Organic Chemistry

Chapter 1 Chemical Bonding

Organic chemistry – Carbon compounds Historically related to life systemsMolecular Structure – Properties relationship

1.1 Atoms, Electrons and OrbitalsMolecular structure – Chemical bondingAtoms – Protons (+) in nucleus

Electrons (-) in orbitals

Obitals – Size / Shape / Directional propertiess-orbital – 1s / 2s

Principal Quantum Number (n) – specify “Shell”related to energy of orbitals

1s / 2s – 1s closer to nucleus / lower energyHydrogen ; 1s1 Helium; 1s2

Electrons – negatively charged / Properties of spinSpin 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 atomInvolved to chemical bonding / reaction

1s2s / 2p3s

octet of electrons – Helium / Neon / Argon (noble gas)“closed-shell” electron configuration / unreactive

1.2 Ionic BondsAtoms combined with one another – Compounds

Attractive forces between atoms – “Chemical Bond”

Ionic bond – oppositely charged ionsCation (+) / Anion (-)Common in inorganic compoundsRare 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 BondsCovalent – Shared electron pair

“stable closed-shell” electron configuration

Lewis structures – electron as dotUsually “octet rule” to form noble gas configuration

CH4 / CF4

1.4 Double bonds and Triple bondsLewis rule – shared electrons

4 electrons – double bonds6 electrons – triple bonds

CO2 - O=C=OHCN – H-C=N

1.5 Polar Covalent Bonds and ElectronegativityIn Covalent bonds – even electron distribution between atoms

Polarized – polar covalent bondPartially charged – Dipole (+/-)

HFElectonegativity – electron attraction

1.6 Formal ChargeLewis 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 distributionsNitrogen – positively chargedOxygen – Negatively charged

1.7 Structural Formulas of Organic MoleculesSystematic 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 IsomerismsSame 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 ResonanceRestrict 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 moleculesThree 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)” modelMaximal separation – Tetrahedral angle (109.5o)

Molecular shape Water – bent / Ammonia – trigonal pyramidal

1.11 Molecular Polaritymolecular geometry with polarity of chemical bonds

electron dipole

H2C=O Formaldehyde – polarCO2 Carbon dioxide – nonpolar

1.12 sp3 Hybridization and Bonding in MethaneCH4 (1s2 2s2 2px

1 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 EthaneCarbon-Carbon covalent bonding

Ethane : CH3-CH3

bond between Methyl groups

1.14 sp2 Hybridization and Bonding in Ethylenesp2 Hybrid orbitals (2s 2p2)

-bond formation of unhybridized 2p orbital

Double bonds – combination of and bondsStronger & shorter carbon bonding

1.15 sp Hybridization and Bonding in AcetyleneAcetylene – CH-CH

Triple bonding between carbons + + bondings

1.16 Summary

Chapter 2 Alkanes and Cycloalkanes

Structure of Organinc chemicals – Reasonably confident predictionsProperties & Chemical reaction

Functional groups – Characteristic patterns of reactivityFrameworks – non-reactive backbones

Nomenclature System – IUPAC rules

2-1. Classes of Hydrocarbons

Hydrocarbons – only Carbon and HydrogenAliphatic (fat) & Aromatic (odor)

Aliphatic Hydrocarbons

Alkanes / Alkenes (Double bond) / Alkynes (Triple bond)Ex) Ethane / Ethylene / Acetylene

Aromatic Hydrocarbons – ArenesEx) 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 compoundsHydrogen replacement

Alcohol ROHAlkyl halide RClAmine RNH2

Expoxide R----REther RORNitrile RC=NNitroalkane RNO2

Thiol R-SH

Note) Carbonyl Group (C=O)Most abundant and biologically significant in Nature

Carbonyl CompoundsAldehyde KetoneCarboxylic acidCarboxylic acid derivatives

Acyl halideAcid anhydride (-H2O)EsterAmide

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)

Methane / Ethane / PropaneB.P. -160 -89 -42

2-5. Conformations of Ethane and Propane

Conformation – Spatial Arrangement of moleculesDue to Rotation about single bond

Ethane based on C-H and C-C bondsStaggered vs. Eclipsed

Drawing as “Wedge-and-Dash”“Sawhorse”“Newman Projection”

Conformational Analysis – to Predict the stability of Molecules

“Staggered conformation” – as stable conformationMost separation of electrons

“Eclipsed conformation” – least stable conformation“Torsional strain”

2-6. Isomeric Alkanes: the Butanes

C4H10 (Butane) – Constitutional Isomersn-Butane (Normal – linear carbon bonds)Isobutane – Branched carbon chain

Methyl group – CH3

Methylene group – CH2

Methine group – CH

n-buthane – High BP and MP pointsStaggered conformation – Zigzag arrangement of C

Anti vs. Gauchi conformation based on Methyl groupGauchi – van der Waals strain (Steric hinderance)

N-butane (65% Anti / 35% Gauche)

2-7 Higher Alkanes

n-Alkanes – Linear structureCH3(CH2)nCH3

Constitutional isomersEx) 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 chainStep2. Substituent groups to parent chainStep3. Numbering of parent chain from shortest

substituent groupStep4. Name using numerical location of

substituent group

1 2 3 4 5 CH3CHCH2CH2CH3 2-methylpentane

CH3

2-10. Alkyl Groups

Alkyl group – lacks one of the hydrocarbons of an alkaneMethyl (CH3-)Ethyl (CH3-CH2-)

Carbon atoms – Degree of substitution by other carbonsPrimary / Secondary / Tertiary / Quarternary

Branched alkyl groupsUsing longest continuous chain as a baseStart 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 rulesBased on Longest chains

Substitution group numbering (shortest distance)Start w/number + substituent group by alphabeticallyName “Alkane”

if equal locants from different numbering directionsthen lower number for first appear substituent

2-12 Cycloalkane Nomenclature

Cycloalkane – a ring of three or more carbonsCnH2n

Attached groups – Numbering carbonsNumbering 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 bondstorsional strainAngle strain of carbon (60o vs 109.5o) – less stable

Cycloalkanes – reducing Torsional & Angle strain

2-14 Conformations of Cyclohexane

Six-ring compounds – nonplanar conformationChair conformation – StableBoat conformation – less stable

Hydrogen bond to carbonAxial hydrogensEquatorial hydrogens

2-15 Conformational Inversion (Ring Flipping) in Cyclohexane

Rotation of carbon bondsRing InversionChair-Chair conversionRing flipping

“Axial and Equatorial conversion”

2-16 Conformational Analysis of Monosubstituted Cyclohexane

Ring inversion in MethylcyclohexaneAxial 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 - SteroisomersOn 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 PointLonger chain – higher BPBranched – lower BP

Gaseous state – Intermolecular Attractive ForcesIAF – dependent upon “Surface Area”Branched – compact – less surface area – lower BP

In Alkanes – as non polar compounds May not be no intermolecular forceHowever, electron – temporary distortion

“Induced-dipole”

Weak attractive force – as “van der Waals force”

Solubility in water – Insoluble in waterPolar solutes into polar solventsNon 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 30-150oCKerosene (C8-14) BP 175-325oC – Disel

Petrochemicals by cracking petroleumSuch 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 /alcoholOr

Halo- (fluoro- / chloro- / bromo- / iodo-) alkaneAs substituent on the alkane chain

Alcohol : Alkanes to alkanolsHydroxyl 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 / Tertiary alcohol (alkyl halide) RCH2G R2CHG 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:

Propane / Ethanol / FluoroethaneBp –42oC 78oC -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 bondsProvide structural oder3-D structure determination

Boiling PointHigher molecule – higher BP / Increased “induced dipole”

Due to electron field

Chlorinated derivatives of methaneIncreased chlorine – increased BP

Fluoroinated derivatives of methaneUnique – Fluorine substitution: decreased “Induced dipole”

Fluorinated hydrocarbon (fluorocarbons)-“Non sticking” Teflon coatin

Solubility in WaterAlkyl halide – insoluble in waterLower MW alcohols – soluble in water

Hydrogen bonding

DensityAlkyl fluorides / chlorides – less denseAlkyl 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 solutionBronsted & Lowry :

Acid – Proton donor / Base – Proton acceptor

Water(Base)+Acid---------Conjugate acid of water+Conjugated BaseOxonium 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 energyReactant – Energized / Activation energy (Eact)Transition state - UnstableProduct

Proton transfer from alkyl halides to waterElementary step – one transition state in concerted reaction

Molecularity – biomolecularCf) series of elementary steps (transition state)

Proton transfer from hydrogen bromide to water / alcohols- most rapid chemical process

Lower activation energyGreater 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 + H-OHAlcohol Hydrogen halide Alkyl halide Water

Reactivity) Acidity HI > HBr > HCl >> HFTertiary alcohols – most reactivitySecondary / Primary – require Heating

Hydrogen bromide (HBr) w/ primary alcoholNeed heating – Forming Alkyl bromideCan be done w/ (NaBr, H2SO4)

Simple reaction equation – based on organic chemicalOmitting water / inorganic on arrow

NaBr, H2SO4

1-Butanol -------------------- 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 reaction1st step – Acid-Base reaction2nd 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 carbonSimple example ; CH3

+

3 valence electrons

3- bonds between C-H ; sp2 hybrid1- 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-seekingUnshared paired electrons which can be used covalent bond

Interaction betweenElectrophilic carbocations – empty p-orbitalsNucleophillic 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 formationsCarbon-halogen bond begins to form before the carbon-oxygen bond of the alkyloxonium ion is completely broken down

Chapter 4 : Alkenes and Alkynes l : Structure and Preparation

Alkenes – Double bond : Reaction siteAkynes – Triple bond : Gas atmospheres of many stars

4.1. Alkene Nomenclature

1) –ene2) 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

CycloalkenesFollowed alkene rules(Carbon position - double bond / Functional group)

Multiple double bonds2 double bonds – Alkadienes (dienes)

Conjugated / Isolated / Cummulated

4.2. Structure and Bonding in Alkenes

sp2-hybridized – double bond contains & componentsTrigonal planar geometry

C=C : 134pm / 121.4o (HCC) + 117.2o (HCH)sp2-hybrided : remain / unpaired p-orbit electrons

Overlapping each other (side-by-side) - bondInteraction between double bonds

Isolated – independent structural unitsConjugated – 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 isomersUnbranched (1) / Branched (1) – double bond at 1Cis / Trans (double bond at different position – 2)

Interconversion between Cis / Trans – Rotation of double bondBut, 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 bondE – “opposite” of higher atomic numbers of double bond

Cahn-Ingold-Prelog Priority Rules1. Higher atomic number2. if identical – Precedence at the first point of difference3. at the point of attachment – counts all atoms4. at the point of attachment – counts one by one5. 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 SubstitutionDouble bond: Alky (R) group substitution

MonosubstitutedDisubstitutedTrisubstitutedTetrasubstituted (more stable than less substitution)

Sp2-hybridized carbons of double bond – Attracting electronAlkyl groups – better electron-releasing substituents than Hydrogen

“Electron Effect”

van der Waals StrainsAlkenes more stable by “trans” than “cis”

Free of stains between substituentsRepulsion – 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 positionEx) 2-methyl-2-butanol to 2-methyl-2-buteneDehydration of alcohol is selective in respect to its directionDouble bond between C2 and C3 than C2 and C1

“Regioselective” – Zaitsev rule

Dehydration – SteroselectiveStable isomers – “trans” predominant than “cis”

4.8. The mechanism of acid-catalyzed dehydration of alcohols (see F4-5)

Dehydration of alcoholConversion of alcohol to alkyl halides

Both reaction – 1) promoted by acids 2) reactivity : 1o < 2o < 3o

Carbocations – Key intermediatesCarbocations 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 ruleSteroselectivity : trans (E) than cis (Z) isomers

4.10. The E2 Mechanism of Dehydrohalogenation

1) the reaction – Second-order kineticsrate = k [alkyl halide][base]

2) rate of elimination depends on the halogenRF < Cl < RBr < RI

Reactivity increased as decreasing C-halo bonding

E2 : Elimination bimolecular – One-step mechanism1) C-H bond breaking2) C=C bonding formation3) 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 breakingCarbocation intermediate followed by deprotonation

E1 – Elimination of unimolecular

First order kineticsRate = k[alkyl halide]

In tertiary / secondary alkyl halides w/o base

4.12. Alkyne Nomenclature

Triple bond : CnH2n-2

Monosubstituted (terminal) alkynesDisubstituted (internal) alkynes

IUPAC rule -yne

4.13. Stucture and Bonding in Alkynes: sp Hybridization

sp- hybridized - & 2 bondingunpaired 2p orbit overlapping

(natural cycloalkynes as anticancer drugs)

4.14 Preparation of Alkynes by Elimination Reactions

Double dehydrohalogenation of dihaloalkanesDihalogenalkanes – 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 : ExothermicRequire metal catalysts (ex, Platinum)

Reaction StepsHydrogen atoms to catalysts surfaceHydrogen 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 intermediatesSecondary carbocation is more stable than primary carbocation

5.5. Acid-Catalyzed Hydration of Alkenes

Alkenes to Alcohol by addition of H2O w/ Acid catalystsElectrophillic addition to acid-catalyzed hydration

Hydration – Dehydration reversible reactionEquilibrium – to minimized any stress applied to it( respond to Concentration change

Water concentrationDiluted sulfuric acid (high water) – alcohol formationStrong acids (low water) – Alkene formationRemoval 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 CycloalkenesSterospecificity – Anti (trans) addition

1st step : Briged “Halonium” ion formationmost stable intermediate as octets of electrons

2nd step : Conversion of Halonium to 1,2-dihaloalkane by halo-

in Aqueous solution – Formation of Vicinal HalohydrinAlkenes w/ Chlorine & Bromine

C=C + X2 + H2O ------- OH-C-C-X + HX

Anti addition

Markovnikov’s rule – RegioslectiveElectrophile (Cl / Br) to less substituted endNucleophile (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 starting2) Well known reactions

ex) Cyclohexane from Cyclohexanol

1) Cyclohexene to Cyclohexane by hydrogenation2) Cyclohexanol to Cyclohexene by dehydration

Alkene for addition of functional groupsThen, How to prepare alkene?

From alcohol by dehydrationFrom alkylhalide by E2 elimination

Process development – Fewest steps

5.8. Electrophilic Addition Reactions of Conjugated Dienes

Electrophilic addition – Akenes / DienesConjugated 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 dieneHalogen (Choride) / Double bond – Different positions

1,3-Butadiene carbocation formation – Allylic carbocation

CH3C+HCH=CH2 ----------- CH3CH=CH-C+H2

Resonance-Stabilized carbocationAllylic 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”

Ionizationof Hydrocarbon – Exceedingly weak acidsR-H ------------------------------ R:- + H+

(Carbanion)

Ka value

HC=CH > CH2=CH2 > CH3CH3

Acetylene Ethylene EthanepKa = 26 ~45 ~62Ka = 10-26 ~10-45 ~10-62

sp hybridized – more electronegative than sp2 / sp3 However, acetylide ion formation in water – less effectiveHC=CH + -OH ----x--- H-C=C- + H-OH(weak acid) (weak base) (strong base) (strong acid)

w/ amide ion – acetylide ion + ammoniaHC=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 reactions1) Conjugated base formationHC=CH + NaNH2 ------HC=CNa + NH3

(Sodium amide) (Sodium acetylide)2) Nucleophillic – Carbon bonding formationHC=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” catalystAddition of hydrogen on the surface of metal – “cis(z)” alkenes

Metal-Ammonia ReductionCH3CH2C=CCH2CH3 ----------CH3CH2CH=CH2CH3

Na / NH3 (t(E)-Hexene)

Sodium and Ammonia as Reactants rather than catalysts

Addition of Hydrogen HalidesReaction w/ electrophilic reagents to form alkenyl halides

RC=CR’ + HX ---- RCH=CR’ X

Regioselectivity based on Markovnikov’s ruleProton to carbon w/ greater protons

Excessive hydrogen halide – Geminal di halidesHC=CH + HF ------- CH2=CHF ----- CH3CHF2

HydrationAlcohol formation – enol formation

Rapid isomerization to aldehydes / KetonesKeto-enol Isomerization / keto-enol tautomerism

Slow OH Fast ORC=CR’ + H2O ------ RCH=CR’ ---------- RCH2CR’ (Sulfuric acid / Mercury sulfate)

Chapter 6 Aromatic Compounds

Aromatic hydrocarbons – ArenesAromatic – Pleasant-smelling plant materialDifferent Characteristics comparing w/ alkenes / alkynesElectophilic Substitution

6.1. Structure and Bonding of Benzene

Benzene – Hexagonal (120o) / 140pm / planar structureIntermediate 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 –BenzeneEx) Bromobenzene / tert-Butylbenzene / Nitrobenzene

Dimethyl derivatives – Xylenes3-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 derivativesorder 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 carbocationRegioselective 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 bondSide-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 formationResonance-stablized form: cyclohexadienyl cation

(arenium ion)

2nd step: Lose proton & electrophilic substitutiondue to rearomatization – “stablilization”

6.8 Intermediates in Electrophilic Aromatic Substitution

Nitration / Sulfonation / Halogenation Friedel-Crafts AlkylationFriedel-Crafts Acylation

6.9. Rate and Regioselectivity in Electrophilic Aromatic Substitution

if one substitution is existingRate 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-benzenm- (91%)

Electrophilic substitution1. All activating substituents – ortho, para directors2. Halogen substituents – deactivating, but ortho,

para directors3. 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 donorTertiary cabocation characters at carbon w/ methyl – Stable

As resonance carbocation

Oxygen containing substituents – O as electron donorAs resonance – Ortho substitution

6.11. Substituent Effects: Deactivating Group

Strong deactivating – Meta directingStrong deactivating substituents – Electron-withdrawing

Aldehyde / Ketone / Carboxylic acid / Acyl chloride / EstersO-atom: electron pulling – negative charged

6.12. Substituent Effects: Halogens

Halogen: Deactivating ortho, para directorsHalogen – electronegative

Hydroxyl group / Amino groupOrtho / para – position : Unshared electron donation for

stablilization

6.13. Regioselective Synthesis of Disubstituted Aromatic Compounds

Planning of Synthesis : order of SubstitutionRegioselectivity

1. Benzene------ Acetophenone ------ m-bromoacetophenone2. 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 / SulfurHeterocyclic 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 superimposabilityGreek word “Cheir” – Hand

7.2. The Stereogenic Center

Chiral vs. Achiral center of carbon

Carbon w/ double or triple bonds – no chiralBut 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: polarimeterWavelength – yellow light by sodium vapor lamp (D-line)Polarizing filter – Plane polarized light

Optical rotation – Optical activeChiral active vs. Achiral

Specific rotation [] = 100 / cl : c: conc. l: length[]D

25

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 stereochemistryE / Z configuration of Alkenes

Sequence rules – absolute configuration based on atomic number of substituents

1. Stereogenic center2. Substituents3. Ranking substituents based on atomic number4. Draw orientation of three highest ranking substituents5. Determine R-S

R-Right (correct) / S-LeftR(-) / S(+)

7.7. Fischer Projections

3-D structure : Wedge-and-Dash drawing

Fischer projection : Vertical bonds –awayHorizontal bonds – point toward

7.8. Physical Properties of Enantiomers

Physical properties of enantiomers – MP / BP / Density : SameHowever, 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-Bromobutaneas racemic mixture

in Living cellsEnzymes 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: Enantiomersbut, I and III or IV not mirror image : diastereomers

7.11. Achiral Molecules with Two Sterogenic Centers

in case of 2,3-ButanediolCH3CHCHCH3 OH OH

only 3 stereoisomers : due to equivalent substitution

(2R,3S) sterogenic center – achiral structureMeso 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 + X-

Alkyl halide to other class of organic compounds byNucleophilic 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 atomR-O-R’

Thiols – containing Sulfhydryl group (-SH)R-SH

In Biological systemHydroxyl group – oxidation / reduction / hydration / dehydrationThiol 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 systemsProteins / 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 alcoholSynthesis of methanal (formaldehyde)

Ethanol - colorless / odorlessSynthesis of other organic chemicalsFermentation 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 antifreezeSweet, 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 AlcoholsHydration of alkene in acidic condition

Alkene + H2OHydrogenation of Aldehydes

Dehydration of Alcohols – Elimination reaction

Oxidation ReactionsAlcohols to aldehydes / ketones / carboxylic acid

By basic potassium permanganate (KMnO4/OH-)Chromic acid (H2CrO4)

Tertiay alcohol – no oxidation

Alcohol metabolism in liver ; Oxidation to CO2Ethanol -- -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 ringPolar compounds

ThymolButylated Hydroxytoluene

Phenol as germicideCarbolic acid (dilute solution of phenol) – antiseptic/disinfectant

13.8 Ethers

R-O-R’ : Structurally related to alcohol (R-O-H)Polar C-O bondingNo hydrogen bond – lower BP than alcohol

But high BP than alkanes

In IUPAC namingR-O- as Alkoxy group

Ex. Methoxy / Ethoxy

In common namingPlacing two alkyl groups, than “ether”

Less reactive, but extremely volatile / high flammable

Preparation of etherDehydration of two alcohols in acidic condition

R-OH + R;-OH ------ R-O-R’ + H2O

Diethyl ether – AnestheticInteraction w/ central nerve system

Accumulation in lipid – paralyze nerve transmission

Halogenated ether – General anesthetics

13.9. Thiols

Similar structure w/ alcoholNauseating aroma – Skunk / Onions / Galics

IUPAC naming – like alcohols : ----thiols

Cysteine – thiolOxidation of two cycteines ----- Disulfide bond

British Anti-Lewisite (BAL) – dithiolAntidote 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 groupHigher BP than hydrocarbonsLower BP than alcohol (intermolecular hydrogen bonds)

Aldehydes / Ketones – Intermolecular hydrogen bonds w/ waterLess than five carbons – water soluble

14.2 IUPAC Nomenclature and Common Names

Aldehydes Determine parent compoundReplace –e to –alCarbon numbering : C1 at carbonyl groupOthers – following normal IUPAC rule

Common names:Aldehyde name: derived from corresponding carboxylic acidSubstitution : using ---

KetonesSimilar to aldehydesReplace –e to –oneNumbering of carbonyl group (as lowest position)

Common names:- ketones (alkyl group: alphabetically or size)

14.3 Important Aldehydes and Ketones

Methanal (Formaldehyde/ Formalin – aqueous) – PreservationEthanal (Acetaladehyde) – Hangover (as a result of Liver metabolism)Propanone (Acetone) – simplest ketone

Water miscible solventButanone

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 KetonesOxidation of corresponding alcohols

(w/Pyridinium dichromate)

Oxidation reactionAldehydes to Carboxylic acid

(cf, Ketones less reactive than aldehydes)Air oxidation to acidsOxidizing reagents: potassium permanganate

Chromic acid

Tollens’ Test : Aldehhyde oxidationAg(NH3)2

+ ------ Ag0 (precipitation)

Benedict’s Test : Aldehyde oxidationCopper(III) hydroxide / Sodium citrate

All simple sugar – either Aldehydes or KetonesBlood /Urine sugar test – Benedict’s test (red copper precipitation)

Reduction ReactionsAldehydes / Ketones to corresponding alcohols

Reducing agents

Hydrogenation in Pressurized vessels w/ heatingHydrogen gas / Catalyst (nickel / Platinum / Palladium)

Carbonyl double bond to single –OH

Dihydroxy acetone interaction w/ proteinsBrown-color : Artificial tanning

Addition Reactions in acid catalystsAldehydes + Alcohols -------- “Hemiacetal” structure (-OR)At high acid / excessive alcohol ------- “Acetal” formation

Ketones + Alcohols ------ “Hemiketal”“Ketal” formation

Hemiacetal / Hemiketal formation in CarbohydratesIntramolecular reaction for “Cyclic” structureHemiacetal / Hemiketal interact w/ hydroxyl group

Intramolecular reaction for C-O-C bond(Glycosidic bond formation)

Keto-Enol TautomersEquilibrium 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-productHigh energy molecules for ATP generation

Aldol Condensation

Aldehydes / Ketones to form larger molecules – New carbon bondsIn Lab by diluted baseIn human by Aldolase during gluconeogenesis

Chapter 15 Carboxylic Acids and Carboxylic Acid Derivatives

Carboxylic Acid -COOHCarbonyl + Hydroxyl groupAcids in waterEster formation : Alcohols + Carboxylic acids

Acyl group: R-COCarboxylic derivatives:

Esters / Acid chlorides / Acid anhydrides / Amides

15.1 Carboxylic Acids

Structure and Physical PropertiesTwo polar functional group:

Carbonyl + Hydroxyl groupsHydrogen bonds : inter / intra molecular, w/water etc.

Higher BP than aldehydes / Ketones / Alcohols

Water solubility decreased as carbon chain increasedLower mw carboxylic acids : shape / sour tastes

Unpleasant odorLonger carboxylic acids ; Fatty acids

NomenclatureDetermine parent compoundReplace –e to –oic acid (two: -dioic acid)Numbering start at Carboxylic carbon Naming w/ substitution

Common Names-ic acid rather than –oic acidSubstitution : using ---

Some Important Carboxylic AcidsFatty acidsCitric acid : preservation / antioxidantAdipic acid (Hexanedioic acid) : tartness / retard spoilageLactic acid : tangy flavor / preservation

Reactions Involving Carboxylic Acids

Preparation of Carboxylic acidsOxidation of alcohols / Aldehydes

Oxidizing agents : Oxygen / Chromic acid

Acid-Base ReactionCarboxylic acid as proton donorDissociation 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

EsterificationCarboxylic acid + Alcohols -------- Esters + H2O

15.2 Esters

Structure and Physical PropertiesEsters ; Mild polar / Pleasant odor

Similar BP as aldehydes / KetonesSmaller MW – water soluble

NomenclatureAs Carboxylic acid derivatives

Name of alkyl or aryl of Alcohol portions as firstEnding –ate of carboxylic acids

Reactions Involving Esters

Preparation of EstersConversion – Heat & trace of H+

Carboxylic acid + alcohol ----- Esters + H2O

Hydrolysis of EstersHydrolysis reactions in water (w/ heat)Base catalyzed hydrolysis – Saponification

Carboxylic acid salts – soapFats & Oils – Triesters of alcohol glycerol

Hydrolyzed by saponificationSoap Production

Historically : Fats + Ash + Water Ash: potassium carbonate / potassium hydroxide)

Small MW soap – water soluble / larger bubbleLarger MW soap – less soluble / fine bubblePotassium – higher water soluble than Sodium

Soap – Micelles formationEmulsion

Condensation PolymersPloyesters : two different nonomers

Dicarboxylic acid + dialcoholEsters 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

PreparationCarboxylic 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-RTwo carboxylic acids with water removal

NamingSame carboxylic acids : -oic AnhydrideTwo different acyl groups

Ordered by Size or AlphabeticallyPreparation

Reaction: Acid Chloride + Carboxylate AnionHydrolysis w/ water & heatReaction 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 moleculeUsing ATP as phosphate donor

Phosphate ester + Phosphate group --- Phosphate anhydride bondAs energy

ATP – forming / break down – body weight each day

Thioester : Carboxylic acid + Thiols : R-S-CO-RIn cell, energy-harvesting pathway

Activating acyl groups for break down reaction

CoA-SH ; Acetyl CoA

Chapter 16 Amines and Amides

Nitrogen containing chemicalsNucleic acids / Proteins

Containing “Amine: -NH2” groupHydrogen may be substituted by other organic groups

Ex) HistamineInflammatory 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-groupsPyramidal structure – Non bonding pair of electrons

Class by # of substitutionPrimary amineSecondary amineTertiary amine

Nitrogen atom – more electronegative than hydrogen atomN-H bond : polar / Hydrogen bonding

Water soluble of smaller amines

Primary amine higher BP than tertiary amineBut, less strong bond than alcohols

Lower BP than Alcohols

NomenclatureIUPAC names – use “Common” names

Chemical Abstracts or CA system-e replace w/ -amine

For secondary / tertiary amineN-alkylamineN,N-(alkyl)2amine

IUPAC (number) Amino-(parental compounds)

Reactions involving Amines

Preparation of AmineReduction of amides and Nitrocompounds (Nitration)

R-CO-NH2 / Ar-CO-NH2 / Ar-NO2

BasicityAmine as week base in water

Alkylammonium ion formation

NeutralizationAlkylammonium salt formation w/ acids

-ammonium salt Drug – Amines, but administration as salts for water solubility

Quaternary Ammonium Salts4 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 / compoundsSome – Lysergic acid diethylamide (LSD) – hallucinogenic

Cocaine – anestheticNicotineMorphineCodeineHeroine

16.3 Amides

Amides: Reaction between carboxylic acid derivatives and ammonia or amines

Carboxyl group + amino group to form “Amide Bond”

Structure and Physical PropertiesMost amides are solid at Rm temperatureHigh BP – Intermolecular hydrogen bonds between amides

C=O and NH2

C=O bond attracting electronsResonance hybrid formation

NomenclatureNaming as carboxylic acid rule

Replace –ic acid to –amide

Reactions Involving Amides

Preparation of amidesCarboxylic acid w/ acid chlorides / acid anhydridesCarboxylic acid --------- Acid Chloride

PCl5

Acid Chloride reaction w/ Ammonia or aminesUse 2 molar equivalents for HCl

Amide bonds – NutraSweet / Neotame

Hydrolysis of AmidesBreakdown 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 tyrosineDopamine – “Parkinson’s disease”

“Schizophrenia”Dopamine induced drugs

Cocaine / Heroin / alcohol / nicotineMarijuana

Epinephrine (adrenaline)Norepinephrine

Serotonin from tryptophan – depression Prozac – antidepression

HistamineRemoving carboxylic acid of histidine

r-Aminobutyric acid and glyciner-aminobutyric acid – removal carboxylic acid from glutamateInhibition of neurotransmitter

AcetylcholineNeuromuscular Junction

Nitric oxide and GlutamateNitric oxide from arginineNO w/ glutamate – learning / forming memories