CIEC Catalysis -- Asymmetric Catalysis

the importance of chirality

chiral catalysis

a catalyst which works

synthesis of menthol

Synthesis of Menthol

Natural menthol is obtained by freezing the oil of a plant mentha arvensis. A big effort was made to synthesise menthol from more readily available raw materials

Question

Can you mark the three chiral centres of menthol?

diagram: the structure of a menthol molecule

Menthol

With three chiral centres how many isomers will there be? The answer is eight. Click to see the structures.

Answer

The answer is eight. Click to see the structures

Answer

The Isomers of Menthol

What is menthol used for?

It is one of the most important flavouring chemicals, with over 6300 tonnes produced per year

Which isomer would you choose to make?

images: menthol products -- toothpaste, throat pastilles, mints, cigarettes

Now look at this chart, which shows the flavour profiles of two of the the three isomers selected on the basis of their cooling effect. A good choice would be high in pleasant flavours and low in unpleasant ones.

diagram: the menthol isomer finally chosen

The desired isomer will give the greatest cooling effect and have the most pleasant flavour. These two bar charts show the result of research into cooling effect and flavour.

Noyori's catalyst gives a 100 % yield of the desired isomer in a synthesis from myrcene, obtained from turpentine.

The Takasago synthesis of menthol

The company has produced 1,000 metric tons per year of synthetic menthol by asymmetric hydrogenation since 1984.

If you are interested in how the catalyst efficiency was developed, click

The table shows how the catalyst was developed over time. The "turnover number" here is defined as the number of moles of product produced by 1 mole of catalyst Because of the expense of the catalyst the turnover number should be more than 50 000

This chart shows the minimum quantity of each isomer required for the cooling effect to be perceived.

Question

Which three isomers would you select on the basis of cooling effect?

Answer

The three requiring the smallest amount to produce the cooling effect:
1R, 3S, 4S
1S, 3S, 4R
1R, 3R, 4S

Question

Which of the two isomers would you select on the basis of both cooling effect and flavour?

Answer

1S, 3S, 4R, though scoring reasonably high in positive flavours, also includes moderate scores in several negative ones. The isomer 1R, 3R, 4S scores very high in postive flavours and low in negative flavours, and has a low cooling threshold. This is the best choice.

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