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MULTISTEP SYNTHESIS OF MANDELIC ACID

Bea Lorraine S. Acosta


Locker No. 82

Chemistry Depertmant, Xavier University Ateneo de Cagayan, Cagayan de Oro City


Dates Performed: September 4-25, 2017
Date Submitted: October 4, 2017

ABSTRACT

Mandelic acid is an alpha-hydroxy acid, which is usually found in cosmetic products


specializing in skin care. It was first synthesized by a German pharmacist Ferdinand Ludwig Winckler
in 1831 by heating an extract of bitter almonds with dilute acid. Mandelic acid was synthesized by
the nucleophilic addition of bisulfite ion to benzaldehyde to form adducts, and then nucleophilic
substitution of cyanide ion to produce mandelonitrile, a cyanohydrin. The mandelonitrile was acid
hydrolyzed with concentrated hydrochloric acid to form mandelic acid, a carboxylic acid. The
synthesis of mandelic acid was unsuccessful due to the very low yield of mandelonitrile. However,
the synthesis of sodium hydroxy(phenyl)methanesulfonate (55.8% yield) and mandelonitrile were
successful. The IR spectra of the two products were also obtained.

INTRODUCTION

Mandelic acid appears as a white crystalline solid, and is soluble in water and polar organic
compounds. It is an alpha hydroxy acid (AHA) and is usually an ingredient for cosmetics products.
Various AHAs are found in skin moisturizers, acne treatment and anti-aging products. AHA-
containing products work by exfoliating or removing the top layers of dead skin cells. They also
increase the thickness of deeper layers skin, promoting firmness. (1) Mandelic acid was first
synthesized in 1831 by German pharmacist Ferdinand Ludwig Winckler (1801-1868). It was
synthesized by heating amygdalin, and extract of bitter almonds, with dilute hydrochloric acid. It is
usually prepared by the acid-hydrolysis of mandelonitrile. (2) In this experiment mandelic acid was
synthesized from benzaldehyde in a series of reactions.
Benzaldehyde was first reacted with bisulfite ion in a nucleophilic addition reaction.
Nucleophilic addition reactions are an important class of reactions that allow the interconversion of
carbonyl group (C=O) into a range of important functional groups. In this type of reaction, three
events occur: (1) a new s bond is formed between the nucleophile, an electron-rich species, and the
electrophilic carbon of the carbonyl group; (2) the p bond to the oxygen is broken resulting to the
formation of an intermediate alkoxide; and (3) when the alkoxide intermediate is protonated, an
alcohol derivative is formed. (3) The product formed in the first step was then reacted with cyanide
ion.
The reaction with cyanide ion is called nucleophilic substitution reaction. Nucleophilic
substitution occurs when a nucleophile reacts at an electrophilic saturated carbon atom attached to
an electronegative group, the leaving group, which can be displaced. (4) The product in this reaction
was then acid hydrolyzed to form the final product, mandelic acid.
Acid hydrolysis is a process in which a protic acid is used to catalyze the cleavage of a
chemical bond via a nucleophilic substitution reaction, with the addition of the elements of water.
(5) In the synthesis of mandelic acid, the second product, which contains a cyano (CN) group, is
hydrolyzed to acid.
The objectives in this experiment were to synthesize mandelic acid from benzaldehyde, and
to characterize and/or identify the synthesized mandelic acid using FT-IR.

MATERIALS AND METHODS

Fifteen grams of benzaldehyde was mixed with 50mL of a saturated solution of sodium
bisulfite. The mixture was stirred via magnetic stir bar and disturbed to yield more crystals. The
crystals were filtered and washed with a little water and ethanol. The crystals were grounded into a
paste with water and added with 15g of 2KCNNaCN in 40mL water. Organic and aqueous layers
were formed. Ether was added to extract mandelonitrile. The mixture was heated via water bath to
remove the ether.
While removing ether off of mandelonitrile, concentrated HCl was added and continued
heating. The mixture was removed from the hot water and was left undisturbed to cool down to
room temperature to procure crystals. The mixture was filtered and the solid was dried overnight.
The melting point of the solid was determined via the melting point analyzer.

RESULTS AND DISCUSSION

In this experiment, multi-step synthesis was employed. The first step was a nucleophilic
addition reaction of benzaldehyde and sodium bisulfite. After mixing benzaldehyde with sodium
bisulfite, very fine white crystals were formed and these crystals were sodium
hydroxy(phenyl)methanesulfonate (Figure 1a). The crystals were actually adducts, a product of
direct addition of two or more distinct molecules and contains all atoms of all components (6). In the
reaction mechanism (Figure 2), the nucleophilic bisulfite ion adds to the aldehyde and yields a
tetrahedral alkoxide intermediate. The resonance form of this alkoxide gives an alcohol group. This
product yielded 5.123 g (55.8%).

a. b.

Figure 1. Sodium hydroxyl(phenyl)methanesulfonate (a) crystals and (b) structure.

When potassium cyanide was mixed with the sulfonate, both organic and aqueous layers
were formed. The sulfonate was quickly dissolved and the oily mandelonitrile (Figure 2a) formed.
The mandelonitrile was found in the organic layer of the mixture. The mandelonitrile was extracted
with ether and then heated to remove the ether. However, the mandelonitrile had very low yield,
thus, synthesis of mandelic acid mas not continued.

OH

N
a. b.

Figure 2. (a) Mandelonitrile and (b) its structure.


O
O
-
S - O O OH O
HO O
H -
S OH S O
H O H O

-
C N

OH OH
O + H O
HCl H
-
N S O
OH
SO32- OH O

Figure 3. Mechanism for the synthesis of mandelic acid.

If the synthesis was resumed, mandelonitrile would be mixed with concentrated HCl in
excess amount for acid hydrolysis. Hydrolysis would be performed simultaneously with removing the
ether. After heating the mixture two layers would be formed, the ether layer (top) and the aqueous
layer (bottom). After cooling down the mixture, the crystals of mandelic acid would appear the
bottom layer.
For the acid hydrolysis of mandelonitrile, nitrogen was first protonated. The water O acts as
a nucleophile attacking the electrophilic C in the cyano group, with the electrons moving towards the
positive center to form an amine. Another molecule of water O attacks the carbon attached to the
amine. The amine is protonated by deprotonating the oxygen from the water molecule. The amine
now becomes a good leaving group; with the use of the electrons of the adjacent oxygen, the
neutral ammonia molecule was pushed out. The oxonium ion is deprotonated to reveal the
carbonyl in the carboxylic acid product. Acid hydrolysis was the preferred condition in order to
produce a free carboxylic acid instead of a salt from base hydrolysis.
OH OH OH
O H
+ NH
H H
N +
N +
H O
H H

OH
OH OH
+ NH2 NH2
NH3
+ H
OH O OH
HO HO
H
H O
H
OH
OH
H OH
OH +
N H + NH4
+ O
O
H H

Figure 4. Detailed mechanism for acid hydrolysis of mandelonitrile to mandelic acid.

Despite the mandelic acid not produced, the IR spectra of sodium


hydroxy(phenyl)methanesulfonate and mandelonitrile were obtained using the PerkinElmer
Spectrum 100 FT-IR. In Figure 4 and 5 is the IR spectra divided into two parts, the functional group
region and the fingerprint region. The top spectra in red correspond to
hydroxy(phenyl)methanesulfonate and the bottom one in green correspond to mandelonitrile.

Figure 4. Functional group region of IR spectra of hydroxy(phenyl)methanesulfonate and


mandelonitrile
Figure 5. FIngerprint region of IR spectra of hydroxy(phenyl)methanesulfonate and mandelonitrile

CONCLUSION
Mandelic acid was synthesized from benzaldehyde. Benzaldehyde underwent
nucleophilic addition and substitution to produce mandelonitrile, which was then acid-hydrolyzed to
produce mandelic acid. The synthesis of mandelic acid was unsuccessful due to the very low yield of
mandelonitrile. However, the synthesis of sodium hydroxy(phenyl)methanesulfonate (55.8% yield)
and mandelonitrile were successful. The IR spectra of the two products were also obtained.

REFERENCES

(1) Mandelic acid. https://en.wikipedia.org/wiki/Mandelic_acid (accessed Sep 18, 2017).


(2) Alpha Hydroxy Acids.
http://www.fda.gov/Cosmetics/ProductsIngredients/Ingredients/ucm107940.htm (accessed Sep 18,
2017).
(3) Ch17: Nucleophilic Addition. http://www.chem.ucalgary.ca/courses/351/Carey5th/Ch17/ch17-3-
0.html (accessed Sep 27, 2017).
(4) Ch 8: Nucleophilic Substitution. http://www.chem.ucalgary.ca/courses/350/Carey5th/Ch08/ch8-
0.html (accessed Sep 27, 2017).
(5) Acid hydrolysis. https://en.wikipedia.org/wiki/Acid_hydrolysis (accessed Sep 27, 2017)
(6) Adduct https://en.wikipedia.org/wiki/Adduct (accessed Sep 27, 2017).