Organic Chemistry
Chapter 1 Chemical Bonding
Organic chemistry – Carbon compounds
Historically related to life systems
Molecular Structure – Properties relationship
1.1 Atoms, Electrons and Orbitals
Molecular structure – Chemical bonding
Atoms – Protons (+) in nucleus
Electrons (-) in orbitals
Obitals – Size / Shape / Directional properties
s-orbital – 1s / 2s
Principal Quantum Number (n) – specify “Shell”
related to energy of orbitals
1s / 2s – 1s closer to nucleus / lower energy
Hydrogen ; 1s1 Helium; 1s2
Electrons – negatively charged / Properties of spin
Spin Quantum Number – (+/- 1/2)
Pauli exclusion principle – electron pair in orbital
p-orbital – 2px / 2py / 2pz
dumbbell-shaped / equal energy / perpendicular
“Hund’s Rule - Single electron occupy each orbital
first before filling each orbitals
Valence electrons – Out most electrons of atom
Involved to chemical bonding / reaction
1s
2s / 2p
3s
octet of electrons – Helium / Neon / Argon (noble gas)
“closed-shell” electron configuration / unreactive
1.2 Ionic Bonds
Atoms combined with one another – Compounds
Attractive forces between atoms – “Chemical Bond”
Ionic bond – oppositely charged ions
Cation (+) / Anion (-)
Common in inorganic compounds
Rare in organic compounds
Electrons – Tendency to be paired (Noble gas configuration)
Na – Na+ + e(Na : 1s2 2s2 2p6 3s1 / Na+ : 1s2 2s2 2p6)
Cl + e- - Cl(Cl : 1s2 2s2 2p6 3s2 3p5 / Cl- : 1s2 2s2 2p6 3s2 3p6)
1.3 Covalent Bonds
Covalent – Shared electron pair
“stable closed-shell” electron configuration
Lewis structures – electron as dot
Usually “octet rule” to form noble gas configuration
CH4 / CF4
1.4 Double bonds and Triple bonds
Lewis rule – shared electrons
4 electrons – double bonds
6 electrons – triple bonds
CO2 - O=C=O
HCN – H-C=N
1.5 Polar Covalent Bonds and Electronegativity
In Covalent bonds – even electron distribution between atoms
Polarized – polar covalent bond
Partially charged – Dipole (+/-)
HF
Electonegativity – electron attraction
1.6 Formal Charge
Lewis structure frequently contain atoms that bear positive /negative
charged atoms
counting electron # of atom in Lewis structure as “owned by
atom” – comparing to “Electron count” of neutral atom
covalently shared electrons – 1/2 is owned
HNO3
3 Oxygen elements to nitrogen atom
different electron distributions
Nitrogen – positively charged
Oxygen – Negatively charged
1.7 Structural Formulas of Organic Molecules
Systematic procedure for writing Lewis Structure
Molecular formula & Atom attachments
Order of attachment – Constitution or Connectivity of molecules
determined by experiments
Condensed Structure formulas
(CH3)2CHOH
Bond-line formulas / Carbon skeleton diagrams
1.8 Isomers and Isomerisms
Same molecular formula, but different compound – Isomers
CH3NO2 – Nitromethane / Methyl nitrite
Structural isomers – different order of in the order
(Constitutional isomer)
Isomerism of organic chemicals
1.9 Resonance
Restrict molecule’s electrons in Lewis structure
O3 (ozone)
The structure of ozone requires that the central oxygen must be
identically bonded to both terminal oxygens (128pm)
(ex, Single bond – 147pm / double bond – 121pm)
Electron distribution – to form most stable arrangement
(delocalized electrons) – Partial bond in Lewis structure
1.10 The Shapes of some simple molecules
Three dimensional structures by using solid wedge / Dashed wedge
A simple line for bond for plane of the paper
CH4 – tetrahedral geometry
“Valance Shell electron-pair repulsion (VSEPR)” model
Maximal separation – Tetrahedral angle (109.5o)
Molecular shape
Water – bent / Ammonia – trigonal pyramidal
1.11 Molecular Polarity
molecular geometry with polarity of chemical bonds
electron dipole
H2C=O Formaldehyde – polar
CO2 Carbon dioxide – nonpolar
1.12 sp3 Hybridization and Bonding in Methane
CH4 (1s2 2s2 2px1 2py1) – only two half filled orbitals
To make 4 hydrogen bonds – sp3 hybrid state of carbon
Tetrahedral arrangement of four  bonds is characteristics of
sp3-hybridized carbon
C(2sp3)-H(1s)  bond
1.13 Bonding in Ethane
Carbon-Carbon covalent bonding
Ethane : CH3-CH3
 bond between Methyl groups
1.14 sp2 Hybridization and Bonding in Ethylene
sp2 Hybrid orbitals (2s 2p2)
-bond formation of unhybridized 2p orbital
Double bonds – combination of  and  bonds
Stronger & shorter carbon bonding
1.15 sp Hybridization and Bonding in Acetylene
Acetylene – CH-CH
Triple bonding between carbons
 +  +  bondings
1.16 Summary
Chapter 2 Alkanes and Cycloalkanes
Structure of Organinc chemicals – Reasonably confident predictions
Properties & Chemical reaction
Functional groups – Characteristic patterns of reactivity
Frameworks – non-reactive backbones
Nomenclature System – IUPAC rules
2-1. Classes of Hydrocarbons
Hydrocarbons – only Carbon and Hydrogen
Aliphatic (fat) & Aromatic (odor)
Aliphatic Hydrocarbons
Alkanes / Alkenes (Double bond) / Alkynes (Triple bond)
Ex) Ethane / Ethylene / Acetylene
Aromatic Hydrocarbons – Arenes
Ex) Bezene
2-2. Reactive Sites in Hydrocarbons
Functional Group as indication of molecule’s reactivity
In Alkane – only “Hydrogen”
CH3-CH3 + Cl2 -------- CH3CH2Cl + HCl
Reaction equation of alkane
R-H + Cl2 ----- R-Cl + HCl
2-3. the Key Functional Groups
Alkanes – “not reactive compounds
Hydrogen replacement
Alcohol ROH
Alkyl halide RCl
Amine RNH2
Expoxide R----R
Ether ROR
Nitrile RC=N
Nitroalkane RNO2
Thiol R-SH
Note) Carbonyl Group (C=O)
Most abundant and biologically significant in Nature
Carbonyl Compounds
Aldehyde
Ketone
Carboxylic acid
Carboxylic acid derivatives
Acyl halide
Acid anhydride (-H2O)
Ester
Amide
2-4. Introduction to Alkanes: Methane, Ethane, and Propane
Alkanes : Molecular formula CnH2n+2
Methane – Natural gas (75%) / Ethane (10%)/ Propane (5%)
Ethanethiol – unpleasant smelling odor (leak detection)
B.P.
Methane
-160
/
Ethane
-89
/
Propane
-42
2-5. Conformations of Ethane and Propane
Conformation – Spatial Arrangement of molecules
Due to Rotation about single bond
Ethane based on C-H and C-C bonds
Staggered vs. Eclipsed
Drawing as
“Wedge-and-Dash”
“Sawhorse”
“Newman Projection”
Conformational Analysis – to Predict the stability of Molecules
“Staggered conformation” – as stable conformation
Most separation of electrons
“Eclipsed conformation” – least stable conformation
“Torsional strain”
2-6. Isomeric Alkanes: the Butanes
C4H10 (Butane) – Constitutional Isomers
n-Butane (Normal – linear carbon bonds)
Isobutane – Branched carbon chain
Methyl group – CH3
Methylene group – CH2
Methine group – CH
n-buthane – High BP and MP points
Staggered conformation – Zigzag arrangement of C
Anti vs. Gauchi conformation based on Methyl group
Gauchi – van der Waals strain (Steric hinderance)
N-butane (65% Anti / 35% Gauche)
2-7 Higher Alkanes
n-Alkanes – Linear structure
CH3(CH2)nCH3
Constitutional isomers
Ex) n-Pentane / Isopentane / Neopentene
(1- methyl) (2-methyl)
2.-8 IUPAC Nomenclature of Unbranched Alkanes
Organic chemicals – Common & Systematic
International Union of Pure and Applied Chemistry
Alkanes:
Carbon numbers as Latin or Greek prefix + ane
(no “n-“)
2-9. Applying the IUPAC Rules: The Names of the C6H14 Isomers
C6H14 – Unbranched isomer : Hexane
Branched hydrocarbons
Step1. Longest continuous carbon chain– Parent chain
Step2. Substituent groups to parent chain
Step3. Numbering of parent chain from shortest
substituent group
Step4. Name using numerical location of
substituent group
1 2 3 4 5
CH3CHCH2CH2CH3
CH3
2-methylpentane
2-10. Alkyl Groups
Alkyl group – lacks one of the hydrocarbons of an alkane
Methyl (CH3-)
Ethyl (CH3-CH2-)
Carbon atoms – Degree of substitution by other carbons
Primary / Secondary / Tertiary / Quarternary
Branched alkyl groups
Using longest continuous chain as a base
Start w/ Substituent group
(CH3)2CH- : 1-methylethyl
(Common name : Isopropyl)
C4H9 Alkyl group
Butyl (n-butyl)
1-methylpropyl (sec-butyl)
2-methylpropyl (isobutyl)
1,1-dimethylethyl (tert-butyl)
2-11 IUPAC Names of Highly Branched Alkanes
IUPAC rules
Based on Longest chains
Substitution group numbering (shortest distance)
Start w/number + substituent group by alphabetically
Name “Alkane”
if equal locants from different numbering directions
then lower number for first appear substituent
2-12 Cycloalkane Nomenclature
Cycloalkane – a ring of three or more carbons
CnH2n
Attached groups – Numbering carbons
Numbering lowest to substituted carbons at the point
of difference
(2- ethyl-1,1-dimethylcyclohexane)
(not 1-ethyl-3,3-dimethylcylcohexane)
if smaller carbon cycloalkyl group attaches to alkane
“n-cyclo----alane”
2-13 Conformations of cycloalkanes
in cyclopropane – all eclipsed bonds
torsional strain
Angle strain of carbon (60o vs 109.5o) – less stable
Cycloalkanes – reducing Torsional & Angle strain
2-14 Conformations of Cyclohexane
Six-ring compounds – nonplanar conformation
Chair conformation – Stable
Boat conformation – less stable
Hydrogen bond to carbon
Axial hydrogens
Equatorial hydrogens
2-15 Conformational Inversion (Ring Flipping) in Cyclohexane
Rotation of carbon bonds
Ring Inversion
Chair-Chair conversion
Ring flipping
“Axial and Equatorial conversion”
2-16 Conformational Analysis of Monosubstituted Cyclohexane
Ring inversion in Methylcyclohexane
Axial Methyl (5%) vs. Equatorial Methyl (95%) in Rm Temp
based on lower free energy predomination
Steric Effect – Repulsion
“Bulky” - Branched carbons always “bulkier”
2-17 Disubstituted Cycloalkanes : Steroisomers
Two substituted groups on ring - Steroisomers
On same side – “cis”
Across – “trans”
Steroisomer – Geometric isomers
In Cyclohexane
Equatorial disubstituents is more stable
Bulky substituent – Equatorial position
Sterochemistry – Reactivity
Exposure vs. Inert under the same conditions
2-18 Polycyclic Ring Systems
Bicyclic / Tricyclic / Steroid
2-19 Physical Properties of Alkanes and Cycloalkanes
Boiling Point
Longer chain – higher BP
Branched – lower BP
Gaseous state – Intermolecular Attractive Forces
IAF – dependent upon “Surface Area”
Branched – compact – less surface area – lower BP
In Alkanes – as non polar compounds
May not be no intermolecular force
However, electron – temporary distortion
“Induced-dipole”
Weak attractive force – as “van der Waals force”
Solubility in water – Insoluble in water
Polar solutes into polar solvents
Non polar solutes into non polar solvents
Intermolecular attractive force between water molecules is
great “induced dipole attraction force” of alkanes
“Hydrophobic effect”
Hydrocarbon – less dense
2-20 Chemical Properties: Combustion of Alkanes
Alkanes – relatively unreactive, but combustion w/ oxygen
CH3CH2CH3 + 5 O2 -------- 3CO2 + 4 H2O
Combustion – Exothermic
Petroleum (Petro- rock / oleum-oil)
Crude oil
Distillation – Straight-run gasoline (C5-10) BP 30-150oC
Kerosene (C8-14) BP 175-325oC – Disel
Petrochemicals by cracking petroleum
Such as ethylene
2-21 Summary
Chapter 3 Alcohols and Alkyl Halides
Organic Reaction of Alcohols & Alkyl Halides – most useful classes
R-OH + H-X ------------- R-X
+
H-OH
3-1. Nomenclature of Alcohols and Alkyl Halides
IUPAC rules for Alcohols & Alkyl halides
Alkyl halides ; fluoride / bromide / iodine /alcohol
Or
Halo- (fluoro- / chloro- / bromo- / iodo-) alkane
As substituent on the alkane chain
Alcohol : Alkanes to alkanols
Hydroxyl group take precedence over alkyl groups
and halogen substituents in determine the direction of
numbering
3-2. Classes of Alcohols and Alkyl Halides
Primary / Secondary
RCH2G
R2CHG
/
Tertiary alcohol (alkyl halide)
R3CG
Based on the carbon w/ functional group - # of carbon bonds
Functional group at Primary carbon – “more reactive”
3-3. Bonding in Alcohols and Alkyl Halides
 - Bonding between C-O / C-Hal : slightly shorter
Carbon slightly + charged
3-4. Physical Properties of Alcohols and Alkyl Halides:
Intermolecular Forces
Boiling point:
Bp
Propane
–42oC
/
Ethanol
78oC
/
Fluoroethane
-32 oC
Non-polar substance – no intermolecular attractive force
Except ‘Induced-dipole (weakest)
Polar substance – “Dipole interaction”
In Ethanol – slightly negatively charged oxygen
“Hydrogen Bond” – High Boiling point
-OH / -NH molecules: electronegative
10-50 times less than covalent bonds
Provide structural oder
3-D structure determination
Boiling Point
Higher molecule – higher BP / Increased “induced dipole”
Due to electron field
Chlorinated derivatives of methane
Increased chlorine – increased BP
Fluoroinated derivatives of methane
Unique – Fluorine substitution: decreased “Induced
dipole”
Fluorinated hydrocarbon (fluorocarbons)
-“Non sticking” Teflon coatin
Solubility in Water
Alkyl halide – insoluble in water
Lower MW alcohols – soluble in water
Hydrogen bonding
Density
Alkyl fluorides / chlorides – less dense
Alkyl bromides and iodides – more dense than water
Poly halogenation – increased the density
All liquid alcohols – approximately 0.8g/l
3-5. Acids and Bases : General Principles
Acid-Base Chemistry – Chemical reactivity
Arrhenius – Ionization theory in Aqueous solution
Bronsted & Lowry :
Acid – Proton donor / Base – Proton acceptor
Water(Base)+Acid---------Conjugate acid of water+Conjugated Base
Oxonium ion (hydronium ion)
Strength of acid – Acid dissociation constant / ionization
constant Ka ( H3O+ , Ka = 55)
pKa = -log10Ka
In any proton-transfer process – Equilibrium favor to
forming weaker acid and weaker base
Stronger the acid, the weaker the conjugate base
Alcohol – alkyloxonium formation
Alcohol reactivity w/ strong acids – increase reavtivity
(as either reagents / catalysts)
3-6. Acid-Base Reactions: A Mechanism for Proton Transfer
In chemical reactions – Change in Potential energy
Reactant – Energized / Activation energy (Eact)
Transition state - Unstable
Product
Proton transfer from alkyl halides to water
Elementary step – one transition state in concerted reaction
Molecularity – biomolecular
Cf) series of elementary steps (transition state)
Proton transfer from hydrogen bromide to water / alcohols
- most rapid chemical process
Lower activation energy
Greater energy change (exothermic – lowest)
3-7.
Preparation of Alkyl Halides from Alcohols and Hydrogen
Halides
Synthetic Organic Chemistry
“Building Block” – Alcohols / Alkyl halides
Preparation of alkyl halides
R-OH +
H-X -------R-X +
Alcohol Hydrogen halide Alkyl halide
H-OH
Water
Reactivity)
Acidity HI > HBr > HCl >> HF
Tertiary alcohols – most reactivity
Secondary / Primary – require Heating
Hydrogen bromide (HBr) w/ primary alcohol
Need heating – Forming Alkyl bromide
Can be done w/ (NaBr, H2SO4)
Simple reaction equation – based on organic chemical
Omitting water / inorganic on arrow
1-Butanol
NaBr, H2SO4
-------------------- 1-bromobutane
heat
3-8. Mechanism of the Reaction of Alcohols with Hydrogen Halides
Reaction of an alcohol w/ hydrogen halide – “Substitution”
Halogen (Chlorine / Bromide) replace Hydroxyl group
(CH3)3COH + HCl ------ (CH3)3CCl + H2O
3 step reaction
1st step – Acid-Base reaction
2nd step – dissociation of alkyloxonium ion to water
and “Carbocation” (positively charged)
3rd step – tert-alkyl halide formation
3-9. Structure, Bonding, and Stability of Carbocations
Carbocation – positively charged carbon
Simple example ; CH3+
3 valence electrons
3- bonds between C-H ; sp2 hybrid
1- empty p-orbital is perpendicular
Carboncation – Primary / Secondary / Tertiary
Alkyl groups directly attached to the positively charged carbon
stablize a carbocation
Carbonations are stabilized by substituents that release or donate
electron density to positively charged carbon
“Inductive effect”
Reaction rate : The more stable “Carbocations”, fast reaction
3-10. Electrolphiles and Nucleophiles
Positive carbon / vacant p-orbital – Carboactions ;
strongly Electrophilic (electron-loving)
Nucleophilles – Nucleus-seeking
Unshared paired electrons which can be used
covalent bond
Interaction between
Electrophilic carbocations – empty p-orbitals
Nucleophillic halide anions – unshared electron pairs
Lewis Acids / Bases
Electron-pair acceptor / Electron pair donor
3-11. Reaction of Primary Alcohols with Hydrogen Halides
Primary alcohols – require high energy to form intermediates
Alternative way rather than carbocation formations
Carbon-halogen bond begins to form before the carbonoxygen bond of the alkyloxonium ion is completely broken
down
Chapter 4 : Alkenes and Alkynes l : Structure and Preparation
Alkenes – Double bond : Reaction site
Akynes – Triple bond : Gas atmospheres of many stars
4.1. Alkene Nomenclature
1) –ene
2) Determination of carbon positions
A. Double bond position – at lowest position number
(Double bonds take precedence over alkyl group halogens)
B. Functional groups
(but, Hydroxyl group outrank the double bond)
- both double bond & hydroxyl group : - en+ -ol
Cycloalkenes
Followed alkene rules
(Carbon position - double bond / Functional group)
Multiple double bonds
2 double bonds – Alkadienes (dienes)
Conjugated / Isolated / Cummulated
4.2. Structure and Bonding in Alkenes
sp2-hybridized – double bond contains  &  components
Trigonal planar geometry
C=C
: 134pm / 121.4o (HCC) + 117.2o (HCH)
sp2-hybrided : remain / unpaired p-orbit electrons
Overlapping each other (side-by-side) - bond
Interaction between double bonds
Isolated – independent structural units
Conjugated – interaction between double bond
(slightly more stable – delocalization of  electrons)
Delocalization - 4 electrons over 4 carbons
(overlapping – extended  orbits)
4.3. Isomers of Alkenes
C4H8 – 4 isomers
Unbranched (1) / Branched (1) – double bond at 1
Cis / Trans (double bond at different position – 2)
Interconversion between Cis / Trans – Rotation of double bond
But, normally not enough energy (heat) for rotation
-orbit must broken at the transition state (less happen)
(p-orbits of C2=C3 to be twisted!)
4.4. Naming Stereoisomeric Alkenes by the E-Z Notation System
Z – “together” of higher atomic numbers of double bond
E – “opposite” of higher atomic numbers of double bond
Cahn-Ingold-Prelog Priority Rules
1. Higher atomic number
2. if identical – Precedence at the first point of difference
3. at the point of attachment – counts all atoms
4. at the point of attachment – counts one by one
5. multiple bonds on substituent – as two same atoms
(look at the table on the inside of the back cover)
4.5. Relative Stabilities of Alkenes
Alkene stability :
1. Degree of Substitution (alkyl --- stabilize double bond)
2. Van der Waals strain (cis alkyl--- destabilize double bond)
Degree of Substitution
Double bond: Alky (R) group substitution
Monosubstituted
Disubstituted
Trisubstituted
Tetrasubstituted (more stable than less substitution)
Sp2-hybridized carbons of double bond – Attracting electron
Alkyl groups – better electron-releasing substituents
than Hydrogen
“Electron Effect”
van der Waals Strains
Alkenes more stable by “trans” than “cis”
Free of stains between substituents
Repulsion – Steric effect
4.6. Preparation of Alkenes : Elimination Reactions
Alkenes in lab – by “Elimination reactions”
X-C-C-Y ------ C=C +
X-Y
Dehydration (H & OH)
Dehydrohalogenation of Alkyl halides (H & Cl / Br / I)
4.7. Dehydration of Alcohols
Dehydration of alcohols w/Acid catalyst (Sulfuric / Phosphoric acid)
Ex) Heating ethyl alcohol w/ Sulfuric acid
Double bond formation at the most substituted position
Ex) 2-methyl-2-butanol to 2-methyl-2-butene
Dehydration of alcohol is selective in respect to its direction
Double bond between C2 and C3 than C2 and C1
“Regioselective” – Zaitsev rule
Dehydration – Steroselective
Stable isomers – “trans” predominant than “cis”
4.8. The mechanism of acid-catalyzed dehydration of alcohols (see F4-5)
Dehydration of alcohol
Conversion of alcohol to alkyl halides
Both reaction – 1) promoted by acids
2) reactivity : 1o < 2o < 3o
Carbocations – Key intermediates
Carbocations as strong acids to lose a proton
To form alkenes
Primary carbocations – too high in energy to
be intermediates. So Alkyloxonium ion lose
a proton to cleave C-O bond
4.9.
Dehydrohalogenation of Alkyl Halides
Dehydrohalogenation reaction w/ strong base (Sodium ethoixide)
in ethyl alcohol as solvent
Regioselectivity by Zaitsev rule
Steroselectivity : trans (E) than cis (Z) isomers
4.10. The E2 Mechanism of Dehydrohalogenation
1) the reaction – Second-order kinetics
rate = k [alkyl halide][base]
2) rate of elimination depends on the halogen
RF < Cl < RBr < RI
Reactivity increased as decreasing C-halo bonding
E2 : Elimination bimolecular – One-step mechanism
1) C-H bond breaking
2) C=C  bonding formation
3) C-X bonding breaking
As same transition state – sp3 to sp2
4.11. A different Mechanism for Alkyl Halide Elimination :
The E1 Mechanism
Possible separated reaction of bond breaking
Carbocation intermediate followed by deprotonation
E1 – Elimination of unimolecular
First order kinetics
Rate = k[alkyl halide]
In tertiary / secondary alkyl halides w/o base
4.12. Alkyne Nomenclature
Triple bond : CnH2n-2
Monosubstituted (terminal) alkynes
Disubstituted (internal) alkynes
IUPAC rule
-yne
4.13. Stucture and Bonding in Alkynes: sp Hybridization
sp- hybridized -  & 2 bonding
unpaired 2p orbit overlapping
(natural cycloalkynes as anticancer drugs)
4.14 Preparation of Alkynes by Elimination Reactions
Double dehydrohalogenation of dihaloalkanes
Dihalogenalkanes – geminal dihalide (same C)
Vicinal dihalide (adjacent C)
Chapter 5: Alkenes and Alkynes II : Reactions
Characteristic Reaction – Addition of Unsaturated hydrocarbons
A-B + C=C --------- A-C-C-B
5.1. Hydrogenation of Alkenes
Hydrogenation : addition of H2
Stronger -bond formation from -bond : Exothermic
Require metal catalysts (ex, Platinum)
Reaction Steps
Hydrogen atoms to catalysts surface
Hydrogen atoms from catalysts to alkenes
“syn addition” – same face of double bond
“Anti addition” –opposite face of double bond
Commercial hydrogenation – vegetable oil to margarine
5.2. Electrophilic Addition of Hydrogen Halides to Alkenes
Polar molecule addition to alkenes
Alkenes + Hydrogen Halides
------- Alkyl Halide
Electrophilic – Electron deficient, so “Electron seeking”
Positively Charged Electrophiles
5.3. Regioselectivity of Hydrogen Halide Addition: Markovnikov’s rule
Hydrogen added to carbon that has greater number of hydrogens
5.4. Mechanistic Basis for Markovnikov’s rule
Hydrogen halide addition–from more stable carbocation intermediates
Secondary carbocation is more stable than primary carbocation
5.5. Acid-Catalyzed Hydration of Alkenes
Alkenes to Alcohol by addition of H2O w/ Acid catalysts
Electrophillic addition to acid-catalyzed hydration
Hydration – Dehydration reversible reaction
Equilibrium – to minimized any stress applied to it
( respond to Concentration change
Water concentration
Diluted sulfuric acid (high water) – alcohol formation
Strong acids (low water) – Alkene formation
Removal water – Alkene formation
5.6. Addition of Halogens to Alkenes
Halogens react with alkenes by Electophilic addition to Vicinal dihalide
C=C + X2
--------
X-C-C-X
In Cycloalkenes
Sterospecificity – Anti (trans) addition
1st step : Briged “Halonium” ion formation
most stable intermediate as octets of electrons
2nd step : Conversion of Halonium to 1,2-dihaloalkane
by halo-
in Aqueous solution – Formation of Vicinal Halohydrin
Alkenes w/ Chlorine & Bromine
C=C + X2 +
H2O ------- OH-C-C-X + HX
Anti addition
Markovnikov’s rule – Regioslective
Electrophile (Cl / Br) to less substituted end
Nucleophile (H2O) to more substituted end
5.7. Introduction to Organic Chemical Synthesis\
Chemical Synthesis – Economical, but Lead to Desired Structure
1) Reason backward form the target to starting
2) Well known reactions
ex) Cyclohexane from Cyclohexanol
1) Cyclohexene to Cyclohexane by hydrogenation
2) Cyclohexanol to Cyclohexene by dehydration
Alkene for addition of functional groups
Then, How to prepare alkene?
From alcohol by dehydration
From alkylhalide by E2 elimination
Process development – Fewest steps
5.8. Electrophilic Addition Reactions of Conjugated Dienes
Electrophilic addition – Akenes / Dienes
Conjugated Dienes – rich spectrum of reactivity
CH2=CHCO=CH2 +HCl -------- CH3CHCH=CH2 + CH3CH=CHCH2Cl
Cl
1,3-Butadiene
3-Chloro-1-butene
1-Chloro-2-butene
(Direct Addition) (Conjugated Addition)
(1,2 addition)
(1,4 addition)
Proton addition – to the end of conjugated diene
Halogen (Choride) / Double bond – Different positions
1,3-Butadiene carbocation formation – Allylic carbocation
CH3C+HCH=CH2 ----------- CH3CH=CH-C+H2
Resonance-Stabilized carbocation
Allylic carbocation stable than alkyl carbocation
A mixture of 1,2 and 1,4 addition w/ Chlorine or Bromine to
conjugated dienes
1,3 Butadiene --------- 3,4-dibromo-1-butene (37%)
(E)-1,4-dibromo-2-butene (63%)
5.9. Acidity of Acetylene and Terminal Alkynes
Alkynes – Unusual “acidity”
R-H
Ionizationof Hydrocarbon – Exceedingly weak acids
------------------------------ R:- + H+
(Carbanion)
Ka value
HC=CH >
Acetylene
pKa = 26
Ka = 10-26
CH2=CH2
Ethylene
~45
~10-45
>
CH3CH3
Ethane
~62
~10-62
sp hybridized – more electronegative than sp2 / sp3
However, acetylide ion formation in water – less effective
HC=CH + -OH ----x--- H-C=C- + H-OH
(weak acid) (weak base) (strong base) (strong acid)
w/ amide ion – acetylide ion + ammonia
HC=CH + -NH2 ------- H-C=C- + H-NH2
(strong acid) (strong base) (weak base) (weak acid)
5.10. Preparation of Alkynes by Alkylation
Triple bond introduction by double dehydrohalogenation of geminal
dihalide or vicinal dihalide
Alkylation – attachment of alkyl groups
Acetylene-----Monosubstituted (terminal alkynes) ----- Disubstituted
derivative of acetylene
two reactions
1) Conjugated base formation
HC=CH + NaNH2 ------HC=CNa + NH3
(Sodium amide) (Sodium acetylide)
2) Nucleophillic – Carbon bonding formation
HC=CNa + R-X ------ HC=CR + NaX
So, Synthetic reaction in liquid ammonia as solvent
(alternatively diethyl ether / tetrahydrofuran)
Dialkylation – Sequential addition
5.11. Addition Reactions of Alkynes
Hydrogenation – similar to alkenes (w/ Pt, Pd, Ni or Rh)
RC=CR’ + 2 H2 ------------------ RCH2CH2R’
Alkenes as intermediates
Alkene formation using Lindlar Palladium – “poisoned” catalyst
Addition of hydrogen on the surface of metal – “cis(z)” alkenes
Metal-Ammonia Reduction
CH3CH2C=CCH2CH3 ----------CH3CH2CH=CH2CH3
Na / NH3 (t(E)-Hexene)
Sodium and Ammonia as Reactants rather than catalysts
Addition of Hydrogen Halides
Reaction w/ electrophilic reagents to form alkenyl halides
RC=CR’ + HX ---- RCH=CR’
X
Regioselectivity based on Markovnikov’s rule
Proton to carbon w/ greater protons
Excessive hydrogen halide – Geminal di halides
HC=CH + HF ------- CH2=CHF ----- CH3CHF2
Hydration
Alcohol formation – enol formation
Rapid isomerization to aldehydes / Ketones
Keto-enol Isomerization / keto-enol tautomerism
Slow
OH Fast
O
RC=CR’ + H2O ------ RCH=CR’ ---------- RCH2CR’
(Sulfuric acid / Mercury sulfate)
Chapter 6 Aromatic Compounds
Aromatic hydrocarbons – Arenes
Aromatic – Pleasant-smelling plant material
Different Characteristics comparing w/ alkenes / alkynes
Electophilic Substitution
6.1. Structure and Bonding of Benzene
Benzene – Hexagonal (120o) / 140pm / planar structure
Intermediate between sp2-sp 2
Resonance forms – less reactive than alkenes
Delocalization energy / Resonance energy
“Aromaticity”
6.2. An Orbital Hybridization View of Bonding in Benzene
Intermediate between sp2-sp - 3- / 3-
6  electron – delocalization over 6 carbons
Cyclic Delocalization – Stabilization
6.3. Substituted Derivatives of Benzene and their Nomenclature
As prefixed –Benzene
Ex) Bromobenzene / tert-Butylbenzene / Nitrobenzene
Dimethyl derivatives – Xylenes
3-isomers: Ortho-; (1,2-dimethyl)
Meta-; (1,3-dimethyl)
Para-; (1,4-dimethyl)
O, m & p- (Common name) for disubstitutes
Nomenclature – Numbering – C1 at benzene derivatives
order is alphabetical
Aromatic ring structure as substituents
Pheny- (C6H5-)
Benzyl- (C6H5CH2-)
6.4. Polycyclic Aromatic Hydrocarbons
As coal tar (absence of O2 at high temp, 100oC)
Naphthalene (bicyclic)
Anthracene (tricyclic – linear)
Phenanthrene (tricyclic – angular)
Numbering of Rings – Start from right side ring to clockwise
6.5. Aromatic Side-Chain Reactions
Benzene ring – affect on side-chain reaction
Aromatic ring – Benzylic carbocation
Regioselective electrophillic addition to side-chain double
bond
Indene + HCl ------ 1-chloroindene
(75-84%)
due to the rate of carbocation formation
Benzene Oxidization w/ Chromic acid (H2SO4 to Na2Cr2O7)
No reaction (also alkanes – no reaction)
But, alkyl group on benzene ring – Oxidation
(Alkyl benzene - Benzoic acid / Benzoic acid derivatives)
in body – as excretion of toluene as benzoic acid
Reduction by catalytic hydrogenation of side-chain of double bond
Side-chain specific hydrogenation
6.6. Reactions of Arenes: Electrophilic Aromatic Substitution
Benzene – Unusual Behavior, when comparing unsaturated alkenes
In normal Alkenes: Electrophilic addition
C=C + E-Y -------- E-C-C-Y
Electrophilic reagents
But, Electrophilic Substitution rather than Addition
Ar-H +
E-Y -------- Ar-E
+ H-Y
6.7. Mechanism of Electrophilic Aromatic Substitution
Electrophilic Aromatic Substitution – Two step process
1st step: Carbocation formation
Resonance-stablized form: cyclohexadienyl cation
(arenium ion)
2nd step: Lose proton & electrophilic substitution
due to rearomatization – “stablilization”
6.8 Intermediates in Electrophilic Aromatic Substitution
Nitration / Sulfonation / Halogenation
Friedel-Crafts Alkylation
Friedel-Crafts Acylation
6.9. Rate and Regioselectivity in Electrophilic Aromatic Substitution
if one substitution is existing
Rate of electrophilic substitution?
Regioselectivity of substitution
Reactivity:
Toluene (CH3-) > Benzene > Trifluoromethyl Benzene
Regioselectivity:
In nitration reaction of toluene – 3 isomers
o- / m- / p-nitrotoulene : o- & p- (97%) / m-(3%)
“Methy group – Ortho, Para director
In nitration reaction of TFM-benzen
m- (91%)
Electrophilic substitution
1. All activating substituents – ortho, para directors
2. Halogen substituents – deactivating, but ortho, para directors
3. Strong deactivating substituents – meta director
6.10. Substituent Effects: Activating Groups
Based on the stability of the intermediates : stable Carbocation
All activating groups – as electron donor
Tertiary cabocation characters at carbon w/ methyl – Stable
As resonance carbocation
Oxygen containing substituents – O as electron donor
As resonance – Ortho substitution
6.11. Substituent Effects: Deactivating Group
Strong deactivating – Meta directing
Strong deactivating substituents – Electron-withdrawing
Aldehyde / Ketone / Carboxylic acid / Acyl chloride / Esters
O-atom: electron pulling – negative charged
6.12. Substituent Effects: Halogens
Halogen: Deactivating ortho, para directors
Halogen – electronegative
Hydroxyl group / Amino group
Ortho / para – position : Unshared electron donation for
stablilization
6.13. Regioselective Synthesis of Disubstituted Aromatic Compounds
Planning of Synthesis : order of Substitution
Regioselectivity
1. Benzene------ Acetophenone ------ m-bromoacetophenone
2. Benzene-------Bromobenzene------p-bromoacetophenone
6.14. A General View of Aromaticity: Huckel’s Rule
Among plana, monocyclic, fully conjugated polyenes, only those
possessing (4n+2) -electrons will be aromatic
6.15. Heterocyclic Aromatic Compounds
Heterocyclic compounds; Nitrogen / Oxygen / Sulfur
Heterocyclic aromatic compounds; Pyridine / Pyrrole / Furan
Chapter 7 Stereochemistry
Three dimensional world:
Spatial Arrangement of atoms and molecules – Stereochemistry
Stereoisomers
7.1. Molecular Chirality: Enantiomers
Mirror image superimposability
Greek word “Cheir” – Hand
7.2. The Stereogenic Center
Chiral vs. Achiral center of carbon
Carbon w/ double or triple bonds – no chiral
But ring structure can be if two different substituents
7.3 Symmetry in Achiral Structures
a plane of symmetry – bisect a molecule to mirror image
- Achiral
7.4. Properties of Chiral Molecules: Optical Activity
Optical activity – plane-polarized light: polarimeter
Wavelength – yellow light by sodium vapor lamp (D-line)
Polarizing filter – Plane polarized light
Optical rotation – Optical active
Chiral active vs. Achiral
Specific rotation [] = 100 / cl : c: conc. l: length
[]D25
Enantiomer –Opposite rotation, so 50:50 mixture – 0 rotation
Racemic Mixture – Optically inactive
7.5. Absolute and Relative Configuration
Spatial arrangement of substituents – Absolute configuration
(+) or (-) configuration
1951: (+) tartaric acid – “absolute configuration”
all “Relative configuration”
7.6. The Chain-Ingold-Prelog R-S Notational System
Nomenclature of stereochemistry
E / Z configuration of Alkenes
Sequence rules – absolute configuration based on atomic number of
substituents
1.
2.
3.
4.
5.
Stereogenic center
Substituents
Ranking substituents based on atomic number
Draw orientation of three highest ranking substituents
Determine R-S
R-Right (correct) / S-Left
R(-) / S(+)
7.7. Fischer Projections
3-D structure : Wedge-and-Dash drawing
Fischer projection : Vertical bonds –away
Horizontal bonds – point toward
7.8. Physical Properties of Enantiomers
Physical properties of enantiomers – MP / BP / Density : Same
However, Spatial arrangement difference
To cause different biological properties
(-)-Carvone – Spearment oil
(+)-Carvone – Caraway seed oil
Chemical Receptors – Chiral recognition
(-)-Nicotine ; more toxic
(+)-adrenaline: constriction of blood vessel
(-)-thyroxine :speed up metabolisms / loss weight
7.9. Reactions that Create a Stereogenic Center
Alkene : addition reaction
(E) / (Z) – 2-butene
-------------- 2-Bromobutane
as racemic mixture
in Living cells
Enzymes are chiral as single enantiomer
So, one enantiomer formation
Asymmetric environment
“The Molecular Asymmetry of Organic Natural Products”
7.10. Chiral Molecules with Two Sterogenic Centers
Sterogenic center carbons – absolute configurations
(R,R-I) (S,S-II) – mirror image ; Enantiomers
(R,S-III) (S,R-IV)- mirror image: Enantiomers
but, I and III or IV not mirror image : diastereomers
7.11. Achiral Molecules with Two Sterogenic Centers
in case of 2,3-Butanediol
CH3CHCHCH3
OH OH
only 3 stereoisomers : due to equivalent substitution
(2R,3S) sterogenic center – achiral structure
Meso form – Plane of symmetry
7.12. Molecules with Multiple Sterogenic Centers
possible 2n stereoisomes
7.13. Resolution of Enantiomers
Separation of racemic mixture to its enantiomer components
Chapter 8 Nucleophilic Substitution
Lewis base acts as a nucleophile to substitute for halide substitution
on carbon
R-X + Y- ---------- R-Y + XAlkyl halide to other class of organic compounds by
Nucleophilic substitution
Chapter 13. Alcohols / Phenols / Thiols / and Ethers
The characteristic functional groups of alcohols / Phenols
-OH (hydroxyl group) : R-OH
Ethers – two alkyl or aryl groups attached to oxygen atom
R-O-R’
Thiols – containing Sulfhydryl group (-SH)
R-SH
In Biological system
Hydroxyl group – oxidation / reduction / hydration / dehydration
Thiol groups in amino acids – 3-D structure
Biological properties
13.1. Alcohols: Stucture and Physical Properties
Hydroxyl group of alcohols – polar / electronegativities (O)
Hydrogen bonding formation – higher boiling point
Hydrophilic alcohol vs. Hydrophobic alcohol (longer carbons)
Diols / Triols – more hydrophilic
In Biological systems
Proteins / Nucleic acids – intramolecular hydrogen bonding
To keep shape and biological function
13.2. Alcohols: Nomenclature
IUPAC Names vs. Common names
13.3. Medically Important Alcohols
Methanol – colorless / odorless ; wood alcohol
Synthesis of methanal (formaldehyde)
Ethanol - colorless / odorless
Synthesis of other organic chemicals
Fermentation of glucose
Scotch (grain) / bourbon (corn)
Burgundy (grapes & grape skin)
Chablis (grapes w/o skin)
“denaturing alcohols” for laboratory use / unfit to drink
2-Propanol (Isopropyl alcohol)
rubbing alcohol – rapid evaporation
2,3-Ethanediol (ethylene glycol)
Automobile antifreeze
Sweet, but extremely poisonuous
1,2,3-Propanetriol (glycerol)
viscous sweet nontoxic liquid
13.4. Classification of Alcohols
Primary / Secondary / Tertiary
13.5. Reactions Involving Alcohols
Preparation of Alcohols
Hydration of alkene in acidic condition
Alkene + H2O
Hydrogenation of Aldehydes
Dehydration of Alcohols – Elimination reaction
Oxidation Reactions
Alcohols to aldehydes / ketones / carboxylic acid
By basic potassium permanganate (KMnO4/OH-)
Chromic acid (H2CrO4)
Tertiay alcohol – no oxidation
Alcohol metabolism in liver ; Oxidation to CO2
Ethanol -- -Acetaldehyde --- Acetic acid ---- CO2
Acetaldehyde –causing morning hangover
13.6. Oxidation and Reduction in Living Systems
Oxidoreductase reaction
13.7 Phenols
Hydroxyl groups on Benzene ring
Polar compounds
Thymol
Butylated Hydroxytoluene
Phenol as germicide
Carbolic acid (dilute solution of phenol) – antiseptic/disinfectant
13.8 Ethers
R-O-R’ : Structurally related to alcohol (R-O-H)
Polar C-O bonding
No hydrogen bond – lower BP than alcohol
But high BP than alkanes
In IUPAC naming
R-O- as Alkoxy group
Ex. Methoxy / Ethoxy
In common naming
Placing two alkyl groups, than “ether”
Less reactive, but extremely volatile / high flammable
Preparation of ether
Dehydration of two alcohols in acidic condition
R-OH + R;-OH ------ R-O-R’ + H2O
Diethyl ether – Anesthetic
Interaction w/ central nerve system
Accumulation in lipid – paralyze nerve transmission
Halogenated ether – General anesthetics
13.9. Thiols
Similar structure w/ alcohol
Nauseating aroma – Skunk / Onions / Galics
IUPAC naming – like alcohols : ----thiols
Cysteine – thiol
Oxidation of two cycteines ----- Disulfide bond
British Anti-Lewisite (BAL) – dithiol
Antidote in mercury poisoning
Co-A : Carrier of acetyl group
Chapter 14. Aldehydes and Ketones
Carbonyl group : Carbon bind to Oxygen
CHO- / C=O
Aldehydes / Ketones – similar physical properties
14.1 Structure and Physical Properties
Aldehydes / Ketones : Polar carbonyl group
Higher BP than hydrocarbons
Lower BP than alcohol (intermolecular hydrogen bonds)
Aldehydes / Ketones – Intermolecular hydrogen bonds w/ water
Less than five carbons – water soluble
14.2 IUPAC Nomenclature and Common Names
Aldehydes
Determine parent compound
Replace –e to –al
Carbon numbering : C1 at carbonyl group
Others – following normal IUPAC rule
Common names:
Aldehyde name: derived from corresponding
carboxylic acid
Substitution : using --Ketones
Similar to aldehydes
Replace –e to –one
Numbering of carbonyl group (as lowest position)
Common names:
- ketones (alkyl group: alphabetically or size)
14.3
Important Aldehydes and Ketones
Methanal (Formaldehyde/ Formalin – aqueous) – Preservation
Ethanal (Acetaladehyde) – Hangover (as a result of Liver metabolism)
Propanone (Acetone) – simplest ketone
Water miscible solvent
Butanone
Aldehydes / Ketones –
As Food & Fragrance chemicals / Medicinals / Ag chemicals
Vanillin / Benzaldehyde / Cinnamon / Citral / Demascone / Octanone
14.4 Reactions Involving Aldehydes and Ketones
Preparation of Aldehydes and Ketones
Oxidation of corresponding alcohols
(w/Pyridinium dichromate)
Oxidation reaction
Aldehydes to Carboxylic acid
(cf, Ketones less reactive than aldehydes)
Air oxidation to acids
Oxidizing reagents: potassium permanganate
Chromic acid
Tollens’ Test : Aldehhyde oxidation
Ag(NH3)2+ ------ Ag0 (precipitation)
Benedict’s Test : Aldehyde oxidation
Copper(III) hydroxide / Sodium citrate
All simple sugar – either Aldehydes or Ketones
Blood /Urine sugar test – Benedict’s test (red copper precipitation)
Reduction Reactions
Aldehydes / Ketones to corresponding alcohols
Reducing agents
Hydrogenation in Pressurized vessels w/ heating
Hydrogen gas / Catalyst (nickel / Platinum / Palladium)
Carbonyl double bond to single –OH
Dihydroxy acetone interaction w/ proteins
Brown-color : Artificial tanning
Addition Reactions in acid catalysts
Aldehydes + Alcohols -------- “Hemiacetal” structure (-OR)
At high acid / excessive alcohol ------- “Acetal” formation
Ketones + Alcohols ------ “Hemiketal”
“Ketal” formation
Hemiacetal / Hemiketal formation in Carbohydrates
Intramolecular reaction for “Cyclic” structure
Hemiacetal / Hemiketal interact w/ hydroxyl group
Intramolecular reaction for C-O-C bond
(Glycosidic bond formation)
Keto-Enol Tautomers
Equilibrium mixtures of two constitutional isomers “Tautomers”
Keto: double bond between O & C (Carbonyl group)
Enol: double bond between C & C ( Hydroxyl group)
Keto- more stable, so equilibrium tend to Keto form
Phosphoenolpyruvate – glycosis end-product
High energy molecules for ATP generation
Aldol Condensation
Aldehydes / Ketones to form larger molecules – New carbon bonds
In Lab by diluted base
In human by Aldolase during gluconeogenesis
Chapter 15 Carboxylic Acids and Carboxylic Acid Derivatives
Carboxylic Acid -COOH
Carbonyl + Hydroxyl group
Acids in water
Ester formation : Alcohols + Carboxylic acids
Acyl group: R-CO
Carboxylic derivatives:
Esters / Acid chlorides / Acid anhydrides / Amides
15.1
Carboxylic Acids
Structure and Physical Properties
Two polar functional group:
Carbonyl + Hydroxyl groups
Hydrogen bonds : inter / intra molecular, w/water etc.
Higher BP than aldehydes / Ketones / Alcohols
Water solubility decreased as carbon chain increased
Lower mw carboxylic acids : shape / sour tastes
Unpleasant odor
Longer carboxylic acids ; Fatty acids
Nomenclature
Determine parent compound
Replace –e to –oic acid (two: -dioic acid)
Numbering start at Carboxylic carbon
Naming w/ substitution
Common Names
-ic acid rather than –oic acid
Substitution : using ---
Some Important Carboxylic Acids
Fatty acids
Citric acid : preservation / antioxidant
Adipic acid (Hexanedioic acid) : tartness / retard spoilage
Lactic acid : tangy flavor / preservation
Reactions Involving Carboxylic Acids
Preparation of Carboxylic acids
Oxidation of alcohols / Aldehydes
Oxidizing agents : Oxygen / Chromic acid
Acid-Base Reaction
Carboxylic acid as proton donor
Dissociation of hydrogen atom – Carboxylate anion
5% dissociation
W/ strong base : Salt formation + Water
(-ate rather than –ic acid)
Long-chain carboxylic acid salts (fatty acid salts) – Soaps
Esterification
Carboxylic acid + Alcohols -------- Esters + H2O
15.2
Esters
Structure and Physical Properties
Esters ; Mild polar / Pleasant odor
Similar BP as aldehydes / Ketones
Smaller MW – water soluble
Nomenclature
As Carboxylic acid derivatives
Name of alkyl or aryl of Alcohol portions as first
Ending –ate of carboxylic acids
Reactions Involving Esters
Preparation of Esters
Conversion – Heat & trace of H+
Carboxylic acid + alcohol ----- Esters + H2O
Hydrolysis of Esters
Hydrolysis reactions in water (w/ heat)
Base catalyzed hydrolysis – Saponification
Carboxylic acid salts – soap
Fats & Oils – Triesters of alcohol glycerol
Hydrolyzed by saponification
Soap Production
Historically : Fats + Ash + Water
Ash: potassium carbonate / potassium hydroxide)
Small MW soap – water soluble / larger bubble
Larger MW soap – less soluble / fine bubble
Potassium – higher water soluble than Sodium
Soap – Micelles formation
Emulsion
Condensation Polymers
Ployesters : two different nonomers
Dicarboxylic acid + dialcohol
Esters w/ remaining two functional group
15.3 Acid Chlorides and Acid Anhydrides
Acid Chlorides : R-CO-Cl
-yl chloride
Noxious / Irritating chemicals / Slightly polar
React with water violently
Used in the Synthesis of Esters / Amides
Preparation
Carboxylic acid + Inorganic acid chloride ---Acid chloride + Inorganic products
Inorganic acid chloride (PCl3 / PCl5 / SOCl2)
Reaction w/ Water – Violent reaction (Be careful!)
Carboxyl chloride + H2O ---- Carboxylic acid + HCl
Acid Anhydrides; R-CO-O-OC-R
Two carboxylic acids with water removal
Naming
Same carboxylic acids : -oic Anhydride
Two different acyl groups
Ordered by Size or Alphabetically
Preparation
Reaction: Acid Chloride + Carboxylate Anion
Hydrolysis w/ water & heat
Reaction w/ Alcohols
Esters + Carboxylic acid
15.4 Nature’s High-Energy Compounds: Phosphoesters & Thioesters
Alcohol reaction w/ Phosphoric acid to form Phosphoester
(Phosphate ester)
In glycolysis : Phosphate ester formation as high energy molecule
Using ATP as phosphate donor
Phosphate ester + Phosphate group --- Phosphate anhydride bond
As energy
ATP – forming / break down – body weight each day
Thioester : Carboxylic acid + Thiols : R-S-CO-R
In cell, energy-harvesting pathway
Activating acyl groups for break down reaction
CoA-SH ; Acetyl CoA
Chapter 16 Amines and Amides
Nitrogen containing chemicals
Nucleic acids / Proteins
Containing “Amine: -NH2” group
Hydrogen may be substituted by other organic groups
Ex) Histamine
Inflammatory response
Antihistamine – Ephedrine
Amides : R-CO-NR2
Carboxylic acid + Amine ----- Amide Bond
Amino acids – Peptide bond ; Amide bond
16.1 Amines
Structure and Physical Properties
Amines – derived from ammonia
(more than one) Hydrogen substitution by R-groups
Pyramidal structure – Non bonding pair of electrons
Class by # of substitution
Primary amine
Secondary amine
Tertiary amine
Nitrogen atom – more electronegative than hydrogen atom
N-H bond : polar / Hydrogen bonding
Water soluble of smaller amines
Primary amine higher BP than tertiary amine
But, less strong bond than alcohols
Lower BP than Alcohols
Nomenclature
IUPAC names – use “Common” names
Chemical Abstracts or CA system
-e replace w/ -amine
For secondary / tertiary amine
N-alkylamine
N,N-(alkyl)2amine
IUPAC
(number) Amino-(parental compounds)
Reactions involving Amines
Preparation of Amine
Reduction of amides and Nitrocompounds (Nitration)
R-CO-NH2 / Ar-CO-NH2 / Ar-NO2
Basicity
Amine as week base in water
Alkylammonium ion formation
Neutralization
Alkylammonium salt formation w/ acids
-ammonium salt
Drug – Amines, but administration as salts for water solubility
Quaternary Ammonium Salts
4 organic groups on Nitrogen
R4-NX- (usually X- as Cl-)
Usually long carbon chain (called “Quats”)
Disinfectant / Antiseptics – detergent activity
Biological system : Choline
16.2 Heterocyclic Amines
Heterocyclic amines – Cyclic compounds w/ N-containing ring structure
Biological important alkaloids / compounds
Some – Lysergic acid diethylamide (LSD) – hallucinogenic
Cocaine – anesthetic
Nicotine
Morphine
Codeine
Heroine
16.3 Amides
Amides: Reaction between carboxylic acid derivatives and ammonia or
amines
Carboxyl group + amino group to form “Amide Bond”
Structure and Physical Properties
Most amides are solid at Rm temperature
High BP – Intermolecular hydrogen bonds between amides
C=O and NH2
C=O bond attracting electrons
Resonance hybrid formation
Nomenclature
Naming as carboxylic acid rule
Replace –ic acid to –amide
Reactions Involving Amides
Preparation of amides
Carboxylic acid w/ acid chlorides / acid anhydrides
Carboxylic acid --------- Acid Chloride
PCl5
Acid Chloride reaction w/ Ammonia or amines
Use 2 molar equivalents for HCl
Amide bonds – NutraSweet / Neotame
Hydrolysis of Amides
Breakdown to form carboxylic acid and ammonia / amine
16.4 A preview of Amino Acids, Proteins and Protein Synthesis
Peptide Bonding formation by amino acids
16.5 Neurotransmitters
All neurotransmitters containing Nitrogen
Catecholamine from tyrosine
Dopamine – “Parkinson’s disease”
“Schizophrenia”
Dopamine induced drugs
Cocaine / Heroin / alcohol / nicotine
Marijuana
Epinephrine (adrenaline)
Norepinephrine
Serotonin from tryptophan – depression
Prozac – antidepression
Histamine
Removing carboxylic acid of histidine
r-Aminobutyric acid and glycine
r-aminobutyric acid – removal carboxylic acid from
glutamate
Inhibition of neurotransmitter
Acetylcholine
Neuromuscular Junction
Nitric oxide and Glutamate
Nitric oxide from arginine
NO w/ glutamate – learning / forming memories