M. Oba
9.92 (br s, 1H). 13C NMR (DMSO-d6) δ 24.0, 118.6 (t, J = 24.4 Hz), 118.8,
122.5 (t, J = 24.9 Hz), 128.2 (t, J = 24.0 Hz), 128.4, 139.2, 168.2.
simple and direct preparation of a D3PO2 solution from
commercially available aqueous 50% H3PO2 and the reductive
deuteration of various aromatic halides, alkenes, alkynes,
epoxides, and O-benzyl derivatives. The deuteration reaction is
catalyzed by Pd/C and performed in D2O in the presence of
Na2CO3 as a neutralization agent. The products are obtained in
high yields with high deuterium contents; and functional
groups such as amides, esters, and nitriles are tolerated.
[4-D]diphenyl ether
Isolated in 99% yield as a colorless oil. 1H NMR (CDCl3) δ 7.03 (d, J = 7.8 Hz,
4H), 7.11 (t, J = 7.8 Hz, 1H), 7.33–7.37 (m, 4H). 13C NMR (CDCl3) δ 118.9,
122.9 (t, J = 24.7 Hz), 123.2, 129.6, 129.7, 157.2.
[4-D]biphenyl
Isolated in 93% yield as a white solid, mp 67–68 °C (lit,16 mp 69–71 °C). 1H
NMR (CDCl3) δ 7.36 (t, J = 7.7 Hz, 1H), 7.46 (t, J = 7.7 Hz, 2H), 7.46 (d,
J = 7.7 Hz, 2H), 7.61 (d, J = 7.7 Hz, 4H). 13C NMR (CDCl3) δ 127.1, 127.2,
128.6, 128.7, 141.2. The deuterated carbon signal was not observed
because of signal overlap.
Experimental section
Melting points were determined using a Yamato MP-21 melting point
apparatus (Yamato Scientific Co., Tokyo, Japan) in open capillaries and
are uncorrected. 1H and 13C NMR spectra were recorded on a Varian
Mercury plus 400 spectrometer (Agilent technologies, Santa Clara, USA)
at 400 and 100 MHz, respectively. All of the chemical shifts are reported
as δ values (ppm) relative to the residual solvent signal (δH = 7.26 for
CDCl3 and δH = 2.50 for DMSO-d6) or the central line of CDCl3 (δC = 77.0)
and DMSO-d6 (δC = 39.5); J values are expressed in hertz.
Diethyl [2,3-D2]succinate
Isolated in 93% yield as a colorless oil. 1H NMR (CDCl3) δ 1.23 (t, J = 7.1 Hz,
6H), 2.57 (br s, 1.88H), 4.12 (q, J = 7.1 Hz, 4H). 13C NMR (CDCl3) δ 14.1, 28.8
(t, J = 19.7 Hz), 60.6, 172.3.
All reagents and solvents were purchased from commercial suppliers
and used as received.
1,2-Diphenyl[1,2-D2]ethane
Isolated in 93% yield as a white solid, mp 48–49 °C (lit,17 mp 52.0–52.5 °C).
1H NMR (CDCl3) δ 7.20–7.23 (m, 6H), 7.28–7.32 (m, 4H), 2.92 (br s, 1.44H).
13C NMR (CDCl3) δ 37.5 (t, J = 19.5 Hz), 125.9, 128.3, 128.4, 141.7.
Preparation of 1-M D3PO2 in D2O
A
commercially available 50% aqueous H3PO2 solution (2.67 g,
3-Phenyl[2,3-D2]propionitrile
20.2 mmol) was diluted with D2O (10 ml), and the mixture was left to
stand for 1 h at room temperature. The solvent was then removed by
evaporation, and fresh D2O (10 ml) was added. The cycle of solvent
evaporation and treatment with D2O (10 ml) was repeated for a total of
three times. The obtained 1-M D2O solution of D3PO2 was directly used
for deuteration reactions or stored for several days after neutralization
with Na2CO3 (1 equiv.).
Isolated in 99% yield as a colorless oil. 1H NMR (CDCl3) δ 2.60 (br s, 0.64 H),
2.93 (br s, 1H), 7.24 (d, J = 7.2 Hz, 2H), 7.28 (t, J = 7.2 Hz, 1H), 7.35 (t,
J = 7.2 Hz, 2H). 13C NMR (CDCl3)
δ 18.9 (t, J = 20.8 Hz), 31.0 (t,
J = 19.9 Hz), 119.1, 127.1, 128.1, 128.7, 137.9.
1,2-Diphenyl[1,1,2,2-D4]ethane
Isolated in 93% yield as a white solid, mp 51–52 °C (lit,17 mp 52.0–52.5 °C).
1H NMR (CDCl3) δ 7.19–7.23 (m, 6H), 7.27–7.32 (m, 4H). 13C NMR (CDCl3)
δ 37.0 (quint, J = 19.7 Hz), 125.9, 128.3, 128.4, 141.6.
General procedure for reductive deuteration
A solution of D3PO2 (1 mmol) in D2O (4 ml) was added dropwise to a
mixture of 4-chlorobenzoic acid (157 mg, 1.00 mmol), Na2CO3
(214 mg, 2.02 mmol), and 10% Pd/C (17.7 mg) in D2O (6 ml) over a
period of 30 min at 50 °C. After stirring for an additional 1 h, the
reaction mixture was cooled and acidified with 1-M HCl, and CHCl3
was added as the extraction solvent. The mixture was then filtered
through Hyflo Super Cel to remove the catalyst, and the organic
phase was separated, dried over MgSO4, and concentrated to give
[4-D]benzoic acid (116 mg, 0.942 mmol) in 94% yield as a white solid,
3-Phenyl[2,2,3,3-D4]propanoic acid
Isolated in 93% yield as a white solid, mp 46–47 °C (lit,18 mp 47–48 °C).
1H NMR (CDCl3) δ 7.23 (m, 3H), 7.31 (m, 2H). 13C NMR (CDCl3) δ 29.7
(quint, J = 19.6 Hz), 34.9 (quint, J = 19.6 Hz), 126.3, 128.2, 128.5, 140.0,
179.5.
2-Phenyl[2-D]ethanol
Isolated in quantitative yield as a colorless oil. 1H NMR (CDCl3) δ 2.86 (m,
1.12H), 3.85 (br d, J = 6.2 Hz, 2H), 7.24 (m, 3H), 7.32 (m, 2H). 13C NMR
(CDCl3) δ 38.7 (t, J = 19.7 Hz), 63.4, 126.3, 128.4, 128.9, 138.4.
mp 119–121 °C (lit,14 mp 122.4 °C). 1H NMR (CDCl3)
δ 7.49 (d,
J = 8.4 Hz, 2H), 8.13 (d, J = 8.4 Hz, 2H). 13C NMR (CDCl3) δ 128.4, 129.3,
130.2, 133.5 (t, J = 24.1 Hz), 172.0.
4-[D]methylanisole
[3,5-D2]benzoic acid
Isolated in quantitative yield as a colorless oil. 1H NMR (CDCl3) δ 2.28
(m, 1.23H), 3.79 (s, 3H), 6.81 (d, J = 8.5 Hz, 2H), 7.09 (d, J = 8.5 Hz, 2H).
13C NMR (CDCl3) δ 20.1 (t, J = 19.1 Hz), 55.2, 113.6, 129.7, 129.8, 157.4.
Isolated in 94% yield as a white solid, mp 119–121 °C (lit,14 mp 122.4 °C).
1H NMR (CDCl3) δ 7.62 (br s, 1H), 8.13 (br s, 2H). 13C NMR (CDCl3) δ 128.2
(t, J = 24.8 Hz), 129.2, 130.1, 133.6, 171.9.
[2,6-D2]benzoic acid
Conflict of Interest
Isolated in 98% yield as a white solid, mp 120–121 °C (lit,14 mp 122.4 °C).
1H NMR (CDCl3) δ 7.49 (br d, J = 7.4 Hz, 2H), 7.63 (br t, J = 7.4 Hz, 1H). 13C
NMR (CDCl3) δ 128.4, 129.1, 129.9 (t, J = 25.5 Hz), 133.8, 172.3.
The authors do not report any conflict of interest.
Acknowledgement
[4-D]acetanilide
Isolated in 93% yield as a white solid, mp 110–112 °C (lit,15 mp 113–
115 °C). 1H NMR (DMSO-d6) δ 2.02 (s, 3H), 7.27 (d, J = 8.4 Hz, 2H), 7.55
(d, J = 8.4 Hz, 2H), 9.93 (br s, 1H). 13C NMR (DMSO-d6) δ 24.1, 119.2,
122.9 (t, J = 23.6 Hz), 128.7, 139.4, 168.6.
English language review.
References
[2,4,5-D3]acetanilide
[1] a) E. M. Simmons, J. F. Hartwig, Angew. Chem. Int. Ed. 2012, 51,
3066–3072; b) K. B. Wiberg, Chem. Rev. 1955, 55, 713–743.
[2] D. W. Young, Top. Stereochem. 1994, 21, 381–465.
Isolated in 94% yield as a white solid, mp 109–111 °C (lit,15 mp 113–
115 °C). 1H NMR (DMSO-d6) δ 2.03 (s, 3H), 7.27 (s, 1H), 7.53 (s, 1H),
Copyright © 2015 John Wiley & Sons, Ltd.
J. Label Compd. Radiopharm 2015, 58 215–219