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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
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
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
a strong base like NaH
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
resonance more stable more resonance stronger acid
Induction is there another atom drawing electron density (like Cl) if so its stabilized and a stronger acid
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
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
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