A scalable
process to the insecticide Isoclast manufactured by
Dow AgroSciences LLC is described. The process involves the de novo construction of a fully elaborated pyridine sulfide
using enamine-mediated cyclization followed by two efficient and inexpensive
oxidations to introduce the sulfoximine.
The Swern oxidation has been widely exploited for the oxidation of alcohols to their respective carbonyl compounds. The cryogenic operating conditions (<-60 °C) employed for the Swern oxidation, however, limit its utility for scale-up operations. Process development efforts on the Swern oxidation have demonstrated that an in-line reactor system can be used for the successful formation of the alkoxysulfonium salt precursor of the carbonyl compound. Two reagent streams, consisting of the alcohol/dimethylsulfoxide/ methylene chloride and the oxalyl chloride, are loaded at ambient temperature to an in-line reactor, allowing the temperature to rise to 40 °C. The alkoxysulfonium chloride intermediate is discharged directly into triethylamine to complete the reaction. Residence times of 0.1-1.4 s in the in-line reactor were demonstrated to produce successful results in 750-gal pilot-plant equipment.
A convenient route to 4-and 7-methoxybenzo [ 6 ] thiophenes has been developed in the course of electrochemical studies of these molecules. The anodic oxidations of 4-methoxy-, 5-bromo-4-methoxy-, 5-methyl-4-methoxy-, and 6-bromo-7-methoxybenzo[b]thiophene, 17a-d, respectively, in methanolic potassium hydroxide at a platinum anode have been investigated. The products obtained from the oxidation of these compounds were temperature dependent. This temperature dependence was most extensively studied for 17a wherein oxidation at or below room temperature, followed by workup, gave primarily 4,7-dimethoxybenzo[b]thiophene. However, oxidation of 17a in methanol at ca. 65 °C gave primarily the quinone bisketal. In a similar manner oxidation of 17b,c gave the respective bisketals of benzo[b]thiophene-4,7-quinones in good yields. Extended acidic hydrolyses of these quinone bisketals afforded the corresponding quiñones in 78-95% yield. Milder conditions for the hydrolyses afforded monoketals of benzo[b]thiophene-4,7-quinones, the products from 17b,c being formed with high regioselectivity. Other chemistry of these quinone bis-and monoketals, initially directed at a synthesis of Caldariellaquinone, is presented and discussed.
The combination of multidimensional analytical technology to
form a single nth-order analyzer can produce reaction process
data more efficiently and may provide data that are inaccessible
using conventional techniques. A 3rd-order analyzer was
assembled utilizing a Mettler RC1 calorimeter, Applied systems,
Inc. ReactIR and Hewlett-Packard 5971A mass selective detector. The 3rd-order analyzer was utilized to simultaneously
perform reaction calorimetry, in situ infrared spectroscopy, and
in situ mass spectrometry on the conversion of a vinyl sulfone
to a vinyl tributylstannane. The goal of complete material and
energy balance, coupled with knowledge of scale-up issues, was
achieved in a single experiment and in real time.
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