Download 201 Organic Reactions Worksheet

Chem 201/Beauchamp
Reactions and Mechanisms Worksheet
1
Starting organic compounds
Br
Br
CH4
Br
Br
o
o
1 given
1 given
1o given
rearrangement example
R-X Compounds (synthesis and reactions = R-Br in our course)
1. Make other R-Br compounds (nine examples for us, 3 primary examples given above and six more made below)
a. R-Br from alkanes using free radical substitution (three part sequence: 1. Initiation 2. Propagation (2 steps) 3.
termination
1. initiation - high energy photon ruptures the weakest bond (= halogen bond = homolytic cleavage)
Br
h
Br
Br
atoms bond energy
Br-Br
46
105
sp3 H3C-H
98
sp3 1o C-H
sp3 2o C-H
95
sp3 3o C-H
92
sp3 C-Br
68
H-Br
88
Br
2a. propagation (step 1) - bromine atom abstracts H from weakest C-H bond and makes an H-Br bond
H2
C
H3C
Br
H
CH2
H3C
H
Br
2b. propagation (step 2) - carbon free radical abstracts Br atom from bromine molecule and makes a C-Br bond
H3C
H2
C
Br
CH2
Br
H3C
Br
Br
3. termination - two reactive free radicals find one another and combine
H3C
H3C
CH2
H2C
CH2
H2
C
H3C
CH3
C
H2
CH3
H2
C
Br
H3C
Br
Other R-Br to make from our starting alkanes. Six possible RBr from our starting alkanes plus three primary RBr are given = 9 total.
Br
H3 C
H3C
Br
h
Br2
h
H3C
CH
H3 C
Br2
CH3
CH3
H2
C
Br2
Br
h
H3C
CH
C
H2
Br2
Br
Br
C
H3C
Br2
h
CH3
Br
h
Br2
h
CH4
shown above
There is no easy way to make a primary R-Br compound in our course yet (from our given starting structures). Three examples are
provided above until we can do this. (Not in 201)
y:\files\classes\201\201 Organic Reactions Worksheets.doc
Chem 201/Beauchamp
Reactions and Mechanisms Worksheet
2
In our course we will propose dibromoalkanes from ethane, propane and butane by using 2 equivalents of Br2/h. We will use these
to make alkynes (ethyne, propyne and but-1-yne)
Br
Br
CH
2 eqs.
Br2
H 3C
C
1. 3 eqs. NaNR2
Br 2. workup
H3C
Br
Br
2 eqs.
Br2
h
C
C
H2
CH3 1. 3 eqs. NaNR2
2. workup
h
H3C
Br
CH3
2 eqs.
Br2
h
1. 3 eqs. NaNR2
2. workup
b. Make R-Br from alcohols (reaction with HBr, SN2 at methyl and primary ROH, SN1 at secondary and tertiary
ROH)
SN2 reactions with with methyl and primary alcohols and H-Br (steps = 1. protonaton 2. SN2 reaction with bromide, with water
leaving group)
H2
C
H3C
H
O
Br
H2
C
H
Br
H 3C
H
Br
O
H3 C
H
H
CH2
H
O
SN1 reactions with secondary and tertiary alcohols and H-Br (steps = 1. protonaton 2. water leaving group forms carbocation
3. bromide adds)
H
CH3
H
C
H3C
CH3
H
H
O
H
C
Br
H
H3C
C
O
H3C
H
SN1 reactions with rearrangement to more stable carbocation
H
H2
C
C
H3C
H3C
H
C
Br
CH3
H
(2S,3R)
Later we will introduce a sequence to avoid
rearrangements in situations like this.
1. Ts-Cl / pyridine
2. NaBr
H
H2
C
H3C
O
H3C
CH3
H3C
H
H2
C
C
H3C
(2S,3R)
H2
C
CH3
H3C
H
(2S)
rearrangement
to more stable
carbocation
add nucleophile
(both sides)
y:\files\classes\201\201 Organic Reactions Worksheets.doc
lose beta H+
(either side)
rearrange
H
O
C
H3C
H
carbocation
reactions (R+)
CH3
H
H
C
C
Br
C
CH3
H
H
O
H
Br
H2
C
C
achiral
CH3
Br
H2
C
H3C
achiral
CH3
H2
C
C
H3C
Br
CH3
Chem 201/Beauchamp
Reactions and Mechanisms Worksheet
3
Examples of other R-Br to make from alcohols. There will be more possibilities as we progreas through organic chemistry.
H3C
H2
C
Br
C
H2
H
H3C
SN2
H2
C
H3C
O
H3 C
O
O
H2
C
H
C
H2
H3C
O
H2
C
H3C
O
H
S N2
H2
C
H3C
C
H2
H
H3C
O
CH3
H3C
CH
C
H2
SN 1
Br
S N1
CH3
H3C
Br
CH3
H
H
O
H3C
Br
SN1
CH
C
H2
H3C
O
shown above
Br
C
H3C
CH3
CH
H2
C
CH3
CH3
CH
O
CH
shown above
H3C
H
CH
CH3
H2
C
O
C
H2
H
SN2
H2
C
H3C
H2
C
H3C
S N2
SN2
H
H2
C
H
H3C
H
O
SN 1
CH3
O
C
H3C
H
H
O
c. Make R-Br from alkenes and H-Br (addition reactions – Markovnikov addition = form most stable carbocation)
Addition reaction of H-Br to alkene - 1. form the most stable carbocation 2. add bromide (possible rearrangements)
H
Br
H3C
CH2
C
H
Br
CH
C
Br
H3C
CH3
H3C
CH3
Make the most stable carbocation
H
(rearrangements are possible)
Alkene addition reactions with rearrangement to more stable carbocation.
H2
C
H
C
C
H3C
H3C
H
H
Br
CH2
H2
C
C
H3C
H
C
H3C
(3R)
H2
C
H3C
CH3
H2
C
C
Br
CH3
H
rearrangement
to more stable
carbocation
(3S)
H2
C
CH3
achiral
H3 C
C
H3 C
H3 C
Br
HBr
H2C
CH3
CH3
CH2
H3C
CH
H3C
Br
H
C
H2
HBr
C
H3C
CH2
shown above
H3C
CH
Br
H
C
H3C
Br
HBr
HBr
y:\files\classes\201\201 Organic Reactions Worksheets.doc
C
C
H2
CH2
C
H3C
Br
Br
CH3
CH3
H3 C
CH3
achiral
Other R-Br to make from alkenes
H2
C
H2
C
CH2
HBr
Chem 201/Beauchamp
d.
Reactions and Mechanisms Worksheet
4
Make RBr2 from alkanes + Br2/hυ (2x free radical substitution) or use Br2 + alkenes (addition reactions with
Br2, forms bromonium bridge followed by anti attack of bromide at more + carbon).
Addition reaction of Br-Br to alkene - 1. forms a bridging bromonium cation 2. adds bromide anti to bridge
H
H
CH2
C
Br
H
Br
C
Br
H
H
C
Br
CH2
H
anti attack at
more + carbon
bromonium bridge is
the most stable cation
Br
Br
C
H2
can be used to make alkynes
Addition reaction of Br-Br to alkene - 1. forms a bridging bromonium cation 2. adds bromide anti to bridge
H
H3 C
CH2
C
Br
H
Br
C
Br
H3 C
H
C
Br
CH2
bromonium bridge is
the most stable cation
H3 C
anti attack at
more + carbon
Br
Br
C
H2
can be used to make alkynes
Addition reaction of Br-Br to alkene - 1. forms a bridging bromonium cation 2. adds bromide anti to bridge
H
H2
C
H3 C
C
CH2
Br
H3C
Br
H
H
Br
C
C
H2
bromonium bridge is
the most stable cation
H3C
Br
CH2
anti attack at
more + carbon
C
C
H2
Br
Br
C
H2
can be used to make alkynes
Double E2 reaction to make alkynes: Use RBr2 + 3 equivalents NaNR2
Double elimination reaction (E2) forms alkynes using NaNR2 as the base. The acidity of sp C-H uses a third equivalent of the base
and can form a terminal acetylide which is either protonated in a workup step or reacted further with an electrophile (2. methyl or
primary RBr or 2. carbonyl compound or 2. epoxide)
R
Na
C
H2N
H
Na
H
Br
C
H H
Br
C
R
R
Na
H
C
R
H
O
2. workup
C
H3 C
Na
O
C
H
C
H
H2
C
C
Br
2. SN2
Na
R
H2
C
C
H
C
H
C
R
y:\files\classes\201\201 Organic Reactions Worksheets.doc
C
C
H
Na
C
C
H
Br
R
H
C
R
C
Na
NH2
NH2
R = H, CH3 or CH3CH2
from our starting materials
H
H
C
C
H3 C
C
C
C
H3 C
H2
Br
CH3
Na
further
reactions
possible
H
C
Chem 201/Beauchamp
Reactions and Mechanisms Worksheet
H
H
C
R
Na
H3C
C
C
C
Na
2. epoxide
opening
R
C
Na
H2
C
C
O
C
H
Na
CH3
H
CH3
R
O
CH
H
H
O
C
H
H2
C
O
C
H
3. workup
Na
O
R
H
R
C
H
O
CH3
C
2. carbonyl
addition
C
H
O
O
C
5
H
3. workup
H
O
CH
H2O
C
R
CH3
Na
Zipper reaction – moves internal alkynes to a terminal position, forming terminal acetylide
The zipper reaction changes a linear internal alkyne into a terminal acetylide that can be made into a terminal alkyne (2. simple workup) or
reacted with one of our three common electrophiles (2. methyl or primary RBr) or (2. aldehyde or ketone 3. workup) or (2. epoxide 3. workup).
The steps of the zipper reaction are similar to the steps of tautomers in base: 1. proton off, 2. resonance, 3. proton on. This continues until
the terminal alkyne is formed. Loss of the sp C-H forms the most stable anion and the reaction stops there until one of the workup possiblities
completes the reaction.
H
H2
C
C
CH2
CH2
C
H
C
C
N
R
C
H
H3C
C
C
C
C
H3C
H3C
R
H3C
H
H
N
R
N
R
N
protonate
o
Me or 1
RBr
aldehyde
or ketone
C
H3C
C
C
H3C
C
H2
R
R
H
R
H
H
C
C
C
H3C
C
C
H2
C
H3C
C
H
H
epoxide
N
C
R
H
R
2. Make other functional groups from R-Br
a. Make alcohols using SN2 reaction with NaOH at methyl and primary RBr. Use SN1 with H2O at secondary and
tertiary RBr (rearrangement is possible).
H
H
H3C
H
O
H
H H3 C
From our starting compounds:
O
H2
C
O
Br
SN 2
H3C
CH3
H
C
C
CH2
Me and primary RBr = 5 possibilities
secondar and tertiary RBr = 4 possibilities
Br
H
H
Br
SN 1
H3 C
CH3 H
rearrangements
are possible
y:\files\classes\201\201 Organic Reactions Worksheets.doc
O
H
O
O
H
H
C
H3C
R
CH3
H
H
O
H
C
H3C
CH3
Chem 201/Beauchamp
Reactions and Mechanisms Worksheet
6
Other alcohols from R-Br (nine possible in our course)
H
H 3C
H2
C
O
SN2
H3C
SN2
NaOH
H 3C
H
H
O
NaOH
SN2
H2
C
Br
H3C
SN2
SN2
NaOH
Br
shown above
O
O
NaOH
Br
H
H
O
Br
Br
given
given
given
CH3
O
H
CH
H3C
H
H
O
SN1
NaOH
H
O
H2O
SN 1
CH3
O
H2O
S N1
H2O
SN1
H2O
Br
CH
H3C
Br
Br
Br
shown above
b. Make ethers using SN2 reaction with NaOR at methyl and primary RBr; SN1 with ROH at secondary and tertiary
RBr
Make alkoxide from alcohol and NaH (acid/base reaction) to use in SN2 reaction
Na
O
H
H
O
R
-16
10
Keq = -37 = 10+21
10
pKa = 16
Na
R
SN2 reactions with alkoxides and methyl and primary RX compounds
R
O
H2
O
C
CH2
R
H3 C
Br
Na
H
C
3
S 2
H
H
pKa = 37
Except E2 > SN2 with:
Na
H3C
Br
H3C
N
SN1 reactions with alcohols and secondary and tertiary RX compounds
H
O
H
CH3
H3 C
H
O
Br
H
C
S N1
H3C
CH3
y:\files\classes\201\201 Organic Reactions Worksheets.doc
K
CH3
H
H
C
R
O
C
O
H
C
R
H3C
O
R
CH3
H
R
O
R
C
H3C
CH3
Chem 201/Beauchamp
Reactions and Mechanisms Worksheet
7
Other ethers from R-Br (9 ROH x 9 RBr = 81 possibilities in our course, some duplicates)
R
H3C
H2
C
O
SN 2
H3 C
SN 2
NaOR
H3C
R
R
O
NaOR
SN2
H2
C
Br
H3 C
SN 2
SN2
NaOR
Br
shown above
O
O
NaOR
Br
R
R
O
Br
Br
given
given
given
CH3
O
R
CH
H3C
R
R
O
SN 1
NaOR
R
O
ROH
SN1
O
ROH
SN1
CH3
SN1
ROH
ROH
Br
CH
H3C
Br
Br
Br
shown above
c. Make esters using SN2 reaction with CH3CO2Na (example carboxylate, more possible later) at methyl, primary and
secondary RBr; and SN1 with CH3CO2H (example acid, other acids are possible later) at tertiary RBr
Make carboxylate from carboxylic acid and NaOH (acid/base reaction) to use in SN2 reactions with methyl, 1o, 2o RX compounds
H
O
O
Na
O
Na
H
O
Keq =
pKa = 5
-5
10 = 10+11
10-16
O
H
O
H
pKa = 16
SN2 reactions with carboxylates and methyl, primary and secondary RX compounds
O
O
H2
C
O
H3 C
Br
Br
O
SN2
SN1 reactions with carboxylic acid and tertiary RX compounds
H3C
H3C
CH3
CH3
C
Br
O
C
SN 1
H3C
CH3
rearrangements
are possible
CH3
H
O
use the C=O
resonance (not shown)
y:\files\classes\201\201 Organic Reactions Worksheets.doc
O
O
C
H3C
CH3
H
B
H3C
H3C
B: = CH3CO2H
(use the C=O)
O
CH3
C
O
Chem 201/Beauchamp
Reactions and Mechanisms Worksheet
8
Other esters from R-Br (only nine examples using ethanoic acid, later more when other carboxylic acids are possible)
O
O
H2
C
C
H3C
O
S N2
H3C
O
SN 2
CH3
O
NaO2CCH3
SN 2
H2
C
Br
O
C
CH3 H3C
NaO2CCH3
O
H3C
O
NaO2CCH3
Br
SN2
NaO2CCH3
Br
Br
shown above
O
O
O
O
O
SN2
O
NaO2CCH3
SN2
O
O
SN 2
NaO2CCH3
SN1
NaO2CCH3
NaO2CCH3
SN 2
O
O
Br
Br
Br
H3C
CH3CO2H
CH3
C
H3C
Br
shown above
Br
d. Make nitriles using SN2 reaction with NaCN at methyl, primary and secondary RBr
SN2 reactions with NaCN and methyl, primary and secondary RX compounds
N
H2
C
C
H 3C
Na
Na
N
Br
Br
C
SN2
Other nitriles from R-Br (eight possible from our starting RBr, tertiary RBr does not work)
N
N
C
C
N
N
C
N
C
C
CH3
SN2
Br
NaCN
CH3
SN2
NaCN
SN2
SN 2
H2
C
Br
Br
N
N
C
NaCN
Br
N
C
SN2
NaCN
C
SN2
NaCN
Br
Br
NaCN
Br
CH3
shown above
SN2
SN2
NaCN
Br
y:\files\classes\201\201 Organic Reactions Worksheets.doc
Not possible
at 3o RX.
NaCN
Chem 201/Beauchamp
Reactions and Mechanisms Worksheet
9
e. Make larger alkynes using SN2 reaction with NaCCR (R = H, CH3, CH2CH3) at methyl and primary RBr.
Make terminal acetylides from NaNR2 and HCCH (acid/base reaction)
Na
H
H
Na
N
H
H
C
C
R
C
10-25
+12
Keq = -37 = 10
10
pKa = 25
C
N
R
H
H
pKa = 37
SN2 reactions with NaCCH and methyl and primary RX compounds (too basic to use at secondary RX =
E2 > SN2)
R
R
C
Na
C
H2
C
C
H3C
Na
C
Br
C
H2
SN2
CH3
Br
Other alkynes from R-Br (five possible from our starting RBr, only works at methyl and primary RBr)
R
R
R
C
C
C
C
C
CH3
C
C
C
C
H2
CH3
S
2
NaCCR
N
SN2
NaCCR
NaCCR
SN2
SN2
NaCCR
H2
C
H3C
Br
H3C
Br
Br
Br
shown above
R
R
C
C
SN2
NaCCR
Br
f. Make azides, then primary amines using: Reaction 1: SN2 reaction with NaN3 at methyl, primary and secondary
RBr Reaction 2: SN2 with LiAlH4 at the azide nitrogen 3. Workup  RNH2
Reaction 1: SN2 reactions with NaN3 and methyl, primary and secondary RX compounds makes azides
a.
N
N
-2
N
N
Na
H2
C
H3 C
H2
C
N
Br
Me, 1o, 2o RBr
N
Na
CH3
Br
SN2
azidoalkane
Reaction 2: a. reduce azide with lithium aluminium hydride with SN2 reaction at nitrogen b. workup
a.
b. workup
H
N
N
N
H2
H
H2
N
C
C
Al
H
N
CH3 H
O
H
N
CH3 H
SN2
H Li
Li
H
y:\files\classes\201\201 Organic Reactions Worksheets.doc
H2
C
H
N
H
CH3
Chem 201/Beauchamp
Reactions and Mechanisms Worksheet
10
Other amines from R-Br (eight possible from our starting RBr, does not work at tertiary RBr)
H
N
H
H2
C
CH3
H3 C
H
1. NaN3
2. LiAlH4
3. workup
H2
C
H3C
Br
shown above
Br
1. NaN3
2. LiAlH4
3. workup
N
H
H
H
1. NaN3
2. LiAlH4
3. workup
Br
H
N
H
N
N
H3C
H
1. NaN3
2. LiAlH4
3. workup
H
H
1. NaN3
2. LiAlH4
3. workup
Br
Br
H
N
N
H
H
H
1. NaN3
2. LiAlH4
3. workup
1. NaN3
2. LiAlH4
3. workup
Br
Two synthetic steps:
N
1. NaN3
2. LiAlH4 H
3. workup
Br
R-Br
NaN3
R-N3
1. LiAlH4
2. workup
Not possible
at 3o RBr
Br
g. Make thiols using SN2 reaction with NaSH at methyl, primary and secondary RBr
SN2 reactions to make thiols with NaSH and methyl, primary and secondary RX compounds
S
Na
H2
C
H
H 3C
Na
Br
SN 2
Br
S
H
Other thiols from R-Br (eight possible from our starting RBr, does not work at tertiary RBr)
S
S
H
SN 2
H3C
CH3
NaSH
H
SN2
Br
Br
C
H2
NaSH
H2
C
CH3
CH3
H
H
H
S N2
S
S
S
NaSH
Br
shown above
y:\files\classes\201\201 Organic Reactions Worksheets.doc
SN 2
Br
NaSH
SN2
Br
NaSH
R-NH2
Chem 201/Beauchamp
Reactions and Mechanisms Worksheet
S
S
S
H
H
NaSH
SN2
NaSH
S N2
Br
Br
11
H
SN 2
Not possible
at 3o RBr
NaSH
Br
h. Make sulfides using SN2 reaction with NaSR at methyl, primary and secondary RBr
Make thiolates with NaOH and thiols (acid / base reaction)
S
O
H
Na
pKa = 8
O
H
H
pKa = 16
S
10-8
+8
Keq = -16 = 10
10
R
H
R
Na
SN2 reactions to make sulfides with NaSR and methyl, primary and secondary RX compounds
S
Na
H2
C
R
H3 C
Na
Br
Br
S
SN2
R
Other sulfides from R-Br (8 RSH x 8 RBr = 64 RSR in our course, does not work at tertiary RBr)
S
S
R
C
H2
CH3
R
SN2
NaSH
Br
CH3
SN2
CH3
NaSH
H2
C
Br
CH3
shown above
R
R
NaSH
SN2
NaSH
SN 2
SN2
SN2
NaSH
Br
Br
NaSH
SN2
Br
S
R
SN2
NaSH
Br
Br
R
R
R
S
S
S
S
S
Br
y:\files\classes\201\201 Organic Reactions Worksheets.doc
Not possible
at 3o RBr
NaSH
Chem 201/Beauchamp
Reactions and Mechanisms Worksheet
12
i. Make Grignard carbanions using 1. Mg with R-Br 2. react Grignard reagents with a. carbonyl (aldehydes and
ketones), b. epoxides and c. carbon dioxide electrophiles 3. Workup
Make Grignard carbanions and bromide anion with Mg metal and RX compounds (oxidation / reduction reaction), Mg+2 inserts itself
between carbanion and bromide
H2
(MgBr)
C
we will
H2 C
Mg
write
it
CH2 Mg+2
H3 C
Br
Br
CH3
this way
H3C
carbanion
Simplified mechanism for our course
Other Grignard reagents (nine possible from our starting R-Br, tertiary does work on this reaction)
(BrMg)
(BrMg)
H2C
CH3
Mg
(BrMg)
(BrMg)
(BrMg)
H2C
H2C
H2 C
CH3
Mg
Mg
Mg
Mg
H2
C
H3C
Br
Br
CH3
Br
Br
Br
shown above
(BrMg)
(BrMg)
(BrMg)
(MgBr)
C
H3C
C
CH3
H
H3C
Mg
Mg
Mg
CH3
CH3
Currently 9 possibilities
from our starting structures,
but there will be more
possibilities later.
Mg
Br
Br
Br
Br
1. React Grignard reagents with aldehydes and ketones 2. workup : makes alcohols (Various carbonyl compounds will become
available when E2 reactions are discussed via oxidation reactions with CrO3. For now we will just list the carbonyl compounds that
will be made later.)
O
(BrMg)
H2C
CH3
(BrMg)
H
y:\files\classes\201\201 Organic Reactions Worksheets.doc
H
O
H
O
O
H
H
Chem 201/Beauchamp
OH
Reactions and Mechanisms Worksheet
13
OH
OH
OH
new
bond
1. H2C
9 x 8 possibilities (some duplicates)
2. workup
OH
OH
OH
H
O
(BrMg)
CH3
Carbonyl compounds (aldehydes and ketones) that will be made later from our starting RBr compounds (available to use until then).
O
O
H
H
shown
O
H
H
O
O
O
O
O
H
H
1. Grignard reagents with epoxides 2. workup : makes alcohols
(BrMg)
(BrMg)
O
H
O
O
H
H2C
H
O
H
CH3
Epoxide compounds that will be made later from carbonyl compounds (available to use anytime until then).
new
OH
OH
OH
bond OH
1. H2C
2. workup
(BrMg)
CH3
O
O
O
OH
O
O
shown
OH
O
OH
O
O
O
y:\files\classes\201\201 Organic Reactions Worksheets.doc
H
9 x 8 possibilities (some duplicates)
Chem 201/Beauchamp
Reactions and Mechanisms Worksheet
14
1. Grignard reagents with carbon dioxide 2. workup : makes carboxylic acids
O
(BrMg)
H
(BrMg)
O
C
H2C
H
O
O
H
CH3
O
H
O
O
Carboxylic acids that can be made from our starting RBr compounds using the Grignard reagents with carbon dioxide.
O
O
O
OH
O
OH
OH
shown
O
O
O
OH
O
O
OH
OH
OH
OH
OH
1. Grignard reagents with nitriles 2. workup hydrolyzes the C=N and makes ketones (C=O)
(BrMg)
H2C
(BrMg)
N
C
H
H2 O
N
O
H
H2N
H
O
H
H3C
H
H
O
C
2. workup
C
H2
CH3
H
H
H
H
H2N
OH2
O
C
C
H2
CH3
N
H
O
y:\files\classes\201\201 Organic Reactions Worksheets.doc
H
N
H
9 RMgBr x 8 RCN = 72 possibilities
(some duplicates)
H
N
resonance
H
H3C
H
H
CH3
H
O
H
H
H
C
H2
H
N
O
H
C
CH3
CH3
H
H3C
H2O
H
N
Ketones from nitriles and Grignard
reagents followed by hydrolysis. The
hydrolysis or the C=N uses an addition
reaction (H2O) followed by an elimination
reaction (NH3) to form a C=O.
resonance
Chem 201/Beauchamp
Reactions and Mechanisms Worksheet
15
Nine Grignard reagents can be made from our starting RBr compounds and reacted with eight possible nitriles from our RBr compounds
make for 72 possible combinations, though some produce similar products. Each "R" below represents nine possibilities.
O
O
O
R
shown with
"R" = ethyl
O
O
R
R
R
R
O
9 possible
O
O
N
R
C
R
R
O
1. R2MgBr
2. workup
R1
R1
8 possible some duplicates
R2
j. Lithium aluminum hydride (LiAlH4) = nucleophilic hydride with methyl, primary and secondary R-Br compounds
(reduces Br to H, we will use LiAlD4 to show where hydride reaction occurs, D = deuteride / deuterium). Also reacts
at carbonyl and epoxide electrophiles, followed by a workup step (similar to Grignard reaction above, except using
nucleophilic hydride or deuteride reagents = LiAlH4 or LiAlD4 (for us). For now we will consider lithium aluminium
hydride (LiAlH4) as equivalent to sodium borohydride (NaBH4) and only use LAH or LAD (LiAlD4).
SN2 reactions to reduce Br to H (or D) with 1. LiAlH4 2.workup, at methyl, primary and secondary RX compounds (not tertiary)
D
Li
8 possible from our
starting structures
Li
H
2
D
Al
D
D
C
Br
SN2
not possible
H3 C
Br
D
at 3o RBr
D
D
D
D
D
D
D
D
Br
Br
Br
H3C
SN 2
Br
1. LiAlD4
2. workup
Br
Br
Br
Br
H3C
shown
1o given
1o given
1o given
1. Nucleophilic hydride addition reactions with aldehydes and ketones 2. workup
Li
D
D
Al
O
H
H
O
Li
: makes alcohols
O
8 possible from our
starting structures
O
D
H
D
y:\files\classes\201\201 Organic Reactions Worksheets.doc
H
H
D
H
workup
H
D
Chem 201/Beauchamp
Reactions and Mechanisms Worksheet
16
Carbonyl compounds (aldehydes and ketones) that will react with LiAlD4 / workup to form alcohols (carbonyl addition reactions).
These carbonyl compounds will be made later from our starting RBr compounds. (RCN are a source of ketones too, see above.)
D OH
D
OH
D
OH
D
OH
D
OH
D OH
D
OH
D
OH
H
H
H
H
H
H
1. LiAlD4
2. workup
O
O
O
H
H
H
O
O
H
O
O
O
H
H
shown
1. Nucleophilic hydride addition reactions with epoxides at less hindered carbon 2. workup
Li
D
Li
O
D
Al
D
:
makes alcohols
H
H
O
O
O
D
S
H
H
8 possible from our
starting structures
D
S
S
workup
D
Epoxide compounds will be made later from the above carbonyl compounds and trimethylsulfonium iodide / n-butyl lithium. The first
step is SN2 attack by hydride or deuteride on the least hindered carbon atom, followed by workup to neutralize the alkoxide.
OH
OH
OH
OH
OH
OH
OH
O
H
D
D
D
D
D
D
D
D
1. LiAlD4
2. workup
O
3.
O
O
O
O
O
O
O
a. E2 elimination reactions can make alkenes from R-Br compounds (E2 reactions using bulky, basic potassium
t-butoxide in our course).
E2 reactions using potassium t-butoxide and primary, secondary or tertiary RBr (eight possible from our starting RBr compounds),
requires anti C-H and C-Br to be able to start forming pi bond in transition state.
O
K
H2
C
H
C
H2
H
Br
E2
y:\files\classes\201\201 Organic Reactions Worksheets.doc
H2 C
CH2
O
K
Br
Chem 201/Beauchamp
Reactions and Mechanisms Worksheet
17
Other E2 reactions (eight possible from our starting R-Br, two are duplicates and one produces a mixture of alkene products)
H2C
CH2
potassium
t-butoxide
potassium
t-butoxide
potassium
t-butoxide
H2
C
CH3
Br
potassium
t-butoxide
Br
Br
Br
shown above
mixture of
mono, cis
and trans
alkenes, not
useful for us
duplicate
potassium
t-butoxide
duplicate
potassium
t-butoxide
potassium
t-butoxide
potassium
t-butoxide
Br
Br
Br
Br
b. E1 elimination reactions can make alkenes from alcohols. ROH and concentrated sulfuric acid and heat forms
alkenes and alkenes distill away from the mixture. Rearrangements are possible due to carbocation intermediates.
E1 reactions using concentrated H2SO4/ and ROH, rearrangements are possible
H
H
H
O
O
SO3H
CH
H3C
CH3
O
H
CH
C
H3C
E1
H
H
H
O
H
C
H
H2C
H3C
C
H2
rearrangements are possible
(but not here)
CH3
CH3
Other alcohol dehydrations to alkenes (eight ROH possible from our starting R-Br, methyl won't work because we need at least two
carbons, the two straight chain, 4C alcohols won't be useful because they will produce a mixture of mono, cis and trans butenes, the
other 4C skeleton produce duplicate alkenes, as do the two 3C skeletons, so only four different alkenes are produce in this E1 reaction.)
H2C
E1
CH2
Mixture of mono,
cis and trans butenes.
C
H2SO4/
H2C
E1
H2
C
H3C
CH3
H
CH3
H2SO4/
H
O
C
H2C
E1
H
O
y:\files\classes\201\201 Organic Reactions Worksheets.doc
E1
H2SO4/
H
O
CH3
H2SO4/
H
O
Chem 201/Beauchamp
Reactions and Mechanisms Worksheet
duplicate
CH3
H2C
E1
duplicate
CH3
Mixture of mono,
cis and trans butenes.
C
H
H2SO4/
E1
H2SO4/
C
H2C
CH3
E1
H2SO4/
E1
CH3
H2SO4/
O
CH
H3C
18
H
H
H
O
H
O
O
shown above
c. A very important E2 elimination reaction involves methyl, primary and secondary alcohols and highly oxidized
chromium +6 (we will write it as CrO3). There are many variations of this overall transformation but for now we
will only present one simplified version, pyridinium chlorochromate (PCC = CrO3/pyridine). A preliminary step
forms an inorganic ester and uses pyridine as a base to pick off protons. A second step is our familiar E2 reaction,
though it occurs across C and O with a Cr leaving group taking electrons with it, instead of C and C and a bromide
leaving group. The details of all the steps are written out for you below. This reaction allows us to make aldehydes
and ketones from methyl, primary and secondary alcohols, a very valuable functional group interconversion (FGI).
The oxidation sequence uses a methyl, primary or secondary alcohol to form a carbonyl group (aldehyde or ketone). In the first step an
inorganic ester is formed and a proton is lost from the OH. In the second step an E2 elimination reaction occurs across the C-O bond.
H
H3C
C
O
H
C = -1
Cr
H
O
H3C
(step 1)
O
PCC conditions
(base = pyridine)
Cr = +6
C
H
N
O
H
O
O
H
O
Cr
O
pyridine = base
acid/base
H3C
N
N
C
H
aldehyde
2o alcohol
ketone
3o alcohol
no reaction
y:\files\classes\201\201 Organic Reactions Worksheets.doc
O
Cr
O
Cr = +6
E2 (oxidation)
methanal
1o alcohol
O
H
C = -1
pyridine = base
methanol
O
H
O
H3C
N
H
C
H
O
C = +1
The oxidation reaction stops
here because there is no water
to hydrate the C=O bond.
Cr
O
O
Cr = +4
Chem 201/Beauchamp
Reactions and Mechanisms Worksheet
19
Carbonyl compounds prepared from alcohols and CrO3/pyridine (PCC).
O
O
O
O
O
O
O
O
C
H
H
CrO3
pyridine
(PCC)
H
O
CrO3
pyridine
(PCC)
CrO3
pyridine
(PCC)
OH
OH
H
H
H
H
CrO3
pyridine
(PCC)
CrO3
pyridine
(PCC)
OH
CrO3
pyridine
(PCC)
CrO3
pyridine
(PCC)
OH
OH
OH
CrO3
pyridine
(PCC)
OH
C
H
H
H
4. Carbonyl addition reactions at aldehydes and ketones with strong nucleophiles (negatively charged, for us).
a. Hydration of carbonyl groups with aqueous hydroxide to make carbonyl hydrates.
1. Nucleophilic hydroxide addition reactions with aldehydes and ketones forms carbonyl hydrates, reversible reaction reforms carbonyl
H
H
O
O
O
Na
Li
Na
O
C
C
C
O
H
O
H
H
CH3
CH3
H
CH3
H
H
O
O
workup
H
H
Other carbonyl compounds (aldehydes and ketones) that will react with hydroxide to form a carbonyl hydrate.
HO
OH HO
H
OH
H
OH HO
HO
H
OH
HO
OH
HO
OH
HO
OH
H
H
H
OH
HO
NaOH (aq)
O
O
H
O
H
H
O
H
shown
y:\files\classes\201\201 Organic Reactions Worksheets.doc
O
O
H
O
O
H
Chem 201/Beauchamp
Reactions and Mechanisms Worksheet
20
b. Carbonyl groups reacting with alcoholic alkoxides form hemi-acetals and hemi-ketals. (Similar to hydration,
above.)
1. Nucleophilic alkoxide addition reactions with aldehydes and ketones forms hemi-acetals and hemi-ketals, reversible reaction
reforms carbonyl
H
H
O
O
O
Na
Li
Na
O
C
C
C
O
R
O
H
R
R
R
R
R
R
1
2
1
alkoxide
(from alcohol + NaH)
1
2
O
workup
R
R
2
O
H
hemi-acetal if R1 or R2 = H
hemi-ketal if R1 and R2 = C
Other carbonyl compounds (aldehydes and ketones) that will react with hydroxide to form hemi-acetals (from aldehydes) and hemi-ketals
(from ketones).
HO OR
HO
OR
HO
OR HO
OR
HO
OR
HO OR
OR
HO
OR HO
H
H
H
H
H
H
NaOR (alkoxide)
ROH
O
O
O
H
H
H
O
O
H
O
O
O
H
H
shown
c. Carbonyl groups reacting with cyanide (C=O addition reaction) to form cyanohydrins.
Nucleophilic cyanide addition reactions with aldehydes and ketones forms cyanohydrins.
O
Na
N
Na
C
C
H
H3C
cyanide
O
O
C
H3C
H
H
O
H
C
C
H
H
H3 C
workup
H
C
N
N
Carbonyl compounds (aldehydes and ketones) that will react with NaCN / workup to form cyanohydrins (carbonyl addition reactions).
N
N
C
OH
H
N
C
OH
N
C
OH
H
H
N
C
OH
N
N
C
OH
C
OH
N
C
OH
C
H
H
1. NaCN
2. workup
O
O
H
O
H
H
shown
O
H
y:\files\classes\201\201 Organic Reactions Worksheets.doc
O
O
H
O
O
H
OH
Chem 201/Beauchamp
Reactions and Mechanisms Worksheet
21
d. Carbonyl groups reacting with terminal acetylides (C=O addition reaction) to form propargylic alcohols, after
workup.
Make terminal acetylide nucleophiles from terminal alkynes and sodium amide, NaNR2, then add electrophile (methyl or primary RBr,
a carbonyl compound or an epoxide).
Na
Na
R
C
C
N
H
terminal
alkyne
R
R
C
C
terminal acetylide
terminal
acetylide
R
React with an electrophile (methyl or primary
RBr, a carbonyl compound or an epoxide).
Nucleophilic acetylide addition reactions with aldehydes and ketones forms propargyl alcohols.
O
Na
R
C
Na
C
C
H3C
H3C
terminal
acetylide
R = H, CH3 or CH2CH3
in our course, for now.
O
O
C
H
H
H
O
H
H
H
C
C
H3C
workup
H
C
C
C propargyl
alcohol
R
R
Carbonyl compounds (aldehydes and ketones) that will react with NaCCR / workup to form propargyl alcohols (carbonyl addition
reactions).
R
R
R
R
R
R
R
R
C
C
C
C
C
C
C
C
C OH
C
OH
C
OH
C
OH
C
OH
C
OH
C
OH
C OH
H
H
H
H
H
1. NaCCR
2. workup
O
O
H
O
H
H
shown
O
H
y:\files\classes\201\201 Organic Reactions Worksheets.doc
O
O
H
O
O
H
Chem 201/Beauchamp
Reactions and Mechanisms Worksheet
22
d. Sulfur ylid additions to aldehydes and ketones – epoxide syntheses
Make sulfur ylid from sulfonium iodide salt and n-butyl lithium (acid/base reaction)
H3C
Li
H
CH2
S
H3C
H2 C
I
trimethylsulfonium
iodide salt
H2
C
H3C
CH3
Li
S
C
H2
buy
n-butyl lithium
H3C
CH2
H2
C
H
C
H2
I
C
H2
CH3
sulfur ylid
nucleophile
Sulfur ylid reactions with carbonyl compounds makes epoxides
O
H
H3C
S
carbonyl
addition
H3C
H3C
H2C
H3C
H2C
CH3
H3C
CH3
epoxide
intramolecular
SN2 reaction
S
H
C
C
O
CH2
O
H
S
CH3
dimethylsulfide
(good leaving group)
CH3
Other epoxides that can form from similar reactions.
O
O
O
O
(CH3)2SCH2
O
H
(CH3)2SCH2
O
H
O
(CH3)2SCH2
O
H
O
(CH3)2SCH2
O
H
y:\files\classes\201\201 Organic Reactions Worksheets.doc
O
O
(CH3)2SCH2
(CH3)2SCH2
(CH3)2SCH2
O
O
O
O
H
(CH3)2SCH2
H
Chem 201/Beauchamp
Reactions and Mechanisms Worksheet
23
e. Hydration of epoxide groups with aqueous hydroxide.
1. Nucleophilic hydroxide addition reactions with epoxides forms diols.
H
R
O
Na
O
Na
H
H3C
R
O
H
O
H
C
R
O
O
CH2
C
R
workup
O
reacts similarly.
H
H3C
H
Na
O
CH2
H
O
diol
H
H
Other epoxide examples also form diols.
OH
OH
OH
OH
OH
OH
OH
O
H
OH
OH
OH
OH
OH
OH
OH
OH
NaOH
O
O
O
O
O
O
O
O
f. Alkoxide addition to epoxide groups.
1. Nucleophilic alkoxide addition reactions with epoxides forms alcohol-ethers.
R
Na
O
Na
H
H3 C
R
O
O
H
C
R
O
H
O
H
H3C
R
CH2
C
R
workup
O
Na
O
CH2
R
O
diol
R
R
Other epoxide examples also form diols.
OH
OH
OH
OH
OH
OH
OH
O
H
OR
OR
OR
OR
OR
OR
OR
OR
NaOH
O
O
O
y:\files\classes\201\201 Organic Reactions Worksheets.doc
O
O
O
O
O
Chem 201/Beauchamp
Reactions and Mechanisms Worksheet
24
5. Substitution reactions at carboxyl functional groups (examples: acid chlorides and esters)
a. Carboxylic acids reacted with thionyl chloride (SOCl2)
Make acid chlorides from carboxylic acids and thionyl chloride (SOCl2)
Cl
O
Cl
O
C
H
H3C
Cl
O
S
S
S
O
Cl
O
H3C
H
H3 C
O
O
O
C
H
O
S
O
Cl
C
Cl
O
O
Cl
C
H3 C
H
O
C
H3C
Cl
Cl
H
Cl
Cl
Nine acid chlorides made from carboxylic acids and thionyl chloride.
O
O
O
O
O
C
H3C
Cl
Cl
Cl
O
O
Cl
O
O
Cl
Cl
Cl
Cl
Cl
SOCl2
Nine carboxylic acids made from our starting RBr compounds using the Grignard reagents with carbon dioxide.
O
shown
O
O
OH
OH
OH
O
O
OH
O
OH
y:\files\classes\201\201 Organic Reactions Worksheets.doc
OH
O
O
OH
O
OH
OH
Chem 201/Beauchamp
6.
Reactions and Mechanisms Worksheet
25
b. Anhydrides from acid chlorides (nine possible above) reacted with carboxylates (nine possible from above)
Make carboxylate from carboxylic acid and NaH (acid/base reaction) to use in reactions with acid chlorides.
O
O
Na
H
H
Na
C
O
CH3
pKa = 5
O
H3 C
Na
C
H2
Na
acyl
substitution
H3C
O
C
C
Cl
O
CH3
ethanoate
(acetate)
propanoyl chloride
C
10-5
+32
Keq = -37 = 10
10
C
H2
O
H
H
CH3
pKa = 37
O
O
C
C
H3C
O
CH3
Cl
O
O
C
C
Cl
Na
O
C
H2
CH3
ethanoic propanoic anhydride
T.I. = tetrahedral
intermediate
Nine acid chlorides x nine carboxylic acids = 81 possible anhydrides (with some duplicates). Only a few examples shown.
O
O
O
O
O
O
O
O
1. NaH
2. O
Cl
O
1. NaH
2.
O
Cl
1. NaH
2.
O
Cl
O
OH
O
O
1. NaH
2.
O
O
O
Cl
O
OH
O
OH
OH
c. Nine acid chlorides reacted with nine alkoxides makes a lot of esters. This is a second way from the SN2
approach. Using the SN2 approach the carboxylate was the nucleophile reacting with the electrophilic RBr
compound and in this approach the acid chloride is the electrophile reacting with the nucleophilic alkoxide.
Make alkoxide from alcohol and NaH (acid/base reaction) to use in acyl substitution reactions with acid chlorides.
Na
H
H
Na
H2
C
O
CH3
pKa = 16
O
H3C
Na
H2
C
C
C
H2
Cl
propanoyl chloride
O
ethoxide
10-16
+21
Keq = -37 = 10
10
acyl
substitution
Na
H3 C
CH3
O
H
H
CH3
pKa = 37
O
O
H2
C
C
C
H2
O
Cl
T.I. = tetrahedral
intermediate
y:\files\classes\201\201 Organic Reactions Worksheets.doc
H2
C
H3C
CH3
Cl
H2
C
C
C
H2
O
ethyl propanoate
Na
CH3
Chem 201/Beauchamp
Reactions and Mechanisms Worksheet
26
Nine acid chlorides x nine alcohols = 81 possible esters. Only a few examples shown.
O
O
O
O
O
O
1. NaH
2. O
O
1. NaH
2.
O
Cl
1. NaH
2.
O
Cl
OH
O
1. NaH
2.
O
Cl
OH
Cl
OH
OH
d. Nine acid chlorides reacted with eight amines makes a lot of amides. In this reaction the amine is both a
nucleophile and a base.
Make amides from amines and acid chlorides using acyl substitution reactions.
O
H3C
C
C
H2
Cl
propanoyl chloride
acyl
substitution
H3C
H2
C
H
CH3
N
O
H
C
C
H2
N
1 amine
(nucleophile)
H
T.I. = tetrahedral
intermediate
H
CH3
Cl
ethylamine
H ethanamine
o
O
H2
C
H3C
H2
C
H2N
C
C
H2
H2
C
N
CH3
Cl
CH3
1o amine
(base)
O
H3 C
Cl
H2
C
C
N
C
H2
CH3
o
2 amide
H
N-ethylpropanamide
Nine acid chlorides x eight amines = 72 possible esters. Only a few examples shown.
O
O
N
H
O
Cl
O
N
N
N
H
H
H
O
O
O
Cl
NH2
O
Cl
Cl
NH2
y:\files\classes\201\201 Organic Reactions Worksheets.doc
NH2
NH2
Chem 201/Beauchamp
Reactions and Mechanisms Worksheet
27
e. Esters reacted with Grignard reagents, followed by workup.
1. React 2 equivalents of Grignard reagent with esters. This occurs in 2 steps. The Grignard reagent adds to the ester carbonyl forming
a tetrahedral intermediate (TI), which collapses back to a carbonyl group with the extrusion of the alkoxide anion. The newly formed
ketone is more reactive than an ester so it immediately reacts with another equivalent of Grignard reagent forming a tertiary alkoxide.
2. The final workup step protonates the alkoxide oxygen forming a tertiary alcohol with 2 identical groups at the alcohol carbon atom.
C
H2C
H3 C
CH3
Grignard
reagent
O
(BrMg)
O
(BrMg)
CH3
O
O
C
H3 C
O
C
H3C
C
H2
CH3
H
H
O
3 alcohol
C
H3C
H2C
C
H2
CH3
OH
O
H
CH3
O
H
2. workup
CH3
OH
Ketones are more
reactive than esters.
TI
H2C
o
CH3
O
CH3
CH2
H3C
ester
(BrMg)
C
H3C
C
CH2 H2
CH3
H3C
OH
OH
OH
H
1. 2eqs.
CH3CH2MgBr
2. workup
O
O
R
H
O
1. 2eqs.
CH3CH2MgBr
2. workup
1. 2eqs.
CH3CH2MgBr
2. workup
1. 2eqs.
CH3CH2MgBr
2. workup
O
O
O
R
R
O
1. 2eqs.
CH3CH2MgBr
2. workup
R
O
R
O
O
Carbonyl compounds (aldehydes and ketones) that will be made later from our starting RBr compounds (available to use until then).
y:\files\classes\201\201 Organic Reactions Worksheets.doc
Chem 201/Beauchamp
Reactions and Mechanisms Worksheet
28
f. Reactions of esters reacted with lithium aluminum hydride (deuteride), followed by workup.
1. React 2 equivalents of hydride (deuteride) from LAH (LAD) with esters. This occurs in 2 steps. The hydride (deuteride) reagent
adds to the ester carbonyl forming a tetrahedral intermediate (TI), which collapses back to a carbonyl group with the extrusion of the
alkoxide anion. The newly formed aldehyde is more reactive than an ester so it immediately reacts with another equivalent of Grignard
reagent forming a primary alkoxide. 2. The final workup step protonates the alkoxide oxygen forming a primary alcohol with 2 identical
groups at the alcohol carbon atom.
CH3
O
Li
O
O
Li
Li
O
CH3
C
C
CH3
D
H3C
O
C
Aldehydes are more
H3C
O
D
H3C
D
reactive than esters.
D
Al
D
T.I. = tetrahedral
D
intermediate
ester
D
D
H
o
1 alcohol
H3C
O
O
C
H
H
D
D
2. workup
H
1. LiAlD4
2. workup
1. LiAlD4
2. workup
H
O
D
D
D
D
D
T.I. = tetrahedral
intermediate
O
D
D
D
D
D
H
O
O
O
C
H3 C
H
H
H
D
D
1. LiAlD4
2. workup
D
D
H
O
Al
1. LiAlD4
2. workup
1. LiAlD4
2. workup
O
O
O
R
H
O
O
O
R
R
O
R
O
R
O
O
Carbonyl compounds (aldehydes and ketones) that will be made later from our starting RBr compounds (available to use until then).
y:\files\classes\201\201 Organic Reactions Worksheets.doc
Chem 201/Beauchamp
Reactions and Mechanisms Worksheet
29
g. Nitriles reacted with aqueous sodium hydroxide, followed by workup.
1. Aqueous base with nitriles can form primary amides (or continue to carboxylic acids).
O
Na
N
Na
N
H
C
C
O
H
nitrile
H
Under forcing
conditions can
continue on to
carboxylic acids
(after workup)
H
O
CH3
CH3
H
H
O
H
O
H
C
CH3
O
H
H
H
N
C
O
N
2. workup
N
NaOH

H
H
N
resonance
C
C
CH3
O
1o amide
O
CH3
CH3
Other nitriles to consider.
O
H
C
H3C
O
O
H
H
N
H
NaOH
NaOH
N
N
H
H
H
NaOH
NaOH
N
C
C
C
H
N
N
N
N
O
C
CH3
O
O
H
H
NaOH
N
C
O
O
H
N
N
N
H
H
H
NaOH
N
NaOH
C
y:\files\classes\201\201 Organic Reactions Worksheets.doc
N
C
N
H
NaOH
C
N
H
Chem 201/Beauchamp
Reactions and Mechanisms Worksheet
30
7. Hydrolysis of nitriles and terminal alkynes in aqueous sulfuric acid.
a. Synthesis of ketones from aqueous acid hydrolysis of alkynes.
H
H
H
C
H
C
O
H
C
H
C
C
H3C
H
C
H3C
H 3C
H
terminal
alkyne
O
C
H 3C
H
C
O
H
H
H
enol
H
O
H
H
O
H
H
H
H
H
H
H
H3C
C
H 3C
H
O
H
H
C
H
O
H
H
C
C
O
H
O
H
ketone
C
H3C
C
resonance
H
H
b. Synthesis of primary amides from aqueous acid hydrolysis of nitriles. Notice the similarities to the reaction,
just above.
H
N
H
C
O
H
H
H
H3C
C
H
nitrile
O
H
H
H3C
resonance
H
H
O
H
H
H3C
H
resonance
N
C
O
H
H3C
O
H
N
C
O
H
H
H
N
C
O
H
primary amide
y:\files\classes\201\201 Organic Reactions Worksheets.doc
H
H
H
H
H3C
O
H
N
C
O
H
O
H
N
C
H
O
H
C
H3C
H
N
C
H3C
N
resonance
H3C
H
H3C
H
N
Several resonance structures not in
the above example because of the
nitrogen and oxygen lone pairs, but
otherwise very similar.
H
O
O
H
Chem 201/Beauchamp
Reactions and Mechanisms Worksheet
31
Basic RX patterns to know, with isoptope substitutions to show mechanism details
(horizontal and vertical perspectives, templates for studying SN and E mechanisms)
Example 1 - two possible perspectives (deuterium and tritium are isotopes of hydrogen that can be distinguished)
T
D
methyl
RX
example
T
H reaction
Br reaction
C
C
conditions
conditions
H
?
?
D
Br
Bold = actual structure
S-bromoderteriotritiomethane
S-bromoderteriotritiomethane
others
= possible structures
R-bromoderteriotritiomethane
R-bromoderteriotritiomethane
Example 2 - two possible perspectives (deuterium is an isotope of hydrogen that can be distinguished)
primary RX example
CH3
D
reaction
conditions
C
H
C
Br
H
D
C
?
H3C
H
D
(1S,2S)- 1,2-dideuterio-1-bromopropane
(1R,2R)- 1,2-dideuterio-1-bromopropane
Bold = actual structure
(1R,2S)- 1,2-dideuterio-1-bromopropane others = possible structures
(1S,2R)- 1,2-dideuterio-1-bromopropane
C
D
H reaction
conditions
?
Br
(1S,2R)- 1,2-dideuterio-1-bromopropane
(1S,2S)- 1,2-dideuterio-1-bromopropane
(1R,2R)- 1,2-dideuterio-1-bromopropane
(1R,2S)- 1,2-dideuterio-1-bromopropane
Example 4 - two possible perspectives (deuterium is an isotope of hydrogen that can be distinguished)
D
secondary RX example
CH3
H
C
C
H
H
C
Br
reaction
conditions
?
CH2CH3
CH3
(2S,3R,4S)-2-deuterio-4-methyl-3-bromohexane
(2R,3S,4R)-2-deuterio-4-methyl-3-bromohexane
(2S,3S,4S)-2-deuterio-4-methyl-3-bromohexane
(2R,3R,4R)-2-deuterio-4-methyl-3-bromohexane
(2S,3S,4R)-2-deuterio-4-methyl-3-bromohexane
(2R,3R,4S)-2-deuterio-4-methyl-3-bromohexane
(2S,3R,4R)-2-deuterio-4-methyl-3-bromohexane
(2R,3S,4S)-2-deuterio-4-methyl-3-bromohexane
y:\files\classes\201\201 Organic Reactions Worksheets.doc
H3C
H
D
H
C
H
C
C
H3C
Br
reaction
conditions
CH2CH3
?
(2S,3S,4S)-2-deuterio-4-methyl-3-bromohexane
(2R,3R,4R)-2-deuterio-4-methyl-3-bromohexane
(2S,3R,4S)-2-deuterio-4-methyl-3-bromohexane
(2R,3S,4R)-2-deuterio-4-methyl-3-bromohexane
(2S,3S,4R)-2-deuterio-4-methyl-3-bromohexane
(2R,3R,4S)-2-deuterio-4-methyl-3-bromohexane
(2S,3R,4R)-2-deuterio-4-methyl-3-bromohexane
(2R,3S,4S)-2-deuterio-4-methyl-3-bromohexane
Chem 201/Beauchamp
Reactions and Mechanisms Worksheet
32
Example 3 - two possible perspectives (deuterium is an isotope of hydrogen that can be distinguished)
D
secondary RX example
CH3
H
C
reaction
Br conditions
C
H
H
C
?
H3C
H
H
H
C
H
C
C
H
D
reaction
conditions
CH3
?
Br
CH3
(2S,3R)-3-deuterio-2-bromobutane
(2R,3S)-3-deuterio-2-bromobutane
(2S,3S)-3-deuterio-2-bromobutane
(2R,3R)-3-deuterio-2-bromobutane
Bold = actual structure
others = possible structures
(2R,3R)-3-deuterio-2-bromobutane
(2S,3S)-3-deuterio-2-bromobutane
(2S,3R)-3-deuterio-2-bromobutane
(2R,3S)-3-deuterio-2-bromobutane
Example 5 - two possible perspectives (deuterium is an isotope of hydrogen that can be distinguished)
D
CH3
tertiary RX example
H
H
C
H
D
reaction
reaction
CH2
C
Br conditions ?
conditions
C
C
?
C
H
CH2CH3
H3C
C
H2
CH2CH3
H
H
C
H3C
Br
CH3
(2S,3S,4S)-2-deuterio-4-methyl-3-bromohexane
(2S,3R,4S)-2-deuterio-4-methyl-3-bromohexane
(2R,3R,4R)-2-deuterio-4-methyl-3-bromohexane
(2R,3S,4R)-2-deuterio-4-methyl-3-bromohexane
(2S,3S,4S)-2-deuterio-4-methyl-3-bromohexane
(2S,3R,4S)-2-deuterio-4-methyl-3-bromohexane
(2R,3R,4R)-2-deuterio-4-methyl-3-bromohexane
(2R,3S,4R)-2-deuterio-4-methyl-3-bromohexane
(2S,3S,4R)-2-deuterio-4-methyl-3-bromohexane
(2S,3S,4R)-2-deuterio-4-methyl-3-bromohexane
(2R,3R,4S)-2-deuterio-4-methyl-3-bromohexane
(2R,3R,4S)-2-deuterio-4-methyl-3-bromohexane
(2R,3S,4S)-2-deuterio-4-methyl-3-bromohexane
(2R,3S,4S)-2-deuterio-4-methyl-3-bromohexane
(2S,3R,4R)-2-deuterio-4-methyl-3-bromohexane
(2S,3R,4R)-2-deuterio-4-methyl-3-bromohexane
Blank Templates
primary RX examples
secondary RX examples
tertiary RX examples
C
reaction
conditions
C
C
Br
C
?
C
reaction
Br conditions
H
C
?
C
C
C
Br
reaction
conditions
?
Br
reaction
conditions
?
C
H
C
C
C
C
Br
y:\files\classes\201\201 Organic Reactions Worksheets.doc
reaction
conditions
?
C
C
C
Br
C
reaction
conditions
?