1,4-Butane sultone

1,4-Butansulton Struktur.svg 85px 1,2λ6-Oxathiane-2,2-dione δ-Butane sultone, δ-Valerosultone, Oxathiane 2,2-dioxide 1633-83-6 15411 216-647-9 4E0C1CLI2C 26967 5-19-01-00010 14670 1S/C4H8O3S/c5-8(6)4-2-1-3-7-8/h1-4H2 MHYFEEDKONKGEB-UHFFFAOYSA-N C1CCS(=O)(=O)OC1 4 3 1 8 Warning 07 08 302 315 319 335 341 351 412 201 202 261 264 270 271 273 280 281 301+312 302+352 304+340 305+351+338 308+313 312 321 330 332+313 337+313 362 403+233 405 501 1,4-butane sultone is a six-membered δ-sultone and the cyclic ester of 4-hydroxybutanesulfonic acid. As a sulfo-alkylating agent, 1,4-butanesultone is used to introduce the sulfobutyl group (–(CH2)4–SO3−) into hydrophobic compounds possessing nucleophilic functional groups, for example hydroxy groups (as in the case of β-cyclodextrinH. Ueda D. Ou T. Endo H. Nagase K. Tomono T. Nagai Drug Dev. Ind. Pharm. Evaluation of a sulfobutyl ether beta-cyclodextrin as a solubilizing/stabilizing agent for several drugs 24 9 863–867 1998 10.3109/03639049809088532 9876538 ) or amino groups (as in the case of polymethine dyesV. Wycisk etal ACS Omega Responsive Contrast Agents: Synthesis and Characterization of a Tunable Series of pH-Sensitive Near-Infrared Pentamethines 1 5 808–817 2016 10.1021/acsomega.6b00182 free 6044694 30023492). In such, the sulfobutyl group is present as neutral sodium salt and considerably increases the water solubility of the derivatives. Preparation A lab scale synthesis of 1,4-butanesultone starts from 4,4'-dichlorodibutyl ether (accessible from tetrahydrofuran treated with phosphorus oxychloride and concentrated sulfuric acid),CV4P0266 K. Alexander, H.V. Towles 4,4‘-Dichlorbutyl ether 1950 30 27 4 266 10.15227/orgsyn.030.0027 K. Alexander, L.E. Schniepp J. Am. Chem. Soc. 4,4'-Dichlorodibutylether and its derivatives from tetrahydrofuran 70 5 1839–1842 1948 10.1021/ja01185a056 18861793 1948JAChS..70.1839A which reacts with sodium sulfite forming the corresponding 4,4'-butanedisulfonic disodium salt. By passing it through an acidic ion exchanger, the disodium salt is converted into the disulphonic acid which forms two molecules of 1,4-butanesultone at elevated temperature and reduced pressure under elimination of water. The yields obtained range from 72 to 80%.CV4P0529 A.O. Snoddy, T.L. Cairns, W.R. Brasen, 4-Hydroxy-1-butanesulfonic acid sultone [1-Butanesulfonic acid, 4-hydroxy-, δ-sultone] 1957 37 55 4 523 10.15227/orgsyn.037.0055 400px|center|Synthese von 1,4-Butansulton aus Bis-4-chlorbutylether Starting from 4-chlorobutan-1-olCV2P0571 D. Starr, R.M. Hixon Tetramethylene chlorohydrin 1937 17 84 2 571 10.15227/orgsyn.017.0084 (from tetrahydrofuran and hydrogen chloride in 54 to 57% yield), the sodium salt of 4-hydroxybutan-1-sulfonic acid is obtained with sodium sulfite. This salt is converted with strong acids (such as hydrochloric acid) into the very hygroscopic 4-hydroxybutanesulfonic acid and cyclized to 1,4-butanesultone under elimination of water. The cyclization of 4-hydroxybutanesulfonic acid in aqueous solution proceeds particularly efficiently when heated with high-boiling, water-immiscible solvents (for example 1,2-dichlorobenzene or diethylbenzene, both boiling at about 180 °C) in which 1,4-butane-sultone dissolves and is thereby protected from hydrolysis in the aqueous medium. 1,4-butanesultone is obtained in yields of up to 99% upon reflux within one hour.EP 0222970 Sulfoalkylierungsverfahren 1987-05-27 1986-07-09 W. Hünicke, R. Gauglitz Agfa-Gevaert AG 400px|center|Synthese von 1,4-Butansulton aus 4-Chlorbutan-1-ol The vacuum distillation of the sodium salt of 4-hydroxybutanesulfonic acid leads in the presence of concentrated sulfuric acid directly to 1,4-butanesultone.US 3146242 Process for the preparation of sultones 1964-08-25 1961-05-21 K.-J. Gardenier, H. Kothe Henkel & Cie GmbH The sodium salt of 4-chlorobutane-1-sulfonic acid, which is obtained from 1,4-dichlorobutane with sodium sulfite, can also be cyclized to 1,4-butanesultone by heating to 180-250 °C.US 3117133 Process for the production of sultones 1964-01-07 1960-10-19 H. Kothe, K.-J. Gardenier Henkel & Cie GmbH 250px|center|Synthese von 1,4-Butansulton aus 4-Chlorbutan-1-sulfonsäure The free-radical initiated sulfochlorination of 1-chlorobutane leads to a mixture of positionally isomeric sulfochlorides and chlorination products and is therefore not suitable for the direct preparation of 1,4-butanesultone.J.H. Helberger G. Manecke H.M. Fischer Liebigs Ann. Chem. Zur Kenntnis organischer Sulfonsäuren. II. Mitt.: Die Sulfochlorierung des 1-Chlorbutans und anderer Halogenalkyle: Synthese von Sultonen und eines Sultams 562 1 23–35 1949 German 10.1002/jlac.19495620104 Properties 1,4-butanesultone is a viscous, clear, colorless and odorless liquid which reacts in boiling water (to 4-hydroxybutanesulfonic acid) and alcohols (to 4-alkoxybutanesulfonic acid) and dissolves in many organic solvents. At temperatures below the melting point, the compound crystallizes giving "large, magnificent plates". [3] Compared to the homologous γ-sultone 1,3-propanesultone, 1,4-butanesultone is significantly less reactive as alkylating agent, but classified as mutagenic and carcinogenic.L. Fishbein Potential Industrial Carcinogens and Mutagens, 1st Edition, in Studies in Environmental Science 4 Elsevier Amsterdam 124 0-444-41777-X 1979 Applications Sulfobetaines 1,4-butanesultone reacts smoothly with nucleophiles such as ammonia to form the corresponding zwitterionic, usually very water-soluble sulfobutylbetaines.J.H. Helberger, H. Lantermann Liebigs Ann. Chem. Zur Kenntnis organischer Sulfonsäuren V. Mitteilung Synthesen des 1,4-Butansultons 586 1 158–164 1954 German 10.1002/jlac.19545860110 400px|center|Synthese von 4-Aminobutan-1-sulfonsäure aus 1,4-Butansulton Sulfobetaines with longer alkyl chains (CnH2n+1 mit n > 10) show interesting properties as surface-active compounds (surfactants, detergents) with antimicrobial properties.D. Wieczorek A. Dobrowolski K. Staszak D. Kwasniewska P. Dubyk J. Surfactants Deterg. Synthesis, surface and antimicrobial activity of piperidine-based sulfobetaines 20 1 151–158 2017 10.1007/s11743-016-1906-8 28111518 5222909 400px|center|Synthese eines Alkylpiperidinsulfobetains-Surfactants In the reaction of N-N-butylimidazole with 1,4-Butansultone in Toluene in a 98% yield is formed 1-butylimidazolium-3-(n-butylsulfonate)F.M.A. Geilen et al Angew. Chem. Selective and Flexible Transformation of Biomass-Derived Platform Chemicals by a Multifunctional Catalytic System 49 32 5510–5514 2010 10.1002/anie.201002060 20586088 600px|center|Synthese von ionischen Flüssigkeiten vom Chlorbutylsulfonat-Typ 1-Butylimidazolium-3-(n-butylsulfonate) catalyses as a component of multifunctional catalysts the reaction of platform chemicals from biomass (for example levulinic acid or itaconic acid) into the corresponding lactones, diols or cyclic ethers. Aminoalkylphosphonic acids (such as aminomethane diphosphonic acid, accessible from phosphorus trichloride, formamide and phosphonic acid US 3870750 Process for the production of aminomethane-diphosphonic acid and its salts 1975-03-11 1972-04-26 K. Wollmann, W. Plöger, K.-H. Wopms Henkel & Cie GmbH) form with 1,4-butanesultone N-(sulfobutyl)aminomethane diphosphonic acids: 500px|center|Synthese von N-(Sulfobutyl)aminomethandiphosphonsäure-Komplexbildnern N-(sulfobutyl)aminomethane diphosphonic acid is characterized by very high water solubility (< 1000 g·l−1) and a strong capability as complexing agent and water softener. US 4250107 N-(Sulfoalkane) amino alkane phosphonic acids and their water-soluble salts 1981-02-10 1978-11-06 K. Sommer, G. Schoebel Benckiser-Knapsack GmbH Sulfobutylation of cyanine dyes leads to readily water-soluble compounds which react with proteins like antibodies and can be used as pH-sensitive fluorescence markers. 400px|center|Sulfobutylierter Cyaninfarbstoff als Fluoreszenzmarker Ionic liquids The ionic liquid 4-triethylammonium butane-1-sulfonic acid hydrogensulfate (TEBSA HSO4) is formed by the reaction of 1,4-butanesultone with triethylamine in acetonitrile to the zwitterion (85% yield) and subsequent reaction with concentrated sulfuric acid.A.R. Hajipour Y. Ghayeb N. Sheikhan A.E. Ruoho Tetrahedron Lett. Brønsted acidic ionic liquid as an efficient and reusable catalyst for one-pot synthesis of 1-amidoalkyl 2-naphthols under solvent-free conditions 50 5649–5651 2009 10.1016/j.tetlet.2009.07.116 40 600px|center|Synthesis of TEBSA HSO4 4-triethylammonium butane-1-sulfonic acid hydrogensulfate can replace conventional mineral acids as effective and easily recyclable acid catalyst in solvent-free reactions. The ring opening of 1,4-butanesultone with organic chloride salts yields ionic liquids of the 4-chlorobutylsulfonate type in quantitative yield.N. Paape W. Wie A. Bösmann C. Kolbeck F. Maier H.-P. Steinrück P. Wasserscheid P.S. Schulz Chem. Commun. Chloroalkylsulfonate ionic liquids by ring opening of sultones with organic chloride salts 3867–3869 2008 10.1039/B805444D 33 18726017 500px|center|Synthesis of ionic liquid 1-Butylimidazolium-3-(n-butylsulfonate) The chlorine atom in the 4-chlorobutylsulfonate anion can be substituted by heating with inorganic (e.g. potassium fluoride) or organic salts (e.g. sodium acetate) by the respective anion. WO 2009152902 Ionic liquids 2009-12-23 2009-05-12 P. Wasserscheid, N. Paape, A. Boesmann, P. Schulz Merck Patent GmbH 700px|center|Exchange reactions involving chlorbutylsulfonate-ILs Sulfobutylated β-cyclodextrin Already in 1949 the reaction of 1,4-butanesultone with the water-insoluble polysaccharide cellulose in sodium hydroxide solution was reported, which leads to a water-soluble product.J.H. Helberger G. Manecke R. Heyden Liebigs Ann. Chem. Zur Kenntnis organischer Sulfonsäuren III. Mitteilung: Die Alkylierungsreaktionen der Sultone 565 1 22–35 1949 German 10.1002/jlac.19495650104 Derived from this the derivatization of β-cyclodextrin to sulfobutyl ether-beta-cyclodextrin (SBECD) is by now an important application of 1,4-butanesultone.38th United States Pharmacopeial Convention Betadex Sulfobutyl Ether Sodium Rockville, MD 6546–6548 978-1-936424-34-4 2015 Sulfobutyl ether-beta-cyclodextrin is a water-soluble inclusion compound for the solubilization and stabilization of sparsely water-soluble and chemically instable components.T. Loftsson D. Duchene Int. J. Pharm. Cyclodextrins and their pharmaceutical applications 329 1–2 1–11 2007 10.1016/j.ijpharm.2006.10.044 17137734 S. Klein, T. Zöller Pharm. ZTG. Cyclodextrine: Molekulare Zuckertüten für Arzneistoffe 26 2008 German http://www.pharmazeutische-zeitung.de/index.php?id=6057 β-Cyclodextrin can be reacted with 1,4-butanesultone in sodium hydroxide solution at 70 °C to the sulfobutyl ether in yields of up to 80% and a degree of substitution of 6.68.D.-Y. Ma Y.-M. Zhang J.-N. Xu Tetrahedron The synthesis and process optimization of sulfo butyl ether β-cyclodextrin derivatives 72 22 3105–3112 2016 10.1016/j.tet.2016.04.039 500px|center|Sulfobutylierung von beta-Cyclodextrin mit 1,4-Butansulton Thereby, the water solubility of the β-cyclodextrin increases from 18.5 g · l-1 to more than 900 g · l-1 at 25 °C. Sulfobutyl ether-beta-cyclodextrin also finds a wide range of applications as an inert vehicle for drug delivery (the drugs transport and release).R. Challa A. Ahuya J. Ali R.K. Khar AAPS Pharm. Sci. Tech. Cyclodextrins in drug delivery: an updated review 6 2 E329–E357 2005 10.1208/pt060243 2750546 16353992 See also 1,3-Propane sultone References Category:Sultones Category:Esters Category:Six-membered rings