Just dug up some references for advancement of tosylate/mesylate esters as feasible, HIGH YIELDING synthetic intermediates to our beloved honey in an aqueous environment. The following is quoted from:
Journal of Organic Chemistry 1988, 53, 4081-4
(R)- Tomoxetine Hydrochloride: A solution of phenyl-3-(2-methylphenoxy)-propyl methane sulfonate [the mesylate group is on the gamma carbon] (450mg, 1.45mmol) and methylamine (10ml, 40% in water) in THF (10ml) was heated to 65'C for 3h. After cooling, the solution was diluted with ether, washed w/ aq. sat. NaHCO3 soln. and brine, and dried with anhydrous K2CO3. After concentration a pale yellow oil was obtained which was dissolved in ether, bubbled w/ dry HCl gas [and you guys certainly know the rest] to produce a white ppt which was recrystallized w/ acetonitrile to yield title compound (400mg, 94%)
Thats amazing !!!! NINETY FOUR freakin percent from an aqueous MeAmine soln!!! Try achieving that with a halogen leaving group on our favorite alkene by cooking the stinky shit up in a pipe bomb w/ alcoholic MeAmine. You can't, if you are lucky 50% will be . Halogens blow as leaving groups compared to sulfonate derivatives as proved by this paper. It is such an advantage to be able to use good 'ol fashioned aqueous MeAmine compared to homebrew anhydrous alcoholic amine solns! The only drawback noticed immediately is the large excess of MeAmine employed by the authors. This shouldn't present a huge problem because the excess amine cooked off during the heating process can be collected by bubbling through HCl. The 65'C rctn temp is the bp of THF so excess amine will be liberated out of the top of the reflux condensor on rctn pot. A slow stream of N2 can be admitted through a bubbler in the second neck of the rctn. flask forcing the methylamine gas to be expelled out the top of the condenser into a beaker of HCl. Simply evap off HCl to obtain your excess amine back as MeAmine hydrochloride.
There is one other procedure for producing alkyl-methylamines from an alkyl mesylate using the exact same protocol listed above with product isolated in 96% yield! This proves the procedures high yields are reproducible, however both examples listed are performed on primary alkyl mesylates. Since we are working with a secondary alkyl mesylate yields may suffer a bit from steric hindrance during the nucleophilic substitution by MeAmine. Well actually, let me restate that.. my chem theory is getting a little weak.. In most if not all nucleophilic substition reactions in the literature compounds with a leaving group always have higher yields in nucleophilic substition rctns than a complementary compnd w/ a secondary leaving group. Therefore the mesylate in our case may not produce the 90+% yields quoted in the literature but it sure will be much higher than that produced by any halogen.
Siegfried: Excellent work in this area. Was wondering if you'd be kind enough to post the physical properties of the tosylate. Simple experience has proved that most tosylates are solids, however you're the only one who knows for sure. A melting pt. would be very useful. Any recrystallization solvent of choice?
Was an attempt ever made at esterifying the propanol produced w/ H2SO4? As a side note any tertiary amine can be used in a similar manner as pyridine to scavenge protons in the esterification rctn. Triethylamine was the amine of choice in the quoted article. Yields of 85% were recognized after several wasteful recrystallizations.
On the subject of hydration of alkene to alcohol, oxymercuration is obviously the most simple method considering rctn. time and yield. However soluble mercury salts just plain suck. It sure would be nice if the H2SO4 thing worked. Another possible synthesis may be a PTC rctn. between aq. NaOH and halosafrole. This is a well documented rctn. however conditions will probably have to be closely monitored to minimize isoalkene formation.
Finally, to sum everything up this is a major breakthrough because of the reactivity of amines to sulfonic esters in aqueous environment. Similar reactions in the past have usually reacted alkyl halides as leaving groups and fickle-to-make alcoholic amine solns with long rctn times or high temperature pipebomb pressure vessels. Not very desirable when compared w/ a 3hr STP reflux. Reported yields are also very poor w/ halide exchange rctns. Comment?