Organic Reagents
Reagent Friday: TsCl (p-toluenesulfonyl chloride) and MsCl (methanesulfonyl chloride)
Last updated: January 9th, 2020 |
TsCl (p-toluenesulfonyl chloride) And MsCl (methanesulfonylchloride) As Reagents In Organic Chemistry
In a blatant plug for the Reagent Guide, each Friday I profile a different reagent that is commonly encountered in Org 1/ Org 2.
A friend of mine works in human resources at a company that runs huge warehouses, and they have a lot of staff turnover. He told me about one forklift driver whose favorite habit was to speed by groups of guys in the warehouse, give them the double finger salute, and yell, “F*** you, bitches!!!” as he sped by, laughing. My friend and his co-workers in upper management were like, “what can we do to get rid of this guy?”.
TsCl and MsCl: Two Reagents That Convert Hydroxyl Groups (OH) Into Good Leaving Groups
Alcohols: there are times you need to get rid of them too. Except there’s one problem. They’re terrible leaving groups. Remember that good leaving groups are weak bases? Hydroxide ions are strong bases, and therefore very poor leaving groups.
However there’s a way to turn the OH group into a good leaving group – if you can convert it into a weaker base.
One practical way this is done is with the sulfonates p-toluenesulfonylchloride (TsCl) and methanesulfonylchloride (MsCl).
Treatment of an alcohol with TsCl or MsCl, usually in the presence of a weak base such as pyridine, results in the sulfonate esters. (The purpose of pyridine is to mop up any HCl that is formed during the course of the reaction.)
Conversion to the sulfonate esters does one thing: the conjugate bases – toluenesulfonate and methanesulfonate are now extremely weak bases, since they’re heavily stabilized by resonance.
Weak bases, you say? That makes them great leaving groups. And you are right. The sulfonate esters participate easily in reactions such as substitution and elimination reactions.
And there you go.
For more, see this post: Three Ways To Make OH Into A Better Leaving Group
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So in the end it turned out that the crazy forklift driver insulted the wrong guy. He called one of co-workers a “dick”, and he then complained to management. (“Bitch” was OK, but “dick” was insulting, apparently). The management wanted to “terminate”, as they say, but my friend told them they didn’t have legal grounds to do so yet: instead, they gave the employee a written warning. He explained it to them this way. “Think of it like putting him on the tee, so that the next time he screws up, we send him down the fairway of life”.
That’s what TsCl and MsCl do. They take an alcohol and put it on the tee, so that the next reaction can send it down the fairway of life.
P.S. You can read about the chemistry of TsCl and more than 80 other reagents in undergraduate organic chemistry in the “Organic Chemistry Reagent Guide”, available here as a downloadable PDF.
Mestyl chloride and the tosyl chloride can be used for the protection of amino acid and in which condition?
You probably don’t want to use them as protecting groups unless you are comfortable with using a reagent like sodium amalgam to remove them, which can be strongly basic. There are much better protecting groups for amines, like carbamates.
Its just awesome!!! Never thought in this way for the reagents being used. Thanks for giving new direction to me…
I can’t find the answer to this question anywhere and I am desperate. I have asked my teachers, googled it endlessly, and asked in youtube comments. Please give me a good answer that a 5th grader would understand. When do you choose to use tosylate to make OH a good leaving group INSTEAD of using an acid to protonate the alcohol??? Like, if you were given a substrate and asked to choose reagents and solvents to achieve the desired SN2 transformation, why would you want TsCl in certain instances instead of acid? Thanks =)
Because strong acid creates R-OH2+ , which is itself a strong acid. What if you wanted to use as your nucleophile the acetylide ion RCC (-) ? That’s a useful way of making a new carbon-carbon bond, right? Well, the acetylide ion is very basic. If acid is present, then the acetylide ion will just be protonated to give the alkyne, ,RCCH. No reaction.
So, in short, one good reason is that a leaving group like OTs or OMs is more compatible with strongly basic nucleophiles. I discuss this more in this post: https://www.masterorganicchemistry.com/2015/03/10/tosylates-and-mesylates/
can this happen in tertiary alcohol as well ?
Tertiary alcohols may be converted to tosylates and mesylates, yes.
Hey quick question about using TsCl to convert the alcohol into a better leaving group. If your keeping track of absolute stereochem on a problem and the alcohol is wedged, will converting it to OT’s switch it to dashed. I am working on a synthesis problem along these lines.
Thank You.
-Matthew
No it absolutely will not. An alcohol treated with TsCl will retain its stereochemistry.
Can’t the chloride ion formed undergo an sn2 with the tosylate formed.
No, chloride ion is a far better nucleophile. Good question though. Alkyl chlorides will undergo substitution with bromide ion and iodide ion.