TatianaPachovaBSc2,chemistry

Assistant:ChandanDey
SciencesIIlab.A

Benzoincondensationcatalyzedby
thiamine(n38)
1. INTRODUCTION

1.1) Purpose

Theobjectiveofthisexperimentistosynthesizebenzoinfromthebenzaldehyde,
usingthiaminehydrochloride.

1.2) Scheme

O O

H
Thiamine
OH

benzaldehyde 2-hydroxy-1,2-diphenylethanone
(Benzoin)

1.3) Mechanism

Step1:Deprotonationofthethiamine:

NaOHattacksthiamineanddeprotonatesit.Itisacondensation,sinceamolecule
ofH2Oisreleased.Thereisaformationofacarbine,whichisveryreactive.

N N R1
N
R2
S
N NH2 H
S

OH

 Step2:nucleophileattackofthebenzaldehydebythedeprotonatedthiamine:

O
R1
R1
N
N
O R2
R2
S
S

H Intramolecular H transfer

R1
R1 N
N HO R2
R1
H2O HO R2
N S
O Ph
O R2 S
Ph
S
Ph
Ph
Ph O

HO

O
R1
N
R2 H2O

S
OH

2. PROCEDURE

2.1) Reaction

Reagents molarmass[g/mol] wt/voltaken n[mmol] equivalence
Thiaminechloride 300.81 3.55g 0.012 1
Benzaldehyde 106.12 20.0mL 0.196 16.33

Ina100mLtwinneckroundbottomflask,3.5gofthiaminehydrochloridewere
dissolved in 8mL of water. Then, 35mL of EtOH at 95% were added and the
solution was cooled down to 0C. Into the agitated solution, first were added
slowly7mLofcoldNaOH3Mandthen20mLofbenzaldehyde.Themixturewas
heatedat60Cfor90min.Thesolutionwascooleddownnaturallythenwithan
icebathuntilcrystallization.

2.2) Isolation

Theobtainedcrystalswerewashedwithwaterandthenrecrystallizedinethanol.




3. DISCUSSIONANDRESULTS

3.1) Observations

When the mixture of thiamin, water and EtOH was cooled down, a white
precipitatewasformed.
Thefinalproductisalmostpearlywhiteandspikycrystals.
Its fusion temperature is 134.7136.2 C which is in agreement with the values
givenbytheprotocol:134136C.

3.2) Yield

nexp
molarmass[g/mol] nth[mmol] yield[%]
[mmol]
212.24 196 44.1 23%


9.3679gofproductwereobtainedafterrecrystallization.Thisrepresentsa23%
yield. The protocol said that the mass should be 10g (48%) but actually 10g
represent 24% of yield (taking benzaldehyde as the limiting reagent). So the
resultissatisfying.

4. SPECTROMETRYDATA

4.1) NMR1H(CDCl3,400MHz)

H6
H5 H7
O
H1
H4 H6
H2
H5

H3 H1 O

H2 H8


bond shift[ppm] multiplicity hydrogen
CH 7.92 multiplet benzeneH1
CH 7.557.27 multiplet benzeneH2,H3,H5,H6,H7
CH 5.97 doublet H4
OH 4.57 doublet H8

 7.92(m,2H);7.557.27(m,8H);5.97(d,J=6.0Hz,1H);4.57(d,6.0Hz,1H)

Thereisaproblemwiththemultipletcorrespondingto7.557.27ppmbecause
the integral should show only 8 hydrogens, but atually shows 9. The problem
couldbethesolvent(CDCl3)thatwouldhavebeenleftintheproduct.

4.2) IR(neat,cm1)

3404;1679;1263;1204;1092;1068;977;753;696;673

We can clearly see major peaks: one at 3404 cm1, corresponding to the OH
stretch and another at 1679 cm1, corresponding to the C=O stretch of an
aldehyde.

ThereforetheIRconfirmsthatitistheexpectedproduct.

5. QUESTIONS

1) Whatisthethiamineformulaandwhatisitsactionmechanisminthereaction
ofbenzoincondensation?

Seemechanism.Thiamineisacatalyst;itisregeneratedeachtimeabenzoin
moleculeissynthesized.

Cl-

N N+

OH
S
N NH2

3-((4-amino-2-methylpyrimidin-5-yl)methyl)-5-(2-hydroxyethyl)-4-
methylthiazol-3-ium chloride

2) Showhowcyanidecanreplacethiamineinthisreaction.

 OH
O O
CN
H
H
CN

H
easy deprotonation because
N C of the dipole in C-N
O

O O OH
H H

CN CN
OH OH O


It is the same mechanism as the one with thiamine. So cyanide can also be
usedasacatalyzer.[3]

3) The pyruvate decarboxylase is an enzyme depending on the thiamine which

catalyses the decarboxylation of pyruvic acid to acetaldehyde. Write a
mechanismforthistransformationandnotedownthebibliographicreference.

Themechanismisanoxidativedecarboxylation,withareleaseofCO2.[4]

O O

R1 O
N+ OH O
R2 S S

OH R2 OH
S OH R2
N+ N+

O R1 R1

2-oxopropanoic acid

S
S OH
CO2 OH
+
R2
R2
N N

R1 R1

H+
H

O
S S
R1 + OH OH
N+ A-
HA R2 H3C H R2 R2
+
N N
S acetaldehyde R1 R1

6. REFERENCES

[1] Travaux Pratiques de Chimie Organique 3me Semestre, 21 Novembre 2011 16

Mars2012,38
[2]Silverstein,Bassler,Morrill,Spectrometricidentificationoforganiccompounds
[3]Organicchemistrylessons,Dr.A.Zumbuehl,p.52
[4]VollhartSchore,Traitdechimieorganique,5meedition,2009,p.1080

7. ANNEXES

IRspectrum,NMRspectrum