SUMMER CHEM 51B FINAL

Ether + Strong Acid

ether cleavage

strong acid:

H-I

H-Cl

Alkyl Halide R-Br + Alkoxide + Alkoxide Conj Acid (Solvent)

Williamson Ether Synthesis

-Ether + NaBr

SN1

- tertiary carbons; polar protic nucleophile

-two steps

-Uses weak nucleophile/base (generally neutral)

-Higher degrees the better (tertiary > secondary > primary>methyl)

- carbocation formation

- rate = k[RX]

- need good leaving group

-Favors Protic Solvents

SN2

- polar apriotic

- 1 step (concerted) “attack of nucleophile on backside.”

- rate = k[RX][Nuc]

-Lower degrees the better (methyl>primary > secondary > tertiary)

-Strong nucleophile (OH-) or strong nuc/weak base (I-, CH3CO2-) required for methyl, primary, and secondary

-Uses strong nucleophiles (generally negative charge)

-check for steric hindrance and inversion/retention

-Stereochemistry: Inversion only

Polar Priotic

-Hydrogen Bonding

-Can act as H-bond donor to nucleophiles

-H-bonds shield nucleophiles and reduce nucleophilicity 

-Solvents: HO, ROH, RCOOH

E1

-2 steps

-Higher degrees the better (tertiary > secondary > primary>methyl)

-needs a more stable carbocation to be fast

- Polar Priotic

- rate = k[RX]

-Weak nuc/weak base (typically solvolysis) for secondary and tertiary carbons; competes with SN1 (without heat)

-Follows Zaitsev’s rule: removes hydrogen from carbon attached to fewest hydrogens

Polar Apriotic

-No hydrogen bonding

-No H-bonds to Nu-, so they are more “naked” and more nucleophilic 

Epoxide + EtOH, H2SO4

Epoxide Opening:

1. Epoxide Protonation

2. Backside attack of Nuc

-Acidic Conditions (ACID: H2SO4) attack the MORE substituted side

-Basic Conditions (BASIC: NaOEt) attack the LESS substituted side

Epoxide + NaOEt, H2O

Epoxide Cleavage via SN2

Result: Cleavage of one C-O bond, Addition of OH

-Basic Conditions (BASIC: NaOEt) attack the LESS substituted side

Alkene + H-Br, ROOR

-Radical Hydrobromination

-makes Alkyl Halide

-Br added anti-Markovnikov

Alkene + H-X

-makes Alkane: alkyl halide

-X added Markovnikov

Alkene + H2O and H2SO4

-Hydration

-Alcohol alkane

-OH added Markovnikov

Alkene + X2 + H2O

-Halohydrin: Adds an X and an OH breaks alkene to alkane

-Anti Addition Reaction: Additions add on opposite sides

-OH on more substituted side while halide is on less substituted

-makes Enantiomer

Halohydrin: Alkane with X and OH + (Base like :OH, NaH, NaOH)

Epoxide formation

:OH attacks H-o

O: attacks C-Br

Br leaves

Racemization

-50:50 mixture of enantiomers

-SN1 + E1

alkene + BH3 and H2O2

-Hydroboration

-Adds BH2 and H where alkene was then turns it to OH and makes it an alkane

-Syn Addition: H and B same side/stereochem

-BH2 and OH added anti-Markovnikov

Alkene + 9BBN + H2O2/HO-

Hydroboration-Oxidation

B attaches to alkene, R group included (weird kite > ((=B

Alkyne + 2 X2

-Halogenation

-makes alkane and adds 4 X

-(dead end for synthesis)

1) Alkene + Br2 2) Alkane + NaNH2 (excess)

-alkene to alkyne synthesis

-makes TERMINAL ALKYNE

-go from alkene to alkyne in two steps (need two hydrogens

Vicinal Dihalide Alkane (diff carbs but same side/cis) + NaNH2 x2

R---R Alkyne

INTERNAL ALKYNE

Alkyne + HX

-Hydrohalogenation

-makes a geminal dihalide (2 X and 2 H)

-X adds Markovnikov

1) Alkyne + BH3 2) H2O2, NaOH

-Hydroboration Oxidation

-makes an aldehyde

-adds alcohol anti-Markovnikov (enol) then becomes a aldehyde

keto-enol tautomerism

Enol form is the one with the alcohol.

Keto form is the one with the ketone.

Keto form is more stable, it is the predominant form.

Ketone

R-C=O,-R

Alkyne + H+, Hg 2+

K/E taut: Hydration

Alkyne + H20, H2SO4,HgSO4

-Hydration

-breaks alkyne and makes ketone and two H

-converts enol to keto tautomer

Addition

Increases numb of bonds, trip to double to single

Oxidation

form C-O, break C-H

Alkane to Alcohol to Aldehyde to Alkane

Reduction

form C-H, break C-O

Carboxylic Acid to Aldehyde to Alcohol to Alkane

Reduces nmb of bonds, single to double to triple

Alkyne + Lindlar's Catalyst + H2

-syn addition

-does not reduces the alkene

-makes a cis alkene

Alkyne + Na/NH3

-anti addition

-does not reduces the alkene

-makes a trans alkene

Alcohol + H2SO4

-E1 reaction

-makes alkene from alcohol

-makes minor and major product

Alcohol + POCL3, Pyridine

-E2 reaction

-makes alcohol to alkene

Alcohol + PBr3 OR SOCl2, Pyridine

-Replaces -OH with X

-1', 2' Alcohol only = alkyl bromide

-sn2 reaction

-X = Br when using PBr3

-X = Cl when using SOCl2

alcohol + TsCl, pyridine

-Tosylation

-replaces alcohol with OTs

-does not invert stereochemistry

1,2-alkyl shift

a carbocation rearrangement wherein an alkyl group migrates to an adjacent atom

1,2-hydride shift

the movement of a hydride ion from one carbon to an adjacent carbon

Alcohol + H2SO4 and heat

-turns alcohol into an alkene

Alkene + X2

-halogenation

-turns alkene to alkane with 2 Xs

-makes an enantiomer

LiAlH4

reduces alkyl halides to alkanes, epoxides to alcohols

E2 Reaction

-needs strong bulky base

-Leaving group must be anti-periplanar to hydrogen to be removed

-FAVORS FORMATION OF STABLE ALKENES (MORE SUBSTITUTED)

-Fav base: KOtBu, DBU, NaNH2 for alkynes, likes bulky bases

-Higher degrees the better (tertiary > secondary > primary)

-rate = k[RX][BASE]

-Follows Zaitsev’s rule: removes hydrogen from carbon attached to fewest hydrogens

-favored by polar aprotic

1) Alcohol + NaH 2) -O product + Br-R

Williamson Ether Synthesis from Alcohol

-Ether + NaBr

Alkene + NBS +hv (ultraviolet light) or ROOR

-keeps alkene and adds Br right next to alkene

-mostly used when alkene cannot react with anything else

Alkyl halide + DBU

-E2 Reaction

-alkyl halide to alkene on the most substituted alkene

1) Alkene + O3 2) Me2S

-Oxidative cleavage

-makes an aldehyde and ketone at cleavage

1) Alkyne with Me + O3 2) H2O

-Oxidative cleavage makes ketone

1) Alkyne with H + O3 2) H2O

-oxidative cleavage

-makes a ketone and 2 O double bonded to a carbon

Alkane + Cl2, hv/heat

-radical reactions

-adds Cl using radicals

Alkane + Br2, hv/heat

-radical reaction

-Adds Br using radical

-Selective to Br being added to most substituted carbon

Alkene +HBr, hv/ROOR

-makes alkane and adds and H and a Br

-Br added anti-Markovnikov

Diene + Dienophile

-creates a six membered ring

-diene and dienophile must be cis to each other

Double Alkene + HBr

-breaks one alkene and adds a H and a Br

-makes a 1,2-addition and a 1,4-addition

1) Alkene + O3 2) Zn, H2O

-oxidative cleavage

-makes aldehyde and ketone

Alkene + mCPBA

-removes alkene makes an Epoxide

Alkane + KotBu

-E2 reaction

-needs leaving group

-need antipreiplanar H

Alcohol + PCC

-Oxidation reaction (not as strong)

-turns alcohol into aldehyde OR ketone

Alcohol + CrO3, H2SO4, H2O

-Oxidation Reaction (Stronger)

-Turns alcohol into carboxylic acid

Alkyl Halide + H2O, NaOH

-turns alkyl halide into Alcohol

Alkene + KMnO4, Lindlar Catalyst

-turns alkene into 2 Alcohols

Alcohol + NaH

-Williamson Ether synthesis

-Sn2 reaction

-turns alcohol to oxygen (ether)

Alkyl Halide + NaOEt

-Sn2 Reaction

-replaces Alkyl Halide with OEt

Alkyl Halide + NaOtBu

-E2 reaction

-Antiperiplanar H makes alkene

Alkyl Halide + CH3OH

-Sn1 + E1 reaction

Akyl Halide + CH3SNa, DMSO

-Sn2 reaction

-inversion of stereochemistry

Alkyl Halide + DBU

-E2 Reaction

-Needs antiperiplanar H

-Makes Diastereomers

Alcohol and Alkyl Halide + NaH

-Six membered ring ether formation

Ether + HI (excess)

-cleaves the ether and replaces it with I

Epoxide + Alcohol, H2SO4

-epoxide break

-Breaks epoxide adds Alcohol to the more substituted side because acidic conditions

1) Alcohol + TsCl, pyridine 2) KOtBu or DBU

-Tosylation of alcohol then E2 Reaction

-get rids of OH for alkene

Alcohol and Br + NaH

-Makes Epoxide by removing Br and the H from OH

Alkene + Pd/C, H2

-Reduction reaction

-reduces alkene to alkane

-syn addition

-makes an enantiomer

Aldehyde + Pd/C, H2

-Reduction reaction

-reduces double bond of O and replaces it with an OH by having the H bond to the O

Ketone + Pd/C, H2

-Reduction reaction

-reduces double bond of O to OH

-Makes diastereomer

Alkyne + Pd/C, H2

-Reduction reaction

-reduces alkyne to alkane

Alkyne + Lindlar’s Catalyst, H2

-reduces Alkane to Alkene

-syn addition in Z (conformer): cis

Alkyne + Na, NH3

-reduces Alkane to Alkene

-anti addition in E (conformer): trans

1) Epoxide + LiAlH4 2) H2O

-breaks epoxide

-replaces O to OH

-is an epoxide opening under basic conditions (on the less substituted side)

1) Alkyl Halide/OTs (Tosylates) + LiAlH4 2) H2O

-gets rid of leaving group and keeps it as an Alkane (and does not change stereochemistry)

1) Alkene + OsO4 2) NaHSO3, H2O

-dihydroxylation reaction

-breaks alkene and adds two OH (2 alcohol bonds)

-in syn-diol addition

1) Alkene + mCPBA 2) Epoxide + KOH

-dihydroxylation reaction

-Makes alkene to epoxide then breaks epoxide to add two alcohols (2 OH bonds)

Aromatic Conditions

1) Is the molecule cyclic?

• each p orbital must overlap with p orbitals on adjacent atoms

2) Are all the atoms sp2 hybridized/is the molecule planar?

• all adjacent p orbitals must be aligned so that the electromn density can be delocalized

3) A molecule must be completely conjugated

• aromatic compounds must have a p orbital on every atom

• if No to the first two then the compound is NON

4) Number of pi electrons must satisfy Huckel’s Rule

• Aromatic: 4n+2 pi electrons

• Anti-Aromatic: 4n pi electrons

-Important Note: when counting the pi electrons the electrons must be within the cyclic molecule

2 X Alkyl halide + NaNH2 (excess), DMSO

-E2 reaction

-double E2

Alkyl Halide + KOCH3

-SN2 and E2 reaction

Alkyl Halide + NaN3, DMSO

-SN2 reaction

R and S configuration

-R configuration: clockwises

-S configuration: counterclockwise

-Wedge H will switch the configuration

Degrees of Unsaturation

-Formula: 2C + 2 + N - H - X/ 2

-O does not add any degrees of unsaturation

Newman Projection

-if wedge faced up newman projection first carbon faced down

-if wedge faced down neman projection first carbon faced up

1) Epoxide + NaOCH3 2) H2O

-breaks epoxide and adds an OH (alcohol bond)