Ruthenium complex-controlled catalytic N-mono- or N,N-dialkylation of heteroaromatic amines with alcohols

Article abstract of DOI:10.1021/jo9516289

Heteroaromatic amines were N-alkylated with primary alcohols at 150-200°C in the presence of a catalytic amount of various ruthenium complexes to give the corresponding monoalkylated and dialkylated amines in good to high yields. For example, 2-aminopyridine reacted with an excess of ethanol at 180°C for 20 h in the presence of dichlorotris(triphenylphosphine)ruthenium [RuCl₂-(PPh₃)₃] to give 2-(ethylamino)pyridine (1) and 2-(diethylamino)pyridine (2) in 9% and 70% yields, respectively. On the other hand, when (η⁴-1,5-cyclooctadiene)(η ⁶-1,3,5-cyclooctatriene)ruthenium [Ru(cod)(cot)] was used as a catalyst, even in the presence of excess ethanol, 1 was obtained in 85% yield with high selectivity. The addition of tertiary phosphines and phosphites to Ru(cod)-(cot) increased the yield of the dialkylated amine.

Full text of DOI:10.1021/jo9516289

4214
J . Org. Chem. 1996, 61, 4214-4218
Ru th en iu m Com p lex-Con tr olled Ca ta lytic N-Mon o- or
N,N-Dia lk yla tion of Heter oa r om a tic Am in es w ith Alcoh ols
Yoshihisa Watanabe,* Yasuhiro Morisaki, Teruyuki Kondo, and Take-aki Mitsudo*
Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University,
Sakyo-ku, Kyoto 606-01, J apan
Received September 6, 1995X
Heteroaromatic amines were N-alkylated with primary alcohols at 150-200 °C in the presence of
a catalytic amount of various ruthenium complexes to give the corresponding monoalkylated and
dialkylated amines in good to high yields. For example, 2-aminopyridine reacted with an excess
of ethanol at 180 °C for 20 h in the presence of dichlorotris(triphenylphosphine)ruthenium [RuCl2-
(PPh3)3] to give 2-(ethylamino)pyridine (1) and 2-(diethylamino)pyridine (2) in 9% and 70% yields,
respectively. On the other hand, when (η4-1,5-cyclooctadiene)(η6-1,3,5-cyclooctatriene)ruthenium
[Ru(cod)(cot)] was used as a catalyst, even in the presence of excess ethanol, 1 was obtained in
85% yield with high selectivity. The addition of tertiary phosphines and phosphites to Ru(cod)-
(cot) increased the yield of the dialkylated amine.
Ta ble 1. Ru th en iu m -Ca ta lyzed N-Eth yla tion of
In tr od u ction
2-Am in op yr id in e w ith Va r iou s Ru th en iu m Com p lexesa
The development of novel and versatile methods for
the selective transformation of primary amines to sec-
ondary or tertiary amines has stimulated the reexamina-
tion of many amino compounds. Several methods for the
N-alkylation of primary amines using alkyl halides,
aldehydes, ketones, and alcohols have been explored,1-8
including the ruthenium complex-catalyzed N-alkyl-
ation6,9-11 and N-heterocyclization6,12-16 of amines using
alcohols.
This paper deals with the first ruthenium complex-
catalyzed N-alkylation of heteroaromatic amines using
alcohols. In the presence of ruthenium complexes,
primary heteroaromatic amines readily react with alco-
hols to selectively give the corresponding N-monoalky-
lated and N,N-dialkylated heteroaromatic amines. The
ratio of N-monoalkylated to N,N-dialkylated products
depends on the molar ratio of amine to alcohol used.10
We now report that the selectivity for the products can
be controlled by the type of ruthenium complex used.
yieldb (%)
run
catalyst
convb (%)
1
2
1
2
3
4
Ru(cod)(cot)
Ru3(CO)12
93
100
100
100
100
51
79
66
28
40
73
31
26
0
3
27
49
37
15
0
RuCl2(PPh3)3
RuH2(CO)(PPh3)3
RuHCl(CO)(PPh3)3
[Cp*RuCl2]2
RuCl3‚nH2O
none
5c
6c,d
7
100
0
21
0
8
a
2-Aminopyridine (4.0 mmol), ethanol (5.0 mL, 85 mmol), and
catalyst (0.20 mmol) at 200 °C for 5 h under an argon atmosphere.
Determined by GLC. c 180 °C. Cp* ) C5Me5.
b
d
Resu lts a n d Discu ssion
N-E t h yla t ion of H et er oa r om a t ic Am in es w it h
Eth a n ol. 2-Aminopyridine was first used as a substrate.
The reactions were carried out at 180-200 °C in the
presence of catalytic amounts of various ruthenium
complexes with an excess of ethanol (eq 1). The results
are summarized in Table 1.
X Abstract published in Advance ACS Abstracts, J une 1, 1996.
(1) Gibson, M. S. The Chemistry of the Amino Group; Patai, S., Ed.;
Interscience Publishers: London, 1968; Chapter 2, pp 45-52.
(2) Malpass, J . R. Comprehensive Organic Chemistry; Sutherland,
I. O., Ed.; Pergamon Press: Oxford, 1979; Vol. 2, Part 6, pp 4-7.
(3) Burdon, J .; McLonghlim, V. C. R. Tetrahedron 1965, 21, 1.
(4) Bissinger, W. E.; Kung, F. E.; Hamillon, C. W. J . Am. Chem.
Soc. 1948, 70, 3940.
(5) Tanigawa, Y.; Murahashi, S.; Moritani, I. Tetrahedron Lett. 1975,
471.
(6) Murahashi, S.; Kondo, K.; Hakata, T. Tetrahedron Lett. 1982,
23, 229.
(7) Griss, R.; Mitchell, T. R. B.; Sutthivaiyakit, S.; Tongpenyai, N.
J . Chem. Soc., Chem. Commun. 1981, 611.
(8) Arcelli, A.; Khai, B.-T.; Porzi, G. J . Organomet. Chem. 1982 235,
93.
(9) Watanabe, Y.; Tsuji, Y.; Ohsugi, Y. Tetrahedron Lett. 1981, 22,
2667.
(10) Watanabe, Y.; Tsuji, Y.; Ige, H.; Ohsugi, Y.; Ohta, T. J . Org.
Chem. 1984, 49, 3359.
(11) Huh, K.-T.; Tsuji, Y.; Kobayashi, M.; Okuda, F.; Watanabe, Y.
Chem. Lett. 1988, 449.
(12) Tsuji, Y.; Huh, K.-T.; Watanabe, Y. J . Org. Chem. 1987, 52,
1673.
(13) Tsuji, Y.; Kotachi, S.; Huh, K.-T.; Watanabe, Y. J . Org. Chem.
1990, 55, 580.
(14) Kondo, T.; Yang, S.; Huh, K.-T.; Kobayashi, M.; Kotachi, S.;
Watanabe, Y. Chem. Lett. 1991, 1275.
(15) Kondo, T.; Kotachi, S.; Watanabe, Y. J . Chem. Soc., Chem.
Commun. 1992, 1318.
(16) Kondo, T.; Kotachi, S.; Ogino, S.; Watanabe, Y. Chem. Lett.
1993, 1317.
The reactions proceeded smoothly to give mixtures of
the corresponding 2-(ethylamino)pyridine (1) and 2-(di-
ethylamino)pyridine (2) in reasonable yields (runs 1-5).
Dichlorotris(triphenylphosphine)ruthenium [RuCl2(PPh3)3]
showed catalytic activity to give N,N-disubstituted amine
2 as a major product (yield 49%, run 3). On the other
hand, when (η4-1,5-cyclooctadiene)(η6-1,3,5-cyclooctatriene)-
ruthenium [Ru(cod)(cot)] was used as a catalyst, N-
monosubstituted amine 1 was obtained in high yield with
high selectivity even in the presence of an excess of
ethanol (run 1). The reaction did not proceed in the
absence of catalyst.
S0022-3263(95)01628-8 CCC: $12.00 © 1996 American Chemical Society

Ru-Catalyzed Alkylation of Amines with Alcohols
J . Org. Chem., Vol. 61, No. 13, 1996 4215
Ta ble 2. Ru Cl2(P P h 3)3-Ca ta lyzed N-Eth yla tion of Heter oa r om a tic Am in es w ith Eth a n ola
run
amine
convb (%)
products (% yieldb)
1
2
3
2-aminopyridine
3-aminopyridine
4-aminopyridine
2-aminopyrimidine
aniline
100
100
86
95
100
2-(ethylamino)pyridine (1) (57)
2-(diethylamino)pyridine (2) (11)
3-(diethylamino)pyridine (4) (53)
-
2-(diethylamino)pyrimidine (7) (7)
N,N-diethylaniline (9) (74)
3-(ethylamino)pyridine (3) (42)
4-(ethylamino)pyridine (5) (81)
2-(ethylamino)pyridine (6) (55)
N-ethylaniline (8) (13)
4
5c
a
b
Amine (4.0 mmol), ethanol (5.0 mL), and RuCl2(PPh3)3 (0.20 mmol) at 180 °C for 5 h under an argon atmosphere. Determined by
GLC. c J . Org. Chem. 1984, 49, 3359.
Ta ble 3. Ru (cod )(cot)-Ca ta lyzed N-Eth yla tion of Heter oa r om a tic Am in es w ith Eth a n ola
run
amine
convb (%)
products (% yieldb)
1
2
3
4
2-aminopyridine
3-aminopyridine
4-aminopyridine
2-aminopyrimidine
aniline
93
95
86
92
25
49
63
2-(ethylamino)pyridine (1) (85)
2-(diethylamino)pyridine (2) (1)
3-(diethylamino)pyridine (4) (1)
3-(ethylamino)pyridine (3) (92)
4-(ethylamino)pyridine (5) (81)
2-(ethylamino)pyrimidine (6) (40)
N-ethylaniline (8) (13)
8 (35)
-
-
5
-
6c
7d
aniline
aniline
9 (6)
9 (8)
8 (43)
a
b
Amine (4.0 mmol), ethanol (5.0 mL), and Ru(cod)(cot) (0.20 mmol) at 180 °C for 5 h under an argon atmosphere. Determined by
GLC. c (Dimethylamino)pyridine (0.5 mmol) was added. Pyridine (0.5 mmol) was added.
d
Ta ble 4. Ru (cod )(cot)-Ca ta lyzed N-Alk yla tion of 2-Am in op yr id in e w ith P r im a r y Alcoh olsa
run
alcohol
temp (°C)
time (h)
convb (%)
products (% yieldb)
1
2
3
4
5
6
methanol
ethanol
1-propanol
1-butanol
1-hexanol
benzyl alcohol
150
180
180
150
150
180
3
5
5
3
3
5
84
93
97
76
83
81
2-(methylamino)pyridine (10) (80)
1 (85)
2-(propylamino)pyridine (11) (85)
2-(butylamino)pyridine (13) (72)
2-(hexylamino)pyridine (15) (77)
2-(benzylamino)pyridine (16) (58c)
-
2 (1)
2-(dipropylamino)pyridine (12) (4)
2-(dibutylamino)pyridine (14) (3)
-
-
a
b
2-Aminopyridine (2.0 mmol), alcohol (3.0 mL), and Ru(cod)(cot) (0.10 mmol) under an argon atmosphere. Determined by GLC.
c Determined by NMR.
Various heteroaromatic amines reacted with ethanol
at 180 °C in the presence of a catalytic amount of RuCl2-
(PPh3)3 to give mixtures of N-monosubstituted and N,N-
disubstituted heteroaromatic amines in high yields. The
results are summarized in Table 2. Aniline readily
reacted with ethanol to give N,N-diethylaniline as a
major product (yield 74%, run 5). In contrast, the
reaction of 4-aminopyridine selectively gave the corre-
sponding N-monosubstituted amine in 81% yield (run 3).
rakis(triphenylphosphine)ruthenium [RuH2(PPh3)4] is ac-
tive for the oxidative transformation of alcohols and
aldehydes into esters and lactones.17 The Ru(cod)(cot)/
2-aminopyridine catalyst system also showed catalytic
activity for ester formation.
Interestingly, methanol reacted with 2-aminopyridine
to give the corresponding 2-(methylamino)pyridine in
high yield. N-Methylation of aminoarenes using metha-
nol with a RuCl2(PPh3)3 catalyst is usually unsuccessful.
We previously reported that only the RuCl3‚nH2O-
P(OBu)3 catalyst system is highly active for the N,N-
dimethylation of aminoarenes with methanol.11 The
present results show that Ru(cod)(cot) is very active for
monomethylation of 2-aminopyridine using methanol.
Effect of Rea ction Tem p er a tu r e on th e N-Eth y-
la tion of 2-Am in op yr id in e. Figure 1 shows the effect
of reaction temperature on the RuCl2(PPh3)3-catalyzed
N-ethylation of 2-aminopyridine. In the case of RuCl2-
(PPh3)3, the maximum yield of 1 (57%) was found at 180
°C. At higher temperatures, the yield of 1 decreased and
that of 2 increased. At 200 °C, 2 was formed in 49% yield.
In contrast, in the presence of a catalytic amount of
Ru(cod)(cot), the yield of 2 was very low, even at 200 °C
(yield 3%). At 180 °C, the yields of 2-(ethylamino)-
pyridine (1) and 2-(diethylamino)pyridine (2) were 85%
and 1%, respectively; i.e., the N-monosubstituted amine
was obtained with high selectivity.
Ru(cod)(cot) showed high catalytic activity for the
N-monoalkylation of 2-, 3-, and 4-aminopyridine (Table
3). 2-Aminopyrimidine also reacted with ethanol to give
the corresponding 2-(ethylamino)pyrimidine in moderate
yield (run 4). In contrast with RuCl2(PPh3)3, Ru(cod)-
(cot) was ineffective as a catalyst with aniline, as
indicated in run 5. This suggests that coordination of a
nitrogen atom on the pyridine ring is essential for Ru-
(cod)(cot)-catalyzed N-alkylation. In the case of 2-ami-
nopyridine, it may act as a bidentate ligand. In the
reaction of 3- or 4-aminopyridine, a second substrate may
participate as a ligand. The addition of 2-(dimethylami-
no)pyridine or pyridine to the Ru(cod)(cot)-catalyzed
N-alkylation of aniline improved the yield of the products
(Table 3, runs 5-7).
Ru (cod )(cot)-Ca ta lyzed N-Alk yla tion of 2-Am i-
n op yr id in e w ith Sever a l P r im a r y Alcoh ols. Several
primary alcohols were used in the N-alkylation of 2-ami-
nopyridine in the presence of Ru(cod)(cot) as a catalyst
(Table 4). These reactions proceeded smoothly to give
N-monosubstituted 2-aminopyridine in high yield with
high selectivity. Only a small amount of N,N-disubsti-
tuted 2-aminopyridine was obtained. In the reactions of
1-butanol, 1-hexanol, and benzyl alcohol, the correspond-
ing Tischenko-type esters were obtained as a byproduct.
Murahashi and co-workers reported that dihydridotet-
Effects of Rea ction Tim e on th e N-Eth yla tion of
2-Am in op yr id in e. The effects of reaction time on the
RuCl2(PPh3)3- and Ru(cod)(cot)-catalyzed N-ethylation of
2-aminopyridine with ethanol were investigated, and the
results are shown in Figures 2 and 3, respectively. In
(17) Murahashi, S.; Naota, T.; Ito, K.; Maeda, Y.; Taki, H. J . Org.
Chem. 1987, 52, 4319.

4216 J . Org. Chem., Vol. 61, No. 13, 1996
Watanabe et al.
F igu r e 3. Effects of reaction time on Ru(cod)(cot)-catalyzed
N-ethylation of 2-aminopyridine with ethanol. Conversion of
2-aminopyridine (0), yield of 1 (O), and yield of 2 (4).
2-Aminopyridine (4.0 mmol), ethanol (5.0 mL), and Ru(cod)-
(cot) (0.20 mmol) at 180 °C.
F igu r e 1. Effects of reaction temperature on RuCl2(PPh3)3-
catalyzed N-ethylation of 2-aminopyridine with ethanol. Con-
version of 2-aminopyridine (0), yield of 1 (O), and yield of 2
(4). 2-Aminopyridine (4.0 mmol), ethanol (5.0 mL), and RuCl2-
(PPh3)3 (0.20 mmol) for 5 h.
ring is enhanced by coordination of the pyridine ring to
a metal. We suggest that the amino group in the
coordinated 4-(ethylamino)pyridine does not have enough
nucleophilicity to overcome steric hindrance, and the
reaction stops predominantly at the monoalkylation
stage. Consequently, only the monoethylated 4-ami-
nopyridine is obtained even with a RuCl2(PPh3)3 catalyst.
When 2-(ethylamino)pyridine (1) was reacted with a
large excess of ethanol at 180 °C for 5 h in the presence
of RuCl2(PPh3)3 or Ru(cod)(cot) as a catalyst, 2-(diethyl-
amino)pyridine (2) was formed in 37% and 6% yield,
respectively (eq 2). Apparently, the present reactions
proceed stepwise.
F igu r e 2. Effects of reaction time on RuCl2(PPh3)3-catalyzed
N-ethylation of 2-aminopyridine with ethanol. Conversion of
2-aminopyridine (0), yield of 1 (O), and yield of 2 (4).
2-Aminopyridine (4.0 mmol), ethanol (5.0 mL), and RuCl2-
(PPh3)3 (0.20 mmol) at 180 °C.
On the basis of the mechanism proposed for the
ruthenium-catalyzed N-alkylation of aminoarenes,10 the
N-alkylation of 2-aminopyridine can be explained as
follows (Scheme 1). 2-Aminopyridine coordinates to the
active ruthenium species 17 to generate 18. In the case
of 3- or 4-aminopyridine, a nitrogen atom of another
pyridine ligand coordinates to the ruthenium to give 18′.
the reaction with RuCl2(PPh3)3 catalyst, 2 was isolated
as a sole product (yield 70%) in 20 h.
These results show that the Ru(cod)(cot)-catalyzed
N-alkylation of the resulting secondary amine proceeds
more slowly than the corresponding RuCl2(PPh3)3-
catalyzed reaction.
Mech a n ism of th e N-Alk yla tion of 2-Am in op yr i-
d in e a n d th e Effects of th e Ad d ition of P h osp h in es.
2-Aminopyridine coordinates to a ruthenium complex to
form a chelated complex.18,19 With 3- and 4-aminopyri-
dine, the nitrogen atom on the pyridine ring coordinates
to ruthenium.20 The nucleophilicity of the amino group
of 3-aminopyridine does not decrease for meta substitu-
tion. In the case of the 4-aminopyridine, the nucleophi-
licity of the exocyclic nitrogen is weakened because the
delocalization of the lone-pair electrons on the aromatic
The alcohol oxidatively adds to 18 to give alkoxide
intermediate 19, and subsequent â-hydrogen elimination
gives an aldehyde-coordinated complex 20. A similar
oxidation pathway has been proposed by several
authors.21-26 The nucleophilic attack of the coordinated
(18) Rosete, R. O.; Cole-Hamilton, D. J .; Wilkinson, G. J . Chem. Soc.,
Dalton Trans. 1979, 1618.
(19) Alteparmakian, V.; Mura, P.; Olby, B. G.; Robinson, S. D. Inorg.
Chim. Acta 1985, 104, L5.
(20) Sutton, J . E.; Taube, H. Inorg. Chem. 1981, 20, 4021.
(21) Sasson, Y.; Blum, J . J . Chem. Soc., Chem. Commun. 1974, 309.
(22) Sasson, Y.; Rempel, G. L. Tetrahedron Lett. 1974, 3221.

Ru-Catalyzed Alkylation of Amines with Alcohols
J . Org. Chem., Vol. 61, No. 13, 1996 4217
Sch em e 1
Ta ble 5. Effects of P h osp h in e Liga n d s on
Ru (cod )(cot)-Ca ta lyzed N-Eth yla tion of 2-Am in op yr id in e
w ith Eth a n ola
amine to the carbonyl carbon of the coordinated aldehyde
takes place to give a Schiff base complex 21. We
previously reported that this is the rate-determining step
for the N-alkylation of aminoarenes.10 Thus, path A
produces the corresponding N-monoalkylated 2-amino-
pyridine and regenerates the active catalyst species 17.
N,N-Dialkylation can be similarly illustrated in path B.
In path B, the catalytic cycle proceeds via an iminium
intermediate 22 to give the N,N-(dialkylamino)pyridine.
The present results suggest that in RuCl2(PPh3)3-
catalyzed N-alkylation, the nucleophilic attack of N-
monoalkylated heteroaromatic amines to the coordinated
aldehyde on the ruthenium takes place with relative ease,
while in Ru(cod)(cot)-catalyzed N-alkylation, this nucleo-
philic attack is hindered. Both steric and electronic
effects should be considered. To investigate these effects,
2-aminopyridine was treated with ethanol in the presence
of a catalytic amount of Ru(cod)(cot) with various phos-
phines (P/Ru ) 2). The results are summarized in Table
5. In the presence of phosphines, the yield of 2-(diethyl-
amino)pyridine (2) increased (runs 1-10). With the
addition of PPh2Cl, 2 was formed in 71% yield with high
selectivity (run 9). However, the nature of the active
ligand is not entirely clear because PPh2Cl reacts with
ethanol and aromatic amines to give PPh2(OEt) or PPh2-
NHAr and a chloride ion.
yieldb (%)
run
phosphine ligand
convb (%)
1
2
1
2
3
4
5
6
7
8
9
PCy3
P(i-Pr)3
PBu3
100
100
100
99
82
64
84
79
77
59
43
71
7
15
35
11
9
P(o-tolyl)3
PPh2Et
PPh3
P(p-C6H4F)3
P(OBu)3
PPh2Cl
P(OPh)3
none
96
8
100
100
98
100
100
93
34
47
24
71
49
1
10
11
36
85
a
2-Aminopyridine (4.0 mmol), ethanol (5.0 mL), Ru(cod)(cot)
(0.20 mmol), and phosphine (0.40 mmol) at 180 °C for 5 h under
b
an argon atmosphere. Determined by GLC. c Cy ) cyclohexyl.
the Ru(cod)(cot) catalyst. In conclusion, N-monoalkyla-
tion and N,N-dialkylation of aminopyridines can be
controlled by the catalysts RuCl2(PPh3)3 and Ru(cod)(cot).
Exp er im en ta l Section
Ma ter ia ls. Ru3(CO)12 and RuCl3‚nH2O were purchased
from Strem Chemicals and Wako Pure Chemical Industries,
respectively, and used without further purification. Ru(cod)-
(cot),27 RuCl2(PPh3)3,28 RuH2(CO)(PPh3)3,29 RuHCl(CO)(P-
The effect of the addition of phosphine ligands is not
yet clear. A quantitative comparison of the ligand effects
of amines and phosphines is required to explain these
results. Our results indicate that N,N-disubstituted
compounds are obtained by the addition of phosphine to
31
Ph3)3,30 and [Cp*RuCl2]2 were prepared as described in the
(27) Pertici, P.; Vitulli, G.; Paci, M.; Porri, L. J . Chem. Soc., Dalton
Trans. 1980, 1961.
(28) Hallmann, P. S.; Stephenson, T. A.; Wilkinson, G. Inorg. Synth.
1970, 12, 237.
(29) Parshall, G. W. Inorg. Synth. 1974, 15, 48.
(30) Ahmad, N.; Levison, J . J .; Robinson S. D.; Uttley, M. F. Inorg.
Synth. 1974, 15, 48.
(23) Chatt, J .; Shaw, B. L.; Field, A. E. J . Chem. Soc. 1964, 3466.
(24) Speier, G.; Marko, L. J . Organomet. Chem. 1981, 210, 253.
(25) Kaesz, H. D.; Saillant, R. B. Chem. Rev. 1972, 72, 231.
(26) Candlin, J . P.; Taylor, K. A.; Thompson, D. T. Reaction of
Transition Metal Complexes; Elsevier: Amsterdam, 1968; pp 299-301.
(31) Ohshima, N.; Suzuki, H.; Moro-oka, Y. Chem. Lett. 1984, 1161.

4218 J . Org. Chem., Vol. 61, No. 13, 1996
Watanabe et al.
literature. 2-, 3-, and 4-Aminopyridine were purchased from
Wako Pure Chemical Industries and recrystallized from
CHCl3/petroleum ether, benzene, and benzene/ethanol, respec-
tively. 2-Aminopyrimidine was purchased from Nacalai Tesque
and used after recrystallization from ethanol.
3-(Dieth yla m in o)p yr id in e (4). 1H NMR (400 MHz) δ 1.16
(t, J ) 7.2 Hz, 6 H), 3.34 (q, J ) 6.8 Hz, 4 H), 6.92 (m, 1 H),
7.06 (m, 1 H), 7.88 (d, J ) 4.4 Hz, 1 H), 8.09 (d, J ) 5.6 Hz, 1
H); 13C{1H} NMR (100 MHz) δ 12.2, 43.9, 118, 123, 134, 136,
143. MS m/z 150 (M+).
4-(Eth yla m in o)p yr id in e (5). 1H NMR (400 MHz) δ 1.25
(t, J ) 7.2 Hz, 3 H), 3.17 (q, J ) 5.2 Hz, 2 H), 4.28 (br s, 1 H),
6.44 (m, 2 H), 8.17 (m, 2H); 13C{1H} NMR (100 MHz) δ 14.3,
37.1, 107, 109, 150. MS m/z 122 (M+).
Gen er a l P r oced u r es. A mixture of 2-aminopyridine (4.0
mmol), RuCl2(PPh3)3 (0.20 mmol), and ethanol (5.0 mL) was
placed in a 50 mL stainless steel autoclave equipped with a
glass liner and a magnetic stirring bar. The mixture was
magnetically stirred at 180 °C for 5 h under an argon
atmosphere. Products were isolated by Kugelrohr distillation.
An a lytica l P r oced u r es. The products were identified by
1H-NMR, 13C-NMR, IR, GC-MS, and elemental analysis. The
yields of the products were determined by GLC. 2-(Ethylami-
no)pyridine (1),32 2-(diethylamino)pyridine (2),33 3-(ethylami-
no)pyridine (3),34 3-(diethylamino)pyridine (4),35 4-(ethylamino)-
pyridine (5),36 2-(ethylamino)pyrimidine (6),37 2-(diethylamino)-
pyrimidine (7),38 2-(propylamino)pyridine (11),39 2-(dipropyl-
amino)pyridine (12),40 2-(butylamino)pyridine (13),41 and 2-(di-
butylamino)pyridine (14),42 are known compounds. 1H- and
13C-NMR data for 1-15 and an elemental analysis for 15 are
cited below.
2-(Eth yla m in o)p yr id in e (1). 1H NMR (400 MHz) δ 1.20
(t, J ) 7.2 Hz, 3 H), 3.20 (q, J ) 6.8 Hz, 2 H), 5.32 (br s, 1 H),
6.33 (d, J ) 8.4 Hz, 1 H), 6.50 (t, J ) 8.8 Hz, 1 H), 7.38 (t, J
) 1.6 Hz, 1 H), 7.93 (d, J ) 5.2 Hz, 1 H); 13C{1H} NMR (100
MHz) δ 14.7, 36.8, 106, 113, 137, 148, 159. MS m/z 122 (M+).
2-(Dieth yla m in o)p yr id in e (2). 1H NMR (400 MHz) δ 1.16
(t, J ) 4.0 Hz, 6 H), 3.50 (q, J ) 7.2 Hz, 4 H), 6.45 (m, 2 H),
7.38 (m, 1 H), 8.14 (d, J ) 4.8 Hz); 13C{1H} NMR (100 MHz)
δ 12.8, 42.3, 105, 110, 137, 148, 157. MS m/z 150 (M+).
3-(Eth yla m in o)p yr id in e (3). 1H NMR (400 MHz) δ 1.24
(t, J ) 8.4 Hz, 3 H), 3.15 (q, J ) 7.2 Hz, 2 H), 3.83 (br s, 1 H),
6.84 (d, J ) 8.0 Hz, 1 H), 7.06 (m, 1 H), 7.93 (d, J ) 4.8 Hz, 1
H), 8.01 (d, J ) 4.8 Hz, 1 H); 13C{1H} NMR (100 MHz) δ 14.5,
37.9, 118, 124, 136, 138, 144. MS m/z 122 (M+).
2-(Eth yla m in o)p yr im id in e (6). 1H NMR (400 MHz) δ
1.39 (t, J ) 7.2 Hz, 3 H), 3.60 (m, 2 H), 5.18 (br s, 1 H), 6.51
(t, J ) 4.8 Hz, 1 H), 8.42 (d, J ) 4.8 Hz, 2 H); 13C{1H} NMR
(100 MHz) δ 14.9, 36.2, 110, 158, 162. MS m/z 123 (M+).
2-(Dieth yla m in o)p yr im id in e (7). 1H NMR (400 MHz) δ
1.19 (t, J ) 7.2 Hz, 6 H), 3.61 (q, J ) 6.8 Hz, 4 H), 6.40 (t, J
) 4.8 Hz, 1 H), 8.28 (d, J ) 4.4 Hz, 2 H); 13C{1H} NMR (100
MHz) δ 13.0, 41.8, 109, 158, 161. MS m/z 151 (M+).
2-(P r op yla m in o)p yr id in e (11). 1H NMR (400 MHz) δ
0.995 (t, J ) 7.2 Hz, 3 H), 1.64 (m, 2 H), 3.21 (q, J ) 6.0 Hz,
2 H), 4.60 (br s, 1 H), 6.37 (d, J ) 8.4 Hz, 1 H), 6.54 (m, 1 H),
7.41 (m, 1 H), 8.07 (d, J ) 4.8 Hz, 1 H); 13C{1H} NMR (100
MHz) δ 11.4, 22.6, 44.0, 106, 112, 137, 148, 159. MS m/z 136
(M+).
2-(Dip r op yla m in o)p yr id in e (12). 1H NMR (400 MHz) δ
0.850 (t, J ) 7.6 Hz, 6 H), 1.54 (m, 4 H), 3.32 (t, J ) 8.0 Hz,
4 H), 6.36 (m, 2 H), 7.29 (m, 1 H), 8.04 (d, J ) 5.2 Hz, 1 H);
13C{1H} NMR (100 MHz) δ 12.0, 21.3, 51.0, 106, 111, 137, 149,
159. MS m/z 178 (M+).
2-(Bu tyla m in o)p yr id in e (13). 1H NMR (400 MHz) δ 0.953
(t, J ) 7.6 Hz, 3 H), 1.42 (m, 2 H), 1.61 (m, 2 H), 3.24 (q, J )
6.4 Hz, 2 H), 4.55 (br s, 1 H), 6.36 (d, J ) 8.0 Hz, 1 H), 6.54
(m, 1 H), 7.4 (t, J ) 7.2 Hz, 1 H), 8.07 (d, J ) 4.8 Hz, 1 H);
13C{1H} NMR (100 MHz) δ 13.8, 20.2, 31.6, 42.0, 106, 113, 137,
148, 159. MS m/z 150 (M+).
2-(Dibu tyla m in o)p yr id in e (14). 1H NMR (400 MHz) δ
0.926 (t, J ) 7.2 Hz, 6 H), 1.33 (m, 4 H), 1.55 (m, 4 H), 3.40 (t,
J ) 7.6 Hz, 4 H), 6.42 (m, 2 H), 7.34 (m, 1 H), 8.10 (d, J ) 2.8
Hz, 1 H); 13C{1H} NMR (100 MHz) δ 14.0, 20.3, 29.8, 48.3,
105, 111, 137, 148, 158. MS m/z 202 (M+).
2-(Hexyla m in o)p yr id in e (15). Pale yellow oil: bp 130-
135 °C (2 mmHg, Kugelrohr); IR (neat) 3422 (N-H) cm-1; 1H
NMR (400 MHz) δ 0.892 (t, J ) 7.2 Hz, 3 H), 1.31 (m, 4 H),
1.40 (m, 2 H), 1.62 (m, 2 H), 3.23 (q, J ) 5.2 Hz, 2 H), 4.51 (br
s, 1 H), 6.36 (d, J ) 8.4 Hz, 1 H), 6.54 (m, 1 H), 7.41 (m, 1 H),
8.06 (d, J ) 4.0 Hz, 1 H); 13C{1H} NMR (100 MHz) 14.0, 22.6,
26.7, 29.5, 31.6, 42.3, 106, 113, 138, 148, 159. MS m/z 178
(M+). Anal. Calcd for C11H18N2: C, 74.11; H, 10.18; N, 15.71.
Found: C, 73.83; H, 10.34; N, 15.62.
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