Carboxylic acids
RCOOH
R C O 2H
O
R C OH
1 C: formic acid, methanoic acid
2 C’s: acetic acid, ethanoic acid
3 C’s: propionic acid, propanoic acid
4 C’s: butyric acid, butanoic acid
O
HO
N
n ia c in (v it a m in B 3 )
C H 2O H
HO
CH
HO
HO
OH
O
O
o x a li c a c id
O
O
OH
V it a m in C
(A s c o r b ic a c id )
Aspirin : Should you take a daily dose?
H
HO
C O 2H
C 5H 11
HO
H
OH
P G F 2  (Prostaglandins
F2)
Prostaglandins are involved in the regulation of a variety of physiological
phenomena, including inflammation, blood clotting, and the induction of
labor. Aspirin act by blocking the biosynthesis of prostaglandins in the
cell.
C O 2H
C O 2H
COX
H
cyclooxygenase
CH3
CH3
O
O
O
A r a c h id o n ic a c id
O
O
O

H
H
O
C O 2H
C 5H 11
O
O
C O 2H
1. P e r o x i d a s e
C 5H 11
O
2. R a d i c a l C l e a v a g e
H
H
OH
OOH

PG G
H
HO
C O 2H
C 5H 11
HO
H
OH
P G F 2
2
RCOOH
RCOO
+ H 2O
Carboxylic Acid
+ H 3O
Carboxylate ion
R C O O H + N aH C O
R C O O N a + H 2O + C O
3
P hen o l + N aH C O
OH
3
N o r e a c t io n
O Na
+ N aO H
+ H 2O
(S o d i u m P h e n o x id e )
2
Electron-withdrawing groups stabilize a conjugate base,
making a carboxylic acid more acidic.
O
C l H 2C
O
OH
C l 2H C
OH
O
p K a = 0 .9
B a se
O
O
H
H
OH
B a se
B a se
C
C l 3C
p K a = 1 .3
p K a = 2 .8
Cl
O
Cl
Cl
O
Cl
C
H
O
Cl
C
Cl
O
Electron-donating groups destabilize a conjugate base,
making a carboxylic acid less acidic.
O
H 3C
O
OH
(H 3 C ) 3 C
OH
p K a = 5 .1
p K a = 4 .8
B a se
B a se
O
O
CH3
H 3C
O
H 3C
C
CH3
O
Alpha Hydroxy Acids in Cosmetics
O
O
OH
OH
H 3C H C
OH
HO
OH
OH
la c t ic a c id
O
t a r t a r ic a c id
O
O
OH
H 2C
OH
OH
g ly c o lic a c id
HO
OH
m a lic a c id
O
Carboxylic acids’ Derivatives
O
O
R
R
OR
NH2
a m id e
e ste r
O
O
R
Cl
a c id c h lo r id e
R
O
O
a n h y d r id e
R
Esters
O
C H 3C H 2C H 2
OH
+
C H 3C H 2O H
e t h y l a lc o h o l
b u t a n o ic a c i d
e s te r ific a tio n
H+
h y d r o ly s i s
O
C H 3C H 2C H 2
O C H 2C H 3
e th y l b u ta n o a te
(s t r a w b e r r y f la v o r in g )
+
H 2O
O
O
O
O
O
e th y l b u ty r a te
iso a m y l a c e ta te
(o d o r o f p in e a p p le )
(o d o r o f b a n a n a )
O
b e n z y l a c e ta te
(o d o r o f p e a c h )
NH2
O
O
O
O
e t h y l p h e n y la c e t a t e
(o d o r o f h o n e y )
m e t h y l a n t h r a n ila t e
(o d o r o f g r a p e )
O
OCH3
O
+ H 2O
C H 3O H
H+
OH
OH
m e t h y l s a lic y la t e
(o il o f w in te r g r e e n )
OH
s a lic y lic a c id
O
O
O
H 3C
O
CH3
a c e t ic a n h y d r id e
OH
O
O
CH3
a c e t y ls a lic y lic a c id
+ C H 3C O O H
Preparing Biodiesel
O
O
H2C
HC
O
O
C
O
C
R1
R2
O
C
OH
H3C
O
C
O
R1
HC
OH
H3C
O
C
R2
O
C H 3O H
O
H2C
N aO H
H2C
R3
T r ig ly c e r id e
H2C
OH
G ly c e r o l
T r a n s e s te r if ic a tio n
H3C
O
C
R3
M o n o a lk y l E s t e r s
Preparing Soaps
O
O
H2C
HC
O
O
C
O
C
R1
R2
O
C
OH
+
Na-O
C
O
R1
HC
OH
+
C
R2
Na-O
O
H 2O
O
H2C
N aO H
H2C
H2C
R3
T r ig ly c e r id e
OH
G ly c e r o l
S p o n if ic a tio n
+
Na-O
C
R3
S o d iu m c a r b o x y la t e s
Amides
O
O
NH2
CH3
NH2
a c e t a m id e
O
b e n z a m id e
O
CH3
H
N H C H 2C H 3
N -e t h y lf o r m a m id e
N
CH3
N ,N -d im e t h y lb e n z a m id e
O
C H2
O
H
N
C
S
N
O
CO2H
H
S
N
OH
N
P e n ic illin V
H
PhH2COCHN
O
S
O
CO2H
P e n ic illin G
H
OCH2 C
H
N
CH3
S
PhH2COCHN
CH3
H
COOH
CW T
(cell wall transamidase)
H
HN
O
O
CW T
CH3
CH3
H
COOH
H
H
S
PhH2COCHN
CH3
O H / H 2O
Z n 2+, C d 2+,
C u 2+, P b 2+
H 2O
S
PhH2COCHN
O
O
H
N
M e ta l l i c s a l ts o f b e n z y l p e n i c i l l o i c a c i d
H
COO
H
PhH2C
CH3
CH3
N
CH3
C OO
O
B ez y lpenicilloic acid
S
CH3
HN
O
HOOC
H
H
CH3
HN
H +/ H 2O
P enicillin G
CH3
-
C OOH
H
S
PhH2COCHN
CH3
N
O
H
H
H
COOH
B enz y lpenillic acid
+ B ez y lpenicilloic acid
H
R
H
S
ROCHN
N
O
X
CH3
A m picillin; X = H
A m ox icillin; X = O H
CH3
H
COOH
p en ic il l in p h arm ac o p h o re
H2N
D -c o n f i g u r a ti o n
Amines
NH3 + H2O
NH4+ + OHRNH2, ArNH2 Primary, 1o Amines
R2NH, Ar2NH Secondary, 2oAmines
R3N, Ar3N Tertiary, 3o Amines
butylamine
N-methylpropylamine
N,N-dimethylethylamine
สารประกอบเอมีนที่มฤี ทธิเ์ ป็ นยา
NH2
H 2C
C
CH3
H
A m p h e t a m in e
(A n tid e p r e s s a n t)
NHCH3
CH3
B enzed rex
(N a s a l d e c o n g e s ta n t)
N
N
N
N
U r o t r o p in e
(A n tib a c te r ia l a g e n t)
CH3
O C H 2C H 2N
C H 2C H 2N H 2
CH3
C
H
N
N
H
h is t a m in e
d ip h e n h y d r a m in e (B e n a d r y l)
HO
HO
O
H 2S O
4
O
N CH3
HO
HO
M o r p h in e
(w a t e r in s o lu b le )
H
N C H3
M o r p h in e S u lf a t e
(w a t e r s o lu b le )
H SO
4
H
H 3C
NH
H 3C
H 3C
H N O 2, H C l
N
N
O Cl
-H C l
H 3C
N
N
O
H 3C
CH3
N -N itr o s o d im e t h y la m in e
N aN O
2
+ HCl
s o d i u m n i tr i te
NaNO2 inhibits the growth of Clostridium botulinum.
H 3C
Nu
NuB io lo g ic a l
N u c le o p h ile
CH3
c a r b o c a ti o n
+ N2
acid or heat
H 3C
N
N
d iaz oniu m ion
CH3
c a r b o c a ti o n
RNH
+ HNO
2
2
RN
+ HCl
+
N C l
2 H 2O
RO H + N2 + HCl
+ ROR + RCl
HO
N
O
H
+
H
O
N
O
N
O
H
+ H 2O
N
O
Quote of The Day
Think like a wise man
but express yourself like
an ordinary one.
จงคิดเหมือนปราชญ ์
แต่แสดงออกเหมือน
สามัญชน
Stereochemistry
is the study of the three-dimensional structure of molecules.
Stereoisomers
Isomers : Different compounds that have the same
molecular formula.
Stereoisomers : Isomers that have the same bonding sequence
but differ in the orientation of their atoms in space.
 Late 50’s, thalidomide was prescribed as an analgesic for
morning sickness and used extensively in Europe and Canada
despite strong warning that it not be used by pregnant women.
 By 1961, it was recognized as the cause for numerous birth
defects (~7-10,000 in 28 countries).
Mirror
H
(-)-lim o n e n e
(le m o n o il)
H
(+ )-lim o n e n e
(o r a n g e s )
H
180° rotation
H
CH3
COOH
H 3C
H
HOOC
H 3C O
OCH3
(S )-n a p r o x e n
(R )-n a p r o x e n
a n t i-in f la m m a t o r y a g e n t
liv e r t o x in
R
NH2
NH2
C
C
COOH
HOOC
H
R
H
L -a m in o a c id
D -a m in o a c id
คู่ enantiomers
 Each enantiomer of a stereoisomeric pair is optically
active and has an equal but opposite-in-sign specific
rotation.
 One enantiomer will rotate polarized light in a clockwise
direction, termed dextrorotatory (+), and its mirror-image
partner in a counter-clockwise manner, termed levorotatory
(–).
 It is common practice to convert the observed rotation,
α, to a specific rotation, [α].
 Although two enantiomers have identical boiling points and
melting points, they rotate the plane of polarized light in opposite
directions. A polarimeter is used to measure the optical rotations of
enantiomers.
(http://www.cem.msu.edu/~reusch/VirtualText/sterism2.htm#isom12)
Specific rotation, [] = amount (degrees) that a substance
rotates plane polarized light expressed in a standard form.
Carvone from caraway: [α]D = +62.5º
Carvone from spearmint: [α]D = –62.5º
Lactic acid from muscle tissue: [α]D = +2.5º
Lactic acid from sour milk: [α]D = –2.5º
How can one identify enantiomerism?
All objects may be classified with respect to chirality (from the
Greek cheir = hand):
Chiral = Objects that are different from theirs mirror image;
i.e. golf clubs, scissors; enantiomers are chiral.
Achiral = Objects that are identical with theirs mirror image;
i.e. a pencil, a T-shirt.
Chiral molecule : (R)-lactic acid
Achiral molecule : water
Water (H2O)
Achiral molecules have either one or both of the following:
 Plane of symmetry
Center of symmetry
Chiral molecules have chiral center (or stereo or stereogenic center):
an atom attached to 4 different atoms or groups.
(chiral carbon)
H
F
Br
CH3
Cl
H3CH2C
H3CO
H
Designating the Configuration of Stereogenic Centers
The CIP system of nomenclature.
(R. S. Cahn, C. K. Ingold and V. Prelog)
 Each stereogenic center in a molecule is assigned a prefix (R or S),
according to whether its configuration is right- or left-handed.
 The symbol R comes from the Latin rectus for right, and S from
the Latin sinister for left.
The assignment of the prefixes depends on the
application of two rules:
The Sequence Rule
The Viewing Rule
Right-Handed
Left-Handed
The Sequence Rule
 Assign sequence priorities to the four substituents by looking at the
atoms attached directly to the chiral stereogenic carbon atom.
 The higher the atomic number of the immediate substituent atom,
the higher the priority; H– < C– < N– < O– < Cl–.
 If two substituents have the same immediate substituent atom,
evaluate atoms progressively further away from the chiral center until a
difference is found.
i.e. CH3– < C2H5– < ClCH2– < BrCH2– < CH3O–.
 If double or triple bonded groups are encountered as
substituents, they are treated as an equivalent set of singlebonded atoms. i.e. C2H5– < CH2=CH– < HC≡C–
H
H
C C
R
IS T R E A T E D A S
C C R
IS T R E A T E D A S
O
C H
IS T R E A T E D A S
H H
C C R
C C
C
C
C
O
C
O
C
C R
C
H
The Viewing Rule
 The chiral center must be viewed from the side opposite the
lowest priority group.
Numbering the substituent groups from 1 to 4, with 1 being the
highest and 4 the lowest in priority sequence, and put a viewers eye
on the side opposite substituent #4.
 If the progression from 1 to 3 is clockwise, the configuration at
the stereocenter is R. Conversely the counterclockwised progression
is assigned as S.
1
HO H
H3C
CO2H
Assign Priorities
HO H
H3C
3
4
CO2H
2
L a c t ic a c id
Twist the lowest
priority to the
back
HO H
H3C
CO2H
(R )-L a c t ic a c id
Rotate Priorities
H
Br
H3C
4
CH2CH3
Priorities
1
2
3
2-Bromobutane
View &
Assign
1
(S)-2-Bromobutane
2
3
If you have troubles looking at the stereocenter, try Fischer Projections.
P r e s s f la t
W
X
W
C
Y
Y
Y
C
X
W
Z
Z
HO H
H3C
CO2H
Z
CH3
HO
H
CO2H
H
Br
H3C
H
CH2CH3
X
Br
CH3
CH2CH3
Only two kinds of motions are allowed for Fischer projec
1) Rotation on page 180˚ is allowed for Fischer projection.
COOH
H
OH
CH3
SA M E A S
HO
CH3
H
COOH
180 0
2) One group can be held steady while the other three rotate in either
a clockwise or a clockwise direction.
COOH
H
OH
CH3
COOH
SA M E A S
HO
CH3
H
Assigning R, S configurations to Fischer projectio
 Assign priorities to the four substituents in the usual way.
 Perform one of the two allowed motions to place the group
of lowest (4th) priority at the top or bottom of the Fischer
projection if it is necessary.
 Determine the direction of rotation in going from priority
1 to 2 to 3, and assign R (clockwise) or
S (counterclockwise).
HO H
H3C
CH3
HO
H
CO2H
CO2H
L a c t ic a c id
CH3
HO2C
OH
H
H
Br
H3C
3
4
H
CH2CH3
2 -B r o m o b u t a n e
Br
CH3
CH2CH3
1
2
4
1
3
2
Compounds Having Two or More Stereogenic Centers
H
OH
1
HN
Stereocenter 1
3
H
CH3
(-)-E p h e d r in e
1
4
CH3
2
adrenalin
e
Stereocenter 2
1
2
(1R), (2S)-(-)-Ephedrine
1
3
2
4
2
3
4
3
2
4
1
H3C
HO H
H NH
CH3
(+ )-E p h e d r in e
HO H
CH3
HN H
CH3
(+ )-P s e u d o e p h e d r in e
H3C
H OH
H NH
CH3
(-)-P s e u d o e p h e d r in e
(+)-Pseudoephedrine and (-)-Pseudoephedrine are
diastereomers of (+)-Ephedrine.
Diastereomers
 Stereoisomers that are not mirror images of each other.
 Diastereomers have similar chemical properties.
 Diastereomers have different physical properties:
melting points, boiling points, solubities in solvent, etc.
 Diastereomers can be separated by fractional distillation,
or crystallization.
H
Ph
H3CHN
H
M ir r o r
OH
H
R
S
CH3
(-)-E p h e d r in e
Diastereomers
HO
H
HO
H3CHN
S
Ph
H
CH3
(+ )-P s e u d o e p h e d r in e
R
CH3
Ph
NHCH3
(+ )-E p h e d r in e
Diastereomers
H
S
S
H
Ph
H
R
R
CH3
OH
NHCH3
(-)-P s e u d o e p h e d r in e
Enantiomers: non-superimposable (different) mirror images;
most of chemical and physical properties are identical.
Diastereomers: are stereoisomers that are not mirror images
(all stereoisomers except enantiomers) and have different
chemical and physical properties.
Relationships Between Stereoisomers
Stereoisomers
Enantiomeric with
Diastereomeric with
(1R), (2S)-(-)-Ephedrine (1S), (2R)-(+)-Ephedrine (1S), (2S)-(+)Pseudoephedrine
and (1R), (2R)-(-)Pseudoephedrine
Cahn-Ingold-Prelog R/S notation = Specifies absolute
configuration of a chiral center;
there is no correspondence between R and + or S and –
COOH
H R OH
HO R H
COOH
m ir r o r
COOH
S
HO
H
H S OH
COOH
(2 R , 3 R )-(+ )T a r t a r ic A c id
COOH
HO S H
HO R H
COOH
(2 S , 3 S )-(+ )T a r t a r ic A c id
(2 S , 3 R )-(+ )T a r t a r ic A c id
m ir r o r
COOH
H R OH
H S OH
COOH
(2 R , 3 S )-(+ )T a r t a r ic A c id
m e s o -T a r t a r ic A c id
(+)-Tartaric Acid:
[α]D = +12º
m.p. 170 ºC
(–)-Tartaric Acid:
[α]D = –12º
m.p. 170 ºC
meso-Tartaric Acid:
[α]D = 0º
m.p. 140 ºC
Meso Isomer:
an achiral molecule with 2 or more chiral centers and
an internal plane of symmetry; the molecule is achiral.
COOH
S
HO
H
HO R H
COOH
180o
(2 S , 3 R )-(+ )-T a r t a r ic A c id
COOH
R
H
OH
H S OH
COOH
(2 R , 3 S )-(+ )-T a r t a r ic A c id
I d e n t ic a l
Number of stereoisomers = a molecule with n stereogenic
centers (and for which a meso isomer isn’t possible) will
have 2n stereoisomers.
Resolution of Racemic Mixtures
There are two basic ways that one can separate the
enantiomers in a racemic mixture:
 Biological Resolution : Using a microbe which metabolizes
one specific enantiomer leaving the other alone.
 Chemical Resolution : The racemate is converted to two
diastereoisomers. Once separated the diasteriosomeric
forms are converted back to enantiomers in separate
containers.
Cl
CH2CH3
C
H
H3C
C
C
Br
E isomer
H
C
CH2CH3
Z isomer
 A competely unambiguous system, based on a set of group
priority rules, assigns a Z (German, zusammen for together) or
E (German, entgegen for opposite) to designate the stereoisomers.
 Z is equivalent to cis and E is equivalent to trans.
Today’s Quote
One learns one’s most
valuable lessons
through hardships.
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