1 Organic Chemistry Courtney Eichengreen [email protected] 719.321.4187 1.

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Organic Chemistry

Courtney Eichengreen

[email protected]

719.321.4187

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Organic Chemistry I

From atoms to molecules and beyond Functional Groups Bonding and Molecular Structure Resonance and Isomers Intermolecular interactions

Hydrocarbons Substitution and Elimination Reactions Oxygen Containing Compounds Amines

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Lewis Dot Structures

Rules for writing Find total # valence e-

1 e- pair = 1 bond; Arrange remaining e- per octet rules Except: Period 3 can have expanded octet (vacant d orbital

required for hybridization)

Formal Charge # valence e- (isolated atom) - # valence e- (lewis structure) Sum of formal charge for each atom is the total charge on

the molecule ACTUAL charge distribution depends on electronegativity

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Structural Formulas

Dash Formula Condensed Formula Bond-line Formula Fischer projection Newman projection Dash-line-wedge Ball and stick

All Images courtesy of Exam Krackers

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Functional GroupsList #1- Critical for the MCAT Alkane C-C Alkene C=C Alkyne CΞC Alcohol R-OH Ether R-O-R Amine R-N-R2 Aldehyde R-CHO Ketone R2C=O Carboxylic Acid RCOOH Ester RCOOR Amide RCONH2

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Functional GroupsList #2- Also Useful Alkyl Halogen Gem-dihalide Vic dihalide Hydroxyl Alkoxy Hemiacetal Hemiketal Mesyl group Tosyl group Carbonyl Acetal Acyl

Anhydride Aryl Benzyl Phenyl Hydrazine Hydrazone Vinyl Vinylic Allyl Nitrile Epoxide Enamine Imine Nitro Nitroso

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Bonds

Types: Ionic

Covalent Coordinate covalent

Polar covalent

Hydrogen Bonds

complete transfer of electrons

shared electrons

One atom provides both electrons in a shared pair.

unequal sharing of electrons

bonds between polar molecules containing H and O, N, or F

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Covalent Bonds Sigma

Between s orbitals Small, strong, lots of rotation

Pi Between p orbitals Discreet structure, weaker than sigma, no rotation

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Covalent Bonds

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Bonds

In the pi bond of an alkene, the electron pair have:

A. 33% p character and are at a lower energy level than the electron pair in the bond.

B. 33% p character and are at a higher energy level than the electron pair in the bond.

C. 100% p character and are at a lower energy level than the electron pair in the bond.

D. 100% p character and are at a higher energy level than the electron pair in the bond.

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Hybridization

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Hybridization

Remember: All pi bonds are between P orbitals “Leftover” P and S orbitals hybridize,

participate in sigma bonds

Ex: H2C=CH2

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Hybrid Bonds

Suffix C bonds Hybridization

Percent

S:P

Bond Angle

Bond Length

Bond Strength

-ane

-ene

-yne

-yl

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Hybrid Bonds

Suffix C bonds Hybridization

Percent

S:P

Bond Angleo

Bond Length

(pm)

Bond Strength

(kJ/mol)

-ane C-C sp3 25:75 109.5 154 346

-ene C=C sp2 33:66 120 134 612

-yne C=C sp 50:50 180 120 835

-yl Side chain

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Special Cases – O and N

Know typical bonding for C, N, O

Bond angles in N compounds Lone pair occupies more space than sigma bond Bond angles 107.3

Bond angles in O compounds Bond angles 104.5

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A) sp2, sp2

B) sp2, sp3

C) sp3, sp3

D) sp3, sp2

For the molecule 1,4 pentadiene, what type of hybridization is present in carbons # 1 and # 3 respectively?

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VSEPR: molecular geometry

valance shell electron pair repulsion GEOMETRY = Minimize electron repulsion

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molecule Lewis structure Shape molecule Lewis structure Shape

BeCl2 Linear, sp

SF4 Seesaw SO3Trigonal

planar, sp2

ICl3 T shaped NO2- Bent

CH4 Tetrahedral, sp3 NH3Trigonal

Pyramidal

PCl5

Trigonal bipyramidal,

dsp3

SF6Octahedral,

d2sp3

IF5 Square Pyramidal ICl4- Square

Planar

VSEPR1. Draw the Lewis dot structure

2. Place electron pairs as far apart as possible

then large atoms, then small atoms

3. Name the molecular structure based on the position of the atoms

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NOW LET’S MOVE STUFF AROUND!We’ve seen static properties of atoms and molecules…

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Delocalized e- and Resonance

Resonance forms differ only in location of e-

To be a significant resonance form, must be stable Remember octet rule, and consider formal charge

Real structure = blend of possible resonance structures, “resonance hybrid”

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Resonance: Acids and Bases

Conjugate stabilized by RESONANCE

Organic Acids- Presence of positively charged H+ present on a OH such as methyl alcohol present on a C next to a C=O such as acetone (alpha C)

Organic Bases- Presence of lone pair e to bond to H Nitrogen containing molecules are most common Oxygen containing molecules can act as bases w strong acids

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Stereochemistry

Isomers: same molecular formula, different spatial arrangements

Different spatial arrangements different physical and chemical properties!

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Stereochemistry: Isomers

CONNECTIVITY

Structural (constitutional) isomers: Different connectivity.

C4H10 - Isobutane vs n-butane

Same connectivity, different spatial arrangement: Stereoisomers

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Stereochemistry: Isomers

ROTATION

Conformational isomers: Different spatial arrangement of same molecule, but doesn’t require bond breaking to interconvert!

“rotational” isomers Chair vs. boat, Staggered vs Eclipsed, Gauche vs Anti

DOES require bond breaking to interconvert: configurational isomers 25

Stereochemistry: Isomers

DOUBLE BOND

Geometric isomers: differ in arrangement about a double bond

Cis vs. trans

Stereoisomers that are not rotational and have no double bond: OPTICAL isomers

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Stereochemistry: Isomers

CHIRAL ARRANGEMENT

Enantiomers: non-superimposable mirror images Same physical properties (MP, BP, density, solubility,

etc.) except rotation of light and reactions with other chiral compounds

Chiral centers that are all opposite each other (R/S)

Diastereomers: chiral molecules with other than exactly opposite stereocenters (not mirror images)

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Stereochemistry: Isomers

What kind of isomers are the two compounds below?

A. DiastereomersB. EnantiomersC. Constitutional isomersD. Geometric Isomers

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Enantiomers differ in rotation of plane-polarized light Excess of one enantiomer causes rotation:

Right, clockwise, dextrarotary (d), or + Left, counterclockwise, levarotary (l), or –

Specific rotation [a] = a / (l*d)

Racemic: 50:50 mixt of enantiomers, NO net rotation

Same as R and S? NO

Meso molecule – NO net rotation, internal symmetry29

Stereochemistry: Rotating Light

Stereochemistry: Chirality R and S:

1. Assign priority by atomic number If attachments are the same, look at the atoms

2. Orient lowest priority (#4) away from the observer3. Draw a circular arrow from 1 to 2 to 3

R = clockwise S = counterclockwise

E and Z: Different than cis and trans Z= same side of high priority groups E=opposite side of high priority groups

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WHAT ABOUT BETWEEN MOLECULES?Now we know everything about what happens WITHIN molecules…

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Intermolecular interactions

Due to DIPOLE MOMENTS Charge distribution of bond is unequal

Molecule with dipole moment = polar Molecule without dipole moment = nonpolar Possible to have nonpolar molecules with polar bonds

Induced Dipoles Spontaneous dipole moment in nonpolar molecule Occurs via: polar molecule, ion, or electric field

Instantaneous Dipole Due to random e- movement

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Intermolecular interactions London Dispersion Forces

Between 2 instantaneous dipoles

Dipole-dipole interactions Dipole-dipole or dipole-induced dipole

Hydrogen Bonds Strongest dipole-dipole interaction

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When albuterol is dissolved in water, which of the following hydrogen-bonded structures does NOT contribute to its water solubility?

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HYDROCARBONS

The first and simplest class of molecules we need to get friendly with for Test Day:

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IUPAC Naming Conventions IUPAC Rules for Alkane Nomenclature

1.   Find + name the longest continuous carbon chain. 2.   Identify and name groups attached to this chain.3.   Number the chain consecutively, starting at the end

nearest highest priority (oxidation) substituent group. 4. Name the compound listing groups in alphabetical

order, preceded by their number in the compound. (di, tri, tetra etc., don’t count for alphabetizing).

MCAT secret: on Test Day, you’ll only ever have to MATCH to the correct name!

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Hydrocarbons

# of C Root Name # of C Root Name

1 meth 6 hex

2 eth 7 hept

3 prop 8 oct

4 but 9 non

5 pent 10 dec

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Hydrocarbons

Saturated: CnH(2n+2)

Unsaturated: one or more pi bonds; each pi bond decreases # of H by 2

Primary, secondary, tertiary, and quaternary carbons Know and be able to recognize the following structures

n-butyl sec-butyl

iso-butyl tert-butyl

n-propyl

Iso-propyl

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Alkanes

Physical Properties: Straight chains: MP and BP increase with length Branched chains:

BP decreases (less surface area, vDW forces) MP – a little more complicated due to crystal structure When compared to the straight chain analog, the straight

chain will have a higher MP than the branched molecule. BUT, amongst branched molecules, the greater the branching, the higher the MP.

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Alkanes-Important ReactionsPretty Darn Unreactive

Combustion: Alkane + Oxygen + High energy input (fire) Products: H2O, CO2, Heat

Halogenation Initiation with UV light

Homolytic cleavage of diatomic halogen Yields a free radical

Propagation (chain reaction mechanisms) Halogen radical removes H from alkyl Yields an alkyl radical, which can make more radicals

Termination Radical bonds to another radical

Reactivity of halogens: F > Cl > Br >>> I Selectivity of halogens (How selective is the halogen in choosing a position on an alkane):

I > Br > Cl > F more electronegative means less selective

Stability of free radicals: more substituted = more stable, so halogenation @ most sub’d C aryl>>>alkene> 3o > 2o > 1o >methyl

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Cycloalkanes

General formula: (CH2)n or CnH2n

Nomenclature: It’s the same! As MW increases BP increases; MP fluctuates

(crystal stacking with different geometry)

Ring strain in cyclic compounds:

Zero for cyclohexane (All C-C-C bond angles: 111.5°) Increases as rings become smaller or larger (up to cyclononane)

http://www.chem.uh.edu/Courses/Thummel/Chem3331/Notes/Chap3/

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Cycloalkanes

Cyclohexane Exist as “chair” and “boat” conformations Chair conformation preferred because it is at the lowest

energy. (WHY?)

Substituents can occupy axial and equatorial positions.Axia (6) - perpendicular to the ringEquatorial (6)- roughly in the plane of the ring

Big substituents prefer to be equatorial – less “crowding”!When the ring reverses its conformation, substituents reverse their relative position

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Cyclohexanes

In a sample of cis-1,2-dimethylcyclohexane at room temperature, the methyl groups will:

A. Both be equatorial whenever the molecule is in the chair conformation.

B. Both be axial whenever the molecule is in the chair conformation.

C. Alternate between both equatorial and both axial whenever the molecule is in the chair conformation

D. Both alternate between equatorial and axial but will never exist both axial or both equatorial at the same time

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REACTIONS!!

Things start getting more exciting once we start substituting H for more interesting functional groups… so let’s get ready for some

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Substitutions

Substitution:

one functional group replaces another

Electrophile: wants electrons, has partial + charge

Nucleophile: donates electrons, has partial – charge

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Eliminations

Elimination:

functional group lost, double bond made

Often, a Lewis base is responsible for taking H leaving behind an extra pair of e- for the =

The opposite of elimination is addition

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Substitution and Elimination

SN1: substitution, nucleophilic, unimolecular Mechanism: two-step

1. spontaneous formation of carbocation (SLOW) 2. Nucleophile attacks carbocation

Kinetics: rate depends only on the substrate, R=k[reactant] Stereochemistry: racemization of chiral substrates Favored with weak or bulky Nu, good LG, stable carbocation

Protic solvents stabilize carbocation Can see carbocation rearrangement

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Substitution and Elimination E1: elimination, unimolecular

Mechanism: two-step 1. spontaneous formation of carbocation (SLOW) 2. Base abstracts beta H

Kinetics: rate depends only on the substrate, R=k[reactant] Favored with good LG, stable carbocation, weak base

Protic solvents stabilize carbocation Can see carbocation rearrangement

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Which of the following carbocations is the most stable?

A.CH3CH2CH2CH2

B.CH3CH2CH2CHCH3

C. (CH3)3C

D.CH3 49

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Substitution and Elimination

SN2: substitution, nucleophilic, bimolecular Mechanism: CONCERTED Kinetics: rate depends on substrate+nucleophile, R=k[Nu][E] Stereochemistry: inversion of configuration

(but watch your R and S!) Favored with poor LG, small + strong Nu

Polar, APROTIC solvents don’t obstruct Nu

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Substitution and Elimination

E2: elimination, bimolecular Mechanism: CONCERTED

Anti-peri-planar transition state determines stereochemistry Kinetics: rate depends on substrate+base, R=k[substrate][B] Favored with strong bulky base

If you see HEAT, think Elimination E2 reactions often run in solvent of conjugate acid (WHY?)

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Benzene

A special molecule, a special case of substitution! Actually, it’s addition and then elimination.

Aromatic molecule, Stabilized by resonance Undergoes net substitution not addition (WHY?)

Substituents determine subsequent reactivity: Electron donating groups activate the ring and are ortho-para directors Electron withdrawing groups deactivate the ring and are meta directors Halogens are electron withdrawing BUT are ortho-para directors

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Benzene: Substituent Effects

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In what order were the substituents added? How can you tell?

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OXYGEN-CONTAINING COMPOUNDSAnother class of molecules we need to be familiar with:

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Oxygen Containing Compounds

Alcohols Aldehydes and Ketones Carboxylic Acids Acid Derivatives

Acid Chlorides Anhydrides Amides Keto Acids and Esters

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Alcohols

One of the most common reactions of alcohols is nucleophilic substitution. Which of the following are TRUE in regards to SN2 reactions:

I. Inversion of configuration occursII. Racemic mixture of products resultsIII. Reaction rate = k [S][nucleophile]

A. I onlyB. II onlyC. I and III onlyD. I, II, and III

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Alcohols Physical Properties:

Polar High MP and BP (WHY?) More substituted = less acidic

(CH3)3COH: pKa = 18.00 CH3CH2OH: pKa = 16.00 CH3OH: pKa = 15.54

Electron withdrawing substituents stabilize alkoxide ion and lower pKa. Tert-butyl alcohol: pKa = 18.00 Nonafluoro-tert-butyl alcohol: pKa = 5.4

General principles H bonding Acidity: weak relative to other O containing compounds

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AlcoholsNaming

Select longest C chain containing the hydroxyl group and derive the parent name by replacing –e ending of the corresponding alkane with –ol.

Number the chain beginning at the end nearest the –OH group.

Number the substituents according to their position on the chain, and write the name listing the substituents in alphabetical order.

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Alcohols-Oxidation & Reduction

Oxidation

Reduction

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Alcohols-Oxidation & Reduction

Common oxidizing and reducing agents Generally for the MCAT

Oxidizing agents have lots of oxygens Reducing agents have lots of hydrogens

Oxidizing Agents Reducing Agents

K2Cr2O7 LiAlH4

KMnO4 NaBH4

H2CrO4 H2 + Pressure

O2

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Making Alcohols: reduction synthesis

Aldehydes, ketones, esters, and acetates can be reduced to alcohols w strong reducing agents such as NaBH4 and LiAlH4

Electron donating groups increase the negative charge on the carbon and make it less susceptible to nucleophilic attack.

Reactivity: Aldehydes>Ketones>Esters/acetates

Only LiAlH4 is strong enough to reduce esters and acetates

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Alcohols to Alkylhalidesvia a strong acid catalyst R-OH + HCl RCl + H20

-OH is converted to a much better leaving group when protonated by a strong acid For tertiary alcohols: HCl or HBr Primary/secondary alcohols are harder, need SOCl2 or

PBr3

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In the reaction above, if the reagents in the first step were replaced with LiAlH4, what product would result?

a) c)

b) d)

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OH

OH

OH

O

OH

OH

OHHO

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CarbonylsCarbon double bonded to Oxygen

Planar stereochemistry Partial positive charge on Carbon

(susceptibility to nucleophilic attack) Aldehydes & Ketones (nucleophilic addition) Carboxylic Acids (nucleophilic substitution) Amides

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Aldehydes and Ketones

Physical properties: Carbonyl group is polar Higher BP and MP than alkanes (WHY?) More water soluble than alkanes (WHY?) Trigonal planar geometry, reduction yields racemic mixtures

General principles: Effects of substituents on reactivity of C=O: e- withdrawing increase

the carbocation nature and make the C=O more reactive Steric hindrance: ketones are less reactive than aldehydes Acidity of alpha hydrogen: carbanions , unsaturated carbonyls: resonance structures

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Aldehydes and KetonesNaming – lalala it’s the same rules!

Naming Aldehydes Replace terminal –e of corresponding alkane with –al. Parent chain must contain the –CHO group The –CHO carbon is C1 When –CHO is attached to a ring, we say “carbaldehyde”

Naming Ketones Replace terminal –e of corresponding alkane with –one. Parent chain is longest chain containing ketone Numbering begins at the end nearest the carbonyl C.

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Aldehydes and Ketones-Acetal and Ketal Formationnucleophilic addition at C=O bond

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Aldehydes and Ketones

Keto-enol Tautomerism: Keto tautomer is preferred (alcohols are more

acidic than aldehydes and ketones).

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Guanine, the base portion of guanosine, exists as an equilibrium mixture of the keto and enol forms. Which of the following structures represents the enol form of guanine?

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Aldehydes and Ketones-reactions at adjacent positions

Aldol (aldehyde + alcohol) condensation: Occurs at the alpha carbon

Pi electrons in enol act as nucleophile Base catalyzed condensation (removal of H2O) Can use mixtures of different aldehydes and ketones

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Aldehydes are easy to oxidize because of the adjacent hydrogen. In other words, they are good reducing agents.

Examples used as indicators: Potassium dichromate (VI): orange to green Tollens’ reagent (silver mirror test): grey ppt. Fehlings or benedicts solution (copper solution): blue to red

Ketones (no adjacent H) are resistant to oxidation.

Aldehydes and Ketones-Oxidation (Aldehydes Carboxylic acids)

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Aldehydes and Ketones Organometallic reagents:

Nucleophilic addition of a carbanion to an aldehyde or ketone to yield an alcohol

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Carboxylic Acids

General Principles: Electrophilic carbonyl C susceptible to nucleophilic

attack! Fairly strong acids (compared to other organic

Oxygen containing compounds) Acidity of terminal H increases with EWG, decreases

with EDG – always consider stability of conjugate base Planar, polar, H bonding

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Which class of compounds would have a higher boiling point, Acyl Chlorides or Carboxylic Acids? Why?

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Carboxylic AcidsNaming

Carboxylic acids derived from open chain alkanes are systematically named by replacing the terminal –e of the corresponding alkane name with –oic acid.

Compounds that have a –CO2H group bonded to a ring are named using the suffix –carboxylic acid.

The –CO2H group is attached to C #1 and is not itself numbered in the system.

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Carboxylic Acids-important reactions

Carboxyl group reactions: Nucleophilic attack:

Carboxyl groups and their derivatives undergo nucleophilic substitution. Aldehydes and Ketones undergo addition (WHY?)

Must contain a good leaving group or a substituent that can be converted to a good leaving group.

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Carboxylic Acids-important reactions

Reduction: Form a primary alcohol LiAlH4 is the reducing agent

CH3(CH2)6COOH CH3(CH2)6CH2OHLiAlH4

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Carboxylic Acids-important reactions

Carboxyl group reactions: Decarboxylation: know that it happens (-CO2)

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Carboxylic Acids-important reactions

Fischer Esterification Reaction: Alcohol + Carboxylic Acid Ester + Water

Acid Catalyzed- protonates –OH to H2O (excellent leaving group)

Alcohol performs nucleophilic attack on carbonyl carbon

These bonds arebroken

H+

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Carboxylic Acids-reactions at two positions

Substitution reactions: keto reactions shown, consider enol reactions

To make ->

SOCl2

   or PCl3

Heat, -H2OR'OH, heat,

H+-

R2NH

heatHO-

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Carboxylic Acids-reactions at two positions

Halogenation: enol tautomer undergoes halogenation

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Acid DerivativesNaming

Acid Halides (RCOX) “-oyl halide” instead of “-oic acid” ex: ethanoyl chloride

Acid Anhydrides (RCO2COR’) Just replace the word acid with anhydride.

2 acetic acid acetic anhydride Unsymmetrical anhydrides are named by citing the two acids alphabetically.

Acetic acid + benzoic acid acetic benzoic anhydride Esters (RCO2R’)

Name R’ (on the –O– side) with “-yl”, R (on the =O side) with “-oate” ex: isopropyl propanoate

Amides (RCONH2) Just use the suffix “amide”

Acetic acid acetamide If the Nis further substituted, first identify the substituent groups and then the

parent amide. The substituents are preceded by the letter N. Propanoic acid + methyl amine N-Methylpropanamide

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Acid Derivatives-Relative Reactivity

A more reactive acid derivative can be converted to a less reactive one, but not vice versa

Only esters and amides commonly found in nature.

Acid halides and anhydrides react rapidly with water and do not exist in living organisms

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Acid Derivatives- Reactions of Derivatives

•Hydrolysis- +water carboxylic acid•Alcoholysis- +alcohol ester•Aminolysis- +ammonia or amine amide•Reduction- + H- aldehyde or alcohol•Grignard- + Organometallic ketone or alcohol

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Acid DerivativesTransesterification

Transesterification: exchange alkoxyl group with ester of another alcohol

Alcohol + Ester Different Alcohol + Different Ester

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