1 c: formic acid, methanoic acid 2 c’s: acetic acid, ethanoic acid 3 c’s: propionic acid,...
TRANSCRIPT
1 C: formic acid, methanoic acid2 C’s: acetic acid, ethanoic acid3 C’s: propionic acid, propanoic acid4 C’s: butyric acid, butanoic acid
Carboxylic acids
RCOOH R CO
OHRCO2HN
niacin (vitamin B3)
HO
O
Vitamin C(Ascorbic acid)
OO
OHHO
CH
CH2OH
HO
O
OH oxalic acidHO
O
Aspirin : Should you take a daily dose?
COOH
O CCH3
O
Aspirin
HO
HO
H
H
CO2H
C5H11
OH
PGF2(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
CH3
Arachidonic acid
H
O O
COXCO2H
CH3
O O O O
O
O
H
H
CO2H
C5H11
OOH
PGG2
1. PeroxidaseO
O
H
H
CO2H
C5H11
OH
2. Radical Cleavage
HO
HO
H
H
CO2H
C5H11
OH
PGF2
cyclooxygenase
Carboxylic AcidCarboxylic Acid Carboxylate ionCarboxylate ion
+ NaHCO3RCOOH + H2O + CO2RCOO Na
+ H2ORCOOH + H3ORCOO
No reaction + NaHCO3Phenol
(Sodium Phenoxide)
+ NaOH
OH
+ H2O
O Na
Electron-withdrawing groups stabilize a conjugate base,
making a carboxylic acid more acidic.
O
OHClH2C
O
OHCl2HC
O
OHCl3C
Base Base Base
O
OC
H
Cl
HO
OC
H
Cl
ClO
OC
Cl
Cl
Cl
pKa = 2.8 pKa = 1.3 pKa = 0.9
Electron-donating groups destabilize a conjugate base,
making a carboxylic acid less acidic.
O
OHH3C
O
OH(H3C)3C
Base Base
O
OH3C
O
OC
CH3
H3C
CH3
pKa = 4.8 pKa = 5.1
Alpha Hydroxy Acids in Cosmetics
O
OHH3CHC
lactic acid
OH
O
HO
tartaric acid
OH
OH
O
OH
O
OHH2C
glycolic acid
OH
O
HO
malic acid
OH O
OH
O
ClR
acid chloride anhydride
esteramide
O
OR R
O
O
ORR
O
NH2R
Carboxylic acids’ Derivatives
EstersO
OHCH3CH2CH2
butanoic acid
CH3CH2OH
ethyl alcohol
+
H+
O
OCH2CH3CH3CH2CH2
ethyl butanoate
H2O+
(strawberry flavoring)
esterification
hydrolysis
ethyl butyrate
O
O
(odor of pineapple)
isoamyl acetate
O
O
(odor of banana)
O
O
(odor of peach)
benzyl acetate
ethyl phenylacetate
O
O
(odor of honey) (odor of grape)
methyl anthranilate
NH2
O
O
CH3OH
OH
O
OH
salicylic acid
H+
OCH3
O
OH
methyl salicylate(oil of wintergreen)
H2O+
H3C O CH3
O O
acetic anhydride
OH
O
O
acetylsalicylic acid
O
CH3
CH3COOH+
HC
H2C O C
H2C
O C
O C
O
O
O
Triglyceride
R1
R2
R3
NaOH
CH3OHHC
H2C OH
H2C
OH
OH
Glycerol
H3C
H3C O C
H3C
O C
O C
O
O
O
Monoalkyl Esters
R1
R2
R3
Transesterification
Preparing BiodieselPreparing Biodiesel
Preparing SoapsPreparing Soaps
HC
H2C O C
H2C
O C
O C
O
O
O
Triglyceride
R1
R2
R3
NaOH
H2O
HC
H2C OH
H2C
OH
OH
Glycerol
+Na-O C
+Na-O C
+Na-O C
O
O
O
Sodium carboxylates
R1
R2
R3
Sponification
Amides
O
NH2
acetamide
N-ethylformamide
CH3
O
NH2
benzamide
O
NHCH2CH3H
O
N
N,N-dimethylbenzamide
CH3
CH3
CWT
OH
N
S
OH
PhH2COCHN
H H
CH3
CH3
COOH
CWT
O
HN
S
OH
PhH2COCHN
H H
CH3
CH3
COOH
CH2 CHN
O
N
S
OCO2H
Penicillin G
OCH2 CHN
O
N
S
OCO2H
Penicillin V
(cell wall transamidase)
N
S
OH
PhH2COCHN
H H
CH3
CH3
COOH
Penicillin G
OH-/ H2OHN
S
OH
PhH2COCHN
H H
CH3
CH3
COO
Bezylpenicilloic acid
O
H+/ H2O
N
S
H
H
CH3
CH3
COOH
Benzylpenillic acid
N
HOOC
PhH2C
+ Bezylpenicilloic acid
Zn2+, Cd2+,Cu2+, Pb2+
H2O
HN
S
OH
PhH2COCHN
H H
CH3
CH3
COO
Metallic salts of benzylpenicilloic acid
O
N
S
OH
ROCHN
H H
CH3
CH3
COOH
penicillin pharmacophore
R
Ampicillin; X = HAmoxicillin; X = OH
X
H2N
D-configuration
Amines
RNH2, ArNH2 Primary, 1o Amines
NH3 + H2O NH4
+ + OH-
butylamine
R2NH, Ar2NH Secondary, 2oAminesR3N, Ar3N
Tertiary, 3o Amines
N-methylpropylamineN,N-dimethylethylamine
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NHCH3
CH3
Benzedrex(Nasal decongestant)
H2C
Amphetamine
C CH3
H
NH2
(Antidepressant)
NN
N
N
Urotropine(Antibacterial agent)
histaminediphenhydramine (Benadryl)
N NH
CH2CH2NH2
C
OCH2CH2NCH3
CH3
H
O
HO
HO
N CH3
Morphine
(water insoluble)
O
HO
HO
N CH3
Morphine Sulfate
(water soluble)
H2SO4
HHSO4
NH
H3C
H3CHNO2, HCl
NH3C
CH3
H
N O Cl -HClN
H3C
H3C
N O
N-NitrosodimethylamineNaNO2 + HCl
sodium nitrite
acid or heat
NH3C
CH3
N
diazonium ion
carbocation
CH3
carbocation
+ N2
Nu-
Biological Nucleophile
H3C Nu
NaNO2 inhibits the growth of Clostridium botulinum.
+ HNO2 + HCl RN N Cl
ROH + N2 + HCl
RNH2
+ 2 H2O
+ ROR + RCl
N OHOH+
N OO
H
H
N O N O
+ H2O
Think like a wise
man
but express
yourself like
an ordinary one.
Quote of The Day
จงคิ�ดเหมี�อนปราชญ์� แต่ แสดงออกเหมี�อนสามี!ญ์ชน
StereochemistrStereochemistryyis the study of the three-dimensional structure of molecules.
StereoisomersStereoisomers
Stereoisomers : Isomers that have the same bonding sequence but differ in the orientation of their atoms in space.
Isomers : Different compounds that have the same molecular formula.
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).
Mir
ror
H
(-)-limonene(lemon oil)
H
(+)-limonene(oranges)
H
180° rotation
(S)-naproxen
anti-inflammatory agent
H3CO
COOH
H CH3
(R)-naproxen
liver toxin
OCH3
HOOC
HH3C
NH2
CCOOHR
H
L-amino acid
NH2
CHOOC R
H
D-amino acid
คิ" คิ" enantiomersenantiomers
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?
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.
All objects may be classified with respect to chirality (from the Greek cheir = hand):
Achiral molecules have either one or both of the following:
Plane of symmetryCenter of symmetry
Chiral molecule : (R)-lactic acidAchiral molecule : water
Water (H2O)
Chiral molecules have chiral center (or stereo or stereogenic center): an atom attached to 4 different atoms or groups.(chiral carbon)
Cl
H
FBr H
CH3
H3CH2CH3CO
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 theapplication of two rules:
The Sequence RuleThe 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 diff
erence is found. i.e. CH3 – < C2 H5 – < ClCH2 – < BrCH2 – < CH3 O– .
If double or triple bonded groups are encountered as substituents, they are treated as an equivalent set of single- bonded atoms . i.e. C
2H5
– <CH
2 =CH– < HC≡C–
C CH H
RIS TREATED AS
C CH H
RC C
C C R IS TREATED AS C CC C
RC C
C HO
IS TREATED AS C HO
O
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.
H3C CO2H
HO H
Lactic acid
Assign PrioritiesH3C CO2H
HO H1
23
4
Twist the lowest priority to the back
Rotate PrioritiesH3C CO2H
HO H
(R)-Lactic acid
2-Bromobutane
(S)-2-Bromobutane
Priorities
View &Assign
CH2CH3
H
BrH3C
1 2
3
4
2 3
1
If you have troubles looking at the stereocenter, try Fischer Projections.
W
C
X
Y Z
W C X
Y
Z
W X
Y
Z
Press flat
H3C CO2H
HO HHO H
CH3
CO2H
Br CH3
H
CH2CH3
CH2CH3
H
BrH3C
1) Rotation on page 180˚ is allowed for Fischer projection.Only two kinds of motions are allowed for Fischer projection.
H
COOH
OH
CH3
1800
SAME AS HO
CH3
H
COOH
2) One group can be held steady while the other three rotate in either a clockwise or a clockwise direction.
H
COOH
OH
CH3
SAME AS HO
COOH
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).
H3C CO2H
HO H
Lactic acid
HO HCH3
CO2H
CH2CH3
H
BrH3C
2-Bromobutane
4
2
1 3
HO2C OHCH3
H 4
2
3
1
Br CH3
H
CH2CH3
Compounds Having Two or More Stereogenic Centers
Stereocenter 1
1
2 3
4
Stereocenter 2
1
23
4
1
3 2
4
1
23
4
(1R), (2S)-(-)-Ephedrine
CH3
H
HN
OH
H
CH3
12
(-)-Ephedrine
adrenaline
H3CHO
H
H
NHCH3
(+)-Ephedrine
CH3
H
H
HO
HNCH3
(+)-Pseudoephedrine
H3CH
H
OH
NHCH3
(-)-Pseudoephedrine
(+)-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.
Diastereomers
Diastereomers
(-)-Ephedrine
HPh OH
H3CHN HCH3
(+)-Ephedrine
HHO PhH NHCH3
CH3
R
S
Mirror
S
R
S
HPh OHH NHCH3
CH3(+)-Pseudoephedrine
HHO Ph
H3CHN HCH3
(-)-Pseudoephedrine
S R
R
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.
- - Cahn Ingold Prelog R/S notation = S pecifies absolute configuratio n of a chiral center;
t her e i s no cor r espondence be t ween R and +or S and –
Relationships Between Stereoisomers
StereoisomersEnantiomeric withDiastereomeric with
(1R), (2S)-(-)-Ephedrine(1S), (2R)-(+)-Ephedrine(1S), (2S)-(+)-Pseudoephedrine(1R), (2R)-(-)-Pseudoephedrineand
(2R, 3R)-(+)-Tartaric Acid
COOHHHO
COOHOHH R
R
mirror
(2S, 3S)-(+)-Tartaric Acid
COOHOHH
COOHHHO S
S
mirror
(2S, 3R)-(+)-Tartaric Acid
COOHHHO
COOHHHO S
R
(2R, 3S)-(+)-Tartaric Acid
COOHOHH
COOHOHH R
S
meso-Tartaric Acid
(+)-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.
(2S, 3R)-(+)-Tartaric Acid
COOHHHO
COOHHHO S
R
(2R, 3S)-(+)-Tartaric Acid
COOHOHH
COOHOHH R
S180o
Identical
Number of stereoisomers = a molecule with n stereogenic ce
nters (and for which a meso iso mer isn’t possible) will have 2
n 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 leavin g 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 .
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.
C C
CH2CH3
BrH
Cl
C C
CH2CH3H
H3C
E isomer Z isomer
One learns one’s most valuable lessons through hardships.
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