orgo reactions

what makes a strong nucleophile

• neg charge

• low electronegativity

what makes a good leaving group

• good resonance

• electronegativity

• larger atom

• chactertistcs of something that can bare a negative charge well

what types of carbons does SN2 prefer

• primary and methyl (SN2 does toooo much meth)

• SN1 prefers secondary and tertiary because that makes for a more stable carbocation

Will strong bases like -OH leave in acidic conditions

No; deprotonation will occur instead 

why can’t E2 happen on a methyl group

no free H to make a double bond

what type of reaction is better in a polar aprotic solvent

SN2 and E2 because the nucleophile does not react with the solvent

what type of reaction is better in a polar protic solvent

SN1 and E1 because the rate of the nucleophile attacking does not effect the rate law 

Zaitsev’s rule

more substituted double bond is more stable

Hofmann’s rule

elimination reactions tend to make the less substituted product

Two ways to make an ether

• williamson ether synthesis

• condesnsation reaction (if desired product is symmetric)

Williamson ether synthesis

• SN2 to make an ether; has selectivity

• can’t be done on tertiary carbons because it is SN2

Condensation reaction

• two alcohols joined together

• only makes symmetrical product

Making a halide from an alcohol

• need alcohol and H-X

• can do sn1 or sn2 depending on the carbon type 

• make OH a good leaving group then do sn1 or sn2

• if sn1, rearrangements may occur

PBr₃ and PCl₃

• SN2 reaction

• inversion of sterochemistry

• can’t do on a tertiary carbon

• final product just has Br or Cl in place of leaving group with inversion

Halogenation of an alpha carbo in basic conditions

• need X₂, base, ketone

• multiple halogenations occur at all alpha carbons 

• an alpha carbon is a carbon one off from a double bond

Halogenation of an alpha carbo in acidic conditions

• need X₂, acid, ketone

• one halogenation occurs at a alpha carbons 

• HOAc is commonly used as the acid 

Epoxide ring opening in basic/neutral conditions

nucleophile attacks at less substituted side of ring

Epoxide ring opening in acidic conditions

nucleophile attacks at more substituted side of ring

Formation of epoxides

• intramolecular nucleophilic substitution 

• -O and halide on Carbon chain is a sign

  • The halide would leave and -O will attack the carbon 

Kinetic conditions for deprotonation of alpha carbon

• LDA and cold

• substrate attaches to less substituted side 

• kinetic product is formed fast and the reaction is irreversible 

Thermodynamic conditions for deprotonation of alpha carbon

• strong base and warm

• substrate attaches to more substituted side 

• thermodynamic product is formed slowly and the reaction is reversible 

Hofmann Elimination

• less substituted product is formed

• need Amine group, CH₃I, Ag₂O, and heat 

• amine group keeps grabbing methyls until it can’t anymore and then leaves 

• normal elimination happens 

is hydride a base or acid

• good base and nucleophile

• takes H

Methyl ester synthesis from Diazomethane

• need carboxylic acid and CH₂N₂ (diazomethane)

• the H in the carboxylic acid is replaced with a methyl group and N₂ is a byproduct 

Amine synthesis from Alkyl Halides

• ammonia acts as the nucleophile

• can’t make primary amines with this because the reaction keeps going

• product is a quatenary amine

• the alkyl halide is in excess

Electrophilic Addition of Bronsted acid to alkenes

• alkene acts as nucleophile and grabs H

• carbocation is formed

• more stable carbocation is created 

• acid adds across the double bond

• if there’s a chiral center, racemic mixture is made

Acid catalyzed hydration of alkene

• double bond is nucleophile in first step and grabs H from acid 

• water is next nucleophile and attaches to carbocation 

• water is next nucleophile again and deprotonates water and leaves OH group

• water is added across double bond and OH is in more stable position

Electrophilic addition is lowkey another word for…

adding across a pi bond

Electrophilic addition of a bronsted acid to an alkyne

• triple bond is two additions

• both halides add to same carbon (geminal)

• halide adds to more stable carbocation position

Acid Catalyzed Hydration of an Alkyne

• triple bond grabs H from acid

• water adds to pi bond as nucleophile 

• water deprotonates other water on big molecule 

• OH is on the more stable position 

• tautomerization creates a ketone in the product

1,2 vs 1,4 product

• higher temp makes the thermodynamic product (1,4)

  • makes more substituted alkene (more stable product)

• lower temp makes the kinetic product (1,2)

  • makes more stable carbocation because that reaction is faster 

  • BRRRRR need to get 2 destination fast

• this is electrophilic addition of an acid across a double bond 

• if creating the 1,4 product, look for resonance to create most substituted alkene

Electrophilic addition via a three membered ring

• creates enantiomers if product is chiral 

• concerted mechanism where the electrophile ends up being the point of the epoxide 

Electrophilic Addition of crabenes

• A carbene is a carbon with two bonds and a lone pair 

  • highly electrophilic

• CH₂ becomes point of epoxide where double bond is 

• makes enantiomers if product is chiral 

• conditions= CH₂N₂ and hv (light)

Epoxide formation from an alkene via a peroxy acid

• MCPBA is the reactant and provides an O

• O is the point of the epoxide 

• product retains stereochemistry 

  • creates enantiomers if product is chiral

Electrophilic Addition with X₂ to alkenes

• concerted mechanism where X becomes point of epoxide and has a + charge 

• leaving group is X and attacks the three membered ring 

• trans stereochemistry across the double bond

Electrophilic addition of X₂ to alkynes

• no three membered ring intermediate

• if there’s an excess of X₂ then X adds twice (no more pi bonds)

• if there’s 1 equivalence of X₂ then X adds once (double bond is created)

• cis and trans stereochemistry if 1 equivalence

  • major product is more stable one

• X₂ is added across the double bond

Synthesis of Halohydrins

• concerted mechanism that begins with X₂

  • X becomes point of the epoxide

• reactions happens in water, so water attacks less substituted side of epoxide 

  • water then deprotonates added water 

• mixed stereochem (Oh and X)

Oxymercuration Reduction of alkene and alkynes

• no carbocation

• OH goes to more substituted side (water adds across double bond)

• anti addition (of OH and H)

• reactants = Hg(OAc)₂/H₂O and NaBH₄/NaOH

• if it’s an alkyne, keto product is made 

  • if internal alkyne, mix of isomers 

  • like up and down ketone

Hydroboration Oxidation of Alkenes and Alkynes

• no carbocation

• syn addition (of OH and H)

• OH to less substituted carbon (anti markovnikov product)

• if alkyne, ketone or aldehyde made depending on where the triple bond is

• reactants = BH₃/THF and H₂O₂/NaOH

Catalytic Hydrogenation of Alkenes

• addition of H₂ across double bond 

• metal catalyst (Pt/C etc.)

• syn addition

• double bond basically goes to single bond

Catalytic Hydrogenation of Alkynes with no poisonous catalyst

• 2 additions of H₂ across double bond

• triple becomes a single bond

Catalytic Hydrogenation of Alkynes with a poisonous catalyst

• poisonous catalyst= Lindlar’s catalyst, pyridine, quinoline

• reactions stops after first addition of H₂ across double bond 

• syn addition

Formation of alkynes

• NaNH₂ and a dihalide 

• makes triple bond 

• count carbons!!! to know where triple bond goes 

rate law of sn2 and e2

rate= k[substrate][nuc]

rate law of sn1 and e1

rate=k[substrate]

Hydride Reduction of Aldehydes, Ketones, imines, and nitriles

• LAH and a separate acid work OR

• NaBH4 and a polar protic solvent

• Reduces ketone, aldehyde, imines, and nitriles to single bond alcohol or amine group with appropriate amount of H’s

• If using LAH, all ketones etc. will be reduced

Addition of Grignard and Alkylithium reagents to aldehydes, ketones, and nitriles

• need grignard/Li and H2O as acid work up

• If ketone or aldehyde, result is OH group and the added carbon chain

• If Nitrile, result is protracted C=N group and the added carbon chain

Wittig Reagents

• need aldehyde/ketone and PPh3

• Sub oxygen of ketone/aldehyde with the carbon chain part of the wittig

• Intermediate has bond connecting O of ketone and P of PPh3

Formation of a Wittig Reagent

• need PPh3 and BuLi (a strong base) in a non polar solvent like hexane

• Br group leaves off of carbon chain and reaction proceeds through SN2 with PPh3

• BuLi deprotonates H and electrons move onto the carbon

Direct 1,2 Addition and Conjugate 1,4 Addition

• 1,2 (kinetic, irreversible)- quicker reaction and things like grignard or alkylithium or LAH or NaBH4 do it

• 1,4 (thermodynamic, reversible)- more stable product is made and things not listed up there do it

Cyanohydrin Formation

• need HCN and ketone and water

• CN attacks a ketone and O of ketone is protonated

Acetal Formation and Hydrolysis

• need OR group and ketone or aldehyde

• start with protonated form of OR group

• OR group is added twice with a series of proton transfers

• Never create a negative charge

Imanie and Enamine formation and hydrolysis

• imamies forms from a primary amine or ammonia

• Enamines form from only secondary amines

• Need one of those and a ketone or aldehyde

• Ammonia attacks ketone, makes OH2 (good leaving group) then stabilizes N-H group (imine is formed when there is a N=C)

• For enamines, secondary amine attacks and product is formed enolate version of enamine is formed