Transcript ภาพนิ่ง 1
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
HO
N
n ia c in ( v it a m in B 3 )
CH2OH
HO
CH
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
CO2H
C5H11
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.
CO2H
CO2H
COX
H
cyclooxygenase
CH3
CH3
O
O
O
A r a c h i d o n ic a c i d
O
O
O
H
H
O
CO2H
C5H11
O
O
1. Peroxidase
2. Radical Cleavage
CO2H
C5H11
O
H
H
OH
OOH
PG G 2
H
HO
CO2H
C5H11
HO
H
OH
P G F 2
RCOOH
RCOO
+ H 2O
Carboxylic Acid
+ H 3O
Carboxylate ion
R C O O H + N aH C O 3
P h en ol + N aH C O 3
OH
R C O O N a + H 2O + C O 2
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 )
Electron-withdrawing groups stabilize a conjugate base,
making a carboxylic acid more acidic.
O
ClH 2C
O
OH
Cl2HC
OH
C
H
O
Cl
O
OH
p K a = 0 .9
B ase
B ase
Cl
Cl3C
p K a = 1 .3
p K a = 2 .8
H
O
Cl
C
H
B a se
O
Cl
O
Cl
C
Cl
O
O
Electron-donating groups destabilize a conjugate base,
making a carboxylic acid less acidic.
O
H 3C
O
OH
(H 3C)3C
p K a = 5 .1
p K a = 4 .8
B ase
B a se
O
H 3C
OH
O
CH 3
O
H 3C
C
CH 3
O
Alpha Hydroxy Acids in Cosmetics
O
O
H 3CHC
OH
OH
HO
OH
OH
la c t ic a c id
O
t a r t a r ic a c id
O
O
H 2C
OH
OH
OH
g ly c o li c a c id
OH
HO
OH
m a lic a c id
O
Carboxylic acids’ Derivatives
O
O
R
R
OR
a m id e
ester
O
O
R
NH 2
Cl
a c id c h lo r id e
R
O
O
a n h y d r id e
R
Esters
O
CH 3CH 2CH 2
OH
+
CH 3CH 2OH
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
CH 3CH 2CH 2
OCH 2CH 3
eth y l b u ta n o a te
( s t r a w b e r r y f l a 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 )
NH 2
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 ey )
m e t h y l a n t h r a n ila t e
(o d o r o f g ra p e )
O
OCH 3
O
CH 3OH
H+
OH
+ H 2O
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
H 3C
O
CH 3
a c e t ic a n h y d r id e
O
OH
O
O
CH 3
a c e t y ls a lic y lic a c id
+ CH 3COOH
Preparing Biodiesel
O
O
H2C
HC
O
O
C
O
R1
C
R2
O
H2C
O
C
R3
T r ig ly c e r id e
N aO H
H2C
OH
H3C
O
C
O
R1
HC
OH
H3C
O
C
R2
C H 3O H
O
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
R1
C
R2
O
H2C
O
C
N aO H
OH
+
Na-O
C
O
R1
HC
OH
+
C
R2
Na-O
H 2O
O
H2C
R3
T r ig ly c e r id e
H2C
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
NH 2
CH 3
NH 2
a c e t a m id e
b e n z a m id e
O
O
H
NHCH 2CH 3
N - e t h y lf o r m a m id e
N
CH 3
CH 3
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
H
S
N
O
OH
CH3
CO2H
COOH
CWT
(cell wall transamidase)
H
S
PhH2COCHN
CH3
H
N
P e n ic illin V
H
PhH2COCHN
S
O
CO2H
P e n ic illin G
H
OCH2 C
H
N
HN
O
O
CWT
CH3
CH3
H
COOH
H
H
S
PhH2COCHN
CH3
S
PhH2COCHN
O
H
N
Metallic salts of benzylpenicilloic acid
COO
PhH2C
CH3
CH3
N
CH3
C OO
H
H
S
CH3
HN
O
Bezylpenicilloic acid
HOOC
H
H
CH3
HN
O
Z n 2+, C d 2+,
C u 2+, P b 2+
H 2O
O
O H / H 2O
H +/ H 2O
Penicillin G
CH3
-
C OOH
H
S
PhH2COCHN
CH3
N
O
H
H
H
COOH
Benzylpenillic acid
+ Bezylpenicilloic acid
H
R
H
S
ROCHN
N
O
X
CH3
Ampicillin; X = H
Amoxicillin; X = OH
CH3
H
COOH
penicillin pharmacophore
H2N
D-configuration
Amines
NH3 + H2O
NH4+ + OHRNH2, ArNH2 Primary, 1o Amines
R2NH, Ar2NH Secondary, 2oAmines
R3N, Ar3N Tertiary, 3o Amines
butylamine
N-methylpropylamine
N,N-dimethylethylamine
สารประกอบเอมีนที่มีฤทธิ์เป็ นยา
NH2
H2C
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 enzedrex
( 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 )
CH 3
OCH 2CH 2N
CH 2CH 2NH 2
CH 3
C
N
N
H
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
H 2S O 4
O
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
H3C
NH
H3C
H3C
H N O 2, H C l
N
N
OCl
-H C l
H3C
N
N - N i t r o s o d im e t h y la m in e
sodium nitrite
NaNO2 inhibits the growth of Clostridium botulinum.
Nu
O
H3C
CH3
N aN O 2 + H C l
H3C
N
NuBiological
Nucleophile
CH3
carbocation
+ N2
acid or heat
H3C
N
N
diazonium ion
CH3
carbocation
RNH2 + HNO2 + HCl
RN
+
N Cl
2 H 2O
ROH + N2 + HCl
+ ROR + RCl
HO
N
O
H+
H
O
H
N
O
N
O
+ H 2O
N
O
Quote of The Day
Think like a wise man
but express yourself like
an ordinary one.
จงคิดเหมือนปราชญ ์
แตแสดงออกเหมื
อน
่
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
( + ) - l im o n e n e
(o r a n g es)
H
180° rotation
H
CH 3
COOH
H 3C
H
HOOC
H 3CO
OCH 3
(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
NH 2
NH 2
C
C
COOH
H
HOOC
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
L a c t ic a c id
4
CO2H
2
Twist the lowest
priority to the
back
HO H
H3C
CO2H
( R ) - L a c t ic a c id
Rotate Priorities
4
H
Br
H3C
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 fla 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 projection.
1) Rotation on page 180˚ is allowed for Fischer projection.
COOH
H
OH
CH3
SA M E A S
HO
CH3
H
COOH
1800
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 projections.
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
4
H
CH2CH3
2 -B r o m o b u ta n e
Br
CH3
CH2CH3
1
2
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
adrenaline
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
R
OH
H
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.
ชีวต
ิ จะไดรั
่ ี
้ บบทเรียนทีม
คามากที
ส
่ ุดทามกลาง
่
่
ความทุกขยาก
์