Mcat Organic Chemistry Lecture 2

Front 1

Alkanes

Back 1

Methane and compounds whose major functional group contains only C-C single bonds

Depending on how many other alkyl groups are attached, C are referred to as:
1. methyl (0 alkyl groups)
2. primary (1)
3. secondary (2)
4. tertiary (3)

Front 2

Physical properties of alkanes

Back 2

boiling point is governed by intermolecular forces

as C are added in single chain, molecular weight increases, intermolecular forces increase, boiling and melting point increases

Branching lowers boiling point but increases melting point

1st 4 alkanes are gases at RT

low density (density increases with molecular weight)

insoluble in water

soluble in hydrocarbons

Front 3

Cycloalkanes

Back 3

alkane rings

some rings structures put strain on the C-C bonds because they bend them away from normal 109.5 degree angle of sp^3 C and cause crowding

Front 4

Ring Strain

Back 4

cyclohexane = 0 but increases as rings become larger or smaller

increases up to 9C ring structure, after which it becomes zero as more C are added

less ring strain means lower energy and more stability

Front 5

Cyclohexane

Back 5

ring straing = 0

3 confomers:
1. chair
2. twist
3. boat

all 3 exist at room temperature, but chair predominates because it is lowest energy

each C in cyclohexane has 2 H

in chair conformation, H are oriented in different directions

Front 6

Equatorial hydrogens

Back 6

H projecting outward from center of ring

substituent groups favored in this position

Front 7

Axial hydrogen

Back 7

H projecting upward or downward

crowding occurs most often in this position with substituents, which raises energy level of ring and causes instability

Front 8

Combustion

Back 8

violent reaction

alkanes mixed with O and energy is added

takes place at high temperatures (inside flame of a match)

generates its own heat and can be self-perpetuation

reactants:
1. alkane
2. oxygen
3. energy, high temperature

products:
1. Carbon dioxide
2. water
3. heat

Front 9

Radical reaction

Back 9

combustion is a type of radical reaction

alkanes reaction with halogens (F, Cl, Br, but not I) in presence of heat or light to form free radicals (each atom in bond retains 1 electron from broken bond)

results in 2 highly reactive species, each with an unpaired electron (free radical)

Front 10

Heat of combustion

Back 10

change in enthalpy (H) of a combustion reaction

can be used to compare relative stabilities of isomers because combustion of isomeric hydrocarbons requires equal amounts of O and produced equal amounts of CO2 and H2O

higher heat of combustion, higher energy level, less stability

Front 11

Halogenation

Back 11

chain reaction with at least 3 steps:
1. initiation
2. propagation
3. termination

exothermic process

stability of alkyl radicals (same as carbocation):
tertiary > secondary > primary > methy

alkyl radical exhibit trigonal planar geometry

Front 12

Initiation

Back 12

halogen starts as diatomic molecule, which is homolytically cleaved by heat or light

resulting in free radicals

Front 13

Propagation

Back 13

halogen radical removes H from alkane

resulting in alkyl radical

alkyl radical reacts with diatomic halogen creating alkyl halide and new halogen radical

may or may not continue indefinitely

stage at which most of product is formed

Front 14

Termination

Back 14

2 radicals bond to end chain reaction or propagation

radical bonds to wall of container to end chain reaction or propagation

Front 15

Reactivity of halogens

Back 15

from most to least reactive:
1. F (can be explosive)
2. Cl
3. Br (requires heat to react)
4. I (nonreactive)

Front 16

Selectivity of halogens

Back 16

how selective a halogen radical is when choosing a position on an alkane

from most to least selective:
1. I
2. Br
3. Cl
4. F

Front 17

Alkene

Back 17

C-C chain that contains a double bond

contain pi-bonds, which are less stable than sigma-bonds, making alkenes more reactive than alkanes

more acidic than alkanes, because pi-bonds are electron-hungry

the more substituted, the more thermodynamically stable

increase molecular weight means increased boiling point

branching decreases boiling point

same physical property trends as alkanes and alkynes

Front 18

Elimination reaction

Back 18

synthesis of alkene

1 or 2 functional groups are removed to form a double bond

base abstracts a H

Front 19

Dehydration of an alcohol

Back 19

E1 reaction, which means rate only depends on 1 species concentration (in this case the alcohol)

alcohol forms alkene in presence of hot concentrated acid

1. acid protonates OH, producing good leaving group H2O
2. (slower, rate determining step) H2O drops off, forming a carbocation (rearrangement may occur if more stable carbocation can be formed)
3. H2O deprotonates carbocation and alkene is formed

major product is most stable, most substituted alkene

Front 20

Carbocation stability

Back 20

follows same trend as radical stability

most to least stable:
tertiary > secondary > primary > methyl

Front 21

Saytzeff rule

Back 21

major product of elimination will be most substituted alkene

Front 22

Dehydrohalogenation

Back 22

E1 if absence of strong base

E2 if high concentration of strong, bulky base

E1: (2 steps)
1. halogen drops off
2. H is removed by weak base

E2: (1 step)
1. Base removes H from C next to halogen-containing C and halogen drops off, leaving alkene

bulky base prevents Sn2 reaction

if base too bulky, Saytzeff rule is violated, resulting in least substituted alkene

Front 23

Substitution reaction

Back 23

nucleophile attacks C

Front 24

Hydrogenation

Back 24

example of addition reaction

heterogeneous catalyst (exists in a different phase than reactants or products, tiny shavings of metal) used

exothermic reaction with high energy of activation

heats of hydrogenation can be used to measure relative stability of alkene

lower heat of hydrogenation, more stable alkene

Front 25

Syn-addition

Back 25

same side addition

hydrogenation

catalyst is usually tiny shavings of metal

1. H and alkene adsorb to surface of catalyst
2. Both Hydrogens add to same size of alkene, forming an alkane

Front 26

Ozonolysis

Back 26

oxidation cleaves alkene at double bond

reactants:
1. alkene
2. ozone (reactive electron pairs with high charge density, very reactive, breaks through alkenes and alkynes)
3. Zinc
4. H2O

products:
1. 2 molecules of O double bonded to C (ketone)

Front 27

Electrophile

Back 27

electron-loving species

partially positive charge

attracted to double bond of alkene because of electron-rich environment

Front 28

Markonikov's rule

Back 28

rule followed when H-halides (HF, HCl, HBr, and HI) are added to alkenes

H will add to least substituted C of double bond

2 steps:
1. H-halide (bronsted-lowry acid) creates positively charged H, which acts as electrophile (slow, rate determining step) and attacks double bond to form carbocation
2. newly formed carbocation picks up negatively charged halide ion

Front 29

Anti-Markovnikov addition

Back 29

If peroxides (ROOR) are present, Br and not H will add to least substituted C

other halogens still follow Markovnikov's rule even in presence of peroxides

Front 30

Hydration of alkene

Back 30

follows Markovnikov's rule

H2O is added to alkene in presence of acid

reverse of dehydration of an alcohol

low temperatures and dilute acid drive reaction toward alcohol formation

high temperatures and concentrated acid drive reaction toward alkene formation

alkene + H2O = alcohol
<--- concentrated acid and heat
---> dilute acid and cold

Front 31

Anti-addition

Back 31

addition from opposite sides of double bond

Front 32

Oxymercuration/demercuration

Back 32

reaction creates alcohol from alkene

follows Markovnikov's rule

1. Hg(OAc)2 partially dissociates to +Hg(OAc), which acts as electrophile, attacking double bone and forming mercurinium ion. Water attacks mercurinium ion to form organomercurial alcohol in anti-addition
2. demercuration to form alcohol by addition of reducing agent or base

in organometallic compounds, metals like to lose electrons and take on full or partial positive charge

Front 33

Hydroboration

Back 33

anti-Markovnikov and syn-addition reaction

produces alcohol from alkene

presence of peroxide

Front 34

Halogenation of alkenes

Back 34

halogens are more reactive toward alkenes and alkynes than alkanes (need heat or light to react)

Br2 and Cl2 add to alkenes via anti-addition to form vic-dihalides (2 halogens connected to adjacent C)

if water present, halohydrin formed (OH and halogen attached to adjacent C)

Front 35

Benzene

Back 35

undergoes substitution and not addition

has resonance, therefore aromatic

flat molecule because resonance atoms are in same plane

stabilized by resonance, therefore C-C bonds have partial double bond character

contains 6 Hydrogens

If contains 1 substituent, remains 5 positions are labeled:
1. ortho (closest to substituent)
2. meta (2nd closest)
3. para (furthest from substituent)

Front 36

Electron withdrawing group

Back 36

is in R position of ring (substituent)

deactivates ring (make less reactive)

directs new substituents to meta position

exception:
halogens are electron withdrawing group and deactivate ring as expected, but direct new substituents to ortho and para positions

Front 37

Electron donating group

Back 37

activates ring (make more reactive)

directs new substituent to ortho and para positions

Front 38

Strongly electron donating group

Back 38

1. O-
2. OH
3. NR2

Front 39

Moderately electron donating group

Back 39

1. OR

Front 40

Weakly electron donating group

Back 40

1. R

Front 41

Strong electron withdrawing group

Back 41

1. NO2
2. NR3+
3. CCl3

Front 42

Moderately electron withdrawing group

Back 42

1. CRO
2. CHO
3. COOR
4. COOH
5. SOOOH
6. CN

Front 43

Weakly electron withdrawing group

Back 43

1. X

Front 44

Benzene compounds

Back 44

1. phenol = benzene-OH
2. aniline = benzene-NH2
3. toluene = benzene-CH3
4. benzoic acid = benzene-COOH
5. nitrobenzene = benzene-NO2

Front 45

Substitution reaction

Back 45

1 functional group replaces another

2 types:
1. SN1
2. SN2

substitution, nucleophilic, unimolecular, bimolecular

# represents order of rate law ans not number of steps

Front 46

SN1 reaction

Back 46

substitution reaction

rate dependent only on 1 of the reactants, independent of nucleophile, directly proportional to concentration of substrate (eletrophile, molecule being attacked by nucleophile)

2 steps:
1. formation of carbocation (Slow, rate determining step), leaving group (group being replaced) breaks away on its own to form carbocation
2. (quick) nucleophile attacks carbocation

only tertiary substrate will undergo SN1

Elimination often accompanies SN1 reactions to produce alkene

strength of nucleophile unimportant

Front 47

SN2 reaction

Back 47

single step

rate dependent on concentration of nucleophile and substrate

1. nucleophile attakcs substrate from behind leaving group and knocks leaving group free while bonding to substrate

results in inversion of configuration on C being attacked by nucleophile

tertiary C sterically hinders nucleophile attack

rate of reaction decreases from:
methyl > primary > secondary

E2 often accompanies SN2 reactions to produce alkene

strength of nucleophile important

Front 48

Nucleophile

Back 48

base always stronger nucleophile (more negative charge and polarizable, less electronegative) than its conjugate acid

basicity not the same as nucleophilicity (decreases up and right on periodic table)

negative charge and polarizability add to nucleophilicity and electonegativity reduces nucleophilicity

nucleophile behaves as base then elimination reaction results

Front 49

Sn1 vs. Sn2

6 things: "the nucleophile and the 5 Ss"

Back 49

1.Nucleophile
2. Substrate
3. Solvent
4. Speed
5. Stereochemistry
6. Skeleton rearrangement

Front 50

Nucleophile

Back 50

Sn2 requires a strong nucleophile

nucleophilic strength doesn't affect Sn1

Front 51

Substrate

Back 51

Sn2 reactions don't occur with sterically hindered substrate

Sn2 requires methyl, primary or secondary substrate

Sn1 requires secondary or tertiary substrate

Front 52

Solvent

Back 52

highly polar solvent increases reaction rate of Sn1 by stabilizing carbocation

highly polar solvent slows down Sn2 reaction by stabilizing nucleophile

Front 53

Speed

Back 53

Speed of Sn2 depends on concentration of substrate and nucleophile

Speed of Sn1 depends only on substrate

Front 54

Stereochemistry

Back 54

Sn2 inverts stereochemistry about chiral center

Sn1 creates a racemic mixture

Front 55

Skeleton rearrangement

Back 55

Sn1 may be accompanied by carbon skeleton rearrangement

Sn2 never rearranges carbon skeleton

Front 56

Elimination

Back 56

Can accompany both Sn1 and Sn2 reactions

occurs when nucleophile behaves as a base rather than a nucleophile (abstracts protons rather than attacking a C)

always results in C-C double bond

E1 and E2 kinetics are similar to Sn1 and Sn2 kinetics respectively

Front 57

Alcohols

Back 57

Boiling point goes up with molecular weight and down with branching

Melting point goes up with molecular weight, unclear trend with branching

boiling and melting points are much higher than alkanes because of hydrogen bonding (increases intermolecular forces, which must be overcome to change phase)

more soluble in water than alkane and alkenes (longer to C chain, the less soluble)

hydroxyl group increases polarity and allows for hydrogen bonding with water

lose proton, therefore act as acid (less acidic than water)

Front 58

Alcohol order of acidity (strongest to weakest)

Back 58

methyl
primary
secondary
tertiary

most stable conjugate base is of strongest acid, weakest negative charge

Front 59

acid & conjugate base

Back 59

H2O --> OH- (water, more acidic)

RCH2OH --> RCH2O- (primary alcohol, neutral)

RCCH3CH3OH --> RCCH3CH3O- (tertiary alcohol, more basic)

Front 60

Grignard Synthesis of an Alcohol

Back 60

1. organometallic compound (strong nucleophile and base) nucleophilic attack on a carbonyl C
2. after acid bath (H3O+), produces an alcohol

Front 61

Reduction Synthesis of an Alcohol

Back 61

nucleophilic attack mechanism

similar to grignard synthesis

hydrides (H-) react with carbonyls to form alcohols

doesn't extend the C skeleton, unlike grignard

NaBH4 & LiAlH4 reduce aldehydes and ketones

only LiAlH4 is strong enough to reduce esters and acetates because carbonyl C has less positive charge because of electron donation and therefore is less attractive to nucleophile

Front 62

Nucleophilic addition

Back 62

1. H2O (alcohol, nucleophile) attacks and connects to substrate
2. positive charged proton will drop off into solution

Front 63

Nucleophilic substitution

Back 63

1. H2O (alcohol, nucleophile) attaches and connects to substrate
2. R group of substrate is kicked off
3. positive charged proton will drop off into solution

Front 64

Oxidation of alcohols

Back 64

primary and secondary alcohols can be oxidized

tertiary alcohols cannot be oxidized

primary alcohols oxidize to aldehydes, which in turn, oxidize to carboxylic acids

secondary alcohols oxidize to ketones

reverse process is called reduction

Front 65

Oxidation or reduction

Back 65

Oxidation:
1. loss of H2
2. addition of O or O2
3. addition of X2 (X = halogens)

Reduction:
1. addition of H2 (or H-)
2. loss of O or O2
3. loss of X2

Neither oxidation nor reduction:
1. addition or loss of H+, H2O or HX

if O to H ratio of a molecule increases, than molecule has been oxidizes

if O to H ratio decreases, than molecule has been reduced

oxidizing agents have lots of O

reducing agents have lots of H

Front 66

alkyl halides from alcohols

Back 66

1. hydroxyl group of alcohol is protonated by Halide and water is good leaving group
2. halide ion (nucleophile) attacks and cinnects to C and kicks off H2O, forming alkyl halide

Sn1 reaction with tertiary alcohol

Sn2 reaction with other alcohols

C-O bond is broken, alcohol is electrophile

O-H bond is broken, alcohol is nucleophile

protonation of hydroxyl group (alcohol) requires strong acid,

Front 67

Formation of sulfonates

Back 67

alcohols form esters called sulfonates

nucleophilic substitution, alcohol acts as nucleophile

tosylates and mesylates are commonly used sulfonates

sulfonate ions are weak bases and excellent leaving groups (Sn1 or Sn2 reactions)

Front 68

Pinacol rearrangement

Back 68

dehydration of an alcohol (vicinal diol) that results in an unexpected product (ketone or aldehyde)

1. 1st OH is protonated and removed by acid to form carbocation
2. methyl group may move to form more stable carbocation, which exhibits resonance
3. water deprotonates most stable resonance (all atoms have octet of electrons) forming pinacolone and regenerating acid catalyst

Front 69

ethers

Back 69

relatively non-reactive (other than epoxides)

hydrogen bond with compounds that contain H attached to N, O or F

polar, soluble in water

organic compounds soluble in ethers (no H need to be broken) making ethers useful solvents

relatively low boiling points, similar to alkanes (making them useful solvents)

undergo one reaction with halo-acids (HI or HBr) to form alcohols or alkyl halides
1. R2O + HBr --> ROH + RBr

oxidized to form peroxides

Front 70

Epoxides

Back 70

3-membered cyclic ethers

more reactive than typical ethers due to ring strain

react with water in presence of acid catalyst to form diols (glycols), in an anti-addition

epoxide O often protonated to form an alcohol, when one of C is attacked by nucleophile

Front 71

acidities of functional groups (weakest to strongest)

Back 71

1. H3C-CH3
2. H2C=CH2
3. H2
4. NH3
5. HC triple bond CH
6. H3CCHO
7. H3C-CH2-OH
8. H2O
9. H3CCOOH