I am trying to design a proper synthesis route for 2‐amino‐3‐(chlorosulfonyl)benzoic acid, though methyl 2‐amino‐3‐(chlorosulfonyl)benzoate—using an ester group in lieu of a carboxylic acid—would also be acceptable.
I am thinking a good starting material would be toluene or benzene. Here is my proposed route.
I determined the ortho-para ratio for toluene nitration from p. 816 of "Organic Chemistry, 6e" by Loudon & Parise.
Typically, para substitution predominates over ortho substitution, but not always. For example, nitration of toluene gives twice as much o-nitrotoluene as p-nitrotoluene. This result occurs because the nitration of toluene at either the ortho or para position is so fast that it occurs on every encounter of the reagents; that is, the energy barrier for the reaction is insignificant. Hence, the product distribution corresponds simply to the relative probability of the reactions. Because the ratio of ortho and para positions is 2 : 1, the product distribution is 2 : 1.
Also, according to the same page,
The boiling points of o- and p-nitrotoluene, 220 °C and 238 °C, respectively, are sufficiently different that these isomers can be separated by careful fractional distillation.
Is there a better method? Please identify any mistakes I may have made in my synthesis and suggest improvements. Note that I install t-butyl as a blocking group in order to direct the sulfonyl chloride group ortho to the amino group.