Solvent for Grignard reaction –MeTHF

(substitution to Tetrahydrofuran and Dichloromethane)

2-Methyltetrahydrofuran (MeTHF)

CAS NO.: 94-47-6,

Molecular Formula: C₅H₁₀O,

Appearance: colorless clear liquid,

Boiling point: 80 centigrade degree.

The advantages as Grignard reaction solvent

1. High reaction temperation bearable and help finish reaction in shorter time.  MeTHF's boiling point - 80 centigrade degree, is higher than tetrahydrofuran(THF)'s.  THF is 66 centigrade degree. Thus, MeTHF could make some slow Grignard reaction complete more rapidly.

2. Reduceing extraction steps and saving solvents, also easy to operation. When using THF as Grignard solvent, it always need toluene or ethyl acetate to replace THF for extraction products and recycling THF. But, it always appear emulsification aroused by toluene water solution and difficult to separate when extraction separation. While useing MeTHF as Grignard solvent, no needing toluene or ethyl acetate, there's no such problem. So, it's easy for phase separation  with no emulsions & rag layers and saving solvents.

3. Especially suitable for produce high concentration bromide Grignard reagents. Magnesium bromide or magnesium iodide, have much higher solubility in MeTHF than THF. For example, at 25 centigrade degree, the solubility for magnesium bromide in MeTHF is more than 40g per 100g, while in THF, is about 5g per 100g. So, this make MeTHF the preferred solvent for produce high concentration bromide Grignard reagents. Furthermore, chosing MeTHF no need filtration to remove magnesium.

4.  High recovery.

     When useing THF, the recovery for benzyl and propenyl Grignard reaction, is very low, for the coupling reaction. Then it need high percent magnesium. While when coming to the MeTHF, the recovery is higher and reduce the usage of magnesium. Permitting higher reaction temperature, and propitious to the cooling of reactor and condenser. The speed of peroxide forming is  much slower than THF, and more safely to use.

Easy to recycle

     Because THF is miscible with water,it needs special technical equipment and charges much when recycling THF from THF water solution. It would be even much harder to recycle THF from THF toluene or ethyl acetate solution.

However, MeTHF is limited to solve in water, and the percent of water in its azeotrope is less than 300ppm. So, it's very easy to recycle MeTHF with much low level water, just via simple Batch Azeotropic Distillation operation.     Energy consumption will reduce 70% percent.

little effect to environment

MeTHF's boiling point is higher,easy to condensate, little loss of volatilization. And high percent recovery of azeotropic distillation, so MeTHF's concentration in waste water is very low, and waste water treatment is very easy and cost little.

Cost saving

Although the price of MeTHF is higher than THF, MeTHF no need toluene or ethyl acetate, and recovery rate is high and cost little. Furthermore, three types of waste treatement charges little. So, MeTHF's use cost is much lower than THF's.

2-MeTHF----a alternative of dichloromethane

    Dichloromethane is usual solvent in pharmaceutical and pesticide production, and controled as other halides.USA National Toxicology Program(NTP) list it as a suspected carcinogen, and America California Proposition 65 list it as known carcinogen.So its application and dosage is restricted more and more. At the same time, dichloromethane, is with the feature of  low boiling point, highly volatile, hard to condensation recycling and much loss. MeTHF is a perfect reagent and could sustitue polar compands such as dichloromethane or dichloroethane, in much production.

Main advantages.

n         Not miscible with water and easy to recycle;

n         Good solubility for polar compands( fro example, Amino Acids, Alcohols, and Organic acids), and high extraction recovery;

n         Strong base stability, general also stable at acidic condition, without by-product;

n         Better extraction solvent in water solution, with clear phase separation, no emulsions;  

n         Water phase at the bottom of reactor, and easy to flow out, while water on the top when coming to dichloromethane;

n         Boiling point up to 80 centigrade degree, so could condense it directly by cool water and save energy;

n         Rich water azeotrope, could drying reactants direct in reactor, just like toluene;

n         Reaction easy for biphasic reaction system, because of water in MeTHF phase;

n         Treatment easier for MeTHF than which for Dichloromethane in waste water.