5.0 4.5 4.0 3.5 3.0 2.5 2.0ppm
0.99 0.96
0.49 0.53
1.00
2.75 2.70 2.65 2.60 2.55 2.50 2.45 2.40 2.35 2.30 2.25 2.20 2.15 2.10 2.05 2.00 1.95
3.90 3.85 3.80 3.75 3.70 3.65 3.60 3.55 3.50 3.45 3.40 3.35 3.30 3.255.35 5.30 5.25 5.20 5.15 5.10 5.05
Problem R-10M (C5H9F2N HCl).
400 MHz 1
H NMR spectrum in D2O
Source: J. Am. Chem. Soc. 2000, 122, 544 (Reich digitized hard copy) g
D
N
D
+
FF
2
3
4
Cl
x x
x
x
x
xx
0
Hz
102030405060708090100120
PLT ex-3-2010-11-gq.plt
5.0 4.5 4.0 3.5 3.0 2.5 2.0
ppm
0.99 0.96
0.49 0.53
1.00
Probem R-10M. Interpret the room temperature 400 MHz 1
H NMR spectrum of a difluoropiperidine ammonium salt
(D2O solvent, expansions on next page, some minor impurities ar marked x) and determine stereochemistry and
conformation (J. P. Snyder, N. S. Chandrakumar, H. Sato, D. C. Lankin J. Am. Chem. Soc. 2000, 122, 544).
(a) Are the two fluorines cis or trans to each other? Explain briefly.
D
N
D
+
FF
(b) Add the fluorines to the cyclohexane conformation below, and explain how you arrived at this conformation. Write
the chemical shifts next to the protons on carbons 2,3, and 4 on the structure, and, in parenthesis, the approximate JH-F
coupling for each proton ( 0.00, n
JH-F = 0.00 Hz).
H
H
H
H
H
H
D
N
D
+
0
Hz
50100150
2
3
4
(c) Why are the signals at  3.3-5.4 broadened compared to the signals at  2-2.7?
2
3
4
24
Cl
PLT ex-3-2010-11-gq.plt
5.0 4.5 4.0 3.5 3.0 2.5 2.0
ppm
0.99 0.96
0.49 0.53
1.00
Probem R-10M. Interpret the room temperature 400 MHz 1
H NMR spectrum of a difluoropiperidine ammonium salt
(D2O solvent, expansions on next page) and determine stereochemistry and conformation ( J. Am. Chem. Soc. 2000, 122,
544).
(a) Are the two fluorines cis or trans to each other? Explain briefly.
D
N
D
+
FF
(b) Add the fluorines to the cyclohexane conformation below, and explain how you arrived at this conformation. Write
the chemical shifts next to the protons on carbons 2,3, and 4 on the structure, and, in parenthesis, the approximate JH-F
coupling for each proton ( 0.00, n
JH-F = 0.00 Hz).
0
Hz
50100150
(c) Why are the signals at  3.3-5.4 broadened compared to the signals at  2-2.7?
2
3
4
22
Cl
H
H
FD
N
D
+ 2
3
4
H
F
H
H
H
FD
N
D
+ 2
3
4
H
F
H
There are two signals for the protons on H4
(2.15,
2.60). If the two fluorines were trans, rapid inversion of
the ring would give only one chemical shift for the H4
protons.
Similarly, the protons at H2
(3.4, 3.8) would have
only one shift, two are observed
H
H
H
H
F
H
H
D
N
D
+
2
3
4
F
H
H
2.16 (3
JHF = 43 Hz, Jax-ax)
2.63 (3
JHF = 15 Hz, Jeq-ax)
5.21 (2
JHF = 45 Hz)
3.77 (3
JHF = 12 Hz, Jeq-ax)
3.42 (3
JHF = 39 Hz, Jax-ax) The two fluorines have to be cis, and both are axial:
There are large JHax-Fax couplings to both H2
and H4
(ca 40 Hz)
H4
ax shows only one additional large coupling (2
JH-H)
H2
ax shows only one additional large coupling (2
JH-H) and no 3
JHax-Hax.
If H3
was axial, there should be a ca 10 Hz J to both H2
ax and H4
axn
H2
: The signals at  3.4-3.8 are probably broadened by small unresolved coupling to the N-14 and the D. There are
also unresolved 3
JHH couplings to the equatorial H3
protons
H3
: There are several unresolved H-H couplings (Jeq-eq and Jeq-ax) to H2
and H4
; also a possible unresolved coupling to
14
N - there is an anti relationship between H3
and N, and the N could be undergoing relatively slow quadrupolar
relaxation (high symmetry).
3
JHF
2
JHH
H4
ax
H4
eq
3
JHF
H2
ax
H2
eq
3
JHF
2
JHH
2
JHF
H3
eq
The small triplet splittings are to H3
eq
2
JHH, 3
JHF
2
JHH
6
13
5
PLT ex-3-2010-11-gq.plt
D
N
D
+
FF
2
3
4
Cl
H
H
H
H
F
H
H
D
N
D
+
2
3
4
F
H
H
2.16 (3
JHF = 43 Hz, Jax-ax)
2.63 (3
JHF = 15 Hz, Jeq-ax)
5.21 (2
JHF = 45 Hz)
3.77 (3
JHF = 12 Hz, Jeq-ax)
3.42 (3
JHF = 39 Hz, Jax-ax)
5.0 4.5 4.0 3.5 3.0 2.5 2.0
ppm
0.99 0.96
0.49 0.53
1.00
2
JHF
H3
eq
H2
eq
2
JHH, 3
JHF
3
JHF
H2
ax
2
JHH
2
JHH
H4
ax
3
JHF
H4
eq
3
JHF
2
JHH
3
JHH3
JHH
2.75 2.70 2.65 2.60 2.55 2.50 2.45 2.40 2.35 2.30 2.25 2.20 2.15 2.10 2.05 2.00 1.95
3.90 3.85 3.80 3.75 3.70 3.65 3.60 3.55 3.50 3.45 3.40 3.35 3.30 3.255.35 5.30 5.25 5.20 5.15 5.10 5.05
0
Hz
102030405060708090100120
x x
x
x
x
Problem R-10M (C5H9F2N HCl).
400 MHz 1
H NMR spectrum in D2O
Source: J. Am. Chem. Soc. 2000, 122, 544 (Reich digitized hard copy) g
PLT ex-3-2010-11-gq.plt