Subject: TS on a SN2 reaction

From: "Dr. Antonio Entrena" <[email-masked]>
Date: Wed, 11 Sep 1996 11:36:24 -0700

Dears CCL users:

	Last week I post a question regarding to a TS on a SN2 reaction. I 
have received some responses and here is the summary:

	My original question was:

**********************************
        I need to calculate the TS for a variety of SN2 reactions using
semiempirical Mopac calculation and I have some problems. I will be very
greatfull for every help that you can gave me.

        The strategy that I have used is the following:

        I have define a dummy atom in order to fix the geometry of the
nuclephile and the leaving group as in the following scheme:

        Du..........C
                    |
                    |
        Nu..........C---L

        I have defined the distance between the dummy atom (Du) and the upper
carbon atom about 10 A and between the nucleophile (Nu) and the lower carbon
atom about 5 A.

        The Du-C-C-Nu and Du-C-C-L dihedral angles have been defined as 0 and
180 degrees, respectively.

        I used the symmetry keyword (option 17) in order to varies the C-C-Nu
bond angle as 180 degrees - C-C-L bond angle during the calculation.

        I believe that with those definitions, the nucleophile, the carbon
atom and the leaving group (L) must be in straight line when the distances
Nu-C is decreased at 0.1 or 0.05 A intervale.

        I expect that when the nucleophile is located at a apropiate distance
the distance C-L begin to increase so that the geometry of higher energy
could be used to optimized the TS of the reaction, but this does not occur.
When the nuclephile is about 2.4-2.2 A, the leaving group is inmediately
ejected to a distance of 3.5 A or more.

        Can anybody with experience in this type of calculations gave me some
orientations to resolve this problem?.

        Please, e-mail directly to me and I will summarized to the net.

        Sincerely

        A. Entrena

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	And the answers are the following:

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From: [email-masked] (Ansuman Lahiri)

Dear Dr. Entrena

Did you try the SADDLE keyword in mopac? What I usually do is to
choose two configurations (in one of which the leaving group is
bonded and in the other the attacking group is bonded to the central
group) and then run SADDLE. The approximate transition state obtained
>from SADDLE can then be further refined using TS.

Hope this helps

Good luck!

Ansuman

*****************************************

From:  "Anatoli Korkin" <[email-masked]>

Hi!

Fixing C-Nu eagual C-L in optimization, you will approach TS closely.
Then compute frequencies and use the resulting force field along with
opt=ts option. But I have feeling, that you guy hardly undertand what
are you doing and why.

regards,

Anatoli Korkin

********************************************************

From:  [email-masked] (Alan Shusterman)

--- You wrote:
I expect that when the nucleophile is located at a apropiate distance
the distance C-L begin to increase so that the geometry of higher energy
could be used to optimized the TS of the reaction, but this does not occur.
When the nuclephile is about 2.4-2.2 A, the leaving group is inmediately
ejected to a distance of 3.5 A or more.
--- end of quoted material ---
I am not sure what Nu/L combinations you are using, but this may be 
reasonable
behavior.

First, if either of the reactants or products are charged, then electrostatic
interactions (ion-dipole) will be very strong and a true transition state may
not even exist.  Consider chloride attacking methyl chloride (degenerate 
rxn):
as chloride approaches the energy falls (favorable ion-dipole interaction),
then sharply rises to give a symmetric TS, then falls again to give the 
product
ion-dipole complex.  The AM1 transition state is only a kcal/mol or two 
higher
than the separated reactants.  Now consider hydroxide attacking methyl
chloride: as hydroxide approaches the energy falls steadily without
intervention of a transition state.  This reaction is very exothermic, and 
bond
energy changes plus electrostatic interactions erase the transition state.  
To
summarize: 1) you may have trouble locating transition states, 2) minima may
correspond to ion-dipole complexes in which reactants approach to within LESS
than the sum of the nonbonded radii, 3) TS, when they do exist, should be
viewed as resonance hybrids of the reactants and products, and therefore
reasonably short CN and CL bond distances are expected.

Finally, least motion paths are interesting, but may not tell the full story.
For example, hydroxide attack on methyl chloride initially gives an 
ion-dipole
complex in which the chloride is close to the methyl hydrogens of methanol.
This is probably not the global minimum, and may not even be a local minimum.
The best structure is probably one in which a hydrogen bond, Cl..HOCH3, holds
the ion and dipole together.

Alan Shusterman
Department of Chemistry
Reed College
3203 SE Woodstock Blvd
Portland, OR  97202

************************************

From:  Hens Borkent <[email-masked]>

Dear Dr. Entrena,

There is no reason why the leaving group should stay in
the neighbourhood of the carbon atom; once you're over
the 'top' (TS), the structure will minimize the C-L
distance. And moreover, there is no reason why the
N-C-L angle should be 180 degrees, unless your carbon
skeleton is symmetrical (methyl, t-butyl).
The savest thing would be to do a grid search, in which
you vary the C-N distance in the range 2.0 2.8, and the
C-L distance something similar, depending on the nature
of the leaving group. In this way you fix both values
and a saddle point should appear in the grid. This
point should be optimized using the TS keyword.
Have a look at:
http://www.caos.kun.nl/tutorials/camm/mopac/gsm.html

Sincerely,
--

  *****    J.H. (Hens) Borkent, CAOS/CAMM Center,
 *CAOS *   P.O. Box 9010, 6500 GL Nijmegen, The Netherlands
*   /   *  Tel 0031 24 36 52137  Fax 0031 24 36 52977
 * CAMM*   e-mail: [email-masked]
  *****    http://www.caos.kun.nl/staff/borkent.html

****************************************************

From:    Jose Ignacio Garcia <[email-masked]>
 
He leido tu pregunta en la CCL. Puede haber varios motivos para el comporta-
miento que describes. En primer lugar, la forma de la superficie de energia
potencial depente por supuesto de la reaccion, de forma que podria suceder
que en la reaccion particular que estas estudiando, haya una zona en la que
el sistema evolucione muy rapidamente. La solucion en este caso es estudiar
mas en detalle dicha region, modificando la distancia de ataque Nu-C con
intervalos mas cortos. Algo parecido sucede cuando se comparan las reacciones
Cl(-) + CH3Cl --> ClCH3 + Cl(-) y
F(-) + CH3Cl --> FCH3 + Cl(-)
En el primer caso, se obtiene un diagrama de reaccion "de libro", pero
en el segundo, dependiendo de la geometria inicial y el intervalo utilizado
puede obtenerse un diagrama en el que aparentemente la energia disminuye
siempre, sin que aparezca barrera de activacion. Resulta necesario estudiar
muy en detalle la region critica para localizar dicha barrera.
Por otra parte, creo que utilizas demasiadas restricciones en el acercamiento
de Nu, lo cual puede dar problemas. Ten en cuenta que cuantas mas 
restricciones
utilices, menos representativa sera la superficie de energia calculada con
respecto a la "verdadera".
Nosotros solemos emplear el siguiente esquema:

Nu ------C-------L    Donde el diedro se fija en 180 grados y los angulos
         |            Nu-C-Du y Du-C-L se fijan en 90 grados. Es estricta
         |            logica, no deberia fijarse ninguna restriccion, pero
        Du            si Nu o L llevan carga neta, la tendencia a dar
                      reacciones "exoticas", como arrancar un proton cercano
                      es bastante grande.
Con las restricciones indicadas, se fuerza a  que el ataque de Nu y la salida
de L se produzcan a lo largo de una linea recta, como usualmente se asume en
las SN2.
Espero que estas observaciones te sean de alguna ayuda.
Un cordial saludo.

Jose Ignacio
--
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Dr. Jose Ignacio Garcia-Laureiro                     Phone : 34-(9)76-762077
Departamento de Quimica Organica                                      761210
Instituto de Ciencia de Materiales de Aragon         Fax   : 34-(9)76-761159
C.S.I.C.-Universidad de Zaragoza                     e-mail: 
[email-masked]
E-50009 ZARAGOZA (SPAIN)                                     
[email-masked]
                                                             
[email-masked]
--------------------------------------------------------------------------------
"And all this science I don't understand it's just my job five days a 
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	Thanks to all af them for their help. 

	Sincerely

	A. Entrena