314 -315 Reactions summary with answers

46 Pages·2009·0.4 MB·English

by  Chemistry Department

Synthetic possibilities Chem 315 Beauchamp 1

Reactions Study List Through Chem 315

For Use as a Study Guide

Beauchamp

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Synthetic possibilities Chem 315 Beauchamp 2

Important acid/base reactions used in the examples below.

Acid Base New Base Comments
sodium hydroxide
O Na O H O
Na Carboxylates are good
C H K = Ka(RCO2H) C nucleophiles,
eq K (H O)
R O a 2 R O S 2 > E2 at Me, 1o and 2o RX
K = 10-5 = 10+11 N
carboxylic acids eq 10-16 carboxylates

sodium hydride
Na H
alkoxides are OK nucleophiles,
CH2 H K = Ka(ROH) CH2 Na SN2 > E2 at Me and 1o RX, and
eq K (H ) strong bases, E2 > S 2 at 2o
R O a 2 R O N
alcohols Keq = 1100--1375 = 10+18 alkoxides and 3oRX.

sodium hydroxide
Na OH
thiolates are good nucleophiles,
HC2 H K = Ka(RSH) CH2 Na SN2 > E2 at Me, 1o and 2o RX,
eq K (H O) and strong bases, E2 > S 2 at
R S a 2 R S N
thiols Keq = 1100--816 = 10+8 thiolates 3oRX.

sodium amide
Na NR
2
terminal acetylides are OK
R C C H K = Ka(RCCH) R C C Na nucleophiles, SN2 > E2 at Me and
eq K(HNR ) 1o RX, and strong bases, E2 > S 2
a 2 N
terminal alkynes Keq = 1100--2357 = 10+12 terminal acetylides at 2o and 3oRX.

n-butyl lithium
H
Li n-Bu Li
N N LDA is a very strong base that
is also very sterically hindered,
K (HNR )
K = a 2 it always acts as a base in our
eq K (H-C H )
a 4 9 course.
diisopropylamine Keq = 1100--3570 = 10+13 LDA = lithium diisopropylamide

LDA = lithium diisopropylamide
O Na NR O
2
enolates are good nucleophiles,
C H K = Ka(RCOCH3) C SN2 > E2 at Me, 1o and 2o RX,
R C eq Ka(HNR2) R CH2 Na and strong bases, E2 > SN2
ketones / aldHe2hydes Keq = 1100--2307 = 10+17 ketone enolates at 3oRX.

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Synthetic possibilities Chem 315 Beauchamp 3

LDA = lithium diisopropylamide
O Na NR O
2
enolates are good nucleophiles,
R C H K = Ka(ROCOCH3) R C SN2 > E2 at Me, 1o and 2o RX,
kOetones / aldCRe2hydes Keeqq = 11K00a--23(57HN=R12)0+12 eOster enolatCeRs2 Na aatn d3 osRtrXon.g bases, E2 > SN2

n-butyl lithium
H Li n-Bu
R R n-butyl lithium removes proton
C X K = Ka(HCR2PPh3) C from Wittig salt and makes a
WRittig salt = PyPlihd3 Keq = 1K0a-3(3H-=C41H09+)17 R PPh3 galodoedh ynduecsle, ofoprhmilien agt aklekteonneess. and
eq 10-50 betaine

n-butyl lithium
n-butyl lithium removes proton
Li n-Bu from dithiane and makes a
good nucleophile at RX compounds.
S C S Keq = KKaa((dHi-thCi4aHne9)) S C S Creaanc trieoancst. o Snuclef uorr atwceitcael ifno rSmNs2
H H K = 10-33 = 10+17 H Li carbonyl group after hydrolysis.
dithiane eq 10-50 dithiane carbanion Makes aldehydes and ketones.

S 2 versus E2 choices at 2oRX.
N

At secondary RX (X= OTs, I, Br, Cl) S 2 and E2 products are in close competition with each other. Anions whose
N
conjugate acids have higher pK ’s (stronger bases have weaker acids) generally produce more E2 relative to S 2. The
a N
two examples that we will emphasize at 2oRX centers are carboxlyates (S 2 > E2) vs hydroxide and alkoxides (E2 >
N
S 2), and cyanide (S 2 > E2) vs terminal acetylides (E2 > S 2). Steric hindrance in RX or the electron pair donor
N N N
also favors E2 > S 2.
N

Similar looking base/nucleophiles (used in our course) that react differently with 2oRX structures. (They all react by
S 2 at methyl and 1oRX and they all react by E2 at 3oRX.)
N

2o RX structures
More basic, so E2 > S 2.
Less basic, so S 2 > E2. More basic, so E2 > S 2. Less basic, so S 2 > E2. N
N N N
O
N C R C C C H O R O
R O
cyanide terminal acetylides carboxylates hydroxide and alkoxides
pKa of conjugate acid = 9 pKa of conjugate acid = 25 pKa of conjugate acid = 5 pKa of conjugate acid = 16-19

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Alkanes with Br / hν. (Synthesis of RX compounds, X = Br, Cl.)
2
Br / hν free radical
CH 2
4 H3C Br halogenation
achiral
free radical
Br2 / hν halogenation
Br
achiral
Br free radical
halogenation
Br / hν
2 enantiomers
(R and S)
free radical
Br halogenation
Br / hν
2
achiral

1. a. RX compounds with NaOH / H O. (Alcohol synthesis.)
2
NaOH
H3C Br H2O H3C OH SN2
E2 S 2
N
NaOH OH
Br
H O
2
major enantiomers
minor achiral
(R and S)
Br NaOH
H2O E2
NaOH
H O OH SN2
2
Br
allylic and benzylic, very fast S 2 reactions
N
NaOH no reaction (vinyl and phenyl RX)
H O
Br 2
Forcing conditions can induce E2 reactions.

b. RX compounds with NaOR / ROH. (Ether synthesis, need to make RO--,Na+.)
S 2
H3C Br O Na O N
E2 SN2
O
Br
O Na
enantiomers
major minor achiral
(R and S)
Br
O Na E2
S 2
N
O Na O
Br
allylic and benzylic, very fast S 2 reactions
N
no reaction (vinyl and phenyl RX)
O Na
Br
Forcing conditions can induce E2 reactions.
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c. RX compounds with potassium t-butoxide (favors E2 > S 2).
N
K
S 2
N
O
H C Br
3
O
K E2
Br O
enantiomers
(R and S)
Br K E2
O
S 2
N
K
O
Br O
allylic and benzylic, very fast S 2 reactions
N
K no reaction (vinyl and phenyl RX)
O
Br
Forcing conditions can induce E2 reactions.
d. RX compounds with sodium carboxylates. Ester synthesis (can hydrolyze with base to ROH and
RCO H).
2
O O
H3C Br Na SN2
R O O
O
O
Br Na
S 2 > E2
R O O N
achiral
O
Br Na
E2
R O
O
O S 2
N
Na
Br O
R O
allylic and benzylic, very fast S 2 reactions
N
O
Na
Br no reaction
R O

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e. RX compounds with NaCN / DMSO. Nitrile synthesis.
NaCN
H3C Br DMSO H3C C N SN2
S 2 > E2
N
NaCN
Br C N
DMSO
achiral
NaCN
Br
DMSO
E2
NaCN S 2
N
DMSO
Br C
N
NaCN
DMSO no reaction
Br
f.
RX compounds with terminal acetylides (need to make). Alkyne synthesis at methyl and primary RX.
Na
H3C Br R H3C R SN2
Na mainly E2
Br
R
enantiomers
(R and S)
Br Na
E2
R
Na SN2
Br
R
R
Na
no reaction
Br
R
g.
RX compounds with conjugate base of phthalimide (need to make). 1o RNH synthesis, after hydrolysis.
2
O
1.
Na
N
1. S 2
H3C Br O H3C NH2 2. acNyl hydrolysis
2. NaOH
3. WK (neutralize)

O
1.
Na 1. S 2
N
N 2. acyl hydrolysis
Br NH2
O
2. NaOH
3. WK (neutralize) achiral

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O
1.
Na
Br N
E2
O
2. NaOH
3. WK (neutralize)
O
1.
Na
N
NH
Br O 2
2. NaOH 1. S 2
N
3. WK (neutralize) 2. acyl hydrolysis
O
1.
Na
N
no reaction
Br
O
2. NaOH
3. WK (neutralize)

h. RX compounds with LiAlH (LAH). Nucleophilic hydride displaces “X” on carbon.
4
1. LiAlH
4
H3C Br 2. WK CH4 SN2
1. LiAlH
4
Br 2. WK SN2
Br 1. LiAlH4 not our
2. WK usual
mechanism
1. LiAlH
4
2. WK S 2
Br N
1. LiAlH
4 no reaction
Br 2. WK
i.
RX compounds with NaBH . Nucleophilic hydride displaces “X” on carbon.
4
1. NaBH
4
H3C Br 2. WK CH4 SN2
1. NaBH
4
Br 2. WK SN2
Br 1. NaBH4 not our
2. WK usual
mechanism
1. NaBH
4
Br 2. WK SN2

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1. NaBH
4 no reaction
Br 2. WK

j. RX compounds with enolates (need to make with LDA/-78oC). Alkylation of carbonyl compounds.
O
Li
H3C Br H C CH4 SN2
2
S 2
N
O
achiral
Li
Br
H C
2
O
O
Br Li
E2
H C
2
O O
Li
S 2
N
Br
H C
2
O
Li
no reaction
Br
H C
2

k. RX compounds with water. Alcohol synthesis (rearrangements are possible).
H O
H3C Br 2 no reaction
S 1 > E1
N
H O
2 OH
Br diastereomers
top & bottom
achiral
Br H2O OH SN1 > E1
top = bottom
H O
2
S 1
Br N
Br
H O
2 no reaction
Br

l. RX compounds with alcohols. Ether synthesis (rearrangements are possible).
OH
H3C Br no reaction
S 1 > E1 diastereomers
N
top & bottom
Br OH achiral
O

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Br O SN1 > E1
OH
top = bottom
OH O SN1
Br
no reaction
OH
Br

m. RX compounds with liquid carboxylic acids. Ester synthesis (rearrangements are possible).
O
H3C Br OH no reaction
O S 1 > E1
N
O
diastereomers
Br OH O
top & bottom
achiral
O
O O S 1 > E1
Br N
OH top = bottom
O
O
Br OH S 1
O N
O
no reaction
Br
OH

2. a. ROH with: SOCl or PCl or HCl or 1. TsCl/pyridine 2. NaCl. Synthesis of R-Cl.
2 3
S 2
N
given reagent S 2
N
OH in the list Cl SN2
S 2
N
OH Cl SN1
given reagent SN1
in the list S 1
N
S 2
N
S 1
N
S 1
given reagent N
in the list SN1
S 1
OH Cl N
S 1
N
OH given reagent Cl S 1
N
in the list S 1
N
S 2
N
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OH given reagent Cl
in the list
S 2 or S 1
N N
b. ROH with: PBr or HBr or 1. TsCl/pyridine 2. NaBr. Synthesis of R-Br.
3
S 2
given reagent N
in the list SN2
OH Br S 2
N
OH Br
S 1
given reagent N
S 1
in the list N
S 2
N
S 1
N
given reagent
S 1
in the list N
S 1
N
OH Br
OH given reagent Br SN1
in the list S 1
N
S 2
N
OH given reagent Br
in the list
S 2 or S 1
N N
c. ROH with: PI or HI or 1. TsCl/pyridine 2. NaI. Synthesis of R-I.
3
S 2
given reagent N
in the list SN2
OH I S 2
N
OH I S 1
N
given reagent S 1
in the list N
S 2
N
S 1
N
given reagent S 1
in the list N
S 1
N
OH I
OH given reagent I SN1
in the list SN1
S 2
N
OH given reagent I
in the list
S 2 or S 1
N N
d. ROH with: CrO / pyridine (PCC). Synthesis of aldehydes or ketones.
3
H
CrO / pyridine
3
OH (PCC) oxidation
O

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