chem 201 name: key final exam key
TRANSCRIPT
Chem 201 Name: ________KEY____________
1
Final Exam Key Unless otherwise indicated, clearly indicate stereochemistry. You may use molecular models.
1. (15 pts) Circle the side of the equation (either all the products or all the reactants) that you expect to be thermodynamically favored. a.
ONa +OO
ONaO
O5-membered
rings are especially favorable
b.
ONa +OO ONaO
OH +
pKa 25 pKa 16
c.
NLi +OO OLiO
NH +
pKa ~36pKa 25
d.
O
P
Ph
Ph Ph+P
Ph
Ph Ph+
O breaks super-strong P=O bond
broken
137 kcal/mol!CC
P=O
64 kcal/mol
formed
89 kcal/molC-O
89 kcal/molC-O
178201 - = + 23 kcal/mol uphill
Endothermic, even if we don't include ring strain.
e.
Cl
N++ O
Cl
OH
N
forms weak
N-Cl bond
broken
137 kcal/mol
81 kcal/mol
formed
48 kcal/molN-Cl
98 kcal/molC-H
146218 - = + 72 kcal/mol uphill
I didn't show you the BDE for C-Cl; but even if you used the BDE for weaker C-Br or C-Ithe enthalpy change is still large and positive
N-H
C-Cl
2. (10 pts) Circle the preferred product of the following hydride reduction.1
O
Me3Si
Me
C8H17
LiEt3BH
THF
- 78 °C
OLi
Me3Si
Me
C8H17
OLi
Me3Si
Me
C8H17
Me
H
O
Me3Si
Me
C8H17
O
C
C8H17
SiMe3Nu
Me
H
SiMe3
OLi
H
C8H17
H
Felkin-Anh
Chem 201 Name: ________KEY____________
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3. (30 pts) Estimate the enthalpy change in the following reaction using bond dissociation energies. Don’t worry about the catalyst. a.
cat.
CF3CO2H
(pKa 0)O
OH
OO
H
bonds broken:
C-O 79 kcal/mol
O-H 110 kcal/mol
bonds formed:
!co 94 kcal/mol
O-H 110 kcal/mol
"H = bonds broken - bonds formed
= 189kcal/mol - 204 kcal/mol
= -15 kcal/mol
b. Draw a plausible arrow-pushing mechanism for the reaction.
+
CF3CO2-
CF3CO2H
OHO H
OHO +
OH
OH
OH
O
OO
CF3
H
..
O- O
CF3
: ..
pKa 0
pKa -4
from pKas Keq 10-4
!G = 4•1.4 = +5.6 kcal/mol
from pKas Keq 10-3
!G ~ 3•1.4 = +4.2 kcal/mol
pKa -7
(doesn't account for ring entropy) c. Sketch a reaction coordinate energy diagram. Clearly indicate the rate-determining step (highest barrier) and the relative energies (no numbers) of the starting materials, products, and intermediates.
5.6
kcal/mol
4.2
15
!G
reaction coordinate
kcal/mol
Chem 201 Name: ________KEY____________
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4. (20 pts) Suggest a plausible arrow-pushing mechanism for the following reaction.2
O
OOH
OCH3CO2H
75 °, 20 min
cat.
H2SO4
70%O
O
O
O
OOH.. H A
O
O OH2
+
.. O
O
OH+
Criegee
O
: O
O
O
OH :A-
+
O
O
O
O
H2O
OH
O
OFischer esterification typically requires hours of heating.e.g., Vogel, A.I. JCS 1948, 624 CH3CO2H
cat. HA
5. (20 pts) Suggest a plausible arrow-pushing mechanism for the following reaction.3
CH2Cl240 °C, 20 h
75%AcO
H
H
OHOH
CH3SO2Clpyridine
O
H
H
With pyridine, formation of the methanesulfonate ester does not involve a sulfene.
..
AcO
H
H
OHOH..
SCl
OO AcO
H
H
OH
OS
OO -
Cl
H
B..
AcO
H
H
OO
S
OO
..
O
H H
AcO
H
H
or
deprotonatefirst
:B
O
H H
AcO
:
+
-
O
H H
Chem 201 Name: ________KEY____________
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6. (20 pts) Suggest a plausible arrow-pushing mechanism for the following reaction.4
ONaH
THF
23 °C
87%HO OSO2CH3
O OMsH
Na
H
- O OMs..
O
O =
Grobfragmentation
strained(Bredt's rule)
7. (10 pts) Suggest a plausible arrow-pushing mechanism for the following reaction.5
N
N O
AcO S
O
O
Et3N
MeCN/H2O
47 °C, 3 h
NAcO NH
O
94%
N
N
O
AcO
SAryl
O
O
NAcO N
+
:
:
OH2:
NAcO N:
O
H
H+
B:
NAcO N:
O H B:
HB+
NAcO NH
O
Beckmannrearrangement
Chem 201 Name: ________KEY____________
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8. (15 pts) Suggest a plausible arrow-pushing mechanism for the following reaction.6 The combination of BF3 and HO2CCO2H (oxalic acid) is being used as an acid catalyst that can be symbolized with “H-A”.
OOH
O
85%
Et2O•BF3
HO2CCO2H
C6H5
80 °C, 30 min
O
OH
H
:HA
O
OH2
H
+
O H
+
:A- O
OOH
..H A
OHOH
+
..
O
HO
H+ O
HO
H
H
H-A:
:HA
don't violate
3-arrow rule
O
HO
H
H
-A:
+
easilyprotonated
enol pushes out L.G. 9. (10 pts) Suggest a plausible arrow-pushing mechanism for the following reaction.7
H2SO4
aq. CH3CO2H23 °C, 5 h
HO 86%
HA+
+
H2O..
O HO
H
H+
:-A
Chem 201 Name: ________KEY____________
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10. (10 pts) Suggest a plausible arrow-pushing mechanism for the following reaction.8
no solvent-70 - 23 °C, 30 min
> 94%
O
n-Pr2B
n-Pr2BO
OB
OB
RR
+-
OB
RRR R
..
11. (10 pts) Suggest a plausible arrow-pushing mechanism for the following reaction.9 Ferric chloride is a Lewis acid catalyst.
S
O
OMe
OB
O
O
no solvent
20 °C, 48 hS
O CO2MeB
O
O
>96%
OB
OB
RR
+-
OB
RR
CO2Me
R R
..
CO2Me CO2MeS S S
Chem 201 Name: ________KEY____________
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12. (15 pts) Suggest a plausible arrow-pushing mechanism for the following reaction.10 Ferric chloride is a Lewis acid catalyst.
OMe
OMeMe3Si
cat. FeCl3
MeNO2
20 °C, 15 min
OMe
95%
Ph
OMe
OMe
Cl3Fe
..Ph
OMe
OMe
:
FeCl3
+
-
Ph
OMe
SiMe3
+
Ph OMe+
SiMe3
FeCl3
OMe:
Ph OMe+
Si
FeCl3
OMe
-
-+
OMe
Me3SiOMe
FeCl3
-
+
FeCl3
Me3SiOMe
-
13. (15 pts) Suggest a plausible arrow-pushing mechanism for the following protodesilylation reaction.11
O
Et
MeBn
SiMe2t-BuTHF
23 °C, 10 min
O
Et
MeBn
86%NH
F-
+
(pyridine•HF)
O
Et
MeBn
SiMe2t-Bu
HA
O
Et
MeBn
SiH
+
F
t-Bu
-
O
Et
MeBn
H
O
Et
MeBn
SiMe2t-Bu
..
F -
O
Et
MeBn
SiMe2t-Bu
HA
F
-
O
Et
MeBn
SiMe2t-BuH
+
..
F -
protonate firstor
F- attacks first
Chem 201 Name: ________KEY____________
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14. (10 pts) Suggest a plausible arrow-pushing mechanism for the following substitution reaction.12
CH3OH
23 °C, 12 h
89%
S
O
O
MeO2SO
OSO2Me
O
OS
MeO2SO
H3COCH3ONa
S
O
O
MsO
OMs
..
O
O
OMs
S+
CH3ONa..
O
OS
MsO
H3CO
Na
+
O
OS
MsO
H3CO
neighboringgroup
participation
episulfonium ion 15. (10 pts) Suggest a plausible arrow-pushing mechanism for the following Arbuzov reaction.13
Ph Br(EtO)3P
200 °C, 24 h
Ph P
O
OEtOEt
Ph Br
(EtO)3P:
Ph P
O
OEtOEt
+
Br -:
Ph P
O
OEtOEt
Chem 201 Name: ________KEY____________
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16. (15 pts) Suggest a plausible arrow-pushing mechanism for the following reaction.14 Also explain the formation of isobutylene and isobutane.
Ii) 2 equiv. t-BuLiTHF, - 78 °C
ii) Ph2C=O
Ph
Ph
OLi+ +
isobutylene isobutane
I
Li
t-BuIt-Bu-
Li+
Li
IH
Li+
O
PhPh
PhPh
O -
Li+
..
Ph
Ph
OLi
17. (15 pts) Suggest a plausible arrow-pushing mechanism for the following Knoevenagel condensation.15
O
t-BuNC
O
t-Bu
CN
O
p-Tol p-Tol
20 mol% CH3CO2H
toluene
110 °C, 8
75%
10 mol%NH
p-Tol
O
+.. p-Tol
O
N
H
H
..HA
p-Tol
HO
N
H
H
+
A:
p-Tol
HO
N
H
..HA
p-Tol
H2O
N
H+
:
HN+
p-Tol N+
O
t-BuNC
HA
H
:
A:
OH
t-BuNC
p-Tol N+
: O
t-BuNC
p-Tol N
H+
..
O
t-BuNC
p-Tol N
H
H
H
A:
+
:
O
t-BuNC
p-Tol
H :A+O
t-BuNC
p-Tol
Chem 201 Name: ________KEY____________
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References 1 Shimazaki, M.; Hisaaki, H.; Suzuki, K. Tetrahedron Lett. 1989, 30, 5447-5450. (The anti product is strongly preferred: >99:1) 2 Ogibin, Yuri N.; Terent'ev, Alexandre O.; Kutkin, Alexandre V.; Nikishin, Gennady I. Tetrahedron Lett. 2002, 43, 7, 1321 – 1324. 3 Jamart-Gregoire, Brigitte; Brosse, Nicolas; Ianelli, Sandra; Nardelli, Mario; Caubere, Paul J. Org. Chem. 1993, 58, 17, 4572 - 4578 4 Mehta, Goverdhan; Kumaran, R. Senthil Chem. Comm. 2002 , 14, 1456 - 1457 5 Keana, John F. W.; Heo, Gwi Suk; Gaughan, Glen T. J. Org. Chem. 1985, 50, 13, 2346 - 2351 6 Bajgrowicz, Jerzy A.; Petrzilka, Martin Tetrahedron 1994, 50, 25, 7461 - 7472 7 Lamture, J. B.; Suryawanshi, S. N.; Nayak, U. R. Indian J. Chem. B 1982, 21, 819 – 822. The full text of this paper was not available. The conditions listed in Reaxys do not include water. H2O was added as a presumptive reagent to facilitate formulation of a mechanism. 8 Bubnov, Yuri N.; Etinger, Marina Yu Tetrahedron Lett. 1985, 26, 23, 2797 - 2800 9 Watahiki, Tsutomu; Akabane, Yusuke; Mori, Seiji; Oriyama, Takeshi Organic Lett. 2003, 5, 17, 3045 - 3048 10 Watahiki, Tsutomu; Akabane, Yusuke; Mori, Seiji; Oriyama, Takeshi Organic Lett. 2003, 5, 17, 3045 - 3048 11 Danheiser, Rick L.; Stoner, Eric J.; Koyama, Hiroo; Yamashita, Dennis S.; Klade, Carrie A. J. Am. Chem. Soc. 1989, 111, 12, 4407 - 4413 12 Hughes, N.A.; Wood, C. J. J. Chem. Soc., Perkin Trans. 1 1986, 695-700. 13 Lynch, E.R. J. Chem. Soc. 1962, 3729 - 3733 14 Rosa, David; Orellana, Arturo Organic Lett. 2011, 13, 3648 – 3651. 15 Miyamoto, Y.; Banno, Y.; Yamashita, T.; Fujimoto, T.; Oi, S.; Moritoh, Y.; Asakawa, T.; Kataoka, O.; Yashiro, H.; Takeuchi, K.; Suzuki, N.; Ikedo, K.; Kosaka, T.; Tsubotani, S.; Tani, Akiyoshi; Sasaki, M.; Funami, M.; Amano, M.; Yamamoto, Y.; Maezaki, H.; Aertgeerts, K.; Yano, J. J. Med. Chem. 2011, 54, 831 – 850. Takeda Pharmaceutical Co., Ltd. “Pyridyl Acetic Acid Compounds” WO2006/90915 A1, 2006.