A half sandwich ruthenium(II) complex with n-4,6-dimethyl-2-pyrimidinylimidazole: Synthesis, crystal structure and application in N-Alkylation of amines with alcohols

Full text of DOI:10.1002/bkcs.10484

Note
DOI: 10.1002/bkcs.10484
BULLETIN OF THE
H.-M. Li et al.
KOREAN CHEMICAL SOCIETY
A Half Sandwich Ruthenium(II) Complex with N-4,6-Dimethyl-2-
pyrimidinylimidazole: Synthesis, Crystal Structure and Application in
N-Alkylation of Amines with Alcohols
*
Hong-Mei Li, Chen Xu, Zhi-Qiang Wang, and Wei-Jun Fu
College of Chemistry and Chemical Engineering, Luoyang Normal University, Luoyang 471022, China.
*E-mail: xubohan@163.com
Received May 26, 2015, Accepted June 18, 2015, Published online September 2, 2015
Keywords: Half sandwich ruthenium(II) complex, Crystal structure, N-Alkylation
The metal-catalyzed C N bond forming reaction is one of the
most important transformations in organic synthesis and plays
a vital role in chemical and biological systems.1 The N-alkyl-
ation of amines with electrophiles such as alkyl halides is the
conventional method to form C N bonds.2 However, this
method is undesirable from an environmental point of view.
Alcohols are of great importance as cheap and readily availa-
ble organic materials for the preparation of many pharmaceu-
tical products and fine chemicals.3 The use of alcohols as
electrophiles instead of alkyl halides in C N bond forming
reactions is particularly attractive because the process pro-
duces only water as byproduct,4 and great progress has been
obtained for the metal-catalyzed hydrogen autotransfer proc-
ess by alcohols as the greener alkylating reagents.5 A number
of reports have shown that Ru6 and Ir7 complexes are effective
catalysts for this transformation. We have alsofound cyclome-
tallated iridium(III) complexes were very efficient catalysts
for α-alkylation using the hydrogen-borrowing strategy.8 As
a continuation of our interest in metal-catalyzed hydrogen
autotransfer processes, we have prepared a new half sandwich
Ru(II) complex with imidazole (Scheme 1) and examined its
activity in the N-alkylation of amines with alcohols.
Complex1isair- andmoisture-stable, bothinsolid stateand
in solution. It was characterized by HRMS, 1H, and 13C NMR.
These spectra were well consistent with the title complex.
Moreover, the molecular structure of 1 has been ascertained
by means of single-crystal X-ray studies. The molecule of
1 together with selected bond distances and angles is shown
in Figure 1. The complex has an essentially octahedral coor-
dination geometry comprising the p-cymene ring carbons
occupying one face of the octahedron leaving the other three
sitestobecoordinated bytwo chlorideatomsandmonodentate
(N-4,6-dimethyl-2-pyrimidinylimidazole) ligand. The Ru N
bond length 2.113(3) Å of 1 is similar to those of the related
arene Ru(II) complexes.9 The imidazole ring and the pyrimi-
dine ring are approximately coplanar (dihedral angle of 9.0ꢀ).
The dihedral angle between the imidazole ring and p-cymene
ring is 38.5ꢀ. In the crystal, there exist intermolecular
C HÁ Á ÁCl hydrogen bonds (HÁ Á ÁCl 2.828 Å) between chlo-
rine atom and the adjacent C H of p-cymene ring, which con-
struct the 1D chain structure.
In 2014, Özdemir et al. reported the first examples of half
sandwich Ru(II) complexes bearing benzimidazole moiety
for the N-alkylation of amines.6c However, the catalytic sys-
tem required a high temperature (150 ꢀC). Initially, the N-
alkylation of m-toluidine with (4-methoxyphenyl)methanol
was carried out with various solvents and bases in the presence
of 1 mol% of 1 at 120 ꢀC for 12 h. The results from this study
are summarized in Table 1. Among the tested solvents, xylene
was much better than toluene and dioxane (entries 1–3). After
screening a variety of bases (entries 4–7), KOH was found to
be the most effective base (96%, entry 5) and KOtBu as well as
CsOH also showed comparable results.
Under the optimized reaction conditions, the N-alkylations
of m-toluidine with a variety of electronically and structurally
diverse aryl methanols were carried out to explore the scope of
this system (Table 2). Similar to the result of (4-methoxyphe-
nyl)methanol, the coupled products 2b–2d were obtained in
excellent yields. Good yields were also obtained with elec-
tron-deficient aryl methanols. For ortho-substituents with
methyl, chloride and bromine groups, the yields of 2i–2j
decreased slightly. In the following experiments, the N-alky-
lations of a variety of amines were investigated (Table 3).
Complex 1 also showed high catalytic activity for the N-alkyl-
ation of (pyridin-2-yl)- methanol. Similar to the results of
varying aryl methanol part, reaction with para-, ortho-, and
Cl
Cl
Cl
N
N
N
Ru
N
Ru
N
N
N
Ru
Cl
N
Cl
Cl
1
Scheme 1. Synthesis of 1.
Bull. Korean Chem. Soc. 2015, Vol. 36, 2557–2560
© 2015 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Wiley Online Library
2557

Note
BULLETIN OF THE
ISSN (Print) 0253-2964 | (Online) 1229-5949
KOREAN CHEMICAL SOCIETY
Table 2. The N-alkylation of m-toluidine with aryl meth-anols
catalyzed by 1.a
HO
Cat 1
NH2
+
NH
R
KOH, xylene
2b-kb
R
NH
NH
2b, 93%
2c, 92%
Br
NH
NH
Figure 1. Molecular structure of complex 1. H atoms are omitted for
clarity. Selected bond lengths (Å) and angles (ꢀ): Ru1–Cl1 2.4099
(10), Ru1–Cl2 2.4197(9), Ru1–N1 2.113(3), and Cl1–Ru1–Cl2
88.88(4), N1–Ru1–Cl1 85.31(9), N1–Ru1–Cl2 85.71(9).
2e, 91%
2d, 95%
F
Cl
NH
NH
2g, 87%
2f, 90%
NO2
Table 1. Influence of solvent and base on the N-alkylation of m-
NH
NH
toluidine with (4-methoxyphenyl)methanol.a
2h, 82%
2i, 88%
OCH3
HO
Cat 1
NH2
OCH3
NH
+
NH
Cl
Base, Solvent
NH
Br
2a
2j, 85%
2k, 86%
Entry
Base
Solvent
Yield (%)b
a Reaction conditions: m-toluidine (1 mmol), aryl methanol (1.1 mmol),
KOH (1 mmol), xylene (3 mL), 120 ꢀC, 12 h.
b Isolated yields.
1
2
3
4
5
6
7
KOtBu
KOtBu
KOtBu
NaOH
KOH
Dioxane
Toluene
Xylene
Xylene
Xylene
Xylene
Xylene
78
82
95
65
96
93
21
spectrometer (Billerica, MA< USA) in CDCl3 with TMS as
an internal standard. Crystallographic data were collected
on a Xcalibur, Eos, Gemini diffractometer (Agilent, Oxford,
UK). CCDC reference number 1402502 for 1.
Dichloro-(N-4,6-dimethyl-2-pyrimidinylimidazole)(p-
cymene)ruthenium(II) (1). A solution of N-4,6-dimethyl-2-
pyrimidinylimidazole (0.5 mmol) and [RuCl2(p-cymene)]2
(0.5 mmol) in toluene (10 mL) was refluxed for 3 h and then
cooled to room temperature. The product 1 was filtered off,
washed with diethyl ether, and dried in air. Red solid, 86%
CsOH
K2CO3
a Reaction conditions: m-toluidine (1 mmol), (4-methoxy- phenyl)
methanol (1.1 mmol), base (1 mmol), solvent (3 mL), 120 ꢀC, 12 h.
b Isolated yields.
meta-amines proceeded efficiently to from the expected pro-
ducts 3a–3i in good to excellent yields. Finally, the coupling
of (pyridin-2-yl)- methanol with 2-aminopyridine also gave
excellent yield.
1
yield. H NMR (400 MHz, CDCl3): δ 8.97 (s, 1H), 7.89 (s,
In conclusion, a new half sandwich Ru(II) complex bearing
imidazole moiety has been synthesized and characterized. It
was an efficient catalyst for the N-alkylation of amines with
alcohols.
1H), 7.44 (s, 1H), 6.95 (s, 1H), 5.49 (d, J = 5.8 Hz, 2H),
5.30 (d, J = 5.8 Hz, 2H), 3.00 (hept, 1H), 2.48 (s, 6H), 2.20
(s, 3H), 1.31 (d, J = 6.8 Hz, 6H). 13C NMR (100 MHz,
CDCl3): 169.2, 152.9, 139.1, 132.6, 118.9, 117.0, 102.8,
97.4, 82.9, 81.5, 30.7, 23.9, 22.3, 18.6. HRMS (ESI) calcd
for C19H24Cl2N4Ru: 480.0422, found: 480.0422; Calcd for
[M-Cl]+: 445.0733, found: 445.0733.
Experimental
Materials and Measurement.
Solvents were dried
General Procedure for the N-alkylation. A reaction tube
was charged with amines (1 mmol), alcohols (1.1 mmol) cat-
alyst 1 (0.01 mmol), the selected base (1.0 mmol), and solvent
(3 mL) under the nitrogen gas. The reaction mixture was
heated at 120 ꢀC for 12 h. After being cooled, the solvent
was evaporated and the product was separated by passing
and freshly distilled prior to use. All other chemicals were
commercially available expect for the N-4,6-dimethyl-2-pyr-
imidinylimidazole was prepared according to published pro-
cedure.10 High-resolution mass spectra were measured on a
Waters Q-Tof MicroTM spectrometer (Waters, Manchester,
UK). NMR spectra were recorded on a Bruker DPX-400
through a silica gel column. The products 2a11a, 2b11b
,
Bull. Korean Chem. Soc. 2015, Vol. 36, 2557–2560
© 2015 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.bkcs.wiley-vch.de 2558

BULLETIN OF THE
Note
KOREAN CHEMICAL SOCIETY
Table 3. The N-alkylation of (pyridin-2-yl)methanol with amines
148.4, 139.1, 137.2, 136.4, 130.5, 129.2, 128.4, 127.5,
126.2, 118.58, 113.5, 109.9, 46.5, 21.7, 19.0. HRMS (ESI)
calcd for C15H17N: 211.1361, found: 211.1361.
catalyzed by 1.a
3-Methyl-N-[(pyridin-2-yl)methyl]benzenamine (3c).
1H NMR (400 MHz, CDCl3): δ 8.55 (d, J = 4.0 Hz, 1H),
7.58 (t, J = 7.6 Hz, 1H), 7.29 (d, J = 8.0 Hz, 1H), 7.13 (t, J
= 6.0 Hz, 1H), 7.04 (t, J = 7.6 Hz, 1H), 6.53 (d, J = 7.2 Hz,
1H), 6.47 (m, 2H), 4.42 (br, 3H), 2.25 (s, 3H). 13C NMR
(100 MHz, CDCl3): 158.7, 149.2, 148.0, 139.0, 136.7,
129.2, 122.1, 121.6, 118.6, 113.9, 110.2, 49.3, 21.7. HRMS
(ESI) calcd for C13H14N2: 198.1157, found: 198.1157.
2-Methyl-N-[(pyridin-2-yl)methyl]benzenamine (3e).
1H NMR (400 MHz, CDCl3): δ 8.57 (d, J = 4.2 Hz, 1H),
7.60 (t, J = 7.2 Hz, 1H), 7.29 (d, J = 7.8 Hz, 1H), 7.14 (t, J
= 5.6 Hz, 1H), 7.07 (t, J = 7.6 Hz, 1H), 6.66 (t, J = 7.2 Hz,
1H), 6.56 (d, J = 8.0 Hz, 2H), 4.71 (br, 1H), 4.48 (s, 2H),
2.24 (s, 3H). 13C NMR (100 MHz, CDCl3): 158.8, 149.3,
148.2, 139.1, 136.9, 129.5, 122.2, 121.7, 118.8, 114.0,
110.3, 49.4, 21.9. HRMS (ESI) calcd for C13H14N2:
198.1157, found: 198.1157.
R
Cat 1
H2N
N
HN
3a-3jb
KOH, xylene
N
OH
R
HN
N
HN
N
N
3b, 94%
3a, 92%
OCH3
HN
N
HN
3d, 96%
3c, 90%
HN
N
HN
N
3e, 86%
3f, 89%
Br
Cl
HN
N
HN
N
2,5-Dimethyl-N-[(pyridin-2-yl)methyl]benzenamine
(3f ). 1H NMR (400 MHz, CDCl3): δ 8.57 (d, J = 4.2 Hz, 1H),
7.59 (t, J = 7.2 Hz, 1H), 7.30 (d, J = 7.6 Hz, 1H), 7.14 (t, J =
6.0 Hz, 1H), 6.94 (d, J = 7.2 Hz, 1H), 6.47 (d, J = 7.2 Hz, 1H),
6.39 (s, 1H), 4.64 (br, 1H), 4.47 (s, 2H), 2.36 (s, 3H), 2.40 (s,
3H). 13C NMR (100 MHz, CDCl3): 158.6, 149.2, 145.8,
136.6, 129.9, 122.0, 121.6, 119.3, 117.8, 110.1, 100.0,
25.0, 21.5. HRMS (ESI) calcd for C14H16N2: 212.1314,
found: 212.1314.
3g, 88%
3h, 85%
NO2
HN
HN
N
N
N
3i, 80%
3j, 93%
a Reaction conditions: amines (1 mmol), (pyridin-2-yl)- methanol (1.1
mmol), KOH (1 mmol), xylene (3 mL), 120 ꢀC, 12 h.
b Isolated yields.
Acknowledgments. This work was supported by the Innova-
tion Scientists and Technicians Troop Construction Projects
of Henan Province and the Science Foundation of Henan
Education Department (Nos. 15B150008 and 14A150049).
2d11a, 2f11c, 2g11d, 2h11e, 2k–j11f and 3a–b12a, 3d–g12b, 3h5b,
3i12c, 3j6a were characterized by comparison of datawith those
in the literature. Other products were determined by HRMS,
1H and 13C NMR.
3-Methyl-N-[(naphthalen-1-yl)methyl]benzenamine
(2c). 1H NMR (400 MHz, CDCl3): δ 8.03 (d, J = 5.6 Hz, 1H),
7.86 (d, J = 5.6 Hz, 1H), 7.77 (d, J = 8.0 Hz, 1H), 7.49 (d, J =
6.0 Hz, 3H), 7.39 (t, J = 7.6 Hz, 1H), 7.08 (t, J = 7.6 Hz, 1H),
6.56 (d, J = 7.2 Hz, 1H), 6.48 (s, 2H), 4.68 (s, 2H), 3.88 (br,
1H), 2.27 (s, 3H). 13C NMR (100 MHz, CDCl3): 148.4,
139.2, 134.6, 134.0, 131.7, 129.3, 128.9, 128.3, 126.4,
126.2, 125.9, 125.7, 123.8, 118.7, 113.6, 110.0, 46.6, 21.8.
HRMS (ESI) calcd for C18H17N: 247.1361, found: 247.1361.
N-(4-Bromobenzyl)-3-methylbenzenamine (2e). 1H
NMR (400 MHz, CDCl3): δ 7.76 (t, J = 8.0 Hz, 2H), 7.42
(d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 7.05 (t, J = 7.6
Hz, 1H), 6.54 (d, J = 7.2 Hz, 1H), 4.25 (s, 2H), 3.98 (br,
1H), 2.25 (s, 3H). 13C NMR (100 MHz, CDCl3): 151.7,
147.9, 139.1, 132.5, 131.0, 129.2, 127.6, 125.8, 118.8,
110.0, 47.7, 21.7. HRMS (ESI) calcd for C14H14BrN:
275.0310, found: 275.0310.
References
1. a) A. Ricci, Modern Amination Reaction, Wiley-VCH, Wein-
heim, 2000; b) S. A. Lawrence, Amines: Synthesis properties
andApplication, CambridgeUniversityPress, Cambridge, 2004.
2. a) S. L. Buchwald, C. Mauger, G. Mignani, U. Scholz, Adv.
Synth. Catal. 2006, 348, 23; b) K. Fujita, Z. Li, N. Ozeki,
R. Yamaguch, Tetrahedron Lett. 2003, 44, 2687.
3. a) G. Tojo, M. Fernández, Oxidation of Alcohols to Aldehydes
and Ketones, Springer, New York, 2006; b) S. Caron,
R. W. Dugger, S. G. Ruggeri, J. A. Ragan, D. H. B. Ripin, Chem.
Rev. 2006, 106, 2943; c) H. M. Li, A. Q. Feng, X. H. Lou, Bull.
Korean Chem. Soc. 2014, 35, 2551.
4. a) G. Guillena, D. J. Ramón, M. Yus, Chem. Rev. 2010, 110,
1611; b) M. M. Reddy, M. A. Kumar, P. Swamy, M. Naresh,
K. Srujana, L. Satyanarayana, A. Venugopal, N. Narender,
Green Chem. 2013, 15, 3474.
5. a) M. Hamid, C. Liana Allen, G. Lamb, A. Maxwell, H. Maytum,
A. Watson, J. M. J. Williams, J. Am. Chem. Soc. 2009, 131, 1766;
b) Q. L. Peng, Y. Zhang, F. Shi, Y. Q. Deng, Chem. Commun.
2011, 47, 6476.
N-(2-Methylbenzyl)-3-methylbenzenamine (2i). 1H
NMR (400 MHz, CDCl3): δ 7.30 (d, J = 7.2 Hz, 1H),
7.14–7.18 (m, 3H), 7.06 (t, J = 7.6 Hz, 1H), 6.53 (d, J = 7.4
Hz, 1H), 6.41–6.45 (m, 2H), 4.23 (s, 2H), 3.65 (br, 1H),
2.35 (s, 3H), 2.27 (s, 3H). 13C NMR (100 MHz, CDCl3):
6. a) S. Agrawal, M. Lenormand, B. Martin-Matute, Org. Lett.
2012, 14, 1456; b) B. Kang, Z. Q. Fu, S. H. Hong, J. Am. Chem.
Bull. Korean Chem. Soc. 2015, Vol. 36, 2557–2560
© 2015 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.bkcs.wiley-vch.de 2559

BULLETIN OF THE
Note
KOREAN CHEMICAL SOCIETY
Soc. 2013, 135, 11704; c) S. Demir, F. Coskun, I. Özdemir,
J. Organomet. Chem. 2014, 755, 134.
11. a) E. J. Hennessy, S. L. Buchwald, J. Am. Chem. Soc. 2003, 125,
12084; b) Y. Zhang, X. Y. Yang, Q. Z. Yao, D. W. Ma, Org. Lett.
2012, 14, 3056; c) K. Anil Kumar, T. S. Sreelekha,
K. N. Shivakumara, K. C. Prakasha, D. Channe Gowda, Synth.
Commun. 2009, 39, 1332; d) Y. L. Zhao, W. Zhang, S. Wang,
Q. Liu, J. Org. Chem. 2007, 72, 4985; e) B. A. Frontana,
C. Moinet, Tetrahedron 1998, 54, 3197; f ) K. Chen,
S. A. Pullarkat, Org. Biomol. Chem. 2012, 10, 6600.
12. a) V. V. Kouznetsov, L. Y. V. Mendez, M. Sortino, Y. Vasquez,
M. P. Gupta, M. Freile, R. D. Enriz, S. A. Zacchino, Bioorg. Med.
Chem. 2008, 16, 794; b) L. C. Misal Castro, J. B. Sortais,
C. Darcel, Chem. Commun. 2012, 48, 151; c) C. K. Jones,
D. W. Engers, A. D. Thompson, J. R. Field, A. L. Blobaum,
S. R. Lindsley, Y. Zhou, R. D. Gogliotti, S. Jadhav,
R. Zamorano, J. Bogenpohl, Y. Smith, R. Morrison,
J. S. Daniels, C. D. Weaver, P. J. Conn, C. W. Lindsley,
C. M. Niswender, C. R. Hopkins, J. Med. Chem. 2011, 54, 7639.
7. a) T. Suzuki, Chem. Rev. 2011, 111, 1825; b)
Y. H. Chang, Y. Nakajima, F. Ozawa, Organometallics 2013,
32, 2210.
8. a) C. Xu, X. Q. Hao, Z. Q. Xiao, Z. Q. Wang, X. E. Yuan,
W. J. Fu, B. M. Ji, M. P. Song, J. Org. Chem. 2013, 78, 8730;
b) C. Xu, X. M. Dong, Z. Q. Wang, X. Q. Hao, Z. Li,
L. M. Duan, B. M. Ji, M. P. Song, J. Organomet. Chem. 2012,
700, 214.
9. a) I. Hyder, M. Jimenez-Tenorio, M. Carmen Puerta, P. Valerga,
Organometallics 2011, 30, 726; b) I. Ivanovic, K. K. Jovanovic,
N. Gligorijevic, S. Radulovic, V. B. Arion, K. S. Sheweshein,
Z. L. Tesic, S. Grguric-Sipka, J. Organomet. Chem. 2014,
749, 343.
10. C. Xu, Z. Li, L. M. Duan, Z. Q. Wang, W. J. Fu, X. Q. Hao,
M. P. Song, Transit. Metal Chem. 2012, 37, 373.
Bull. Korean Chem. Soc. 2015, Vol. 36, 2557–2560
© 2015 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.bkcs.wiley-vch.de 2560