4
Tetrahedron
shows product and impurity levels for the hydrodebromination under different reaction conditions. The main byproducts were 3-
chlorosalicylic acid (3-CSA), 6-chlorosalicylic acid (6-CSA) and 3,5,6-TCSA.
The final stage of the process involved isolation and purification of 3,6-DCSA. Toward this end, a solvent swap from ethyl acetate to
xylenes was carried out. Once the ethyl acetate had been removed, the mixture was slurried in hot xylenes. Isolation and drying of the
product afforded 3,6-DCSA in 98.1% purity (77% mass recovery, Table 5). The byproducts identified in 3,6-DCSA were 3-CSA
(1.4%) and 6-CSA (0.3%) and 3,5,6-TCSA (0.2%). All other byproducts were present in less than 0.1%.
A summary of our synthesis of 3,6-DCSA from SA that includes the above process improvements is shown in Scheme 5. The
process produced 3,6-DCSA in 60% overall yield from SA and in 98% purity. [21]
In summary, we have developed a new process for preparing 3,6-DCSA, the penultimate intermediate in the synthesis of dicamba.
The new route commences from SA, an inexpensive and readily available raw material. Our approach utilizes a telescoped process for
converting SA into novel compound BDCSA, which minimizes solvent usage and unit operations. The final step features a selective
conversion of BDCSA into 3,6-DCSA. The process converts SA into 3,6-DCSA in four chemical steps, which is two steps more than
the TCB Process but one step less than the DCB Process. The new route avoids the capital-intensive Kolbe-Schmitt carboxylation used
in the current manufacturing processes. Furthermore, the sequence produces 3,6-DCSA in 60% overall yield and 98% purity, which is
competitive with the existing dicamba manufacturing routes.
Acknowledgment
We thank Doug Malkin, Karen Regina and Wensheng Li for analytical support. We thank Dan Dukesherer for a generous supply of 3,6-
DCSA and dicamba. We thank Bayer Crop Science St. Louis Chemistry Leadership for encouraging the publication of this work.
References
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similar yields of BDCSA to that of chlorine gas.
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[19] In a few instances, the hydrodebromination using palladium on activated carbon would fail to produce 3,6-DCSA. It was determined that iodine from the
prior chlorination was not completely washed away from BDCSA wet cake and subsequently poisoned the palladium catalyst. However, reslurrying BDCSA wet
cake in xylenes at 80 oC for 4 h removed the catalyst poison and hydrodebromination was restored.
[20] Davis, W. T. US Patent 3,181,934, May 4th, 1965.
[21] If a purity greater than 99% for 3,6-DCSA is desired, it can be reslurried in dichloromethane (3 mL/g) to afford 3,6-DCSA [99.3% purity (HPLC and 1H
NMR), 97% mass recovery].