Last month, I had a job interview at Circa group. They are based in Melbourne and they are carrying out chemistry that involves levoglucosenone. They gave the position to somebody else for some reason, but it got me thinking about levoglucosenone.
While it has been known for several decades that levoglucosenone is obtained by the pyrolysis of cellulose, Circa have apparently developed a continuous pyrolysis process that produces the levoglucosenone more cheaply. Levoglucosenone possesses two chiral centres and this process produces pure (--) levoglucosenone. Levoglucosenone is a bicyclic oxygen heterocycle that contains a five, a six and a seven membered ring. There are a number of ways to draw it:
While it has been known for several decades that levoglucosenone is obtained by the pyrolysis of cellulose, Circa have apparently developed a continuous pyrolysis process that produces the levoglucosenone more cheaply. Levoglucosenone possesses two chiral centres and this process produces pure (--) levoglucosenone. Levoglucosenone is a bicyclic oxygen heterocycle that contains a five, a six and a seven membered ring. There are a number of ways to draw it:
Levoglucosenone
The first view shows the six membered ring well but the five and seven membered rings poorly. The second view shows the five and the six membered rings well but makes the seven membered ring look more spread out than it is. The third view (which I prefer) shows the seven and five membered rings very well and the six membered ring could be viewed from into the plane of the page at the bottom right. I like this view best as it shows an equal level of vulnerability for each ring to be cleaved.
One of the most striking advantages to levoglucosenone is that it only has three oxygens to six carbons. So unlike the carbohydrate monomers that make up cellulose, levoglucosenone will be soluble in organic solvents, which makes it a candidate for many more synthetic reactions than carbohydrates ever can be. The pyrolysis process must of course be releasing CO2 in order to reduce the ratio of oxygens to carbons.
Circa are exploring a number of avenues for useful compounds from levoglucosenone. The main one they told me about is that they hydrogenate at the C=C double bond to make dihydrolevoglucosenone to use as a solvent, which they call Cyrene.
Hydrogenation of levoglucosenone
They told me that they have a pilot plant the prepares 1 Kg batches of
dihydrolevoglucosenone. They use a Parr hydrogenator with 100 g of palladium on charcoal catalyst. They do the hydrogenation neat (no solvent) and distill off 80% of the product. The other 20% remains in the flask and becomes part of the product for the next batch. Therefore the 100 g of palladium on charcoal catalyst is reused for each batch and they don't know yet how often it needs to be changed over. They soon plan to build a larger plant that can prepare 1 tonne at a time. They tell me that they have customers in the pharmaceutical industry who wish to buy dihydrolevoglucosenone to use as a dipolar aprotic solvent. They have published a paper on the use of this solvent and have measured it's BP at 202 °C.
dihydrolevoglucosenone. They use a Parr hydrogenator with 100 g of palladium on charcoal catalyst. They do the hydrogenation neat (no solvent) and distill off 80% of the product. The other 20% remains in the flask and becomes part of the product for the next batch. Therefore the 100 g of palladium on charcoal catalyst is reused for each batch and they don't know yet how often it needs to be changed over. They soon plan to build a larger plant that can prepare 1 tonne at a time. They tell me that they have customers in the pharmaceutical industry who wish to buy dihydrolevoglucosenone to use as a dipolar aprotic solvent. They have published a paper on the use of this solvent and have measured it's BP at 202 °C.
I'm interested in pursuing ring opening products of levoglucosenone as fragrance compounds. Circa apparently haven't gone down this path but have focused more on the pure chiral centres. I asked their head chemist what happens when levoglucosenone is exposed to HBr. He told me that it reacts with the double bond so that the major product has the bromine β to the carbonyl; this is due to the partial positive charge on the α carbon that will tend to repel the incoming bromide which forms a bond by an SN2-like process.
Exposure of levoglucosenone to HBr
The reason I ask about exposure to HBr is more because cyclic ethers are known to undergo ring opening reactions. And this type of ring opening is more favoured the more ring-strain there is. Five membered rings react this way with HBr at room temperature with no catalyst. I have carried this out on 2-methyl-tetrahydrofuran and discussed it on a different entry of this blog. Bromine containing compounds are unwanted as fragrance compounds as they are going to be sprayed into the skin, but a HBr elimination later can recover the C=C double bond.
At this point it is useful for me to list a few examples of known fragrance compounds and what they smell like. The acylated versions of fragrant alcohols are frequently used as softer versions of the more raw alcohol product.
At this point it is useful for me to list a few examples of known fragrance compounds and what they smell like. The acylated versions of fragrant alcohols are frequently used as softer versions of the more raw alcohol product.
Known oxygen containing fragrance compounds
What I think would happen upon treating the bromolevoglucosenone with HBr is that the five membered ring would break open and leave either a six membered or seven membered ring, depending upon which of the two oxygens are attacked by H+. I think a tandem ring opening is highly unlikely.
Ring opening on bromolevoglucosenone
Which of the four possible products here is likely to be favoured? It's probably easier to just try it and see rather than try to predict. Let's not forget, we can also try the ring opening on the dihydrolevoglucosenone.
Ring opening on dihydrolevoglucosenone
Here we have two compounds (marked with a red asterisk) which would undergo a HBr elimination to give compounds that have a good chance at having desirable fragrant properties. The acyl groups may be cleaved back to the raw alcohols depending upon the conditions used for the elimination, but they can always be re-acylated.
HBr elimination on ring opened products
This is not the only way to open cyclic ethers. Another way to try these ring openings, which may give different products to HBr, is to use TMS-Cl and DMSO. This has been described in a 20 year old paper (D. C. Snyder. Conversion of alcohols to chlorides by TMSCl and DMSO. J. Org. Chem., vol 60, issue 8, p2638, 1995).
Another avenue I would like to pursue is to use levoglucosenone to try to chelate precious metals in order to use it for extraction. I am also curious about the solubility of nitrite ions in dihydrolevoglucosenone as I have a feeling they may be just the right shape to fit into it in a 'cage-like' manner.
Precious metals or nitrite ions may fit inside dihydrolevoglucosenone
I unfortunately do not know what levoglucosenone itself smells like. It may be with its BP and viscosity that it makes a useful fixative ingredient, rather like benzyl alcohol does.