1 c: formic acid, methanoic acid 2 c’s: acetic acid, ethanoic acid 3 c’s: propionic acid,...

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

สารประกอบเอมี�นที่��มี�ฤที่ธิ์��เป�นยา

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.

ช�วิ�ต่จะได&ร!บบที่เร�ยนที่��มี�คิ ามีากที่��ส'ดที่ ามีกลางคิวิามีที่'กข์�ยาก

Today’s Quote