Vol. 74 No.

2 February 1997 Journal of Chemical Education 201

R e se a rch : S ci e n ce & E d u ca ti o n
What are Isodesmic Reactions?
D. A. Ponomarev
St. Petersburg Academy of Forest Technology, Faculty of Chemical Engineering, 194018, Institutski 5, St. Petersburg,
Russia
V. V. Takhistov
St. Petersburg State University, Chemical Faculty, 198904, St. Petersburg, Petershof, Russia
The ter m i sodesmi c was i ntr oduced by the quan-
tum chemi stry speci al i sts Hehre, Di tchfi el d, Radom, and
Popl e i n thei r publ i cati on of 1970 (1). An i sodesmi c r e-
acti on i s a hypotheti cal (not exi sti ng i n r eal i ty) chemi -
cal pr ocess i n whi ch the number of bonds of each for mal
type r emai ns the same on each si de of the equati on but
wi th changes occurri ng i n thei r mutual rel ati onshi ps. I n
other wor ds, the heat of i sodesmi c r eacti on i s a measur e
of devi ati ons fr om the addi ti vi ty of bond ener gi es. The
devi ati on thus for med for a gi ven system can then be
i nter pr eted i n ter ms of physi cal or gani c chemi str y.
Quantification of StructureStability Relationships
for Molecules
Use of numer i cal val ues for the heats of i sodesmi c
r eacti ons, i nvol vi ng the compounds bei ng exami ned and
thei r model s, i s a si mpl e but effecti ve tool for search and
quanti tati ve esti mati on of the di ver se effects of stabi l i -
zati on/destabi l i zati on i n or gani c mol ecul es. A str ai n en-
ergy (H
str
) i n cycl i c compounds i s esti mated from known
heats of for mati on of cycl i c compounds and thei r acycl i c
anal ogs as model s (eq 1) (the val ues of the heats of for-
mati on H
f
for gas phase ar e taken fr om r ef 2).
CH
3
CH
2
CH
2
CH
2
CH
2
CH
2
CH
3

H
f
(kcal mol
1
) = 44.86
(1)

CH
2
CH
2
\

|
CH
2
+ CH
3
CH
3
+ Q
CH
2
CH
2

/
H
f
= 18.26 20.03 6.57
Equati on 1 r epr esents a for mal chemi cal r eacti on
wi th conser vati on i n both i ts par ts of the number of
bonds of a gi ven type. To equal i ze the val ues on the l eft
and the r i ght we add 6.57 k cal mol
1
to the r i ght and
thi s val ue, desi gnated by Q, r epr esents the heat of
i sodesmi c r eacti on 1. I ts negati ve si gn i ndi cates desta-
bi l i zati on of the mol ecul e on the r i ght (cycl opentane) as
compar ed wi th i ts anal ogue n-al kane on the l eft. Hence
we have H
str
= Q = 6.57 kcal mol
1
. Another appl i ca-
ti on of i sodesmi c r eacti ons i s the esti mati on of the heat
(ener gy) of conjugati on i n butadi ene (eq 2) and ar oma-
ti ci ty i n benzene mol ecul es (eqs 3 and 4). Fr om her e on
we omi t the val ues of the heats of for mati on, whi ch the
r eader can fi nd i n r ef 2, and gi ve onl y the r esul ti ng Q
val ues i n kcal mol
1
.
CH
2
=CHCH
3
+ CH
3
CH=CH
2

CH
2
=CHCH=CH
2
+ CH
3
CH
3
Q = 3.30
(2)
3CH
2
=CHCH=CH
2
+ 3CH
2
=CH
2
Q = 21.48 (3)
3 + + 3 Q = 30.51 (4)
Q val ues i n eqs 3 and 4 r efl ect the di ffer ence i n the
heats of for mati on of benzene and i ts hypotheti cal i so-
mer 1,3,5-cycl ohexatr i ene. Equati on 3, usual l y used for
esti mati on of ar omati ci ty, seems to be i ncor r ect, si nce i t
negl ects the str ai n ener gy i n 1,3,5-cycl ohexatr i ene as
compar ed wi th butadi ene. Hence i t i s better to use eq 4.
Cal cul ati on of the heats of for mati on of di cyano fr om
cyano deri vati ves (eqs 57) reveal s a general feature: oc-
cur r ence of negati ve Q val ues, whi ch mani fest the r e-
pul si ve thr ough-bond i nter acti on of two str ong el ectr on
wi thdr awi ng NC gr oups:
2 CH
3
CH
2
CNNCCH
2
CH
2
CN+CH
3
CH
3
Q = 5.47 (5)
2 CH
2
=CHCNNCCH=CHCN+CH
2
=CH
2
Q = 6.54 (6)
2 C
6
H
5
CN N

CC
6
H
4
C

N + C
6
H
6
(7)
Q = 4.47 (ortho-i somer ),
3.30 (meta-)
1.99 kcal mol
1
(para-i somer )
The r epul si on i s better conducted by than by bonds
(compar e eqs 5 and 6). The i nter acti on of two gr oups de-
pends on the di stance between them (eq 7). Repul si ve
i nter acti on i n the ortho-i somer (eq 7) i s smal l er than i n
the acycl i c anal ogue (eq 6) owi ng to di ssi pati on of the
charges i n the benzene ri ng. Si mi l ar effects are observed
i n Q val ues (kcal mol
1
) for Cl CH
2
CH
2
Cl (2.96), trans-
FCH=CHF (4.79), ci s-FCH=CHF (4.09), trans-
I CH=CHI (2.07), p-di fl uor obenzene (1.9). Thus we can
tal k about the gener al char acter of destabi l i zati on for
str ong substi tuents i nter acti ng at a shor t di stance.
Cal cul ati on of Q for the i sodesmi c r eacti on
2 CH
2
=CHCl trans-Cl CH=CHCl + CH
2
=CH
2
gi ves Q = 4.12 kcal mol
1
(stabi l i zati on ?); thi s means
that the heat of for mati on of one of the chl or oal kenes,
gi ven i n r ef 2, i s wr ong! The gener al char acter of the
pol ar i nter acti ons between substi tuents i s suppor ted by
fur ther exampl es (2, 3).
2 C
6
H
5
OH p-HOC
6
H
4
OH + C
6
H
6
Q = 3.27 (8)
C
6
H
5
OH + C
6
H
5
NO
2
HOC
6
H
4
NO
2
+ C
6
H
6
(9)
Q = +1.48 (para-), +4.13 (ortho-)
C
6
H
5
NH
2
+ C
6
H
5
NO
2
p-H
2
NC
6
H
4
NO
2
+ C
6
H
6
(10)
Q = +3.16 kcal mol
Equati on 8 i ndi cates, as expected, the destabi l i za-
H
202 Journal of Chemical Education Vol. 74 No. 2 February 1997
R e se a rch : S ci e n ce & E d u ca ti o n
ti on of the system. I t i s wor thwhi l e to noti ce that the
HO-gr oup appear s to be a str onger el ectr on-wi thdr aw-
i ng substi tuent than hal ogens, si nce Q i s cl ose to zer o
i n anal ogous r eacti ons i nvol vi ng p-di chl or obenzene and
p-di i odobenzene. Equati ons 8 and 9 reveal the dual char-
acter of the HO gr oup: i f i n p-di oxybenzene i t shows
wi thdr awi ng pr oper ti es, i n the pr esence of the much
str onger NO
2
gr oup i t becomes el ectr on-r el easi ng. The
NO
2
group extracts l arger stabi l i zati on energy from the
better el ectr on-donati ng p-NH
2
than fr om the p-OH
gr oup (eqs 9 and 10). We hope the r eader has guessed
that i ntr amol ecul ar H-bondi ng i s a better sour ce of sta-
bi l i zati on i n the ortho-i somer than i n the para-i somer
(eq 9).
Quantification of StructureStability Relationships for
Cations and Free Radicals
Her e we consi der an i sodesmi c r eacti on i nvol vi ng
cati ons (eq 11) (the val ues of the heats of for mati on, i n
uni ts of kcal mol
1
, ar e taken fr om r efs 4 and 5).
CH
3
CH
2
CH
2
+
+ CH
2
=CHCH
3

H
f
= 207 4.8
CH
3
CH
2
CH
3
+ CH
2
=CHCH
2
+
+ Q (11)
H
f
= -25.0 225
Q = (207 + 4.8) (25.0 + 225) = +11.8 kcal mol
1
The absolute val ue of the heat of for mati on of al l yl
cati on i n the gas phase (225 kcal mol
1
) i s l ar ger than
that of pr opyl cati on (207 kcal mol
1
) (i n other wor ds the
for mer i s l ess stabl e than the l atter, over al l , as a ther-
modynami c system). However, when we excl ude the con-
tr i buti on of the heats of for mati on of the i on skel etons
to the heats of for mati on, we i mmedi atel y obtai n the op-
posi te resul t: al l yl cati on i s by 11.8 kcal mol
1
more stabl e
than pr opyl cati on i n the sense that del ocal i zati on of i ts
posi ti ve char ge i s better. I n our di scussi on we shal l not
use the compl ete desi gnati on of i sodesmi c r eacti ons but
r ather the shor t for ms: for exampl e, CH
3
CH
2
CH
2
+

CH
2
=CHCH
2
+
+ Q, omi tti ng the neutr al mol ecul es. The
compari son of Q val ues for seri es of cati ons i ndi cates that
the same el ectr on-r el easi ng substi tuent (say, Me) gi ves
di ffer ent stabi l i zati on effects (whi ch ar e r efl ected i n di f-
fer ent Q val ues) when i ntr oduced to cati ons wi th di ffer-
ent stabi l i ti es: the Q (H Me) val ue i s smal l er for more
stabi l i zed systems (eq 12). Q val ues i n kcal mol
1
ar e
gi ven on the ar r ows.
+88.4 +42.7 +22.2 +11.1
HO
+
CH
3
+

+
CH
2
CH
3

+
CH
2
OH
+
CH
2
Ph

+67.8

+42.7

+22.3

+18.8

+15.1
(12)
MeO
+
MeCH
2
+


Me
+
CHCH
3
Me
+
CHOH Me
+
CHPh
Wher eas substi tuents possessi ng the defi ni te el ec-
tr on-r el easi ng pr oper ti es (Ph, CH
2
=CH, OH, NH
2
, etc.)
behave i n the same manner as Me, those wi th dual char-
acter (F, Cl , CHO, CN) r eveal a mor e compl i cated be-
havi or (negati ve Q val ue means destabi l i zati on) (eq 13).
+23.6 +5.2 6.8
CH
3
+

+
CH
2
F
+
CHF
2
CF
3
+
(13)
The smal l Q val ue i n eq 14 mani fests the near l y
equal stabi l i ti es of acycl i c and cycl i c cati ons of al l yl i c
type wi th a sl i ghtl y enhanced stabi l i ty of the cycl i c part-
ner owi ng to a l ar ger chai n l ength fr om both si des of
the posi ti ve char ge i n the cycl i c cati on:
CH
3
CH=CH
+
CHCH + Q

(14)
H
f
(kcal mol
1
) = 183.5 198.2 +1.5
An i sodesmi c r eacti on
CH
2
=CHCH
2
+
+ RH CH
2
=CHCH
3
+ R
+
+ Q
can be used to eval uate the rel ati ve thermodynami c sta-
bi l i ti es of or gani c cati ons (Tabl e 1).
Anal ysi s of the data i n Tabl e 1 gi ves some i nter est-
i ng obser vati ons. The type of hybr i di zati on of a car bon
atom bear i ng the posi ti ve char ge i nfl uences stabi l i ty of
the i on: HC

C
+
(sp-hybr i di zati on) i s l ess stabl e by 81.7
kcal mol
1
than CH
2
=CH
+
i on (sp
2
-hybri di zati on) and the
l atter i s l ess stabl e by 17.4 kcal mol
1
than CH
3
CH
2
+
i on
(sp
3
-hybri di zati on). Now i t i s evi dent why the nucl eophi l -
i c substi tuti on r eacti ons of Me
3
CX ar e monomol ecul ar,
wher eas the same r eacti ons wi th C
2
H
5
X and CH
3
X spe-
ci es proceed vi a a bi mol ecul ar mechani sm. The hi gh sta-
bi l i ty of Me
3
C
+
encour ages i ts for mati on fr om Me
3
CX
wi th the hel p of a sol vent, wher eas the l ow stabi l i ty of
C
2
H
5
+
and CH
3
+
pr events C
2
H
5
X and CH
3
X mol ecul es
fr om pr oducti on of the for mer. The hi gher stabi l i ty of
secondar y, compar ed wi th pr i mar y, i ons appear s to be
the dr i vi ng for ce for pr ocesses l i ke CH
3
CH
2
CH
2
+

CH
3
+
CHCH
3
. What i s ver y i mpor tant i s that al l these
cal cul ati ons r est now on quanti tati ve gr ounds.
Some questi ons coul d be put for war d for the r eader.
Why among the coupl es of i somer s cycl o-C
3
H
3
+
and
HC

CCH
2
+
, cycl o-C
7
H
7
+
(tr opyl i um) and PhCH
2
+
, and
+
CH
2
OH and CH
3
O
+
i s the fi r st i on mor e stabl e than the
second? What i s the expl anati on for the fact that the sta-
bi l i ty of the i ons i ncr eases i n the or der Me
3
C
+
< Me
3
Si
+
< Me
3
Ge
+
? Why i s cycl opentadi enyl cati on, compr i si ng
two el ectr on -r el eas i n g -bon ds , l es s s tabl e th an
CH
2
=CHCH
2
+
? Why does r epl acement of Me by Ph gi ve
di ffer ent Q val ues for di ver se cati ons33.1, 20.9, and
9.7 kcal mol
1
for RCH
2
+
, R
+
CMe
2
, and R
+
C=O i ons, r espec-
ti vel y (R = Me and Ph)?
An i mpor tant pr obl em i n or gani c chemi str y i s an
eval uati on of the ener gy (heat) of ar omati ci ty and
( s e i t i l i b a t S c i m a n y d o m r e h T e v i t a l e R . 1 e l b a T Q s n o i t a C f o )
l o m l a c k ( e s a h P s a G n i
1
)
n o i t a C Q n o i t a C Q n o i t a C Q
H
+
6 . 5 4 1 H C
2
H O 0 . 6 H C (
2
) H C =
3
C
+
4 . 9 3
C H C
+
1 . 5 1 1 e M
2
H C
+
3 . 6 e M C h P
2
1 . 0 4
O e M
+
5 . 9 7 e M O O C 8 . 5 1 O = C h P 6 . 0 4
H C
3
+
8 . 8 5 H C h P
2
+
1 . 7 1 e M
3
e G
+
3 . 4 4
H C
2
H C =
+
4 . 3 3 C H ( ) C
3
C
+
3 . 8 1 h P
3
C
+
4 . 6 5
h P
+
1 . 8 2 e M
3
C
+
2 . 9 1 e M
2
H C = N
2
0 . 9 5
C H H C C
2
+
5 . 6 1 H
3
O
+
9 . 0 2 2 . 0 6
t E
+
0 . 6 1 5 . 0 3 H N
4
+
7 . 2 6
n r P -
+
3 . 2 1 O = C e M 9 . 0 3 H N ( C
2
)
3
5 . 7 7
4 . 1 e M
3
i S
+
9 . 6 3
H C
2
H C H C =
2
+
0 l y t n a m a d A - 1
+
4 . 7 3
+
+
+
+ +
+
+
Vol. 74 No. 2 February 1997 Journal of Chemical Education 203
R e se a rch : S ci e n ce & E d u ca ti o n
anti aromati ci ty. For charged parti cl es such as tropyl i um
cati on and cycl opentadi enyl ani on and cati on, thi s pr ob-
l em can be easi l y sol ved usi ng i sodesmi c r eacti ons by
cal cu l ati n g th e h eats of for mati on of cl as s i cal
(nonar omati c) speci es of the same str uctur e fr om the
known heats of for mati on of acycl i c anal ogs (eq 14). The
model speci es sel ected for the tr opyl i um cati on and for
the cycl opentadi enyl ani on and cati on wer e, r espec-
ti vel y, (CH
2
=CHCH=CH)
2
+
CH, CH
2
=CHCH=CH

CH
CH
2
=CH

CHCH=CH
2
, and CH
2
=CH
+
CHCH=CH
2
. The fol -
l owi ng r esul ts have been obtai ned (see r ef 4):
H
f
cl assi cal i on (cal c.) 225.4 38.6 226.7
H
f
cl assi cal i on (exp.) 203.6 18.3 253.5
H (ar om) (kcal mol
1
) 21.8 20.3 26.8
Such cal cul ati ons gi ve si mi l ar resul ts to those made
by the methods of quantum chemi str y, but cost nothi ng.
When i sodesmi c r eacti ons ar e appl i ed to descr i pti on of
the r el ati ve stabi l i ti es of fr ee r adi cal s the obvi ous r esul t
i s obtai ned: the l ess stabl e free radi cal extracts a l arger
stabi l i zi ng effect fr om the same substi tuent than the
mor e stabl e one (eq 15) (the heats of for mati on used for
cal cul ati on of Q val ues ar e taken fr om r efs 4 and 6).


-
2.4
-
1.5
-
11.8
-
4.3
-
10.2
H

C=O

SH

CH
2
CN

CH
3

NH
2
OH

+2.7

+2.9

+4.0

+6.0

+9.5

+14.9 (15)
Me

C=O Me

S Me

CHCN Me

CH
2
Me

NH Me

O
As ear l y as 1965 i n thi s J ournal, S. Benson (7) sug-
gested the i dea of compar i ng fr ee r adi cal stabi l i ti es (E
S
)
usi ng eq 16:
E
S
= H
f
(R

) + H
f
(R
1
H) H
f
(RH) H
f
(R
1

) (16)
Actual l y, i t i s an expr essi on for Q val ue of the fol -
l owi ng i sodesmi c r eacti on wher e E =Q (eq 17):
R

+ R
1
H RH + R
1

+ Q (17)
Thus Benson was the fi rst who tri ed i sodesmi c reacti ons
(al though wi thout usi ng thi s name) to descri be free radi -
cal stabi l i ti es. Her e, eq 17 (R = Me) i s used to cr eate a
general scal e of rel ati ve thermodynami c stabi l i ti es of free
r adi cal s (Tabl e 2).
Si nce free radi cal stabi l i zati on, i n general , paral l el s
the r egul ar i ti es i n stabi l i zati on of cati ons (see above),
the r eader i s i nvi ted to answer the questi ons: Why does
the ther modynami c stabi l i ty of fr ee r adi cal s i ncr ease i n
the order HCC

< CH
2
=CH

< CH
3
CH
2

; F

< Cl

< Br

< I

; Me
3

C < Me
3
Si

or NH
2

< PH
2

; Me

< MeCH
2

<
Me
2
CH

< Me
3
C

, MeO

< MeCH
2

; F

<

OH< NH
2

< Me

;
NC

< HCC

; CF
3
COO

< CH
3
COO

? The extr emel y

hi gh stabi l i ty of

NO fr ee r adi cal s was expl ai ned wi th

i ts noncl assi cal str uctur e .
:
N::
.
O.
:
(ei ght el ectr ons at both
atoms) [7].
We hope that we achi eved the goal of the publ i ca-
ti on n ot on l y an s wer ed th e qu es ti on Wh at ar e
i sodesmi c reacti ons? but al so demonstrated the obvi ous
uti l i ty of thi s modest i nnovati on for var i ous topi cs of or-
gani c chemi str y. We al so showed that appl i cati on of
i sodesmi c r eacti ons i s not si mpl y a game but r ather a
ver y ser i ous sci enti fi c exer ci se whi ch i s, never thel ess,
accessi bl e to ever ybody.
Literature Cited
1. Hehr e, W. J.; Di tchfi el d, R.; Radom, L.; Popl e, J. A. J . Am. Chem.
Soc. 1970, 92, 47964801.
2. Pedl ey, J. B.; Nayl or, R. D.; Ki r by, S. P. Thermochemical Data of
Organic Compounds, 2nd ed.; Chapman and Hal l : London, 1986.
3. Fi nch, A.; Gar dner, P. J.; Wu, D. Thermochim. Acta 1983, 66, 333
342.
4. (a) Takhi stov, V. V. Or gani c Mass Spectr ometr y (Russ.) Leni ngr ad.
Nauka (Sci ence) 1990; (b) Ponomar ev, D. A.; Takhi stov, V. V. Org.
Mass Spectrom. 1994, 29, 395412.
5. Li as, S. G.; Bar tmess, J. E.; Li ebman, J. F.; Hol mes, J. L.; Levi n,
R. D.; Mal l ar d, W. G. J . Chem. Phys. Ref. Data 1988, 17(Suppl .
1).
6. McMi l l en, D. F.; Gol den, D. M. Ann. Rev. Phys. Chem. 1982, 33,
493532.
7. Benson, S. W. J . Chem. Educ. 1965, 42, 502518.
( s e i t i l i b a t S c i m a n y d o m r e h T e v i t a l e R . 2 e l b a T Q e e r F f o )
l o m l a c k ( s l a c i d a R
1 -
)
R Q R Q R Q
O N 3 . 5 5 e M
3
i S 7 . 4 1 H C
3
0
H S S 8 . 3 3 H S 3 . 3 1 F C
3
3 . 1 -
J 5 . 3 3 l y t n a m a d A - 1 5 . 2 1 O O C e M 4 . 1 -
h P
3
C 4 . 9 2 e M
3
C 0 . 1 1 H N
2
3 . 4 -
O N
2
0 . 6 2 e M
2
H C 3 . 9 H C
2
H C = 3 . 5 -
F N
2
8 . 3 2 H C
2
H O 8 . 8 F C
3
O O C 9 . 7 -
H C
2
H C H C =
2
5 . 8 1 ) H O ( N
2
7 . 7 h P 0 . 9 -
H C h P
2
2 . 8 1 C
2
H
5
0 . 6 H O 5 . 4 1 -
r B 3 . 7 1 l C 6 . 1 C H C 1 . 6 1 -
H P
2
7 . 6 1 H 6 . 0 CN 0 . 1 2 -
O O H 7 . 6 1 O e M 4 . 0 F 6 . 1 3 -