Sydenhams chorea
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amines from alkyl halides using arylsulfonamide salts
While browsing the patent GB1069797, which describes the preparation of aminoketones related to cathinone, an interesting tidbit was found:
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Alternatively, the alpha-haloketone of the formula II can be reacted with a salt of an N-R³ arylsulphonamide, preferably an N-R³ toluenesulphonamide
of the formula
(in which R³ is as hereinbefore defined), with formation of a potassium halide, e.g., potassium bromide, and an intermediate which can be hydrolysed,
e.g., under reflux for several hours with concentrated hydrochloric acid, to the compound of formula I and an arylsulphonic acid.
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This was reminiscent of the Gabriel synthesis, and in fact, while checking this wiki, it states that "Most such reagents, e.g. the sodium salt of saccharin, are
electronically similar to the phthalimide salts. In terms of their advantages, some such alternative reagents hydrolyze more readily, extend the
reactivity to secondary alkyl halides, and allow the production of secondary amines". It goes on to refer to this paper:
Novel Gabriel reagents
Ulf Ragnarsson , Leif Grehn
Acc. Chem. Res., 1991, 24 (10), pp 285–289
DOI: 10.1021/ar00010a001
...to which I unfortunately have no access.
I wasn't aware that alkali salts of arylsulfonamides existed, and I am unable to find much on their properties and more specifically to a use
analogeous to the Gabriel synthesis, more than this line: "Use of p-toluenesulphonamide as a derivative of ammonia activated to alkylation by alkyl
halides is exemplified by the synthesis of N-tosyl-2,3-dihydroisoindole from o-xylylene dibromide. "
source: http://chemicalland21.com/specialtychem/finechem/PTSA.htm
I wonder if anyone here knows more specifics about this reaction, the preparation of these salts and the theory behind it?
Attachment: aminoketone_derivatives_GB1069797.pdf (75kB)
This file has been downloaded 428 times
Il n'y a point de sots si incommodes que ceux qui ont de l'esprit.
François de La Rochefoucauld.
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DJF90
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I did a few reactions using substituted aryl sulfonamides (from sub aniline and TsCl). Because the desired reaction occured by deprotonation of the
nitrogen I set about looking for a pKa value. Off the top of my head, the value I found was less than 10; 6-8 rings a bell. I was actually quite
suprised it was THAT acidic.
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gypsyNo2
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This might help you
Attachment: gab synth .pdf (703kB)
This file has been downloaded 837 times
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Nicodem
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N-Alkylation of tosylamides and other sulfonamides is trivial and there are plenty of literature examples you can find. However, as a route to amines
it is not the most trivial one, due to selectivity issues resulting from the reductive cleavage commonly required for the N-detosylation (or
desulfonylation in general, though some relatively mild reductive cleavage conditions were developed recently). For this reason, this strategy is
rarely used or used only on robust enough substrates, especially since there exist alternative strategies (N-alkylation of azide or phthalimide for
primary amines, or of carbamates for secondary amines). It does some advantages though: sulfamides are relatively quite acidic in aprotic polar
solvents and thus there is less elimination side reaction when compared to the N-alkylation of carbamates or carbamides (see the pKa of sulfamides and
particularly that of sulfanilides in DMSO; also with carbamides problems with O- vs. N-alkylation selectivity can result, particularly with hard
electrophiles).
There are some sulfamides which can be N-alkylated to give N-alkylsulfamides which can easily be desulfonylated. One such is saccharin and the others
are the o-nitrobenzenesulfonamides. The first can be cleaved hydrolytically under acceptably mild conditions and the second ones can be cleaved
nucleophilically (for example, with thiolates).
Quote: Originally posted by Sydenhams chorea  | | This was reminiscent of the Gabriel synthesis, and in fact, while checking this wiki, it states that "Most such reagents, e.g. the sodium salt of saccharin, are
electronically similar to the phthalimide salts. In terms of their advantages, some such alternative reagents hydrolyze more readily, extend the
reactivity to secondary alkyl halides, and allow the production of secondary amines". |
If try to UTFSE of this topic, you get: Forest of amines! (saccharin to cyclic and asymmetric amines)
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
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Sydenhams chorea
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Thank you gypsyNo2 for providing the paper and Nicodem for your erudite explanation of the subject matter.
Il n'y a point de sots si incommodes que ceux qui ont de l'esprit.
François de La Rochefoucauld.
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gypsyNo2
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Anytime, I'm actually working on some amine synth myself so it was good for me to get hold of the paper.
Cheers
GypsyNo2
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