Orgo bag

r

re

res

reserv

reserve

reserved

reserved

reserve

Friedel craft acylation (ACID CHLORIDE)

Reagents: 1. AlCl3 2. H2O

Friedel craft acylation (ACID CHLORIDE)

Reagents 1. AlBr3 2. H2O

Clemmensen reduction

Reduce a carbonyl group to a methylene

Wolff-Kishner reudction

Reduce a carbonyl group to a methylene

Aniline oxidation and susbstitution

1. NaNO2 Nuc

—> ——>

HCL

Nuc: Replaces the N2 After

CuCn

CuBr/CuCl

HBF4

H20

D3PO2

EAS Aromatic rules to know

Electron Withdrawing group - Deactivating - Meta Directing (Ortha and para have less electron density so they are less nucleophilic here)

Halogens - Slightly deactivating - Ortho & Para directing (they r electronegative and inductively withdraw electromagnetic density which makes aromatic system less nucleophilic

Sterics are important if electronic effects are similar & IF there are multiple substituents the more activating one controls the directions. (or more donating etc if they da same)

Nitro group (No2) prevents freideiyl crafts.

Nucleophilic aromatic substitution (SNAr)

Leaving Groups: Cl, Br, F

anion can be resonance stabilized 3 times

without EWG snar cant happen

Pyridine can bypass EWG CUZ OF THE N STABLIZING NEG CHARGE
(Heteroaromatics or EWGs for snar)

SNAR Rates

Explain

Electronics of heteroaromatocs

If the electron pair is part of aromatic it’s electron rich if not it’s electron poor

Chichibanbin reaction

1. KNH2/NH3

2. H2O

SINCE ITS A PYRIDINE AND ELECTRON OOR IT IS ACTIAVTED ENOUGH IN SNAR WHERE IT DOESNT NEED AN OFFICAL LEAVING GROUP

Carbonyl Nomenclature

Carbonyl Hydration BASIC

Carbonyl Hydration ACIDIC

key reactions are addition and elimination

nucleophiles can be added directly or the addition can be accelerated by protonation first

Generally strong nucleophiles like OH directly, but weak ones like water need protonation

oxocarbenium are much more electronegative/reaction that regular carbonyls

no strong bases and acids

Stability of hydrates

Cyanohydrin synthesis

NaCN

H2O

Bisulfite Addition

Synthesis of an ACETAL (ADDITION REACTIONS FOLLOWED BY WATER LOSS)

REVERSE Reaction: Acetal removal reaction

H2o
h3O

Stable hemi-acetals (CYCLIC VERSION!)

Why do i care about this… protection groups? for synthesis?

Protection Group (Protecting Carbonyl group by forming acetal)

Acetals are stable to base or nucleophiles.

Protection groups : Acetal

Formation of cyclic acetals is very favorable. Why the second step becomes intramolecular (cuz intra is hella faster)!

Protection group: Protect Alcohol as acetals

oxyvarbeneudn

Protection group: Protect Alcohol as acetals REMOVING IT

N-Based Nucleophiles pimrary amine

Imine formation PRIMARY AMINE

N-Based Nucleophiles (SECONDARY AMINE)

CANT FORM IMINE BUT WE OBSERVE FORMATION OF AN ENAMINE

Why do primary amines NOT form enamines?

only in situations where imine formation is not possible we will observe formation of enamines
WE DONT HAVE AN ACIDIC NH WHICH IS WHY WE FORM A ENAMINE IN SCENARIOS.

Organometallic nucleophiles

Addition of alkyl lithium to a carbonyl & Grignard addition

Metal hydrides are strong nucleophiles

Lithium Aluminum Hydride (LiAIH4) Ketone Reduction

Wittig Reaction (IRREVERSIBLE RXN)

Make the reagent R3-PPh3

Wittig is the Reverse of Ozonolysis

MeLi Addition approach ( basically ignore this u need to do a wittig rxn for the double bond there cuz itll be inside)

Synthesis of carbonyl overview

Oxidation of alcohols gives carbonyl compounds (tert acholhols have no rxn cuz no hyrogen to remove)

(tert acholhols have no rxn cuz no hyrogen to remove)

Oxidations of primary OH with Chromium (COLLINS REAGENT)

Cr03/ aromatic benzene with N - Collins reagent

Oxidations of primary OH with Chromium (PYRIDINIUM CHLOROCHROMATE) - PPC

Oxidations of primary OH with Chromium - OH into a carboxylic acid

CrO3 + H2O
use water as the pyridine , deprotonate w that

Secondary OH provide ketones! CAUSE THEY CANT OVEROXIDIZE

misc

Swern Oxidation (only oxidizes one time)

1brick , dmso
etn3

Oxidation of Diols (oxidative cleavage)

not on exam yay
HiO4
H2sO4
only works an adjacent OH’s

RECAP OMEGA!

Nomenclature of acids

Synthesis of carboxylic acid

syntehsis of carboxylic acid

Fisher esterification

Remember under acidic condition u cant kick out bases. that why we protonate

Ester hydrolysis

we kick out OH?

synthesis of esters via SN2

Part II using methane (sn2 ester synthesis)

Synthesis of amides

DCC

Acid chloride synthesis

nswiwb

anhydride makeing

LiAlh4 acid chloride

bad

selectivity

carboxlylic acid to ketone

grinard wont work, its negatsivey charged species thats y so u need lith
a random OH spawns somehow

Anhydride DDC

beta keto acid & 1,3 diacid (DECARBOXYLATION)

Use heat we retain left and remove right for co2 and rotate ur bond

Keto/Enol tautomerization

nomenclature

Carboxylic acid derivatives

Acid chloride review

Ester hydrolysis (saponification) BASIC CONDITIONS

DIBALH (GIVES ALDEHYES FROM ESTERS)

Hydrolysis of amines under BASIC CONDITIONS (SLOWW ASF)

Hydrolysis of amines under ACID CONDITIONS (FAST CUZ MAKING IT BETTER ELETROPHILE OR SUMSHI)

Amide TO AMINE with metal hydride (RMBR THE QUENCHHH)

Reaction Of Nitriles (SYNTHESIS)

Nitrile Synthesis (amide dehydrogentation)
Phosphorous pentaoxide (P2O5) + heat —→ h3po3 + R - CN Triplebond

Hydrolysis of nitriles (ACIDIC CONDITIONS) (SKILS AMIDE GOES TO CARBOXLYLLIC ACID)

Hydrolysis of nitriles (BASIC CONDITIONS) (STOPS AT AMIDE)

Nitriles with alyk lith grinards make ketone

mechanism
Reagaents - r-li and h3o h20

Nitrile reduction to a primary amine

Reagent LiAlH4 + ACID

Bayer Villiger (KETONE TO ESTER) rearrange (return ketone to oxycarbenium)

Use Peroxy acid to react + stff

Beckman rearrangement (amide from ketones via oximes)

For becker migrating group always has anti pariplanar to leaving group

ketocarbene are prepared from diazo ketones

Wolffe Rearrangement (ketocarbene to ketene)

diazomethane + acid chloride = diazoketone + light + heat = keto carbene one step into the elctrophilic product

Arndt Eistert reaction

h30/h20

Curtius (acyl azides from carbomate esters via isocyanates)

Hoffman rearrangement (AMIDES TO AMINE)

stops as isocyanate cuz basic

reactivity of carbonyl compounds

CAN AHPPEN UNDER ACIDIC OR BASIC CONDITIONS (KETONE NOMENCLATURE)

keto-enol tautermizrrization

it will react at carbon because it more electron dense (what will though?)

Alpha Dueteration under BASIC

mechanism , D is labeled heavy and stronger so it prefers to grab H

Alpha Dueteration under Acidic

catalytic acid or base

Acidity comparisions (on the right u can have resonance structures so its harder to make the desired enol bc of those resonance forms/slower

Enolates by derotonation

LDA = dissopropylamide (strong and hindered base)

Halogenation (ACID)

Mechanism w acid (same as dueteraton)

Halogenation (BASIC)

Haloform

start w ketone add base

Alkylation

LDA good for monosubstituted

Alkylation examples

Malonic Ester example

Alkylation of 1,3 dicarbonyl compound (beta carbonyl compounds)

1,3 dicarbonyl compound can be decarboxylated (one carbonyl has to be an acid)
keto favored

Alkylation of enamines

EXAMPLE PROBLEM FOR DICARONYL