D
A. Naraoka, H. Naka
Cluster
Synlett
smoothly in the presence of a palladium(II) catalyst with
acetamide as a water donor, affording the corresponding di-
amides in high yields. Notably, the current protocol is the
first to achieve efficient conversion of 1,3-dinitriles into
1,3-diamides without significant side reactions.
(9) For acceptor-controlled transfer dehydration of amides, see:
Okabe, H.; Naraoka, A.; Isogawa, T.; Oishi, S.; Naka, H. Org. Lett.
2019, 21, 4767.
(10) (a) Noyori, R.; Hashiguchi, S. Acc. Chem. Res. 1997, 30, 97.
(b) Bhawal, B. N.; Morandi, B. Angew. Chem. Int. Ed. 2019, 58,
10074.
(11) Reactor A was used throughout the experiments unless other-
wise noted.
Funding Information
(12) Typical Procedure for Double Transfer Hydration
To a 500 mL round-bottom flask equipped with a stirring bar
and a 2-necked Teflon stopcock were added glutaronitrile (1a,
942.1 mg, 10.0 mmol), acetamide (5900.5 mg, 99.9 mmol), and
acetic acid (20 mL). The mixture was stirred at 50 °C for 30 min
under open air (760 mmHg). Pd(CH3CN)4(BF4)2 (4.52 mg, 0.0102
mmol) was added to start the reaction, and the mixture was
stirred at 50 °C for 2 h under reduced pressure (1–3 mmHg). The
internal pressure was continuously reduced by means of a belt
drive rotary vane vacuum pump (SATO VAC INC. USW-50)
equipped with a 450 mL liq. nitrogen trap (for acetonitrile and
acetic acid). The resulting pale-yellow crude mixture was
washed with acetonitrile (50 mL) with sonication for 1 h to
remove acetamide. The precipitate was collected by filtration on
a membrane filter (Merck Millipore JHWP04700 0.45 m pore
size, hydrophilic PTFE membrane, 47 mm diameter) and dried
in vacuo at 120 °C overnight to afford glutaramide (2a, 1043.3
mg, 80% yield) with minor contamination with acetamide (27.0
mg, as determined by 1H NMR spectroscopy). The product
(499.7 mg) was recrystallized from methanol to give analyti-
cally pure 2a (418.9 mg, 69% overall yield).
H.N. is grateful for financial support from the Japan Society for the
Promotion of Science (JSPS KAKENHI Grant Number JP17K05859) and
Toyota Physical and Chemical Research Institute (Toyota Riken).
J
a
p
a
n
S
o
c
i
etyforth
e
Pro
m
oti
o
n
of
S
c
i
e
n
c
e
(J
P
1
7
K
0
5
8
5
9)
Acknowledgment
Generous support and warm encouragement from Profs. R. Noyori
and S. Saito (Nagoya U.) are acknowledged. The authors are grateful to
the reviewers for their constructive suggestions.
Supporting Information
Supporting information for this article is available online at
S
u
p
p
orti
n
gInformati
o
n
S
u
p
p
orit
n
gInformati
o
n
References and Notes
(1) (a) Chen, P.; Gao, M.; Wang, D.-X.; Zhao, L.; Wang, M.-X. J. Org.
Chem. 2012, 77, 4063. (b) Hu, H.-J.; Chen, P.; Ao, Y.-F.; Wang, Q.-
Q.; Wang, D.-X.; Wang, M.-X. Org. Chem. Front. 2019, 6, 808.
(2) (a) Gellman, S. H.; Dado, G. P.; Liang, G.-B.; Adams, B. R. J. Am.
Chem. Soc. 1991, 113, 1164. (b) Liang, G.-B.; Desper, J. M.;
Gellman, S. H. J. Am. Chem. Soc. 1993, 115, 925.
(3) (a) Ahmed, T. J.; Knapp, S. M. M.; Tyler, D. R. Coord. Chem. Rev.
2011, 255, 949. (b) García-Álvarez, R.; Crochet, P.; Cadierno, V.
Green Chem. 2013, 15, 46.
(4) (a) Murahashi, S.-I.; Sasao, S.; Saito, E.; Naota, T. Tetrahedron
1993, 49, 8805. (b) Chin, C.-S.; Kim, S.-Y.; Joo, K.-S.; Won, G.;
Chong, D. Bull. Korean Chem. Soc. 1999, 20, 535. (c) Ghaffar, T.;
Parkins, A. W. J. Mol. Catal. A 2000, 160, 249. (d) Goto, A.; Endo,
K.; Saito, S. Angew. Chem. Int. Ed. 2008, 47, 3607. (e) Crestani, M.
G.; García, J. J. J. Mol. Catal. A 2009, 299, 26. (f) Kiyota, S.; Kobori,
T.; Soeta, H.; Ichikawa, Y.-I.; Komine, N.; Komiya, S.; Hirano, M.
Polyhedron 2016, 120, 3. (g) Tomás-Mendivil, E.; Francos, J.;
González-Fernández, R.; González-Liste, P. J.; Borge, J.;
Cadierno, V. Dalton Trans. 2016, 45, 13590.
(13) Analytical Data of Selected Products
Compound 2a: white solid; mp 181–182 °C. 1H NMR (600 MHz,
DMSO-d6): = 1.67 (quin, J = 7.6 Hz, 2 H), 2.03 (t, J = 7.6 Hz, 4
H), 6.69 (br s, 2 H), 7.24 (br s, 2 H). 13C{1H} NMR (150 MHz,
DMSO-d6): = 21.3, 34.6, 174.5. IR (KBr): 3381 (NH), 3190 (NH),
1650 (CO) cm–1. HRMS (FAB): m/z calcd for [C5H10N2O2Na+] [M +
Na+]: 153.0640; found: 153.0633.
Compound 2d: white solid; mp 153–154 °C. 1H NMR (600 MHz,
DMSO-d6): = 0.98 (d, J = 6.9 Hz, 3 H), 1.45–1.51 (m, 1 H), 1.62–
1.69 (m, 1 H), 1.95–2.09 (m, 2 H), 2.19 (sext, J = 6.9 Hz, 1 H),
6.69 (br s, 2 H), 7.23 (br s, 2 H). 13C{1H} NMR (150 MHz, DMSO-
d6): = 17.8, 29.3, 32.9, 39.0, 174.0, 177.5. IR (KBr): 3396 (NH),
3210 (NH), 1660 (CO) cm–1
. HRMS (FAB): m/z calcd for
[C6H12N2O2Na+] [M + Na+]: 167.0796; found: 167.0796.
Compound 2e: white solid; mp 157–159 °C. 1H NMR (600 MHz,
DMSO-d6): = 2.16–2.17 (m, 4 H), 4.15 (dquin, J = 6.1, 4.8 Hz, 1
H), 4.87 (d, J = 4.8 Hz, 1 H), 6.81 (br s, 2 H), 7.28 (br s, 2 H).
13C{1H} NMR (150 MHz, DMSO-d6): = 42.8, 65.1, 172.8. IR
(KBr): 3411 (NH), 3184 (NH), 1651 (CO) cm–1. HRMS (FAB): m/z
calcd for [C5H10N2O3Na+] [M + Na+]: 169.0589; found: 169.0581.
(5) (a) Breuilles, P.; Leclerc, R.; Uguen, D. Tetrahedron Lett. 1994, 35,
1401. (b) García-Garrido, S. E.; Francos, J.; Cadierno, V.; Basset,
J.-M.; Polshettiwar, V. ChemSusChem 2011, 4, 104.
1
Compound 2f: white solid; mp decomp. >150 °C. H NMR (600
MHz, DMSO-d6): = 3.59 (s, 2 H), 6.99 (br s, 1 H), 7.27–7.30 (m,
2 H), 7.38 (dt, J = 7.6, 1.4 Hz, 1 H), 7.43 (br s, 1 H), 7.47 (dd,
J = 7.9, 1.7 Hz, 1 H), 7.68 (br s, 1 H), 8.22 (br s, 1 H). 13C{1H} NMR
(150 MHz, DMSO-d6): = 39 (overlapped with DMSO-d6), 126.4,
128.0, 129.6, 130.4, 134.0, 136.8, 170.7, 172.8. IR (KBr): 3394
(NH), 3195 (NH), 1650 (CO) cm–1. HRMS (FAB): m/z calcd for
[C9H10N2O2Na+] [M + Na+]: 201.0640; found: 201.0632.
(6) (a) Tachinami, T.; Nishimura, T.; Ushimaru, R.; Noyori, R.; Naka,
H. J. Am. Chem. Soc. 2013, 135, 50. (b) Matsuoka, A.; Isogawa, T.;
Morioka, Y.; Knappett, B. R.; Wheatley, A. E. H.; Saito, S.; Naka,
H. RSC Adv. 2015, 5, 12152. (c) Ushimaru, R.; Nishimura, T.;
Iwatsuki, T.; Naka, H. Chem. Pharm. Bull. 2017, 65, 1000.
(7) Kanda, T.; Naraoka, A.; Naka, H. J. Am. Chem. Soc. 2019, 141, 825.
(8) For Pd-catalyzed conversion of nitriles with amides, see:
(a) Maffioli, S. I.; Marzorati, E.; Marazzi, A. Org. Lett. 2005, 7,
5237. (b) Dubey, P.; Gupta, S.; Singh, A. K. Dalton Trans. 2017,
46, 13065.
© 2019. Thieme. All rights reserved. Synlett 2019, 30, A–D