Module Two

How do molecules add across double bonds?

module purpose
This module is designed to enable learners to appreciate and understand the
addition reaction mechanism. Learners will develop hands-on experience
how this is achieve in the laboratory and the parameters that goes with it.

outcomes
on successful completion of the module the learner will be able to:
1. develop an understanding and practical skills in setting up organic
reactions over an extended period of reaction time using the reflux
setup
2. develop practical skills in assessing stages in the purification of organic
compounds including crystallization and melting point determination

How do we transform double bonds to a new functional group?

Transforming multiple bonds like an alkene, into a different functional group are generally attained via
addition reaction mechanism. In this mechanism, multiple bonds are converted from unsaturated to a
more saturated sites. The electrophilic addition across double bonds, is a two-step mechanism whereby
the alkene pi () bond is replaced with two sigma () bonds. The first step involves an electron-poor
electrophile (E+), attacking an electron-rich -bond of the alkene to form the first carbon-electrophile
sigma bond on a positively charged intermediate (a carbocation). In this scheme, the double bond acts
as a nucleophile, attacking the electrophile.

step 1

In next step, the positively charged carbocation picks up an electron-rich species nucleophile (Nu-)
forming a second carbon-nucleophile sigma bond.

step 2

The importance of addition reaction cannot be understated. For instance, addition reaction is involved
in the reversible hydration of fumarate to malate catalyzed by the enzyme fumarase. The reaction is
critical for cellular energetics as a part of the tricarboxylic acid cycle, which produces reducing
equivalents to drive oxidative ATP synthesis.

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Yeon Hee K
ONG,
a
Youn Ock J
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Chang-Won C
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Dongwook S
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Soojin P
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Jeonghae RHO,
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and Sang Yoon CHOI
Yeon Hee K
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ONG,
a
Youn Ock J
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Chang-Won C
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Dongwook S
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Soojin P
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Jeonghae RHO,
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Module 2 Chemical Safety Data Summary
Using information from MSDS sheets, complete the table below.

trans-cinnamic 2,3-dibromo-3- CH2Cl2 Ethanol

acid phenylpropanoic
acid
solubility in water

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 Health Hazards
Identification
Inhalation
Skin
Eyes
Ingestion
Carcinogen
Toxicity
Chronic effects on humans
Suspected carcinogen (Y/N)
source where you
got these
information:
(web address)

maleic acid fumaric acid HCl bromine solution

solubility in water Soluble Slightly Soluble Soluble Soluble

Health Hazards
Identification
Inhalation Causes May cause  May be fatal  Irritation
respiratory
respiratory if inhaled. May may lead to
tract
irritation. tract irritation. cause severe chemical
May cause irritation of pneumonitis
effects similar the and
to those respiratory pulmonary
described for tract with sore edema.
ingestion. The throat, Inhalation
toxicological coughing, may be fatal
properties of shortness of as a result of
this substance breath and spasm,
have not been delayed lung inflammation,
fully edema. edema of the
investigated. Causes larynx and
chemical bronchi,
burns to the chemical
respiratory pneumonitis
tract. Causes and
corrosive pulmonary
action on the edema.
mucous Causes
membranes. respiratory
tract
irritation with
possible

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 burns.
Skin Contact with May cause skin Contact with
skin causes
irritation. May liquid is
irritation and
possible be absorbed corrosive and
burns, through the causes severe
especially if skin. burns and
the skin is ulceration.
wet or moist.
May cause The severity
dermatitis. of injury
May be depends on
harmful if the
absorbed
through the concentration
skin. of the solution
and the
duration of
exposure.
Eyes May result in  Contact may May cause
corneal
cause transient irreversible
injury.
Contact with eye irritation. eye injury.
eyes may Exposure to Vapor or mist
cause severe solid may may cause
irritation, cause pain and irritation and
and possible
eye burns. redness. severe burns.
Contact with
liquid is
corrosive to
the eyes and
causes severe
burns.
Ingestion May cause May cause Causes severe
kidney
irritation of the digestive tract
damage. May
be harmful if digestive tract. burns with
swallowed. The abdominal
toxicological pain,
properties of vomiting, and
this substance possible
have not been death. May
fully cause
investigated. corrosion and
Exposure may permanent
cause tissue
gastrointestinal destruction of
disturbances the esophagus
and kidney and digestive

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 tract.
Carcinogen Not available Not Available
Toxicity
Chronic effects on Chronic Not Available Prolonged or
humans exposure
repeated skin
may cause
kidney contact may
damage. cause
dermatitis.
Repeated
exposure may
cause erosion
of teeth.
Repeated
exposure to
low
concentrations
of HCl vapor
or mist may
cause
bleeding of
nose and
gums. Chronic
bronchitis and
gastritis have
also been
reported.
Suspected N/A
carcinogen (Y/N)
source where
you got these
information:
(web address)

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 Part A Module Two
Stereochemistry of bromine addition to trans-cinnamic acid

Cinnamic acids are naturally occurring aromatic carboxylic acids formed in the biochemical route that
yields lignin, the polymeric material that provides mechanical support to the plant cell wall [Xu]. It is
similarly a precursor for the synthesis of a huge number of plant substances, including lignin, tannins,
flavonoids, pigments, many of the flavor components of spices, and various alkaloids, such as morphine
and colchicine. Cinnamic acid was found to have low toxicity and a broad spectrum of biological
activities and its derivatives in the ester, amide, aldehyde and alcoholic forms, showed significant
growth inhibition against one or several bacterial and fungal species (Guzman).

This module is focused on assessing the reactivity of the double bond in

cinnamic acid via addition reaction bromine. Cinnamic acid (C6H5CHCHCOOH) is
an odorless white crystalline acid, slightly soluble in water, and melts at 1330C.

Procedure

1. Weigh 0.6g of trans-cinnamic acid (avoid skin contact!) directly on to a

round bottom flask. Immerse in an ice water bath, then add 10 mL of dry
dichloromethane (CH2Cl2). Add 1 mL of 10% bromine in CH2Cl2. Mix to
dissolve the solid.

2. Add boiling chips and fit a condenser to complete a reflux setup. Reflux in
a 500C water bath for 20 minutes. Transfer the reaction mixture in a
small beaker. Cool undisturbed on the table top for a few minutes.
Observe the formation of a precipitate.

Figure 2.1 Reflux setup

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Important notes:
a) If the orange color still persists, add Na2S2O4 solution dropwise
while swirling until the color of the reagent disappears.
b) If no solid precipitate out, cool in ice bath. Scratch the sides of the
beaker using a glass rod to induce crystallization, if necessary.
3. Vacuum filter the precipitate and recrystallize with ethanol/water. Press
dry the product between pieces of filter paper, take the weight and
calculate the % yield.
4. Determine the melting point to detect whether you isolated the
compounds 2 and 3 (mp 2040C) or compounds 1 and 4 (mp 950C).

Br O
Br O Br O Br O

OH OH OH OH

Br Br Br Br

1 2 3 4

references
For the synthesis section, see:
Experiment 18: Bromination of trans-Cinnamic Acid Reading, www.occc.edu/kmbailey/CHEM2122/Expt_18.doc, ,
downloaded 18 July 2018.
Fü lö p, Ferenc, Kiss, Lorá nd, and Szatmá ri, Istvá n (2015). Practical’s of Organic Chemistry, University of Szeged , Szeged.
Lehman, J. W. (1999) Operational Organic Chemistry, 3rd Ed., pp. 175 – 181, Prentice Hall, Upper Saddle River, NJ.
Prabhu, Aarti (2014). Stereochemistry of Bromine Addition to an Alkene, https://www.odinity.com/stereochemistry-of-
bromine-addition, downloaded 18 July 2018.
Supplementary information for Comprehensive Organic Chemistry Experiments for the Laboratory Classroom © The
Royal Society of Chemistry, (2017), Bromination of Cinnamic acid

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 Part B Module Two
Isomerism in maleic acid (cis-butenedioic acid)

Geometric isomerism, of which cis-trans isomers belong, are present in compounds that have different
configurations of groups rigidly placed in different spatial point relative to a carbon-carbon bond, e.g.,
double bond. Referencing this C-C double bond connotes restriction on the rotation for the groups
attached on it, which defines a central feature of this type of isomerism. In geometric isomerism, at least
two different groups attached to the carbon on which there is restricted rotation should be present.

In the example shown above, notice the location of the methyl group (-CH 3) when they are on the same
side (cis) and when they are on opposite sides (trans). For more complex substitution patterns, i.e., four
differing groups attached on the double bond, the E-Z notation is the preferred IUPAC label. In this
module, we will examine the interconversion of these isomers on the butenedioic system.

procedure

Part A. Converting Maleic acid to Fumaric acid

1. Mix 2g of maleic acid and 5mL of distilled water in a clean dry
round bottom flask. Swirl and warm in a hot water bath to
slightly to dissolve the acid.
2. Add boiling chips, 5mL of concentrated HCl and reflux for 15
minutes at 60-70oC.
3. Cool the solution to room temperature then onto an ice bath.
Suction filter the precipitate. Rinse the flask with 3mL ice-cold
distilled water to get most of the crystals. Keep the vacuum
suction for 5 minutes to dry out the crystals. Wash the crystal in
the Buchner funnel with additional 3mL ice-cold distilled water.
4. Recrystallize in water and transfer the crystals to a small beaker
and dry in a 1200C oven for 10 minutes. Weigh the dried crystals
Figure 2.1 Reflux setup
of fumaric acid. Calculate the % yield.

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Part B. Differentiating Maleic acid from Fumaric acid
Part B.1 Solubility:
Mix 0.1g of each isomer with 1mL of water in separate test tubes.
Shake (use Vortex mixer) to dissolve and note which isomer is
more soluble.
Part B.2 Melting point:
Determine the melting points of the two isomers either by using a
melting point apparatus or the manual capillary method.
Test solutions for reactions parts B.3 and B.4:
Into two labelled test tubes (M=maleic; F=fumaric), suspend about
0.1g each of the acid in 2mL of water. Use Vortex mixer to mix well.
Part B.3 Bromine Addition: Transfer half of solution M to a new
clean dry test tube and add 2 drops of bromine water to the
suspension. Shake and observe the colour for each tube. Do the
same for solution F (note: do the bromine addition side-by-side so
you can compare well the change simultaneously).
Part B.4 Acidity: from the remaining sample test solutions,
measure the pH of these solutions using a pH meter.

references
Chatterjee, S., Pedireddi, V. and Rao, C.N. (1998). Unexpected isomerization of maleic acid to fumaric acid on co-
crystallization with 4,4′-bipyridine, Tetrahedron Letters, 39(18), 2843-2846
Das, R. K., Brar, S. K. and Verma, M. (2016). Chapter 8: Fumaric Acid: Production and Application Aspects, Platform
Chemical Biorefinery, 133-157
Guzman, J.D., (2014). Molecules, 19, 19292-19349; doi:10.3390/molecules191219292
He, J., Yang, W., Yao, F., Zhao, H., and Yuan, Z. (2011). Determination of fumaric and maleic acids with stacking analytes
by transient moving chemical reaction boundary method in capillary electrophoresis, Journal of Chromatography A,
1218(24), 3816-3821
Li, Q., Tao, W., Li, A., and Zhou, Q., and Shuang, C. (2014). Poly (4-vinylpyridine) catalyzed isomerization of maleic acid to
fumaric acid, Applied Catalysis A: General, 484, 148-153
Lian, H.Z., Mao, L., Ye, X.L. and Miao, J. (1999). Simultaneous determination of oxalic, fumaric, maleic and succinic acids
in tartaric and malic acids for pharmaceutical use by ion-suppression reversed-phase high performance liquid
chromatography, Journal of Pharmaceutical and Biomedical Analysis, 19(3–4), 621-625
Smith, J. (2017). Organic chemistry (5th ed.). New York: McGraw-Hill.
Wojná rovits, Lá szló , Taká cs, Erzsébet and Emmi, Salvatore S. (2008). Nucleophilic and electrophilic radical attack on
maleic and fumaric acids in aqueous solution, Chemical Physics Letters, 460(4–6), 451-456
Xu, Qing, Li, Shuang, Huang, He and Wen, Jianping (2012). Key technologies for the industrial production of fumaric
acid by fermentation, Biotechnology Advances, 30(6), 1685-1696
Xu, Z.; Zhang, D., Hu, J., Zhou, X., Ye, X., Reichel, K., Stewart, N., Syrenne, R., Yang, X., and Gao, P. (2009). Comparative
genome analysis of lignin biosynthesis gene families across the plant kingdom. BMC Bioinform., 10, S3.

For the synthesis section, see: (a) Carmel Holy Word Secondary School (AL Chemistry). Form 6 Chemistry Practical,
intranet.chw.edu.hk/~sci/chem/F6_Chem/exp18.doc, downloaded June 21, 2018.

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Module 2. Group Discussion Questions (GDQ 2)

_______________________________________________
trans-Cinnamic acid
1. Draw the detailed mechanism on how bromine adds to a double bond using butene as the alkene.
Refer to your lecture textbook reference.

2. What are the differences in the structure of compounds 1 to 4. What is their structural relationship (different
compounds, isomers, etc) ?

3. Explain if the following methods or instruments can be used to differentiate compound 3 from compound 4 ?

a) Polarimeter: Using polarimeter, it is difficult to distinguish compound 3 from compound 4 because on

paper we can determine whether it is (R) or (S) but it is difficult to predict if the structure we call (R) or
(S) will rotate polarized light clockwise or counterclockwise.

b) Refractometer: A refractometer uses an angle of refraction, and it is related to an index value called index
refraction. So, the angle of refraction depends on the index of refraction and temperature. Both compound 3 and
compound 4 have the same index of refraction but have different melting points. Compound 3 has a melting point
of 204 °C while compound 4 has a melting point of 95 °C.

c) Density measurement: Since diastereomers have different physical properties including the density of the
compounds, density measurement can be used to differentiate compound 3 from compound 4.

4. What are the differences in the melting points structure of compounds 1 to 4. Which isomers have identical
melting point and which differ? Explain.
Compounds 1 and 4 are threo isomers that have a melting point range of 93.5 °C - 95 °C, while compounds 2 and 3
are erythro isomers that have a melting point range of 202 °C - 204 °C. Erythro isomers (Compounds 2 and 3)
have identical melting points because they have two identical substituents on different sides, while threo isomers
(Compounds 1 and 4) have different melting points due to the different 3-dimensional arrangement.
Maleic acid to Fumaric acid

1. Draw the detailed mechanism on the conversion of maleic acid to fumaric acid.
Refer to your lecture textbook reference.

2. Assuming maleic acid to fumaric acid is an equilibrium process, which isomer would you think is more stable?
Explain based on their structure.

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3. Strictly based on structural reasoning, explain why maleic and fumaric acids behave differently on
(a) solubility and (b) melting point.

4. Would it be possible to use IR spectroscopy to differentiate maleic from fumaric acid? Explain.

practice problems module two (PLS 2)

1. Write a structural formula for each of the following.

(a) trans-3-methyl-3-hexene (b) 2,6-hexadiene (c) 3,3-dimethylhexene (d) (Z)-2-hexene

2. Which of the following will decolorize the red-orange color of Br2/CH2Cl2 reagent?
(a) ethenyl benzene (styrene) (b) methyl benzene (toluene) (c) hydroxyl benzene (phenol) (d) cyclohexanol

3. Draw the structure of the product(s) formed when Br/CH2Cl2 reacts with limonene (essential oil found in citrus
rind).

4. Predict the structure of compound A with the formula C6H6O and rationalize your answer. Compound A contains
double bond but it did not decolorize bromine reagent. It has the following IR signals: (a) strong broad signal at
3300 cm-1, (b) medium and sharp signal at 1601 cm-1 and 1500 cm-1, (c) medium and sharp signal at 3100 cm-1.

5. Which IR signals will (a) appear and (b) disappear in the synthesis shown below. Explain your answer.

references
Grovenstein, Erling Jr. and Lee, Donald E. (1953) The stereochemistry and mechanism of the transformation of cinnamic
acid dibromide to β-bromostyrene, J. Am. Chem. Soc., 75 (11), 2639–2644.
Guzman, J.D. (2014), Natural Cinnamic Acids, Synthetic Derivatives and Hybrids with Antimicrobial Activity, Molecules,
19, 19292-19349; doi:10.3390/molecules191219292
For the synthesis section see: (a) Purdue Polytechnic Institute, Experiment 8_Br2-Cinnamic Acid.Pdf - Chem 241,
http://www.rsc.org/suppdata/ books / 184973/ 9781849739634/bk9781849739634-chapter%204.1.1.pdf,
downloaded July 3, 2018; (b) Solano, D. M. Addition of Bromine to trans-Cinnamic Acid , Department of Chemistry &

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 Biochemistry California State University, Bakersfield.
https://www.csub.edu/chemistry/organic/manual/Lab9_BromineAddition.pdf, downloaded 3 July 2018.
The Royal Society of Chemistry (2017). Supplementary information for Comprehensive Organic Chemistry Experiments
for the Laboratory Classroom.

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