Orgo I: Chapter 11: Reactions of Alkyl Halides: Nucleophilic Substitution and Eliminations

are alkyl halides nucleophilic or electrophilic

electrophiles

reaction rate for nucleophilic substitution

reaction rate = k [RX] [OH]

what does SN2 stand for

substitution nucleophilic 2nd order

what are SN2 reactions characterized by

single step reaction without intermediates

substrate: best for methyl and primary substrates, secondary substrates react slowly and tertiary don't react do to steric hindrance

nucleophile: negatively charged nucleophiles work best

leaving group: good leaving groups prefered

solvent: polar aprotic solvents

folllowing an SN2 reaction, what happens to stereochemistry

Opposite configuration (R->S, S->R)

what is the mechanism of SN2 reaction

Nu- forces out the X- from the backside (opposite to the leaving group)

neopentyl

2,2-dimethylpropyl

order of relative reactivity of alkyl halides (increasing) for SN2

tertiary, neopentyl, secondary, primary, methyl

order relative reactivity of nucleophiles (increasing) for SN2

H2O, CH3CO2-, NH3, Cl-, HO-, CH3O-, I-, CN-, HS-

order of leaving group reactivity (increasing) and why for SN2

OH-, NH2-, OR-, F-, Cl-, Br-, I-, TosO-, the weaker the base the better the leaving group

which compounds do not undergo SN2 reactions typically

alkyl fluorides, ethers (except for with epoxides), amines, and alcohols(without being converted to a better leaving group like from -OH to -OH2 or -OH to -X or -OH to tosylate)

what solvents work best for SN2 reactions

polar aprotic solvents (solvents that are polar but don't have an OH or NH group)

order of solvent reactivity (increasing) for SN2

CH3OH, H2O, DMSO, DMF, CH3CN, HMPA

order of relative reactivity of alkyl halides (increasing) for SN1

methyl, primary, secondary, tertiary

what does SN1 stand for

substitution, nucleophilic, 1st order

reaction rate formula for SN1 reaction

k[RX]

why are SN1 1st order

because spontaneous dissocation of alkyl halides forming a carbocation take the most time and that step doesn't involve the nucleophile

What is the stereochemical outcome of SN1?

racemic-ish 50-50 mixture of enantiomers bc products come from an achiral carbocation that can go either way but more inversion bc of ion pairs

characteristics of SN1 reactions

substrate: need most stable carbocation (so tertiary most stable methyl least stable), secondary allylic or benzylic carbocation as stable as tertiary alkyl carbocation and primary is as stable as secondary

leaving group: about the same reactivity as SN2

nucleophile: does not have much of an effect, neutral are just as effective as negative

solvent: strongly polar protic solvents bc of transition state energy leading to the carbocation intermediate

Zaitsev's Rule

while elimination reactions are complex, elimination reactions generally give the more stable product

which bond breaks first in E1 reactions

C-X yielding a carbocation intermediate which undergoes subsequent base abstraction of H+ to yield the alkene

which bond breaks first in E2 reactions

base induced C-H bond cleavage is simultaneous with C-X bond cleavage, yielding an alkene in a single step

what bond breaks first in E1cB reactions

The C-H bond breaks via base abstraction leaving a carbanion intermediate which loses the X- to yield the alkene

what does E2 stand for

elimination, bimolecular

when do E2 reaction occur

when an alkyl halide is treated with a strong base (like hydroxide (HO-) or alkoxide (RO-))

rate law for E2 reactions

rate = k [RX] [Base]

what is the geometry of an E2 reaction

periplanar (all 4 reacting atoms hydrogen, carbons, and leaving group on the same plane), anti periplanar (H and X on opposite sides) is preferred allowing the electron pair from a neighboring C-H bond push the leaving group on the opposite side of the molecule (like the SN2 backside attack), for cyclohexane rings the anti periplanar requirement can only be met with an trans diaxial leaving group and H

what does E1 stand for

elimination, unimolcular

True or False: The best E1 substrates are also the best SN1 substrates

True

what types are products are resulting from E1 reactions

SN1 products (substituted alkanes) and E1 products (alkenes)

what geometric requirements are there for E1 reactions

None, due to the fact that the H and X leave separately, this also means Zaitsev's rule is favored but there's a minor product that is less favored

what types of leaving groups are in E1cB reactions

poor leaving groups like -OH

how to tell if SN2 will happen to primary alkyl halides

a good nucleophile is used

how to tell if E2 will happen to primary alkyl halides

strong sterically hindered base is used

how to tell if E1cB will happen to primary alkyl halides

the leaving group is two carbons away from a carbonyl group (C=O)

how to tell if SN2 will happen to secondary alkyl halides

weakly basic nucleophile is used in a polar aprotic solvent

how to tell if E2 will happen to secondary alkyl halides

strong base is used

how to tell if E1cB will happen to secondary alkyl halides

the leaving group is two carbons away from a carbonyl group (C=O)

how to tell if SN1 and E1 will happen to secondary allylic and benzylic alkyl halides

if a weakly basic nucleophile is used in a protic solvent

how to tell if E2 will happen to tertiary alkyl halides

base is used

how to tell if E1 and SN1 will happen to tertiary alkyl halides

if it occurs neutral conditions like pure ethanol or water

how to tell if E1cB will happen to tertiary alkyl halides

the leaving group is two carbons away from a carbonyl group (C=O)

generally how will each substrate react

RCH2X --> Mostly SN2

R2CHX --> SN2 with nonbasic nucleophiles, E2 strong base

R3CX --> Mostly E2 (SN1 and E1 in nonbasic solvents)