1

Benzoin synthesis

Group 3H3

2

CONTENTIntroduction to benzoin synthesis

Mechanism of synthesis

Synthetic procedure

Results and precautions

Applications and modern synthetic procedure3

INTRODUCTION

4

Chemical name:

2-hydroxy-1,2-diphenylethanone

soluble in warm alcohol

insoluble in water

5

It is chiral and exists as pair of enantiomers:

(R)-benzoin

(S)- benzoin

It is an alpha hydroxy ketone attachedto two phenyl groups

6

The condensation of two moles of benzaldehyde to form a new carbon-carbon bond is known as

the Benzoin condensation.

Catalysts that promote this reaction are namely ;

Cyanide ion

Thiamine hydrochloride

7

8

It has pyrimidine portion

Thiazole portion

The active portion is thiazole portion

The thiazolium ion has the right balance of

nucleophilicity

Ability to stabilize the intermediate anion

Has leaving group properties

Thiamine catalyzes three important types of

enzymatic reactions:

Nonoxidative Decarboxylations of alpha keto

Acids

Oxidative Decarboxylations of alpha keto acids

Formation of acyloins (alpha hydroxy ketones)

9

10

UMPOLUNGNucleophilic addition

Carbonyl functional group is electrophilic and therefore attacked by a nucleophile such as cyanide ion

The nucleophilic attack leads to the reversal of the normal polarisation of the Carbonyl.

This permits the subsequent condensation with another molecule of Benzaldehyde in benzoin synthesis and loss of the cyanide ion

Such a reaction is known as an impolungarrangement

POLARISED NATURE

Mechanism of synthesis

13

14

NaCN/EtOH

Thiamine HCl

15

16

Synthetic procedure

Thiamine catalysed

Cyanide catalysed

17

• Cool in ice bath

5M NaOH solution

• Cool for several minutes and add 96% ethanol followed by NaOHsolution to yield a yellow solution

Solid thiamine HCL + 4ml of water

• Swirl continuously (solution becomes yellow and then, clear)

Add 1.3ml benzaldehyde to the yellow solution

• Suction filter crude product and wash cold water and ethanol (2:1)

Stopper flask and place in cabinet for 24hrs

• Allow to dry in oven

Recrystallize from hot ethanol

19

• Cyanide Solution

1.5g of NaCN + 15 ml of water

• Add boiling chips

Cyanide solution + 30ml of ethanol +16g of Benzaldehyde

• Remove flask from steam and cool in ice bath to form crystals

Reflux in boiling water for 30 minutes

• Wash in 50% ethanol and more water

• Dry in oven

Filter to obtain crystals

Recrystallize with 40ml of hot ethanol

Cyanide

catalysed

20

RESULTS AND PRECAUTIONS

21

%YIELD ,RECOVERY AND ERROR

The %yield measures the reaction efficiency.

Percentage yield=𝑡ℎ𝑒𝑜𝑟𝑒𝑡𝑖𝑐𝑎𝑙 𝑚𝑎𝑠𝑠

𝑒𝑥𝑝𝑒𝑟𝑖𝑚𝑒𝑛𝑡𝑎𝑙 𝑚𝑎𝑠𝑠x 100%

The theoretical yield is estimated based on the limiting reagent. This allows researchers to determine how much product can actually be formed based on the reagent present at the beginning of the reaction.

Actual yield can not be 100% due to limitations

22

Given that for benzoin,the weight after recrystallization was “x”

the weight before recrystallization was “y”

Percentage recovery= weight after recrystallization x 100%

weight before recrystallization

𝑥

𝑦x 100%

Percentage recovery = z%

23

The %recovery gives an indication of how much of the pure substance you were able to extract (recover) from the crude

i.e., it gives an indication of the efficiency of the recrystallization process. Thus a higher recovery may indicate a good recrystallization.

The converse is true for a lower recovery. However, due to high level of impurities, even a good recrystallization may still give a lower recovery.

24

Percentage yield obtained w%

The melting point of the pure crystals are determined.

The standard melting point for benzoin is (132-137)°C.

Melting point is an indication of purity.

Impurities lower melting point and increase the range.

Other methods like absorbance, NMR ,and UV may also be used to assess the purity

Major impurities in benzoin may be unreacted benzaldehyde and thiamine

25

The benzaldehyde used should be free from benzoic acid

After the NaOH was prepared, it should be kept on ice to cool, this is because NaOH can react vigorously with water liberating heat which can decompose the benzoin compound formed.

Minimum amount of solvent should be used for the recrystallization so that a supersaturated solution would be formed for benzoin to precipitate out of the solution.

The reaction mixture should not be heated above 65°C.This is because thiamine degrades at high temperature and so can be destroyed due to high temperature.

26

OTHER SYNTHETIC METHOD AND APPLICATIONS OF BENZOIN CONDENSATION

27

REDUCTION OF BENZIL

28

NaBH4 in ethanol

Furfural to furoin Anisaldehyde to Anisoin

29

KCN/EtOHKCN, EtOH, H2O

REFERENCES

P.,D. L. Lampman, G. M.Chriz, Introduction to organic lab technique; CollegePublishing, New York,1982 experiment no 40

Bruice, T. C. and Benkovic, S. Bioorganic Mechanism. Vol. 2. New York: W. A. Benjamin, 1966.Chap. 8, “Thiamine pyrophosphate and Pyridoxal-5’-Phosphate.

Bernhard, S. The Structure and Function of Enzymes. New York: W. A. Benjamin, 1968. Chap. 7,“Coenzymes and Cofactors

Ajibola et al, Essential inorganic and pharmaceutical chemistry, 2nd edition, Hope publication, Ibadan, Nigeria, page 274-276

30

Benzoin synthesis

Group 3H3

31