Physical Properties of Solvents

Properties CPME 2-MeTHF THF Ether DCM 1,4-Dioxane MTBE Stabilizer Required No Yes Yes Yes Yes No No Green Chemistry Density (20 °C) [g/cm3] 0.86 0.86 0.89 0.71 1.32 1.03 0.74 Dielectric constant (25 °C) 4.76 6.97 7.58 4.197 8.93 2.227 — Supporting the Advancement of Chemistry Boiling point [°C] 106 80 65 34.6 39.8 101 55 Heat of Vaporization 69.2 87.1 98.1 86.1 80.5 98.6 81.7 through Sound Environmental, Social, and (bp)[Kcal/kg] Solubility of Solvent in Water Fiscal Responsibilities 1.1 4.1 Infi nite 6.5 1.3 Infi nite 4.8 (23 °C) [g/100g] Solubility of Water in Solvent 0.3 14.4 Infi nite 1.2 0.2 Infi nite 1.5 (23 °C) [g/100g] Azeotropic temperature with 83 89 64 34 39 88 52 Water [°C] Flash point [°C] –1 –11.1 –14.2 –45 — 12 –28 Explosion range [vol%] 1.1% / 9.9% — 1.84% / 11.8% 1.85% / 48% 14% / 22% 2% / 22% 1.6% / 15.1% Lower / Upper limit

Peroxide Formation of Ether Solvent 250

200

150

100 Peroxide wt ppm 50

0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 Days (x)

CPME THF Stabilized THF Rate of Peroxide Formation by days (x) Y = 0.2033x Y = 0.8218x Y = 15.277e0.0962x Conditions - 20 mL of each sample in a brown bottle (capacity of 65 mL) - Stored at room temperature, in a dark place and in the presence of air. CPME is a product of Zeon Corporation with approval by Toxic Substances Control Act (TSCA) and European List of Notifi ed Chemical Substances (ELINCS).

For more information, please contact your Check out the new Sigma-Aldrich representative: SpecComparison page Name to fi nd the perfect Sigma-Aldrich Title solvent for your application. Phone: (xxx) xxx-xxxx sigma-aldrich.com/solvents fi [email protected] Alternative Solvents World Headquarters Order/Customer Service (800) 325-3010 • Fax (800) 325-5052 3050 Spruce St., St. Louis, MO 63103 Technical Service (800) 325-5832 • sigma-aldrich.com/techservice (314) 771-5765 Increased Safety, Low Peroxides Formation • Cyclopentyl methyl ether sigma-aldrich.com Development/Bulk Manufacturing Inquiries (800) 244-1173 Reduce your Environmental Footprint • 2-Methyltetrahydrofuran ©2007 Sigma-Aldrich Co. All rights reserved. SIGMA, , SAFC, , SIGMA-ALDRICH, ALDRICH, , FLUKA, , and SUPELCO, are trademarks belonging to Sigma-Aldrich Co. and its affiliate Sigma-Aldrich Biotechnology, L.P. Sigma brand products are sold through Sigma-Aldrich, Inc. Sigma-Aldrich, Inc. warrants that its products conform to the information contained in this and other Sigma-Aldrich publications. Purchaser must determine the suitability of the product(s) for their particular use. Additional terms and conditions may apply. Please see reverse side of the invoice or packing slip.

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33704704 GGreenreen Chemistry.inddChemistry.indd 1-Sec1:11-Sec1:1 110/17/20070/17/2007 11:27:5811:27:58 AAMM Green Chemistry The aim of green chemistry is to reduce chemical related impact on human health and virtually eliminate contamination of the environment through dedicated, sustainable prevention programs. Green chemistry searches for alternative, environmentally friendly reaction media and at the same time strives to increase reaction rates and lower reaction temperatures. The green chemistry concept applies innovative scientifi c solution to solve environmental issues posed in the laboratory. Paul T. Anastas, an organic chemist working in the Offi ce of Pollution Prevention and Toxins at the EPA, and John C Warner developed the Twelve Principles of Green Chemistry in 1991. These principles can be grouped into Reducing Risk and Minimizing the Environmental Footprint.

Safer and More Environmentally Friendly Solvents The Sigma-Aldrich Global Commitment Sigma-Aldrich Corporation is committed to providing safer and more environmentally friendly solvents, Sigma-Aldrich has a proud tradition of sound environmental, social, and fi scal responsibility. such as 2-Methyltetrahydrofuran (2-MeTHF) and Cyclopentyl methyl ether (CPME). We are committed to sustainable growth which is good for the environment, our people, our customers.

2-Methyltetrahydrofuran (2-MeTHF) Cyclopentyl methyl ether (CPME) CAS No.: 96-47-9 CAS No.: 5614-37-9

A Truly Green Alternative to Dichloromethane 2-Methyltetrahydrofuran Cat. No. List Price $ Safe, Environmentally Friendly Alternative to Cyclopentyl methyl Ether Cat. No. List Price $ and Tetrahydrofuran Anhydrous, ≥99.0% 414247-100ML 55.00 Tetrahydrofuran Anhydrous, ≥99.9% 675970-100ML 33.10 2-MeTHF is manufactured from such by-products of agricultural waste as Contains 250ppm BHT 414247-1L 111.50 CPME provides a green solution for those looking to improve their 675970-1L 88.90 corncobs and bagasse (the biomass that remains after sugarcane stalks 414247-6X1L 546.00 chemical process. Using CPME is an environmentally sound choice, not 675970-2L 164.50 are crushed to extract their juice.) 414247-2L 155.50 only by reducing energy waste, but its low water solubility limits it as a ReagentPlus®, ≥99.9% 675989-500ML 37.00 potential environment contaminate. 61.70 Unlike THF, which is completely miscible in water, 2-MeTHF doesn’t mix 414247-4X2L 513.00 675989-1L with water. This makes 2-MeTHF not only more environmentally safe, but 414247-200L-P2 4,000.00 This totally new hydrophobic ether solvent is an excellent alternative 675989-4L 207.00 it also makes it easier and faster to complete organometallic chemistry Anhydrous, ≥99.0% 673277-100ML 59.00 to Tetrahydrofuran (THF), 1,4-Dioxane (carcinogenic) and 1,2- reactions with less waste. Inhibitor-free 673277-12X100L 531.00 dimethoxyethane (DME). 673277-1L 135.00 Based on the chemistry and the application used, 2-MeTHF is more stable Features & Benefi ts than THF in the formation of peroxides (2-MeTHF still requires the use of 673277-200L-P2 7,000.00 ® ≥ • Higher boiling point (106 °C) a stabilizer to prevent the formation of peroxides.) ReagentPlus , 99.9% 155810-100ML 25.100 Contains 250ppm BHT 155810-12X100ML 237.00 • Relative stability under acidic and basic conditions CPME is a proven alternative • Formation of azeotropes with water 155810-500ML 79.10 to THF. Better yields, higher • Narrow explosion range 155810-4X4L 679.00 Features & Benefi ts • More stable than THF when it comes to forming peroxides selectivity and optical purity 155810-20L 760.00 • Quickly produces clean water phase splits (density of 0.86 g/mL • Does not require the addition of a stabilizer. than THF. at 25 °C) without forming emulsions For more information on our 200L Returnable • Conventional drying is unnecessary for general organometallic • More easily dried than THF or DCM Container, please visit us at sigma-aldrich.com/rc reactions • Very stable even in highly acidic environments • Non-reactive, aprotic polar solvent CPME Applications • Forms an effective azeotrope with water Higher optical purity or selectivity Nucleophilic Reactions Reactions using metals • Higher boiling point (78–80 °C) were observed • Amide synthesis by the reaction of • Reaction of ketone using NaBH4 • Lower solvent loss during refl ux • Asymmetric Michael Alkylation acid chloride with amine • Reaction of acetylenes with Ti(OR)4

• Michael addition of R2CuLi • Sillylation and desillylation • Reaction using n-BuLi or Lithium • Alkylation of chiral amide • Reaction of Carbon anion with Diisopropyl Amide Alternative to Tetrahydrofuran for Alternative to Dichloromethane for • Glycosidation aldehyde • Radical cyclization of trichloroacetate Organometallic Reactions Biphasic Reactions • Asymmetric hydrogenation of NaBH • Debenzylation using Cu cat • Grignard • Alkylation 4 • Hydrosilylation by Ru cat • Alkylation of amine • Reduction of ethyl benzoate using • Reformatskii (Reformatsky) • Amidation • Selective methylation of phenols Lithium Aluminium Hydride • Lithiation • Nucleophilic Substitution Reaction • Bromination of alcohol with PBr • Formation of sodium dispersion • Hydride Reduction 3 • Sulfonylchloride synthesis by the • Intramolecular ene reaction using • Metal-Catalyzed Coupling (Heck, Stille, Suzuki) reaction of sulfonic acid with PCl5 ZnCl2

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33704704 GGreenreen Chemistry.inddChemistry.indd Sec1:2-Sec1:3Sec1:2-Sec1:3 110/17/20070/17/2007 11:28:1111:28:11 AAMM