Orgo chapter 10-12

1 eq of Cl2 and heat

1 eq of Br2 and heat

major monobromination (1 eq of br2)

Br is favored to attach to the tertiary position, then secondary, then primary. NEVER quaternary

Radical Br2 with an existing chiral center

allylic bromination

Bromine is added at allylic position

Addition of HBr

Since Br is at the most substituted carbon this is markonikov addition

HBr and ROOR (peroxide)

This is the anti markonikov addition of HBr due to the addition of peroxide

Radical addition of HBr that forms a chiral center

Br versus Cl

Br is slower and more selective than Cl, Br avoids mixtures

Halogenation at a chiral center

racemic mixture is always obtained

New chiral center created

both stereoisomers are produced

For allylic bromination NBS is used instead of Br2…

To avoid competing ionic addition reactions

Two step synthesis to change position of a halogen

ozonolysis of a terminal alkyne

hydrohalogenation of an alkyne (h-x)

Formation of an Alkyne

xs NaNh2 adds a triple bond

Hydrohalogenation of an Alkyne

xs Hx breaks a triple bond allowing more than one halogen to bond (xs br2 would add 4 br, xs hbr will add 2)

acid catalyzed hydration

alkyne reacts with the mercury of HgsO4, H2SO4 is the acid (h3o can also be used) and the h2o is the hydration

hydroboration oxidation

R2BH can be used for alkynes to prevent a second addition

first step generates a leaving group the second step can convert to an alcohol (enol for alkynes which then becomes a ketone)

Halogenation (1 eq)

CCl4 is a solvent so only the x2 gets added and halogens tend to add in the anti formation rather than syn

Halogenation ( 2 eq)

CCl4 is a solvent and with xs x2 now 4 of the halogens are added (disregard the red dot)

Alkylation

NaNH2 keeps the triple bond, the halogen gives a space for the R group to be added to deprotonate the H

Hydrogenation with poisoned catalyst

H2 and Lindlars transforms alkyne to an alkene

Hydrogenation

H2 and a metal (pt,pd etc) will turn both alkynes and alkenes to alkanes

Dissolving metal reduction

Converts internal alkynes to trans alkenes

Na creates a radical anion intermediate then the ammonia donates a proton creating the trans alkene

Alkyl halide transformations

1) NaOEt major product is a double bond

2)HBr adds Br at most subbed carbon (unless peroxide is present)

3)t-BuOK forms the hoffman product so double bond is added to the least subbed carbon

Use of TsCl, py

OH→OTs

Alkane to alkene

Alkene to alkyne

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Convert an alkene to an alcohol

Can more than one set of reagents provide the same outcome?

Yes! orgo loves making life hard

How to change carbon skeleton?

React with a nucleophile with carbons to add to the carbon chain or to reduce it use ozonlysis to cleave bonds

Adding to carbon chain

Reduce carbon chain

Creating an internal alkyne

Target: Alkane

Target: Alkyl Halide

Target: alcohol

Target: Nucleophiles

Target: Alkene

Target: Alkyne

Target: Ketones and Aldehydes

Target: Carboxylic Acid

Na, NH3 (l)

Reduce a triple bond to a doube

Adding Carbons and forming an alkene

t-BuOK

Form a double bond

OsO4, NMO

Creates a diol and is steriospecific

Charge Stability

Acidity

Deprotonate an alcohol

1) a strong base like NaH

2) Li, Na, or K

These will produce the alkoxide ion (conj base of alcohol) and release hydrogen gas

To convert alkoxide into corresponding alcohol

treat with H3o

What impacts acidity

1) resonance more stable more resonance stronger acid

2) Induction is there another atom drawing electron density (like Cl) if so its stabilized and a stronger acid

3) Solvation effects if a compound is not sterically hindered its more solvated (stabilized) so a stronger acid (less substituents stronger acid)

Preparing alcohols

Primary needs sn2 and a strong nucleophile while tertiary needs sn1 and a weak nucleophile

secondary alcohols cannot be prepared with sn1 as it would be too slow and it cannot use sn2 as it will favor elimination so substitution wont occur

Produce alcohol from alkene

Oxidation states

If each electron goes to the more electronegative atom how many electrons will it have? bonds-electrons=oxidation state

oxidation/reduction

an increase in oxidation state means the atom was oxidized while a decrease in oxidation state means it was reduced formic acid → methane is a reduction

Reducing agents that can be used to convert ketones/aldehydes into alcohols

1) Metal catalysts like pt, pd, ni but need high temps and high pressure rarely used

2)NaBH4 very commonly used

3)LiAlH4 (LAH) stronger reagent still commonly used BUT too reactive with protic solvents like water so the ketone/aldehyde must be treated with LAH then separately treated with H2o or H3o

Selectively reducing carbonyl groups

NaBH4 and LAH can select only to reduce the carbonyl group while the metals will get rid of the double bond as well

LAH versus NaBH4

LAH can reduce a carboxylic acid or an ester to produce an alcohol due to it being more reactive than NaBH4

Formation of diols via reduction

Diols formed via dihydroxylation

Grignard Reagents

Carbon nucleophiles that can attack a large range of electrophiles R-Mg-x

Stepwise

Proton source needs to be added separately since Grignard is a strong base it will deprotonate water

Grignard producing an alcohol

The second reaction forms a chiral center so there is a racemic mix of enantiomers

Grignards reacting with esters

Adds two R groups and produces an alcohol

Grignard and carboxylic acid issues

They are not compatible as it would deprotonate and the grignard reagent couldnt form

Protection of Alcohols

Protecting groups are used to prevent the grignard reagent from interacting with an OH group

TBAF

Sn1 rxn with tertiary alcohols

Sn2 rxn with primary alcohols

Primary or Secondary alcohols reacting with an Sn2 process

Tertiary alcohols E1

elimination favors more subbed alkene

Tertiary alcohols E2

To use E2 the hydroxyl group must first be converted and then a strong base can be employed

Alcohols during the oxidation process

Primary alcohol: can be oxidized twice first it produces an aldehyde and then the second produces a carboxylic acid

Secondary alcohol: can only be oxidized once since it only has one proton on the alpha carbon and it forms a ketone

Tertiary alcohol: Has no protons on the alpha carbon so they will not undergo oxidation

Chromic acid oxidations

first stage: formation of chromate ester

second stage: E2 process that forms a carbon oxygen pi bond

Primary Alcohol oxidized with Chromic acid

forms a carboxylic acid since its hard to stop it at the aldehyde

Primary Alcohol → aldehyde

need a selective oxidizing reagent that wont react with the aldehyde only the alcohol like PCC

Secondary Alcohol to ketone

treated with a chromium oxidizing agent like chromic acid or PCC

Swern oxidations

stage 1 DMSO reacts with (COCl)2 to convert into chlorodimethysulfonium ion which is meant to function as the active oxidizing agent stage 2 the carbon atom undergoes oxidation to make a ketone

Swern oxidation can convert primary alcohols into aldehydes

these conditions lead primary alcohols converting to an aldehyde

Dess-Martin periodinane (DMP) oxidation

converts primary alcohols into aldehydes and secondary alcohols into ketones

DMP oxidations employ nonacidic conditions and can occur at room temp

Chromium-based oxidations

require acidic conditions and high temps

NADH

Important reducing agent its less reactive than NaBH4 and LAH so it requires a catalyst

NAD+

Oxidized form of NADH it can act as an oxidazing agent and can accept a hydride from an alcohol so NAD+ can be reduced to produce NADH

Phenol oxidation

phenol can undergo oxidation more readily than primary and secondary alcohols

interconversions of bonds

Secondary alcohols

Primary alcohols

Oxidation states conversions

Conversions of chap 12 summary

c-c Bond formation

can use grignard reagent and a ketone or aldehyde

Ester and grignard reagent

2 new c-c bonds formed

Addition of carbon-carbon bond summary

Aldehyde → ketone

Conversion of an alcohol to an aldehyde with an addition to carbon chain

Secondary alcohol → tertiary alcohol

Preparation of alcohols using reduction

Preparation of alkoxides

Na will deprotonate

Using grignard to prepare alcohols

Protection and deprotection of alcohols

The addition of a protecting group and the removal