Reaction Solvents that could be Worked-Up with Acetic Anhydride

Solvents that could be distilled away from acetic anhydride (bp. 140 C) and taken up into any solvent immiscible with acetic acid, after the hydrolysis of the acetic anhydride chaser and admixture with a little additional water to enhance immiscibility of the two layers:

Chlorobenzene

Nitro propane

Methyl chloroacetate

Cyclopentanone

Diethyl carbonate

Dimethyl sulphite

Tetrachloroethylene

2-nitropropane

Methylisobutyl ketone

N-methylmorphiline

Nitromethane

Toluene

1,1,2-trichloroethane

Trifluorotoluene

1,4-dioxane

Nitromethane

Methylcyclohexane

Heptane 

Propionitrile

Dibromomethane

Dimethylcarbonate 

Trichloroethylene

Isopropyl acetate

1,2-dimethoxyethane

Fluorobenzene

1,2-diethoxyethane

1,2-dichloroethane

Cyclohexane

Acetonitrile

Cyclohexane

Benzene

methylethylketone 

2-methyltetrahydrofuran

Ethyl acetate 

Butyl chloride

Carbon tetrachloride

Petroleum ether

Hexane

Diisopropyl ether

Chloroform

Perfluorohexane

1,1-dichloroethane

Methyl acetate

Carbon disulphide

Dimethoxymethane

Pentane 

Diethyl ether

Methyl t-butyl ether

Organic Solvents and Various Means for their Removal

 

Co-distillation

If two liquids are essentially immiscible, distillate comes over when the sum of their vapor pressures equals the pressure inside the distillation apparatus. The effect is that a small amount of a high boiling material will co-distill along with a larger amount of a lower boiling material. So long as the low boiling material is inexpensive and the higher boiling material is easily separable from this large amount of low boiler, co-distillation can physically separate the high boiler from less volatile or non volatile  components mixed with it. Aside from using water (which is classified below as steam distillation), the inexpensive material most frequently used in a co-distillation is kerosene/paraffin/lamp oil/coal oil. Much less frequently silicone oil (dimethicone KF-96L-2cs) has been used as the high boiling component.

Steam Distillation

Steam distillation represents the particular case of co-distillation using water. Many higher boiling solvents can be chased by steam distillation. Nitrobenzene and 1,1,2,2-tetrachloroethane are frequently removed this way after Friedel-Craft reaction. The steam can be preheated to temperatures above 100 C thereby co-distilling a larger portion of the lower boiling material while minimizing the volume of water. Codistillation including steam distillation can also be done under vacuum so that the material of interest is not exposed to as much heat.

Reversible Degradation

Some special compounds can be used as solvents that are reversibly cracked into smaller more volatile fragments by heating. Piperylene sulfone has solvent characteristics very similar to tetramethylene sulfone. The essential difference for our consideration here is that the former is fragmented by heat into  1,3-pentadiene and sulfur dioxide. These can be trapped together as a distillate whereupon they reform piperylene sulfone.

  Likewise, dicyclopentadiene upon heating can disaggregate into the monomeric cyclopentadiene and be distilled out of a reactor and away from less-volatile products.

Hydroxymethanesulfonic acid is a strong acid solvent that upon heating breaks apart into formaldehyde, water, and sulfur dioxide before reforming when they are recondensed together. 

Degradation

Some solvents can be hydrolyzed into water-soluble fragments.

 

Acetic anhydride can be hydrolyzed into acetic acid.

 

Dimethylformamide can be hydrolyzed by acid into dimethylamine and formic acid.

 

Dimethylacetamide can be hydrolyzed into acetic acid and dimethylamine.

 

Propylene carbonate can be hydrolyzed into 1,2-propanediol and carbon dioxide.

Is Glycerol the Best Green Solvent for Process Chemistry?

In a paper published online in 2006, Glycerol as a Green Solvent for high product yields and selectivities,  A.Wolfson, C. Dlugy, and Y. Shotland provide ineluctable evidence that increased utilization of glycerol should be forthcoming in organic chemistry processing.  Their reasoning included environmental, economic, safety, handling, and product isolation considerations. The only difficulty using glycerol appears to be a viscosity much higher than with standard organic solvents.

Yet irrefragable as their teaching was there are still things unsaid that further boost this processing chemical! Glycerol can be used to conveniently perform all kinds of solvent switches which are otherwise a weakness with the standard reactors in multipurpose plants. 

The best solvent for conducting a chemical reaction may not be the best solvent to purify the product thereof. Furthermore, when a first and a second reaction in a process scheme are telescoped (avoiding the isolation and purification of the product of that first reaction) the best reaction solvents for the first and second reactions are likely to be different. But, as I have explained in another blog article, switching solvents in the plant cannot be done in the simple fashion of evaporating a first solvent to dryness on a rotary evaporator and pouring in the second solvent. Because of the non-zero minimum stirrable volume problem, the complete removal of a first solvent becomes complex and time-consuming.

 

This problem can be solved if a volume of glycerol sufficient to completely occupy the minimum stirrable volume is placed into the reactor.  Then, all of a first solvent (for example a first reaction solvent) can be removed without distilling any of the glycerol, which is so high-boiling, yet the reactor remains stirrable throughout because glycerol occupies the minimum stirrable volume and provides continuous mass and heat transport.   All of the product, coproducts, byproducts, and other processing chemicals (everything that can’t distill with the first solvent) remain with the glycerol. Now, all that is necessary to complete a solvent change is to add a second solvent that is immiscible with glycerol but will solubilize and extract at least the desired product and potentially the entire non-solvent reaction contents.

Here, another benefit of glycerol becomes apparent. According to the (1974-1975) CRC Press, Handbook of Chemistry and Physics, (the old one I have) glycerol is immiscible with at least:

acetone, benzene, butyl acetate, carbon tetrachloride, chloroform, dibutyl ether, diethyl ether, ethyl acetate, isoamyl alcohol, methyl isobutyl ketone (MIBK), nitromethane, petroleum ether, tributyl phosphine.

Furthermore, by analogy, glycerol can be expected to be immiscible with the additional common solvents:

 hexane, cyclohexane, methylcyclohexane, heptane, toluene, methylene chloride, trichloroethylene, tetrachloroethylene, isopropyl acetate, nitroethane, 2-nitropropane, and t-butyl methyl ether.

So a variety of extractions are possible. 

In a further extension, glycerol can be used as a cosolvent with fluids with which it is miscible, such as the lower alcohols methanol, ethanol, isopropanol, etc. It can also form gas-expanded liquid phases with such amines as ammonia, methylamine, and ethylamine. A mixed solvent will generally have a more moderate viscosity than glycerol alone and so will at the same time make processing easier. All the above materials, immiscible or miscible with glycerol, can be completely expelled from the reactor so long as the amount of glycerol equals, at least, the minimum stirrable volume.

When a reaction is conducted wherein the desired product is itself usefully volatile, glycerol can act as an effective chaser in a distillation that purifies the desired product.

Glycerol is cheap, biodegradable, and has a bp of 182 ºC @ 10 mm Hg. It would be expected to remain behind in a standard distillation when combined with any of the common organic reaction solvents. Even DMSO (bp 189℃), DMF (bp153℃), and NMP (bp 81-82℃ 10 mm Hg) would be expected to be chased by glycerol.

The distilled first solvent contaminated with traces of glycerin upon simple treatment might be ready for reuse. Thus the first solvent is no longer waste and there are no mixed fractions of solvents to dispose of. The waste glycerin is a biodegradable material and the quantity used is no more than the minimum stirrable volume of the reactor.

Whether used just to drive the removal of a first solvent during reaction work-up or as cosolvent for the first reaction and then a chaser for the first solvent, glycerol it seems has the properties that enable simpler processing.

What can You Trust about Chemical Patents?

Advice About Reading Patents

In my career, I have been the inventing scientist and I have been the person drafting a patent before being sent to a patent agent to incorporate the legalese.  I have even been both for the same patent! What can you learn from a patent? What part is ‘fake news’?

The conscientious scientist writes down the experimental description of the significant experiments carried out. The scientist explains what his/her interpretation of these results means generally. He explains what application of the present theoretical understanding of his subject leads him to predict generally based on this work. He states why he believes it is useful and may prove more widely useful.

Then the conscientious patent agent takes over. The patent agent's professional responsibility is different. You see, you have to pay to hold a patent: there are annual fees that must be paid to maintain this monopoly and it isn’t worth paying money unless the barrier to use is strong enough to prevent competitors from learning from your insight, slightly tweaking your protocol and getting essentially the same benefit. But it isn’t worth the time filling out your precious scientific expertise to perform all the possible permutations and combinations of every aspect of the methodology so everything can be presented in its own experimental and claimed in its own claim. Instead, the patent agent asks you to imagine, using your experience, imagination, knowledge of the literature, and knowledge of chemical theory to guess all the other conditions that would give, to some degree, the claimed outcome. 

The patent agent then writes a description of your invention including the full breadth of your considered opinion of what could work. Claims are also constructed encompassing both your educated guesses and what you have shown experimentally works. These are called the broad claims. They are there to prevent those who follow what you have taught from escaping your legal protection by making inconsequential or obvious changes or substitutions.

So what can you trust? According to US patent law at least one narrow claim must cover the best protocol for practicing the invention that the scientist has found out at the time that the invention patent is filed. Normally what is described in the experimental and talked about most completely in the body of the patent is the part that has been proven in the lab.