2,3,4,6-Tetramethyl- (CAS NO.: ), which is also known as D-, 2,3,4,6-tetramethyl-, could be produced through the following synthetic routes.

This preparation must be carried out in a hood having good ventilation. Methyl sulfate has a high vapor pressure in spite of its high boiling point and is very poisonous. is a specific antidote and should be kept on hand to destroy any of the ester accidentally spilled. It is advisable to wash the hands in dilute ammonium hydroxide frequently.

In a 2-l. distilling flask immersed in a 4-l. water bath are placed 25 g. (0.14 mole) of anhydrous glucose and 15 ml. of water. The flask is fitted with a cork through which passes a strong mechanical stirrer and a dropping tube connected by rubber tubing and a screw clamp to a 500-ml. reservoir flask. The side tube of the flask is connected to a water condenser, fitted with a suction flask, from which fumes are led to a flue by a piece of tubing. The temperature of the water bath is raised to 55°, and the glucose is brought into solution with rapid stirring, which is maintained throughout the process. A mixture of 90 ml. (120 g., 9.5 moles) of methyl sulfate and 125 ml. of carbon tetrachloride is added from the reservoir as quickly as possible to the flask. The clamp is closed, and 400 ml. (580 g.) of 40% (by weight) sodium hydroxide is placed in the reservoir. The alkali is admitted to the flask at the rate of 1 drop in 2 seconds for 5 minutes, then 1 drop per second for 5 minutes, and then 3 drops per second until the distillation of carbon tetrachloride slackens or ceases. This is usually accomplished in 15–20 minutes and after the addition of 70–90 ml. of alkali. The heat of reaction generally maintains the proper temperature of 50–55° throughout this stage without the necessity of heating the water bath externally. The remainder of the alkali is added as quickly as possible, and the bath temperature raised to and maintained at 70–75°. Then 160 ml. (208 g., 1.65 moles) of methyl sulfate is placed in the reservoir immediately and added at the rate of 3–4 drops per second (slower if the mixture foams seriously).

After all the methyl sulfate has been added, the bath is boiled for 30 minutes with continued stirring. The contents of the flask are cooled, diluted with sufficient water to dissolve most of the separated sodium sulfate, and extracted four times with 150-ml. portions of chloroform; the chloroform and water layers are separated carefully. The combined chloroform extracts are placed in a 2- or 3-l. distilling flask (with condenser attached) with 400 ml. of 2 N hydrochloric acid, and the chloroform is removed by distillation. A rapid current of steam is then passed through the solution for 1 hour, care being taken to maintain the volume approximately constant by heating the flask. Five grams of Norite is added to the hot solution, which is then cooled and filtered. The filtrate is saturated with sodium sulfate and extracted four times with 150-ml. portions of chloroform. The combined chloroform extracts are dried with sodium sulfate, 1 g. of Norit is added, and the mixture is filtered. The chloroform is removed as completely as possible in a boiling water bath without vacuum and finally at the water pump. The heavy syrup is treated with 40–50 ml. of petroleum ether (30–60°) and shaken for a short time, whereupon it sets to a mass of crystals. After cooling in an ice bath for 30 minutes, the crystals are filtered, washed with a little cold petroleum ether, and dried over calcium chloride under reduced pressure. The yield is 15–18 g. (46–55%). The specific rotation, [α]_D26, in water was found to be about +79–79.5°, when c = 4; a drop of 15% ammonia was added to speed equilibration, and the readings were made 1 hour after the solution was prepared in a 2-dm. tube.

The slightly impure product is recrystallized from petroleum ether (b.p. 30–60°) containing 0.5% of anhydrous ether in a continuous extractor, using 100 ml. of solvent per 6–7 g. of compound. One crystallization is generally sufficient to give a pure product. The specific rotation of pure tetramethyl-d-glucose prepared by this method is approximately [α]_D20 +81.3°.