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Summary of Chapter 11 Material

SN2 Reaction

Substrate: NO SN2 ON A TERTIARY HALOALKANE!!order of reactivity is as follows: Methyl > 1 > 2Sterically less hindered substrates have faster rates in SN2

Nucleophile: If the reacting atom is the same in a series, nucleophilicityparallels basicity (i.e. -OH > -OCH3 > -OCH2CH3 > H2O)

For the halogens in GAS PHASE: F-

> Cl-

> Br-

> I-

For the halogens in SOLUTION: I- > Br- > Cl- > F- (due tosolvation of nucleophile, rendering it inactive)Negatively charged nucleophiles give neutral productsNeutral nucleophiles give cationic productsIn SOLUTION nucleophilicity increases down a column in theperiodic table (i.e. -OCH3 > -SCH3 > -SeCH3)Anionic nucleophiles are usually stronger than neutral ones

Leaving Group: Best leaving groups are those that best accomodate anegative charge (large anions such as I-)The best leaving groups are WEAK BASESAccording to this criteria, the worst leaving groups are:

F-, OH-, OCH3-, CN-, N3-, NH2

The best leaving groups are: H2O, CH3OH, OTs, I-

Notes: The SN2 reaction is bimolecular - it depends on amountsof nucleophile and leaving groupIn synthesis, always convert an OH leaving group into anOTs leaving groupConverting an OH into an OTs will NOT change thestereochemistry!!

SN2 reaction goes with inversion about the stereogeniccarbon

Solvent: Polar protic solvents are the worst for SN2; theysolvate the nucleophile so it cannot attack

Polar aprotic solvents stabilize the transition state andspeed SN2 reactions upPolar aprotic solvents are DMSO, DMF, CH3CN, HMPA

SN1 Reaction

Substrate: SN1 reactions work best on a TERTIARY! NO SN1 ON A PRIMARY!!

Order of reactivity: 3 > 2Benzylic and Allylic carbons have increased reactivitybecause of resonance stabilization

Nucleophile: Has NO effect upon the rate of reaction!! Rate limiting stepdoes not include the nucleophile!!

To convert OH to a good leaving group use HX

Leaving Group: Same as for SN2 reactions!!

Solvent: Polar aprotic solvents work well Polar protic solvents work even better because they

stabilize the carbocation intermediate

Notes: SN1 is unimolecular and depends only on amount ofsubstrate!SN1 goes through a carbocation intermediateStereochemistry is lost during an SN1 reaction and theproducts usually display a small excess of inversion productWatch out forCARBOCATION REARRANGEMENTS!

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E2 Reaction

Substrate: Requires antiperiplanar geoemtry between the halide andhydrogenRelative rates of reaction: 3 > 2 > 1

Stereochemistry: The stereochemistry of the starting material willdetermine whether you get the Z or E isomer whenpossible

Small strong bases always give the Zaitsev product

Bulky strong bases always give the Hoffman product

Notes: This is a bimolecular reaction whose rate dependson the base and substrate usedWhenever you have a basic nucleophile usedon a 2 alkyl halide, you can expect a mixtureof the E2 and SN2 reaction with the E2 being the majorproduct

Bases: The following bases give E2 on 3 and 2 alkyl halides-OH, -OCH3, -OCH2CH3, -OC(CH3)3, CN

-

Remember that the secondary halides will also give SN2minor product

E1 Reaction

Substrate: Works best on 3 (and 2) substratesDoes not require the antiperiplanar geometry!

Stereochemistry: This reaction proceeds through a carbocationintermediate!Typically favors the Zaitsev productWatch out forCARBOCATION REARRANGEMENTS!

Notes: On 3 alkyl halides, this reaction competes with the SN1For a given SN1 reaction, your minor product will alwaysinclude the E1 product

Nucleophiles

SN2 nucleophiles (only on Methyl, 1 and 2 alkyl substrates):N3

- I- NH3 Br- Cl- CN- HS-

SN1 nucleophiles with E1 minor products (only on 3 alkyl substrates)H2O, CH3OH, CH3CH2OH, HX (only on tertiary alcohols)

E1 bases (only on 3 alkyl halides)H2SO4 with H2O and heat gives purely E1 eliminationSN1 nucleophiles also give minor E1 products

E2 bases (only with 3 and 2 alkyl halides)-OH, -OCH3, -OCH2CH3, -OC(CH3)3, CN

- (only on 3 alkyl halide)

Substrates

Primary: SN2 reaction with good nucleophilesE2 with VERY strong bases

NO E1 or SN1!!

Secondary: With basic nucleophiles, get mixture of E2 (major) andSN2 (minor)With pure nucleophiles (not basic) get only SN2With weak nucleophiles, get SN1 with minor E1

Tertiary: With strong bases, get E2 exclusivelyWith weak nucleophiles, get SN1 with minor E1 product

NO SN2 ON A TERTIARY!!