solvents and decision tree

ethanol

polar protic CH3CH2OH

Methanol

Polar protic, CH3OH

water

H2O, Polar protic

Acetone

H3CC=OCH3, polar aprotic

DMSO

Polar aprotic, dimethyl sulfoxide, H3CS=OCH3

DMF

Dimethylformamide, Polar aprotic, HC=ON(CH3)2

diethylether

polar aprotic CCOCC

THF

Polar aprotic, tetrahydrofuran, 4 membered ring with oxygen

benzene

Non polar

Toluene

non polar, benzene with ch3

DCM

dichloromethane, methylene chloride, polar aprotic

chloroform

Polar aprotic, CHCl3

carbon tetrachloride

non polar, CCl4

Polar aprotic solvents favor

Bimolecular, SN2, E2 by keeping the nu and base strong and reactive

Polar Protic solvents favor

unimolecular, SN1, E1 reactions by stabilizing th carbocation intermediate

What is the substrate: methyl

SN2

What is the substrate: primary, 1

SN2 or E2

Primary substrate, fast Nu, strong base

SN2 major, E2 minor

Primary substrate, fast Nu, weak base

SN2

Primary substrate, slow Nu, strong base

E2 major

Primary substrate, slow Nu, weak base

No reaction

• A primary substrate cannot form a stable carbocation for SN1/E1, and the weak base and slow nucleophile are too unreactive to force a substitution or elimination reaction. 

• prevent SN2 and E2

What is the substrate: secondary, 2

SN2, E2, SN1, E1

Secondary substrate, fast Nu, strong base

E2 favored, SN2 minor

Secondary substrate, fast Nu, weak base

SN2

Secondary substrate, slow Nu, strong base

E2

Secondary substrate, slow Nu, weak base, heat

E1

Secondary substrate, slow Nu, weak base, no heat

SN1

What is the substrate: tertiary, 3

E2, E1, SN1

Tertiary substrate, fast Nu, strong base

E2

Tertiary substrate, fast Nu, weak base, polar aprotic

no reaction

Tertiary substrate, fast Nu, weak base, polar protic

SN1

Tertiary substrate, slow Nu, strong base

E2

Tertiary substrate, slow Nu, weak base, heat

E1

Tertiary substrate, slow Nu, weak base, no heat

SN1

DBN

Strong base, weak NU, E2

DBU

strong base, weak nu, E2

OH- (NaOH)

strong nu and strong base, E2 or SN2, SN2= primary, E2= major for secondary and only product for tertiary

MeO-

Strong base, strong nu

EtO-

Strong base, strong nu

I- (NaI)

weak base, strong nu

Br- (NaBr)

weak base, strong NU

Cl- (NaCl)

weak base, strong nu

RS-

weak base, strong nu

HS-

weak base, strong nu

RSH, NaSH

weak base, strong nu, used in SN2 reactions

H2S

weak base, strong nu

H2O

weak base, weak nu, heat will typically favor E1 over SN1

MeOH

weak base, Weak nu, alcohol, used in SN1 and E1, Heat will favor E1 over Sn1

EtOH

Weak base, weak nu

NaOR (NaOME or NaOEt)

strong nu and strong bases, E2 or SN2 depending on substrate type

t-BuOK

Strong base, strong nu, sterically hindered so favors E2 over SN2

• when there is more than one regiochemical outcome E2 will favor Hofmann product (less substituted) because it is bulky base

SN2

concerted, bimolecular

• nu attacks alpha position where LG is connected

• nu replaces the LG with inversion of configuration

E2

concerted, bimolecular

• zaitsef product is generally favored, unless bulky base then hofmann is favored

• trans disubstituted alkene will be favored over cis if applicable

• ANTI-Periplanar

  • want to be exactly 180 degrees apart, staggered

SN1

Stepwise, unimolecular

• nu attacks the carbocation, rearangements can occur

• racemic mixture

E1

Stepwise, unimolecular

• zaitsev product is always favored over hofmann

• trans disubstitued alkene will be favorerd over cis

IF leaving group is bad?

• TsCL, Py to create OTs

  • OH is a bad leaving group covert to OTs to perform reaction

• weakest acid and least stable conjugate base= bad leaving group

• a good leaving group is a conjugate base of an acid with a pka<0

• good leaving group= increases as you go right and down the periodic table

  • most commonly used leaving groups are halides (I−, Br−, Cl−) and sulfonate ions (RSO3-)