Chemistry 605 (Reich)

SECOND HOUR EXAM Tue. April 13, 2010

Practice Exam 2 answer

Question/Points R-09G R-09H R-09I R-09J R-09K R-09LM Total /25 /10 /15 /15 /16 /18 /100 Average Hi Mode Median AB BC 65 86 72 65 75 50

Grading
Name

If you place answers anywhere else except in the spaces provided, (e.g. on the spectra or on extra pages) clearly indicate this on the answer sheets.

25
Problem R-09G (C12H16O2). Determine the structure (or part structure) of R-09G from the 1H NMR, 13C NMR provided. The IR spectrum shows no strong peaks in the region from 1650 to 1800 cm -1. 1 (a) DBE 5 (b) Interpret the 13C NMR spectrum. Identify what kind of carbon each signal corresponds to, and write possible part structures (e.g. sp3 OCH3, Aromatic C-H, ketone C=O, N-CH2) ). 1 142.6 2 138.7 5 3 129.7 4 128.3 5 127.5 sp2 aromatic/alkene Quat aromatic/alkene sp2 CH (CH=C) aromatic/alkene sp2 CH (CH=C) aromatic/alkene sp2 CH 2x (o/m) aromatic/alkene sp2 CH (p) 6 126.3 7 8 9 10 75.6 71.9 30.4 29.4 aromatic/alkene sp2 CH 2x (o/m) sp3 CH-O (possible HC=C-O) sp3 C-O (quat) CH3 CH3

606.0

591.5 590.5 588.0

572.7

Solution 1=2 c-=(3+5)/2 = 591.5 ab- = - = sqrt((7-1)(5-3)) = 0 c- -/2 = 591.5 591.5 c+=(6+4)/2 = 598.27 ab+ = + = sqrt((8-2)(6-4)) = 9.18 c+ +/2 = 593.9 584.7 Intensity Calculation 8 Solution 1=2 1+ = 0.5 arcsin(JAB/2D+) = 29.4 1- = 0.5 arcsin(JAB/2D-) = 45 i10 = i11 = 0.929 A B The signs of JAX and JBX are different JAB JAX JBX A B AB A B 15.4 -2.4 +6.8 592.7 588.1 4.6 5.93 5.88 7 8 1 2 64 3 5
Peak
1 3 5 7 2 4 6 8

Hz
576.1 (591.5 - JAB) 591.5 591.5 606.9 (591.5 + JAB) 572.75 588.00 590.53 606.04

This is the special ABX pattern with Solution 1 = Solution 2 (one of the ab quartets has collapsed to a singlet), To use the normal method for ABX solution, put in calculated frequencies for the - ab quartet - both central lines superimposed, the outer lines +-J (although the position of the outer lines does not affect the calculation - ab- will always be 0 if the central lines are identical)

525.6 524.1 522.0 520.5

(c) Do a mathematically accurate analysis of the expansion below, and report your results. If there are two solutions, report them both. Show a coupling tree.

(d) What part structure is suggested by the shifts and couplings of this part of the spectrum? HB HB However, both JAX and JBX would be positive for HX structures of this type, unless R = O. In this case, the Also possible: R chemical shifts are way off. JBX is also too small HA HX HA (e) Determine the structure of R-09G. If more than one structure is possible, show them, and circle your best choice. Base: 5.25 Base: 5.25 off OH HA HA OH 1.38 Ph-gem CH OH gem 0.64
2

Ph 8 8 OH Ph 4
1

OH

CH2OH cis -0.01 Calc Obs. 5.88 5.93

Ph 6 H Ph Ph H 5

OH

CH2OH cis Calc Obs.

-0.01 6.62 5.93

HA OH H HO H

OH OH

HO Ph 5 OH

OH 5

H
12.5 3.74

13

6.46 (14.4, 6.9) 3.86

H OEt 1.27 H
4.17 (14.4, -1.9)

147.5 54.9

96.0

OMe

*TET-78-425

XLS

Problem R-09G (C12H16O2) 100 MHz 1H NMR Spectrum in CDCl3 Source: H. J. Reich, 1975

606.0

591.5 590.5 588.0

572.7

525.6 524.1 522.0 520.5

30

20

10

Hz

6.2

6.0

5.8

5.6

5.4

5.2

5.16 6.14 2.00 1.08

1.99

8.5

8.0

7.5

7.0

6.5

6.0

5.5

5.0

4.5

4.0 ppm

3.5

3.0

2.5

2.0

1.5

1.0

0.5

0.0

XLS

Problem R-09G (C12H16O2) 25 MHz 13C NMR Spectrum in CDCl3 Source: H. J. Reich, 05-05

75.6 71.9

142.6 138.7 129.7 128.3 127.5 126.3

30.4 29.4

Normal

200

180

160

140

120

100 ppm

80

60

40

20

10

Problem R-09H. The two simulated spectra below differ only in the relative chemical shift of the protons 5 and 6. J12 = 0.00, J13 = 3.00, J14 = 0.00, J15 = 14.0, J16 = 6.00 J23 = 6.00, J24 = 3.00, J25 = 0.00, J26 = 0.00 J34 = 1.00, J35 = 0.00, J36 = 3.00 J45 = 0.00, J46 = 5.00 J56 = 8.00 56 = 40.0 Hz

56 = 10.0 Hz

220

200

180

160

140

120 Hz

100

80

60

40

20

(a) Explain why most of the multiplets look so different in the two spectra. What phenomenon is this? H5 and H6 are coupled to each other. When the chemical shift between H-5 and H-6 are small (comparable to or smaller than J56) then we see the effects of "virtual coupling" - this causes second order effects (additional lines and false coupling) in the signals for H-5 and H-6, as well as for all protons coupled to them (H-1, H-3 and H-5). (b) Specifically explain why only H2 is unchanged in the second spectrum. H2 is the only proton which is NOT coupled to either H 5 or H6 - so it remains perfectly first order

15
Problem R-09I This problem requires you to analyze the 1H NMR spectrum of a steroid, and determine the stereochemistry at three centers. A planar projection and conformational drawing is shown below. O CH3 CH3
17 17

H H
3 7

H OSiMe2t-Bu (OTBS)

P
3

U H

S Q

t-BuMe2SiO H

19 co

(a) Assign the signal at C-3 ( 3.4 ). Explain how you identified the signal, and make a stereochemical assignment: P = H , Q = OTBS (H or OTBS). The multiplet at 3.4 is a tt, J = 11, 4 Hz. This must correspond to two Jaa and two Jae couplings, and can only be H-3. H-7 has only 3 neighbors, and H-17 only two. Since there are two large axial couplings, H-3 must be axial, and the OTBS group equatorial. (b) Assign the signal at C-7 ( 3.81 ). Explain how you identified the signal, and make a stereochemical assignment: R = H , S = OTBS (H or OTBS). This signal is probably a broad quartet, with J = 3 Hz, thus at least 3 nearest neighbors. None of couplings are axial-axial, thus the proton must be equatorial.

19 so

1 e c t

(c) Assign the signal at C-17 ( 2.52 ). Explain how you identified the signal, and make a stereochemical assignment: T = Ac , U= H (H or CH3C(=O)). This is the only other downfield signal (no other protons are adjacent to a carbonyl group). The signal is a triplet, J = 9 Hz. Examination of the conformation shows that if T = H then one of the couplings should be very small, since is likely to be near 90. On the other hand, if U = H then both couplings will be fairly large, since one has near 0, the other with near 180. (d) Why is the methyl group at 2.1 so much taller (i.e. sharper) than the one at 0.6? The ring Me group has small W-couplings to the trans-diaxial protons, the Me-C(=O) group is essentially uncoupled We don't, however, know which of the bridgehead methyl groups we are looking at, the other one is under the t-butyl signals (e) Assign and explain the signals at 0.00 to 0.10 H
3

T H

O CH3 CH3 HH H OTBS

7 17

H H

The SiMe2 groups are each diastereotopic, so we see four Me signals

OTBS

XLS

Problem R-09I (C33 H62 O2 Si2) 300 MHz 13C NMR Spectrum in CDCl3 Source: I. L. Reich, K. Plessel/Reich 040-04 O

Bu SiMe2

17

H H
3 7

H OSiMe2t-Bu

t-BuMe2SiO H

H17

30

20

10

Hz

H7 q, J = 2.5 Hz
2.55 2.50 0.95 0.90 0.85

0.10

0.05

0.00

H3

dt, J = 11, 4 Hz

3.8

3.7
CHCl3

3.6

3.5

3.4

3.3

ppm

15
Problem R-09J. You are asked to determine which of two possible isomers of a dibromo anhydride is the correct one, and assign the protons . The complete spectrum is shown on the next page. (a) Assign the protons, draw appropriate coupling trees on the spectrum below, and label each one with a proton assignmment (HA, HB, etc). It is not necessary to report couplings, although you might wish to measure them to aid in your analysis.

1
Me Me

HC Br HE H A HF Br HB HD O

2
H O O Br Br H O O O or Me Me

O Br HE H A HF Br HB HD

H O HC O Br Br H

O O O

HB
dd, J = 16, 8
30 20 10 0

Hz

8 HC
t, J=9 actually probably ddd, J=9, 8.5,1)

HA
d, J=16 possible dd, J=16, 1)
3.00

HD
ddd, J=10.5, 9.5, 9
0.90 0.91 1.00

3.6

3.5

3.4

3.3

3.2

3.1 ppm

3.0

2.9

2.8

2.7

2.6

2.5

dd, J = 15, 10 HE

dd, J = 15, 9

HF

(b) Which isomer

(1 or 2) is correct? Explain briefly how you decided which was correct.

Isomer 1 has an axis of symmetry, HC = HD, HA = HF and HB = HE, so spectrum would be much simpler (only 3 chemical shifts, rather than 6) Can also make arguments based on the individual coupling constants: in isomer 1, H C should be coupled to HA and HD with large couplings (aa), and H A with a small one (ae), we see only two medium sized couplings. On the other hand, for isomer 2, HC might be coupled to HA by only a very small J, since the ee coupling should be near 0 for a flattened ring like this. O HC Br Br HE H HE H O A A O Me Me HC Me O or Me HB HE HF HB O HF HB dd, J = 16, 8 O Br Br HD HD dd, J = 15, 10

HC
t, J-9 actually probably dd, J=9, 8.5,1)

HA

d, J=16 possible dd, J=16, 1)

3.00

HF
dd, J = 15, 9

HD
ddd, J=10.5, 9.5, 9
0.90 0.91 1.00

3.6

3.5

3.4

3.3

3.2

3.1 ppm

3.0

2.9

2.8

2.7

2.6

2.5

(c) Explain why the proton at 2.95 shows such a simple multiplet. Proton at 2.95 is HA Br Me O O The diaxial group steric interaction will significantly O flatten the ring. This makes Jee get smaller, and Jae get HC larger (JCD) 18 16 14 12 HE Me HF Br HD HB O Br HE H A Me Me HF Br HB HD O HC O O O O HA HC Front carbon rotates clockwise - AC 90, JAC goes to 0, and 10 BC 0 JBC gets larger 8 J / Hz 6 4 HC is basically a triplet because JCA 0, leaving only the eq-ax couplings, JCB and JCD, which are unusually large 2 0 180 150 120 J1-c H1 axial 60 30 0

1-c / 30 H1 Hc Ht

60

90

120

18 16

Me Br HD

Hc H1 Ht H1 equat.

14 12 10 J / Hz

J1-t

J1-c

J1-t 8 6

J1-t

Flattened cyclohexane J1-c

4 2 0

90 1-t /

60

30

Problem R-09J (C10H12Br2O3) 300 MHz 1H NMR spectrum in CDCl3 (Source: Allen Clauss 11/32) Hz

HB

HE

HC HD
x
3.6 3.5 3.4 3.3 3.2

30 20 10

HA

HF

3.1 ppm

3.0

2.9

2.8

2.7

2.6

2.5

O Br HE H A Me Me HF Br HB HD

H O HC O Br Br H

O O O

or HC Br HE H A Me Me HF Br HB HD O H O O Br Br H O O O

2.1

2.0 ppm

5 ppm

16
Problem R-09K C8H18O3. This problem requires you to analyze the 1H NMR spectrum of the diethyl acetal of ethoxy acetaldehyde. The complete spectrum with integrations is on the next page. A B O D E O C O

A B
30 20 10 0

Hz

D B E x x F

4.70 4.65 4.60

3.8

3.7

3.6

3.5

3.4

1.30 1.25 1.20 1.15

(a) Give the chemical shift(s), multiplicity and couplings ( 3.23, dt, J = 8, 2 Hz) of each unique proton in the spectrum. You may use first order analysis.

2 6 1 1 2 2 2

A B C D E

1.23, t, J = 7 Hz 3.71, dq, J = 10, 7 Hz, 3.58, dq, J = 10, 7 Hz (B protons are diastereotopic) 4.63, t, J = 5 Hz 3.48, d, J = 5 Hz 3.55, q, J = 7 Hz 1.20, t, J = 7 Hz

(b) To show you understand the pattern, put a marker (x) over each peak corresponding to proton E.

Problem R-09K: C8H18O3 300 MHz 1H NMR spectrum in CDCl3 Source: Aldrich Spectra Viewer/Reich

O
30 20 10 0

Hz

EtO

9.16 8.32

3.8

3.7

3.6

3.5

3.4

1.00

1.30 1.25 1.20 1.15 4.70 4.65 4.60

10

18
Problem R-09L and R-09M (C13H16O2). The 270 MHz 1H spectra are of the isomers below: cis coupling should be larger ( = 0): J = 7.5 Hz OCH3 CH3O H O O

H
H

trans coupling should be smaller: J = 3 Hz

CH3 R-09 L

CH3 R-09 M

(a) Identify a key feature of the spectra which allows confident assignment of the stereochemistry. Explain and label the structures above appropriately. It is not necessary to analyze the spectra completely. The most reliable stereochemical feature is the 3J coupling cis and trans in the cyclopropane, with the expectation that Jcis > Jtrans. Each isomer has an isolated doublet at ca 3.3 corresponding to the CH-OMe proton 8 R-09L has a d, J = 7.5 Hz at 3.36, thus the two Hs are cis R-09M has a d, J = 3 Hz at 3.22, the two H s are trans 4 for chemical shift arguments 1-2 for others (b) Explain the differences in the chemical shift of the sharp singlet at 3.25 in R-09L and 2.9 in R-09M. Apparently, in R-09M the MeO group is over the shielding portion of the aromatic ring, so shifted upfield to 2.9 from its "normal" position - alkyl ethers like Me 2O are typically at 3.4-3.5. 3.29 2.92 CH3O H O O

E u c

H
H

OCH3

(c) Assign and interpret the signal at 1.65 (explain the coupling) in the spectrum of R-09L. Give the chemical shift of the corresponding signal in the spectrum of R-09M 1.86 . 2 This is roughly a t, J = 7 Hz, although actually almost a ddd, J = 7, 6, 1, which can be assigned from its chemical shift (upfield of the other cyclopentane protons) and coupling. It must have a dihedral angle near 90 to one of the vicinal CH2 protons The corresponding proton in R-09M is at 1.86, ddd, J = 7.5, 3, 1.5 Hz J=1 H OCH3
3

H3
H 18 16

60

30 H1 Hc

1-c / 30 Hc H1

60

90

120

J=7

18 16 14

H
Ar

O J=7 R-09L

Hc eclipsed with H1 Hc H1 Ht

H 1.7 1.6

14 12 J / Hz 10 8 6 4 J1-c J1-t Ht

Ht

12 10 J / Hz

J=3 CH3O

J=2 H H
3

J1-c

J1-t 8 6

J1-t

H
Ar

4 J1-c 60 30 0 2 0

O J=7 R-09M

H 1.9

2 Cyclopropane 0 180 150 120 90 1-t /

Problem R-09L (C13H16O2) 270 MHz 1H NMR Spectrum in C6D6 (Source: Nora Hornung/Casey 11/16)

3.29

OCH3
6 3 4

H CH3O
5

30

20

10

H
2
13.33

or

CH3 Hz q, J=7.5 ddd, J = 8, 7.5, 5

CH3

H4

H4

H6
2.2 2.1 2.0 1.9

H3 H
C6D5H
5

H5

3.97

3.84

4.2

4.1

3.40 3.35

1.7

1.6

2.21 1.06

1.00

8.0

7.5

7.0

6.5

6.0

5.5

5.0

4.5

4.0 ppm

3.5

3.0

2.5

2.0

1.5

1.0

0.5

0.0

Problem R-09M (C13H16O2) 270 MHz 1H NMR Spectrum in C6D6 (Source: Nora Hornung/Casey 11/16)

30

20

10

Hz

H6
2.92

H5

Since the couplings are nearly the same, the OCH2 must be nearly eclipsed with the vicinal CH2 dt, J = 8, 6

H5

OCH3
6 3 4

dt, J = 8, 6 CH3 or H CH3O

3.8

3.7

3.6

3.5

3.4

3.3

3.2

4 5

H4
ddt, J = 12, 8, 7

dddd, J = 12, 7, 6, 2 CH3

H3
ddd, J = 7, 3, 2

4.09

C6D5H
3.21 3.06 3.11

2.20

1.9

1.8

1.7

1.6

1.5

1.00

0.94 0.98

8.0

7.5

7.0

6.5

6.0

5.5

5.0

4.5

4.0 ppm

3.5

3.0

2.5

2.0

1.5

1.0

0.5

0.0