Names | |
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Preferred IUPAC name Oxolan-3-ol | |
Other names
Tetrahydrofuran-3-ol Tetrahydro-3-furanol 3-OH THF | |
Identifiers | |
CAS Number | |
3D model (JSmol) | |
ChemSpider | |
ECHA InfoCard | 100.006.564 |
PubChem CID | |
CompTox Dashboard (EPA) | |
InChI
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SMILES
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Properties | |
Chemical formula | C4H8O2 |
Molar mass | 88.106 g·mol |
Density | 1.087 g/cm @19 °C |
Boiling point | 179 °C (354 °F; 452 K) (88−89 °C @17 mm Hg) |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C , 100 kPa). Infobox references |
3-Hydroxytetrahydrofuran (3-OH THF) is a colorless liquid with a normal boiling point of 179 °C and boiling at 88−89 °C at 17 mmHg, with density (1.087 g/cm at 19 °C). 3-OH THF is a useful pharmaceutical intermediate. The enantiopure (absolute configuration S) version of this compound is an intermediate to launched retroviral drugs.
Synthesis
3-Hydroxytetrahydrofuran was prepared in 1910 by Pariselle via cyclization and hydrolysis of 3,4-Dibromo-1-methoxybutane. Chiral 3-hydroxytetrahydrofuran (both (S) – and (R)-forms) has been synthesized in high enantiomeric purity from (S)- and (R)-1,2,4-butanetriol, respectively, obtained from chiral feedstocks. Thus, the chiral (S)-1,2,4-butanetriol intermediate was cyclized to chiral (S)-3-hydroxytetrahydrofuran in the presence of p-toluenesulfonic acid (PTSA) catalyst at temperatures of 180−220 °C. Similarly, (S)-3-hydroxytetrahydrofuran was prepared in 95.8% optical purity from L-malic acid via an esterification-reduction-cyclodehydration sequence. 3-hydroxytetrahydrofuran has been synthesized via hydroboration of 2,3- and 2,5-dihydrofuran employing various borane reagents and chiral 3-hydroxytetrahydrofurans have also been prepared by catalytic asymmetric hydroboration of 2,3- and 2,5-dihydrofurans with a borane in the presence of a homogeneous chiral platinum complex, followed by oxidation. Racemic 3-hydroxytetrahydrofuran may be prepared in analogous fashion from racemic butanetriol, employing PTSA catalyst for the dehydrocyclization. Alternatively, 1,2,4-butanetriol may be converted to 3-hydroxytetrahydrofuran by treating with ethylene carbonate, followed by pyrolysis of the resulting carbonate ester.
Applications
3-Hydroxytetrahydrofuran is an intermediate to the AIDS drugs amprenavir and fosamprenavir. Additionally, 3-OH THF has been an intermediate to developmental drug substances, such as chemotherapy agents. For example, reaction of phosphorus pentasulfide with 3-hydroxytetrahydrofuran has been used in the synthesis of bis(O,O-di(tetrahydrofuran-3-yl)hydrogen dithiophosphate)platinum(II), a cisplatin analog. 3-hydroxytetrahydrofuran may be converted into a range of tetrahydrofuran derivatives, many of which also serve as intermediates to compounds of pharmaceutical interest. For example, tetrahydrofuran-3-one (3-ketotetrahydrofuran) and 3-aminotetrahydrofuran have been synthesized from 3-hydroxytetrahydrofuran and used in pharmaceutical syntheses. Additionally, additive amounts (0.05-0.15 weight %) of the nitrate ester manufactured by sulfuric acid-nitric acid nitration of 3-hydoxytetrahydrofuran have been found to increase the quality (cetane number) of diesel fuel.
References
- J. Lesage (1969). Bulletin de la Société Chimique de France. 11: 4147–4151.
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: CS1 maint: untitled periodical (link) - Rostylaw Dowbenko (1966). Chemistry & Industry. 50: 2097–2098.
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: CS1 maint: untitled periodical (link) - Sigurd Olsen (1950). "Über die Umsetzung von Formaldehyd mit Allylacetat. I. Eine neue Synthese des 1,2,4-Butantriols und des 3-Oxytetrahydrofurans". Acta Chemica Scandinavica. 4: 462–472. doi:10.3891/acta.chem.scand.04-0462.
- ^ Venkata Mandava, et al., "Preparation of fosamprenavir calcium" U.S. Pat. Appl., 20110224443 (2011)
- Pariselle (1910). "Derivatives of Butanetriol (1,2,4)". Comptes Rendus. 149: 295–8.
- Vishnu K. Tandon; Van Leusen, Albert M.; Wynberg, Hans (1983). "Synthesis of enantiomerically pure (S)-(+)-3-hydroxytetrahydrofuran, and its (R)-enantiomer, from malic or tartaric acid". Journal of Organic Chemistry. 48 (16): 2767–2769. doi:10.1021/jo00164a027.
- Xiaoqin Wang; Zhu, Derong; He, Minghua (2009). "Study on synthesis of drug intermediates (S)-3-hydroxytetrahydrofuran". Huaxue Yanjiu Yu Yingyong. 21 (7): 1070–1072.
- Herbert C. Brown; Prasad, J. V. N. Vara; Zee, Sheng Hsu (1985). "Hydroboration. 71. Hydroboration of representative heterocyclic olefins with borane-methyl sulfide, 9-borabicyclononane, dicyclohexylborane, and disiamylborane. Synthesis of heterocyclic alcohols". Journal of Organic Chemistry. 50 (10): 1582–1589. doi:10.1021/jo00210a004.
- Anita Schnyder, et al., "Preparation of optically active 3-hydroxytetrahydrofurans by catalytic asymmetric hydroboration of dihydrofurans" Ger. Offen., 19807330 (1998)
- Dexter B. Pattison (1957). "Cyclic ethers made by pyrolysis of carbonate esters". Huaxue Yanjiu Yu Yingyong. 79: 3455–3456.
- Anthony Lowe, et al., "Dithiophosphato platinum complexes for the treatment of cancers" PCT Int. Appl., 2005095425 (2005)
- H. Wynberg (1963). "Tetrahydrofuran-3-one, spirans, and dithienyls". Angewandte Chemie. 75 (10): 453. Bibcode:1963AngCh..75R.453W. doi:10.1002/ange.19630751014.
- Liren Jin, et al., "Process for preparation of (R)-3-aminotetrahydrofuran" Faming Zhuanli Shenqing Gongkai Shuomingshu, CN 1660829 A 20050831 (2005)
- Allen H. Filbey, "Diesel fuel composition" U.S. Pat., 4406665 (1983)