I
John S. M e e k
University of Colorado
Boulder, 80302 I The Determination of a Mechanism of
bomerization of Maleic Acid to k m a r i t Acid
I n undergraduate organic laboratory work students are
expected t o know t h e mechanism of one preparative reac-
tion after another. They obtain this information by read-
ing their text a n d rarely see t h a t alternative mechanisms
can b e suggested for a reaction a n d seldom learn on what
experimental evidence t h e mechanism is based. At present
mechanistic experiments seem t o be confined t o obtaining
d a t a which enable students t o determine whether a reac-
tion is first- or second-order i n terms of reactants, b u t
they d o not enable t h e m t o obtain d a t a on which t o ex-
clude a plausible mechanism a s being inoperative a n d t o
deduce one in accord with experimental facts which they
obtain.
I n seeking such a n experiment t h e isomerization of ma-
leic acid t o fumaric acid by heating with hydrochloric acid
h a s proven t o he almost ideal. T h e mechanism is not
readily guessed nor is it t o be found i n current lecture
texts. In fact for t h e past year we have been asking col-
leagues, visiting professors, and graduate students what
was t h e mechanism of this reaction a n d obtained t h e cor-
rect answer only once, before we received late i n M a y t h e
5 t h Edition of "Laboratory Practice in Organic Chemis-
try" by T. L. Jacobs, W. E. Truce, a n d G. R. Robinson,
Macmillan Publishing Co., Inc., New York, 1974. I n this
laboratory text a procedure for isomerizing maleic acid t o
fumaric acid is given and t h e mechanism of isomerization
by hydrochloric acid is well delineated, b u t t h e laboratory
exercise is still t h e typical preparative type of experiment
rather t h a n one designed t o elucidate a mechanism.
O u r handout, which has been successfully tested on u n -
dergraduate majors, was designed t o teach some history,
some concepts of stereochemistry, a n d t o encourage de-
ductive reasoning. O u r latest version reads a s follows.
The Mechanism of the lsomerization ol Maleic t o
Fumaric Acid by Hydrochloric Acid
Historical Information
Scheele in 1785 isolated an acid from unripe apples. This acid
is still called malie aeid after the Latin ward malum meaning
apple. The acid also occurs in grapes and rhubarb and is levoro-
tatary. Structural studies have shown it to be L(-)hydraxysuc-
cinic acid. The racemic form is manufactured today and is used
as a food acidulant without restriction since the compound is eas-
ily metabolized.
In 1817 dry distillation of malic acid by Braconnet and inde-
pendently by Vauquelin led to the discovery of two acids which
became known as maleic acid and fumaric acid. The first name is
based on the French "maleique acide" which appears to he a
variation of malic acid. The second acid derives its name from
the fact that the acid is found in fumitory plants. These belong to
the genus furnoria, a common European herb.
Studies by Pelouze in 1836 indicated these acids were isomers,
and Liebig in 1838 showed they had the same composition and he
believed that fumaric acid (mp 300-30Z°C) was a polymer of ma-
leic acid (mp 139-140°C d). This idea was mentioned by Erlen-
meyer in 1870 and again in 1886.
Kekule in 1861 reduced both substances to succinic acid (buta-
nedioic acid) and wrote
-CHCOOH
I A . Thermal
-CHCOOH
for fumaric acid and
for maleic acid. Later work by Swarts in Kekule's laboratory led
to a publication in which fumaric acid was depicted with a dou-
ble bond
CHCOOH
II
CHCOOH
In 1874 van't Hoff suggested that carbon atoms were tetrahe-
dral and explained why malic aeid and other compounds with
four different groups on one carbon atom could exist as optical
isomers. In discussing the tetrahedral shape he wrote "Double
linking is represented by two tetrahedrons with one edge in com-
mon" and he pointed out that when two tetrahedrons are so at-
tached isomerism results if each tetrahedron has two different
substituents at the two noncantiguous corners of each tetrahe-
dron. These can be depicted thus
HCCOOH HOOCCH
II
HCCOOH HCCOOH
H HOOC H
ma1eic acid 1umwic a d
The first of these structures was assigned to maleic acid by
van't Hoff since maleic acid melts at 140°C and loses water to
make an anhydride while fumaric acid does not do this at its
higher melting point. Only the cis isomer could make a cyclic an-
hydride
maleic anhydt.ide
Kekule and Strecker in an 1884 publication observed that ma-
leic acid, when warmed with hydrochloric acid, was easily con-
verted to fumaric acid. Isomerization by halogens and hydrogen
halides aided in establishing structures and relative stabilities of
geometrical isomers. Once the cis-trans nature of maleie and fu-
maric aeid was established, advances in stereochemistry could
take place. Wislecenus in 1881 correctly interpreted Kekule's 1863
conv;rsion of maleic acid to meso tartaric accd as being the result
of a cis opening of the double bond.
Kalbe attacked van't Hoff's stereochemical ideas as did Fittig,
Lassen, and others, but Wislecenus became a leader in recogniz-
ing the value of the new theory. After Fittig, Erlenmeyer, Mi-
chael, Beilsteip, and Ansbutz had a succession of failures in solv-
ing structural problems without using vanst Hoff's new concepts,
apposition gradually disappeared and acceptance emerged.
However, a really satisfactory explanation of the mechanism of
the hydrochloric acid isomerization of maleic aeid to fumaric acid
was not advanced until almost 60 years after Kekule and Streeker
discovered the reaction. Skraup studied the isomerization in great
depth and published his results in 1891 without giving an ade-
quate explanation, but did comment on the plausibility of Wisle-
cenus' suggestion that hydrogen chloride added to give chlorosuc-
cinic acid which upon loss of hydrogen chloride gave fumaric acid.
Theoretical Section
Mechanisms which can be considered for the isomerization are
as follows:
One of the double bonds breaks, rotation occurs and then
the double bond reforms.
Volume 52, Number 8, August 1975 / 541
B. Eleetraphilic
1) Addition of a proton gives
CMH
~OOH
Loss of a proton now givesfumsric acid.
2) The cation above reacts with water to give malic acid
which in acid solution dehydrates and produces fumaric acid.
3) The cation above reacts with itself to form a ladone. This
opens to give malic acid and then dehydrates tofumsric acid.
4) The cation above picks up a chloride ion and so forms chla-
rosuccinic acid. Loss of hydrogen chloride now occurs to form
fumaric acid.
5) Protonation does not occur on the carbon atom hut on the
carbonyl group of a carboxyl group. Due t o resonance the elec-
trons in the double bond are delocalized so that the following
can occur
/OH
2) Place your six filled test tubes in either a steam bath or a
beaker of water a t its boiling point. Swirl the test tuhes in order
to dissolve the solids. Once solution has occurred, they need no
further swirling. Heat them for 15 min and record your observa-
tion of any changesnoted in the test tubes.
3) If s solid forms in a test tube by the end of the 15-min peri-
od of heating, coal the contents and remove the solid by filtration,
using a Hirsch funnel. Wash the solid with a milliliter of water,
dry the solid, and determine its weight and melting point. Pour
the eontentsar filtrate from tube 66 into the jar provided.
Melting points of the acidsdiscussed above are as follows:
L(-)malic acid, 99-100°C
DL-malic acid, 128-129°C
maleic acid, 139-140"dC
fumaric acid, 300-302°C
L(-)chlorosuccinie acid, 176°C
DL-chlorosuceinie acid, 153-154°C
Generally the higher the melting point of a d i d the higher are
the forces holding the molecules together in a crystalline solid.
These forces have t o he overcome uoon solution: thus i t should
not be surprising that the higher melting fumarie acid is much
less soluble than any of the other acids listed above.
Theoretical Section
If the isomerization of maleie acid to fumaric acid is merely a
thermal reaction, which test tuhes should give rise to fumaric
acid?
If the mechanism of isomerization is B1, which test tuhes

fummir neid + Hi - H,
C
11
,CiOHl,
- H\C/C\OH
11
n+
should give rise to fumaric acid"
W h ~ shouldgive
h positiw rerulrsior H2. HR. erc.?
What mechanism dr,vot. feel is in accord with sour facts7
Questions
1) In simple esterifieations such as the conversion of benzoic
C. Nueleaphilie acid and methanol to methyl benzoate small amounts of hydro-
Addition of a chloride ion gives an anion which upon inver- gen chloride or sulfuric acid are equally satisfactory as catalysts.
sion of the carbanion or rotation around the C2-C3 bond and However, when a methanol solution of maleic acid is esterified
lossof chloride ion results in fumaric acid. This anion is using sulfuric acid a liquid ester is obtained, but if hydrogen ehlo-
C0,H ride isuseda solid ester is formed. Explain.
I 2) Maleic acid on treatment with thionyl chloride gives fumar-
yl chloride and maleyl chloride was unknown for many years after
fumaryl chloride was first prepared. What conditions would be
Hk- needed for preparing rnaleyl chloride?
I 3) Ultraviolet light can convert fumaric aeid to maleic aeid.
C0,H
Why is it obvious that visible light can not do this?
D. Unsuggested 4) What is the melting point of D(+)malic acid? Why does DL
It must he realized that mechanisms are proposed theories malic acid melt higher than the L form? Why does DL chlorosuc-
and that they can be tested. If not in accordance with known einie acid melt lower than the L farm?
facts then the mechanism is incorrect. Even if a mechanism is 5) Fumaric acid is formed in the body in what is known as the
in accord with all known facts this does not make it the cor- Krebs cycle. Since the compound is easily metabolized it is al-
rect mechanism since a n unconceived mechanism might be lowed in foods as an acidulant. What property, however, makes
the true one. fumaric acid less desirable in many cases than malic acid?
For example one can postulate that the isomerization of 6) Skraup tried the isomerization of maleic acid using perchlo-
maleie aeid t o fumaric acid is due to light in the laboratory. It ric acid as the catalyst as well as hydriadic acid. Consider the po-
is known that ultraviolet light will convert fumaric acid to larizability of the perchlorate and iodide ions and the difference
maleie acid. in charge delocalization in the ions as affecting their nueleophili-
Another suggestion could be that it is due t o heavy metal city. Now list in order of increasing efficiency how HCI, HI and
catalysis due to impurities present in the hydrochloric acid. HClO. solutions should rank as catalysts for the isomerization
Skraup reported heavy metal catalyzed isomerization does in- reaction.
deed occur. A third explanation is that a free radical adds to 7) Scheele has the mineral calcium tungstate named scheelite
the double bond to eive a radical intermediate similar t o the in his honor. Liebig condensers and Erlenmeyer flasks are still
cation pictured in B1, rotation around the remaining single used today. Fittig, Kolbe, Strecker, Skraup, Swarts, and Michael
bond, CZ-C3, occurs and then loss of the radical restores the have reactions named for them and Lossen has a rearrangement
double bond. This mechanism has been postulated since coupled with his name. Give an example of each of these organic
under certain conditions bromine plus light converts maleic reactions.
acid to fumarie acid.
Experimental Results and Discussion
Experimental Section Fumaric acid crystallizes only in tubes z l and 24. If the mecha-
1) Label six medium sized test tubes and fill them first with nism was a simple thermal isomerization not due to hydrochloric
the solids as shown below and then with the solvents. acid it is obvious the first four test tubes would have given fu-
maric acid. The yield is about 85% of practically pure fumaric
Test acid melting very close to the value reported in a handbook. With
Tube Solids Solvents no recrystallization involved the experimental and theoretical
rl 1g maleic acid 3 ml hydrochloric acid work are easily completed in less than a laboratory period.
2 1e maleic acid 3 ml sulfuric acid Since no fumaric acid was formed in tube ;2, the cation, pro-
3 e
1 maleic acid and 1e NHICI---- 3~-~~~
ml water posed originally by Palanyi, in mechanism B1 is not correct nor is
g
~ ~~
- 0

4 1 maleic aeid and 1g NH&l 3 ml sulfuric aeid the mechanism B5 valid. Since the tuhes with malic b i d and
5 1g maleic acid 3 ml hydrochloric acid chlorosuccinic aeid do not give fumaric acid, neither of these suc-
6 1.3 g chlorosuecinic acid 3 ml hydrochloric acid cinic acids can be intermediates in the real pathway and Wislec-
enus' suggestion is thereby eliminated, and mechanism B2, 83,
The acid solutions are made up by pouring cautiously two vol- and B4 must be discarded. The lack of fumaric acid formation
umes of the concentrated acid intoone volume of water. with ammonium chloride in tube $4 shows the nueleophilic meeh-

542 / Journal of Chemical Education

anism C is unimportant and the student is left with D, a n un-
suggested meehanism. The next suggestions in D can be ruled out.
Light in the visible region is not absorbed by white maleic acid
and ultraviolet light, if it had been involved, would have caused
the first four tubes to give positive results.
If one suggests that an unknown catalyst causes the isomeriza-
tion, then test tube 22 shows the postulated material was not in
the sulfuric acid or maleic aeid used and tube 23 shows that no
such catalyst existed in the tap water or the ammonium chloride
used. However, if one postulates sulfuric acid and ammonium
chloride generate a "catalyst," then the results of tubes x 1 and -4
clearly indicate the same results in regard to rate and that the
material generated in tube 24 is clearly hydrochloric aeid and
nothing else. Thus heavy metal catalysis can be ruled out. Ruling
out a free radical mechanism is almost as simple. All samples
were exposed to the diradical oxygen and obviously that radical
does not affect maleic acid.
At this point i t becomes obvious that both the hydronium ion
and the chloride ion are required and if the reader bas not yet de-
duced the meehanism, pause and do so.
The reasoning required is quite simple. Protonation can occur
an two sites as was pointed out in the mechanisms proposed. If it
occurred on a carbon atom, then isomerization would bave oc-
curred. If it occurred on oxygen, then it is obvious that the cation
formed in mechanism B5 can not rotate around the C2-C3 bond
or both sulfuric and hydrochloric acid would give fumaric acid.
Now one only has to decide how this cation would react reversibly
with a chloride ion to permit isomerization. The students usually
come up with the statement that the isomerization is due to "a
reversible conjugate addition." Better ones will point out that in
the compound formed by conjugate addition there is free rotation
around the C2-C3 band and that the bisulfate or sulfate ion is not
as nucleophilic as the chloride ion and sulfuric acid does not add
in a conjugate fashion.
The major drawback to assigning this mechanistic exercise is
the commercial unavailability of chlorosuccinic acid. One can
purchase bromosuceinic acid and switch to bydrobromic acid and
ammonium bromide but the cost of doing the experiment in-
creases and does not follow the historical development with hy-
drochloric acid. The cast of maleic and racemic malic acid is very
low and attractive in these days of inadequate budgets.
One can omit test tube 6 if the students are told that Horrex
found that when DC1 in heavy water was used to treat maleic an-
hydride, fumaric acid farmed. If the acid was crystallized from
ordinary water i t was found to have no deuterium in it. Recrys-
tallization of fumaric aeid in heavy water introduces only two
deuterium atoms. These data can then be interpreted to rule out
mechanisms, but we feel it is better to bave the students get all
the data themselves.
Thus we had t o seek a preparation df racemic chlorosuccinic
acid, and found the syntheses reported were not amenable to ad-
aptation by undergraduates, and had to devise the relatively
quick simple method given below.
Eight grams of DL-malic acid, 20 ml of redistilled reagent grade
thionyl chloride, and four drops of dimethylformamide are heated
on a steam bath with gentle refluxing in a good hood. The solid
acid gradually dissolves and towards the end of the reaction the
liquid in the flask is swirled to wash down particles of malic acid
adhering to the upper portion of the flask. About 40 mi" of reflux
is sufficient and the completion of the conversion to ehlorosuccin-
yl chloride is signalled by the cessation of bubbling. At this point
the flask is removed and the contents poured into a small beaker.
Two milliliters of water are added and swirled with the acid chlo-
ride which almost immediately starts to hydrolyze. Evolution of
hydrogen chloride becomes brisk but little heat is evolved. In ap-
proximately 10 min the material has formed a solid cake in the
beaker. This is broken loose, crushed, and placed in a drying oven
for a short time a t 100°C. This removes the odor of thionyl chlo-
ride and hydrogen chloride. The yield of cream colored solid is
about 9 g and is suitable for use even without drying. The melting
point is about 149-152°C and can be improved slightly by recrys-
tallization. Solvents such as acetic acid, water, ether-benzene,
acetane-benzene, ethyl acetate, benzene-hexane, etc., have been
tried. Chlorosuceinic aeid is quite soluble in water, ether, acetic
acid, ethanol, and other solvents and its solutions deposit solid
cakes only after several hours of standing in a refrigerator. We
recommend recrystallizing from concentrated hydrochloric acid.
Cooling 9 g of product dissolved in about 8 ml of solvent gives a
rapid deposition of solid, but again, well formed crystals are not
observed.
The method of preparation and this recrystallization show the
student cblarosuccinie aeid does not yield fumaric acid under the
conditions used far test tube c6. Thus we feel if the students do
make the compound they should do i t after they have deduced the
mechanism and their product should then be used for the classes
next year. Since chlorosuccinic acid m n be extracted from aque-
ous solutions with ether and easily recovered far reuse, our direc-
tions call for saving the solutions from tube 16.
Notes
1) Much of the historical data is based on the papr of Ihde (1)
and the references therein.
2) The use of dimethylformamide to catalyze the formation of
a n acid chloride is based on the work of H. H. Bosshard and ca-
workers (2). See also Fieser and Fieser (3).
3) The use of thionyl chloride to convert optically active malic
aeid into the (+) rotatory chlorosuccinic acid in 30% yield by
McKenzie and Barrow (41 was the starting point for our prepara-
tion of the lower melting racemic form of the acid.
4) C. Horrex published his work in 'IYansxtions of the Fara-
day Society (51.
5) Essentially the conjugate addition mechanism was deduced
save for the rotation around the C2-C3 bond by Nozaki and Ogg
(6). They gave a mechanism in terms of two Walden inversions of
C-3 and one of C-2. Their isomerization using potassium thiocy-
anate is a good example of nucleophilic catalyhs and a student
could be asked to deduce the intermediate in that reaction. The
paper has much of interest in regards to energies of activation,
rate constants, etc.
6) The author does not write textbooks and trusts any inter-
ested reader will feel free to adopt this experiment for his classes
or laboratory textbook. The author hopes the mechanism of the
isomerization will continue to be omitted in lecture texts and
hopefully in future laboratory manuals so that the mystery of the
mechanism will continue t o exist for all students.
Literature Ciled
(1) Ihde.A..J.CHEM.EDUC..3L330l1959).
121 Rnsrhard. H. H.. H e l u Chim Acto. 42. 165311959).
(31 Fieser. L. F., and Fiosor. M.. ''Reagents for Organic Synthesis." vol. I. D.C.Heath,
Xew York, p.289,
141 McKenzie, A,, and Barrow, F.,J. Chem Sae., 99, 1919 119111.
15) Hones. C.. l h n s ForadqvSoc.. 33,57011937).
161 Uozaki. K.,and 0gg.R.. Jr.. J. A m m Chem Soe., 6% 2583 IIS411.
Volume 52, Number 8. August 1975 / 543