chemical synthesis

1. UCL SCHOOL OF PHARMACY
BRUNSWICK SQUARE
Chemical Synthesis
Workshop
Stephen Hilton
s.hilton@ucl.ac.uk

2. UCL SCHOOL OF PHARMACY
BRUNSWICK SQUARE Forward Synthesis
R
OH
Halide Formation - Alcohol to Halide
Br
R
HBr
R
Br
Alcohol Formation - Halide to Alcohol
OH
R
NaOH
Note the type of halide is important as elimination will occur
in the case of secondary or tertiary halides
R
Br
Primary Amine Formation - Halide to Amine
NH2
R
NH3
R
Br
Secondary/ Tertiary Amine Formation -
Halide to secondary or tertiary Amine
N
R
N
H
R
2
2
R
1
1
R
2
2
R
1
1
Remember
reaving
group

3. UCL SCHOOL OF PHARMACY
BRUNSWICK SQUARE Forward Synthesis
NH2
R
N
H
R
Secondary Amine formation - primary to secondary
R 1
1
X R 1
1
X = I, Cl, Br
N
H
R
N
R
Tertiary Amine formation - secondary to tertiary
R 1
1
X R 1
1
X = I, Cl, Br
R 3
3
R 3
3
NH2
R
N
H
R
Amine to amide - primary or secondary react in the same
way
R 1
1
X R 1
1
X = Cl, Br
O
O
NH2
R
N
H
R S
Amine to sulfonamide - primary or secondary amines react
in the same way
X = Cl, Br
O
O R
2
2
O
S
O
X R 2
2

4. UCL SCHOOL OF PHARMACY
BRUNSWICK SQUARE Forward Synthesis

5. steps for chemical
synthesis
① know functional groups
① keep it simple
③ Do not rush
④ Do ¥0
thing yii.io
don't know
⑤ recognise the nucleophile and electrophile

6. UCL SCHOOL OF PHARMACY
BRUNSWICK SQUARE Forward Synthesis

7. UCL SCHOOL OF PHARMACY
BRUNSWICK SQUARE
Outline a one-step retrosynthesis of the following
compounds using a disconnection approach
Retrosynthesis
/
"
.

8. UCL SCHOOL OF PHARMACY
BRUNSWICK SQUARE
Outline a one-step retrosynthesis of the following
compound using a disconnection approach
Retrosynthesis
Outline a two-step retrosynthesis of the following
compound using a disconnection approach
OH
= 0 ] equivalence

9. UCL SCHOOL OF PHARMACY
BRUNSWICK SQUARE Retrosynthesis – 2-step disconnection

10. UCL SCHOOL OF PHARMACY
BRUNSWICK SQUARE Retrosynthesis
Exam
question
I

11. UCL SCHOOL OF PHARMACY
BRUNSWICK SQUARE Retrosynthesis of Chloroquine

12. UCL SCHOOL OF PHARMACY
BRUNSWICK SQUARE Fexofenadine analogue retrosynthesis
N
OH
O
O
CH3
OH
O
HO

13. UCL SCHOOL OF PHARMACY
BRUNSWICK SQUARE Retrosynthesis
Assuming the yield from each step is 70% - calculate the overall yield starting from the
aldehyde

14. UCL SCHOOL OF PHARMACY
BRUNSWICK SQUARE Retrosynthesis
If company A wanted to make 100 analogues of the final molecule by changing
the aromatic ring shown in red, would you suggest changing the synthetic route?
If yes, how would you change it?