Cyclohexanone—continued metalation

A. 2-Hydroxymethylenecyclohexanone, Method 1. A mixture of 23 g. (1 g.-atom) of sodium metal cut in approximately 1-cm. cubes, 2 1. of dry ether, 98 g. (103 ml., 1 mole) of redistilled cyclohexanone, and 110 g. (120 ml., 1.5 moles) of ethyl formate is placed in a 5-1. three-necked flask equipped with a stirrer, stopper, and vent tube. The reaction is initiated by the addition of 5 ml. of ethyl alcohol to the stirred mixture, which is then placed in a cold water bath. Stirring is continued for 6 hours. After standing overnight, 25 ml. of ethyl alcohol is added, and the mixture is stirred for an additional hour. After the addition of 200 ml. of water, the mixture is shaken in a 3-1. separatory funnel. The ether layer is washed with 50 ml. of water, and the combined aqueous extracts are washed with 100 ml. of ether. The aqueous layer is acidified with 165 ml. of 6N hydrochloric acid, and the mixture is extracted twice with 300 ml. of ether. The ether solution is washed with 25 ml. of saturated sodium chloride solution and then is dried by (he addition of approximately 30 g. of an-... 

Methoxyphenyllithium and cyclohexanone were reacted in a batch mode at —10 and —65 °C to give yields of 32 and 80%, the expected tertiary alcohol, respectively [34]. Such temperature effect was also planned to be used in the microreactor. The metal-halogen exchange step could be performed at —14 ° C with 17 s residence time and the lithium intermediate further reacted with cyclohexanone in batch mode at —40°C. Lower temperatures were not possible because of chiller limitations, and the availability of only one microreactor accounted for the combined continuous flow-batch processing. In this way, a yield of 87% yield at a throughput of 54g/h was achieved. 

The oxidation of cyclohexanone is a reaction which has been the subject of considerable study over the years. Continued research in this area has given rise to many recent patents and papers. The product of the oxidation reaction is rather dependent on the metal complex which is used as a catalyst. When manganese(III) complexes are used the major reaction product is adipic acid [280-288]. Selectivity to adipic acid is about 70% in most cases. When copper(II) complexes are used, 5-formylvaleric acid predominates [289, 290] whereas iron complexes catalyze the formation of e-caprolactone [291,292] in up to 56% yield. In fact, liquid phase air oxidation of 2-methyl-cyclohexanone at 100 °C in the presence of copper stearate gave e-methyl- -caprolactone [292a]. Reaction scheme (190) shows the predominant reaction pathways. 

Special care must be taken in the design and operation of adsorption units handling ketone solvents, such as methyl ethyl ketone (MEK), methyl isobutyl ketone (MIBK), and cyclohexanone, because of their reactivity in the presence of activated carbon. Traces of metal compounds in the carbon act as catalysts for decomposition reactions, which are further accelerated by the presence of heat and moisture. The decomposition reactions are exothermic and if allowed to continue can cause hot spots in the bed and ultimately fires. According to Collins (1988), ketone adsorption and recovery can be accomplished safely if these guidelines are followed ... 

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