4-pentanediol (anti-diol) in acetalization and of the corresponding acetals in hydrolysis: the syn-diol reacts faster to form a more stable acetal than the anti-diol, which in turn is more susceptible to hydrolysis by Brønsted acid. Acetalization of a 2,4-pentanediol diastereomeric mixture (syn/anti = 45:55) with acetophenone (0.95 equiv relative to syn-diol) leads to the formation of a syn-enriched acetal mixture with a syn/anti diastereomeric ratio (dr s/a ) of 6:1, leaving an anti-enriched diol mixture (dr s/a = 1:7). Subsequent kinetic resolution via selective hydrolysis of the minor anti-acetal with a catalytic amount of 1.0 N HCl at ambient temperature affords the pure syn-acetal (dr s/a > 99:1) in the organic phase and the anti-enriched 2,4-pentanediols (dr s/a = 1:6) in the aqueous phase, which are conveniently separated by a phase cut. Hydrolysis of the syn-acetal is facile in alcohol solvents at elevated temperatures (60–80 °C), yielding the pure syn-diol. A second acetalization of the anti-enriched 2,4-pentanediols leads to the pure anti-2,4-pentanediol. This separation gives the syn-diol in 75–79% yield with dr s/a > 99:1 and the anti-diol in 79–85% yield with dr a/s > 98:2. Additionally, the acetophenone used for the acetalization can be recovered in 88–92% yield, and therefore, the overall process is high-yielding, atom-economical, and potentially recyclable.

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Section: ■ Results and Discussionmentioning

confidence: 95%

Section: ■ Results and Discussionmentioning

confidence: 99%

Section: ■ Results and Discussionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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Efficient Separation of Diastereomeric Mixtures of syn- and anti-2,4-Pentanediol

Pan

Zhang

et al. 2015

Org. Process Res. Dev.

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A Facile Method for the Preparation of Pure cis‐2,4‐Pentanediol.

2004

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Alcohols P 0110A Facile Method for the Preparation of Pure cis-2,4-Pentanediol. -Pure cis-2,4-pentanediol (II) is prepared from diastereomeric mixture of (II) and (III) via acetal formation with acetophenone (IV), which favours an axial position of the phenyl substituent. Hydrogenolysis of this compound (VI) gives the diastereomerically pure title compound. -(BONNER, L.; FRESCAS, S.; NICHOLS*, D. E.; Synth.

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Effect of Remote Aryl Substituents on the Conformational Equilibria of 2,2-Diaryl-1,3-dioxanes: Importance of Electrostatic Interactions

et al. 2015

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The conformational preference of a variety of 2,2-diaryl-1,3-dioxanes bearing remote substituents on the phenyl rings has been studied via equilibration of configurationally isomeric 2,2-diaryl-cis-4,6-dimethyl-1,3-dioxane epimers, X-ray crystallography, (1)H NOESY analysis, and B3LYP/6-311+G* calculations. When the aryl ring bears a remote electron-withdrawing substituent, the isomer having both the higher dipole moment and the electron-withdrawing group in the equatorial phenyl ring and/or an electron-donating group in the axial ring has the lower energy. These results differ from the conclusions reported in a previous study of similar systems. The conformational energy differences of para-substituted 2,2-diaryl-1,3-dioxanes are linearly related to the Hammett σ values with a slope (ρ) of 0.6. In addition, there is a trend toward longer bond lengths between the C(2) ketal center and the aryl ring as the electron-withdrawing nature of the para-substituent is increased. Electrostatic interactions, rather than a hyperconjugative anomeric effect, appear to be responsible for the conformational behavior of such molecules.

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A Facile Method for the Preparation of Purecis‐2,4‐Pentanediol

Cited by 3 publications

References 8 publications

Efficient Separation of Diastereomeric Mixtures of syn- and anti-2,4-Pentanediol

Efficient Separation of Diastereomeric Mixtures of syn- and anti-2,4-Pentanediol

A Facile Method for the Preparation of Pure cis‐2,4‐Pentanediol.

Effect of Remote Aryl Substituents on the Conformational Equilibria of 2,2-Diaryl-1,3-dioxanes: Importance of Electrostatic Interactions

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