From: Jacob Zabicky (zabicky$##$bgumail.bgu.ac.il)
Date: Thu Feb 21 2002 - 07:49:40 EST
Hello Richard,
The postulates you mention are good guidelines in case you have a "simple"
(or shall I better say straightforward) process. Now consider the
following situation:
1. "Thiol is a better leaving group than alcohol" makes one expect the
sulfur analogs reacting faster.
2. But which one gets protonated more effectively -OR or -SR? If it's
the oxygen analog, then a more extensive protonation may compensate for the
more sluggish scission of the leaving group.
You may find it profitable to look for the ester and thioester functional
groups in Patai's series "The chemistry of Functional Groups".
All the best,
Jacob
At 8:45 20/02/2002, Richard Feinman wrote:
>The deltaG0, standard free energy, of hydrolysis of thioesters is about
>-8 kcal as compared to -(3-4) kcal for oxygen esters. (As we teach in
>biochemistry, thioesters are"high energy" compounds.) this is what I
>meant by "thioesters are thermodynamically unstable relative to oxygen
>esters." According to the Hammond (or Hammond-Leffler) postulate, thermodynamic
>instability generally correlates with kinetic reactivity, that is, the
>transition state resembles the reactant that it is closest to on a free
>energy diagram. so, an endergonic reaction must get up to a high TS
>at which point it resembles the (unfavorable) product. This rule is
>generally followed for acyl derivatives, e.g. esters are more reactive,
>kinetically AND thermodynamically than amides. The exception is supposed
>to be thioesters which hydrolyze at the same rate as oxygen esters.
>I wondered how general this was. There are, of course, two transitions
>states, to and fromthe tetrahedral intermediate. The second step is surely
>faster with thioester since thiol is a better leaving group than OR.
> Is there a difference in rate determining step ? I know this is sort
>of a basic question but obvious references (Jencks) don't seem to address
>it explicitly.
>
>--
>Richard Feinman
>rumford$##$onebox.com - email
>(718) 404-3901 x6280 - voicemail/fax
>
>
>
>---- zabicky$##$bgumail.bgu.ac.il (Jacob Zabicky) wrote:
>> Hello Richard,
>>
>> As far as I understand it, the rate of reaction depends on the energy
>> difference between the ground and the transition states of the substrate,
>> assuming that the energy levels of the products are much lower (otherwise
>> complications with reversible reaction kinetics pop up). Therefore,
>> the
>> relative thermodynamic stability of the different substrates is irrelevant.
>> BTW, what do you mean quantitatively by "thioesters are thermodynamically
>> unstable relative to oxygen esters"?
>>
>> All the best,
>>
>> Jacob
>>
>> At 19:51 14/02/2002, Richard Feinman wrote:
>> >I don't know about questionable but mechanistic problems that I am
>> interested
>> >in which I'm having a little trouble getting a grip on (although it
>> may
>> >be elementary) are:
>> >
>> >1. It's usually assumed that although thioesters are thermodynamically
>> >unstable relative to oxygen esters, the rates of hydrolysis are similar.
>> > I wonder about the evidence for this. Fedor & Bruice studied
>>trifluoroacetate
>> >esters and I wonder if this is representative.
>> >2. Along the same lines, it is also generally stated that thioesters
>> >are like ketones (due to poor electronegativity of S and limited
>> >delocalization).
>> > Is there comparative data on rates of hydrate formation of ketones
>> relative
>> >to formation of tetrhedral intermediates in ester and thioester hydrolysis
>> >?
>> >
>> >--
>> >Richard Feinman
>> >rumford$##$onebox.com - email
>> >(718) 404-3901 x6280 - voicemail/fax
>> >
>> >
>> >
>> >---- "G. Robert Shelton" <rshelton$##$chem.ufl.edu> wrote:
>> >> orglist-ers,
>> >>
>> >> Just wanted to throw out a general question to the active people
>> of
>> >> the list, and some of those not so active like myself who are waiting
>> >> for phyiscal organic question to be asked. And from there maybe
>> start
>> >> some threads of conversation that would be of interest to some of
>> us
>> >> that are not solely organic synthesis people. Hopefully this is
>> the
>> >> place for this question. So In your opion, what are the most questionable
>> >> chemical mechanisms?
>> >>
>> >> -Robert
>> >>
>> >
>> >__________________________________________________
>> >FREE voicemail, email, and fax...all in one place.
>> >Sign Up Now! http://www.onebox.com
>> >
>> >__________________
>> >
>> >ORGLIST - Organic Chemistry Mailing List
>> >Website / Archive / FAQ: http://www.orglist.net/
>> >List coordinator: Joao Aires de Sousa (jas$##$mail.fct.unl.pt)
>>
>> x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x
>> Prof. Jacob Zabicky
>> Institutes for Applied Research
>> Ben-Gurion University of the Negev Private: POB 12366, Beer-Sheva
>> 84863
>> POB 653, Beer-Sheva 84105, ISRAEL Tel. +972-8-6496792
>> http://profiler.bgu.ac.il/site/main.cfm
>> Tel. +972-8-6461271/6461062/6472754
>> Fax. +972-8-6472969
>> x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x
>>
>>
>>
>
>
>__________________________________________________
>FREE voicemail, email, and fax...all in one place.
>Sign Up Now! http://www.onebox.com
x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x
Prof. Jacob Zabicky
Institutes for Applied Research
Ben-Gurion University of the Negev Private: POB 12366, Beer-Sheva 84863
POB 653, Beer-Sheva 84105, ISRAEL Tel. +972-8-6496792
http://profiler.bgu.ac.il/site/main.cfm
Tel. +972-8-6461271/6461062/6472754
Fax. +972-8-6472969
x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x-x
__________________
ORGLIST - Organic Chemistry Mailing List
Website / Archive / FAQ: http://www.orglist.net/
List coordinator: Joao Aires de Sousa (jas$##$mail.fct.unl.pt)
This archive was generated by hypermail 2.1.4 : Fri Sep 19 2003 - 12:16:54 EDT