2,5-dimethyl isosorbide

Structural formula
General
Surname	2,5-dimethyl isosorbide
other names	1,4: 3,6-dianhydro-2,5-di- O -methyl- D -glucitol 1,4: 3,6-dianhydrosorbitol-2,5-dimethylether (3 R , 3a R , 6 S , 6a R ) -3,6-dimethoxyhexahydrofuro [3,2- b ] furan DMI
Molecular formula	C 8 H 14 O 4
Brief description	clear, colorless liquid
External identifiers / databases
CAS number 5306-85-4 EC number 226-159-8 ECHA InfoCard 100,023,782 PubChem 62990 Wikidata Q5807233
properties
Molar mass	174.19 g mol −1
Physical state	liquid
density	1.15 g cm −3 at 25 ° C
Melting point	−70 ° C
boiling point	93-95 ° C at 0.1 mmHg 125-129 ° C at 20 mmHg 235 ° C
Vapor pressure	0.013 kPa at 25 ° C
solubility	soluble in water (56.2 g l −1 at 20 ° C ) soluble in all common solvents
Refractive index	1.4622 (20 ° C, 589 nm)
safety instructions
GHS labeling of hazardous substances no GHS pictograms H and P phrases H: no H-phrases P: no P-phrases
Toxicological data	6.530 mg kg −1 ( LD 50 ,  rat ,  oral ) 5.416 mg kg −1 ( LD 50 ,  mouse ,  iv )
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . Refractive index: Na-D line , 20 ° C

2,5-Dimethyl isosorbide is an ether of the bicyclic diol isosorbide , which is of great interest as a bio-based platform chemical made from renewable raw materials.

Dimethyl isosorbide is suitable as a low-toxicity solvent for pharmacologically active substances whose penetration into the skin it promotes.

Occurrence and representation

2,5-dimethyl isosorbide is z. B. obtained by Williamson ether synthesis from isosorbide in water with the simultaneous addition of dimethyl sulfate and 30% sodium hydroxide solution in 77% yield.

Because of the high tendency of dimethyl sulfate to hydrolyze in alkaline media, water or dilute sodium hydroxide solution are rather less suitable as a reaction medium.

In acetone as the solvent, DMI is obtained in 82.6% yield after vacuum distillation under similar process conditions.

The conventional Williamson synthesis provides dimethyl isosorbide in 91 to 93% yield with a number of alkylating agents , such as dimethyl sulfate, methyl iodide or methyl p -toluenesulfonate in tert- butanol as solvent.

More recently, syntheses for 2,5-dimethyl isosorbide have been published which produce the bio-based dimethyl ether while avoiding carcinogenic alkylating agents with less problematic methyl group donors.

In particular, dimethyl carbonate DMC is being investigated more intensively as a “green” alkylating agent, with a one-pot reaction starting from D -sorbitol being described.

The DMI synthesis using dimethyl carbonate as a condensation and methylating agent requires very long reaction times (10 to 72 h), high temperatures (90 to 200 ° C) and high pressures (20 to 85 bar) in laboratory batches (mostly 10 millimolar). Isolation by vacuum distillation and purification by column chromatography usually provides relatively low calculated yields of DMI (e.g. 69%), which means that the requirements for an economically viable industrial process cannot yet be met.

properties

2,5-dimethyl isosorbide is a clear, colorless liquid with a faint odor that mixes with water and many organic solvents. Because of its favorable properties (e.g. low eye and skin irritation and very low toxicity), DMI was used as a bio-based ether and replacement for problematic solvents such as B. Ethylene glycol dimethyl ether glyme or tetrahydrofuran THF examined and classified. The ether DMI is not toxic to aquatic organisms, but despite its "green" origin, it is not biodegradable. The main disadvantage is its high boiling point, which makes complete separation of the DMI difficult.

Applications

2,5-dimethyl isosorbide has proven to be a useful solvent for palladium- catalyzed cross-coupling reactions , such as. B. the Sonogashira coupling , the Heck reaction and the Suzuki coupling proved.

Thus, in the reaction of bromobenzene with methyl acrylate in DMI in the presence of triethylamine and the catalyst bis (triphenylphosphine) palladium chloride, methyl cinnamate is obtained in 98% yield.

In addition to technical applications such as B. as a fuel additive, as an electrolyte component in lithium batteries or as a solvent in semiconductor production, DMI is suitable as a formulation and stability improver in cosmetic and pharmaceutical dermal preparations. As a penetration enhancer (similar to dimethyl sulfoxide DMSO), DMI accelerates and increases the transport of dissolved active ingredients, e.g. B. the self-tanner dihydroxyacetone DHA or the active ingredient against acne benzoyl peroxide , in and through the epidermis and dermis layers of the skin. In crop protection formulations, too, dimethyl isosorbide increases the penetration of the active ingredients into the wax layer ( cuticle ) of leaves.

2,5-dimethylisosorbide is u. a. as Super Refined® Arlasolve® DMI from Croda International, Dottisol® from Dottikon ES Holding and Salibide® DMI from Salicylates & Chemicals Pvt. Ltd. in trade.

Individual evidence

1. ↑ ^{a b c d e f} data sheet Isosorbide dimethyl ether from Sigma-Aldrich , accessed on May 11, 2019 ( PDF ).
2. ↑ ^{a b} Anna & George Wypych: Databook of Green Solvents, 2nd Edition . ChemTec Publishing, Toronto 2019, ISBN 978-1-927885-43-7 , pp. 336-337 .
3. ↑ ^{a b} Patent US4322359 : Process for the preparation of 2,5-dimethyl-1,4: 3,6-dianhydrosorbitol. Applied March 19, 1981 , published March 30, 1982 , Applicant: American Cyanamid Co., Inventor: RL Hillard, ID Greene. ‌
4. ↑ ^{a b} P. Tundo, F. Aricò, G. Gauthier, L. Rossi, AE Rosamilia, HS Bevinakatti, RL Sievert, CP. Newman: Green synthesis of dimethyl isosorbide . In: ChemSusChem . tape 3 , no. 5 , 2010, p. 566-570 , doi : 10.1002 / cssc.201000011 .
5. ↑ ^{a b c d} Arlasolve DMI. In: Full Public Report, File No: STD / 1052. NICNAS, May 12, 2004, accessed May 22, 2019 . 
6. ↑ Safety Data Sheet (Dimethyl Isosorbide). Parchem, December 21, 2016, accessed May 22, 2019 . 
7. ↑ M. Rose, R. Palkovits: Isosorbide as a renewable chemical platform for versatile applications - quo vadis? In: ChemSusChem . tape 5 , no. 1 , 2012, p. 167-176 , doi : 10.1002 / cssc.201100580 .
8. ↑ F. Aricò, P. Tundo: Isosorbide and dimethyl carbonate: a green match . In: Beilstein J. Org. Chem. Volume 12 , 2016, p. 2256-2266 , doi : 10.3762 / bjoc.12.218 .
9. ↑ ^{a b} W. Zhang, BW Cue: Green Techniques for Organic Synthesis and Medical Chemistry, 2nd Edition . John Wiley & Sons, Hoboken, NJ, USA 2018, ISBN 978-1-119-28817-6 , pp. 27 .
10. ^ R. Montgomery, LF Wiggins: 77. The anhydrides of polyhydric alcohols. Part IV. The constitution of dianhydro sorbitol . In: J. Chem. Soc. 1946, p. 390-393 , doi : 10.1039 / JR9460000390 .
11. ↑ Patent EP0205770B1 : Process for the preparation of 2,5-dimethyl- or 2,5-diethyl-1,4: 3,6-dianhydrosorbitol. Registered on March 21, 1986 , published on September 10, 1991 , applicant: Rütgerswerke AG, inventor: M. Maurer, W. Orth, W. Fickert. ‌
12. ↑ ^{a b c} F. Aricò, AS Aldoshin, P. Tundo: One-pot preparation of dimethyl isosorbide from D-sorbitol via dimethyl carbonate chemistry . In: ChemSusChem . tape 10 , no. 1 , 2017, p. 53-57 , doi : 10.1002 / cssc.201601382 .
13. ↑ Green approach to the isosorbide conversion into dimethyl isosorbide. (PDF; 241 KB) 4th International Congress on Catalysis for Biorefineries, accessed on May 20, 2019 (English). 
14. ↑ ^{a b} C.M. Alder, JD Hayler, RK Henderson, AM Redman, L. Shukla, LE Shuster, HF Sneddon: Updating and further expanding GSK's solvent sustainability guide . In: Green Chem. Band 18 , no. 13 , 2016, p. 3879-3890 , doi : 10.1039 / C6GC00611F .
15. ^ KL Wilson, J. Murray, HF Sneddon, C. Jamieson, AJB Watson: Dimethylisosorbide (DMI) as a bio-derived solvent for Pd-catalyzed cross-coupling reactions . In: Synlett . tape 29 , no. 17 , 2018, p. 2292-2297 , doi : 10.1055 / s-0037-1611054 .
16. ↑ Dottisol. Dottikon Exclusive Synthesis, 2019, accessed May 22, 2019 .