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Organic & Biomolecular Chemistry
the model reaction which was conducted in 1,2-dichloroethane and Er realized conversions of 28.2%, 25.7%, 30.2%, 36.3%
(DCE) at 90 °C for 5 h in the presence of 5 mol% urea (based and 25.2%, respectively, with EHN as a single product (entries
on HNO3) (Table 1). In contrast to the catalytic nitration of 10–15). Nevertheless, Ce(OTf)3 was an exception that afforded
2-ethylhexanol, M(OTf)n-free reactions were conducted (entries a confused distribution of products, just like Cu(OTf)2 and Fe
1 and 2, Table 1). The reaction results showed that in the (OTf)3. It was notable that Eu(OTf)3-catalyzed nitration could
absence of urea it took place in a disorderly manner to afford also become disorderly in the absence of urea (entry 16).
a product mixture of EHN, isooctanal (IOA), 2-ethylhexanoic Prolonging the reaction time increased the conversions. Eu
acid (EHA) and 2-ethylhexyl 2-ethylhexanoate (EHEH), (OTf)3 achieved a higher conversion (56.3%) than the triflates
meaning that the nitration, oxidations and esterization of Sm, alkaline earth metal Ca and Group VA metal Bi (entries
occurred together and that the oxidations were the main reac- 16–19) in the course of 10 h.
tions. When urea was employed as the stabilizer of HNO3, the
To further optimize the reaction conditions, we evaluated
nitration afforded a single product EHN, and the oxidations the solvent, the loading amounts of both Eu(OTf)3 and urea,
could be avoided completely. Therefore, further tests were con- temperature, and reaction time (Table 2). As can be seen, the
ducted to screen M(OTf)n with 5 mol% urea. As can be seen, in nitration worked more preferably in nonpolar solvents than in
comparison with the poor performance of the alkali metal Na, low-polarity solvents. The conversions achieved in cyclohexane,
the triflates of the alkaline earth metals Mg, Ca, and Ba dis- n-heptane and isooctane were higher than those achieved in
played comparative catalytic activities (entries 3–6). Bi(OTf)3 DCE and dichloromethane (entries 1–5, Table 2). In polar
realized 21.2% conversion (entry 7), which was lower than the acetonitrile and ethyl acetate, the conversions reached 88.3%
efficiencies of aryl C-nitrations.10 As always, transition metals and 86.3%, but the selectivity of EHN decreased to 65.1% and
worked well, and Cu and Fe helped achieve conversions as 1.4%, respectively (entries 6 and 7, Table 2). GC-MS detected
high as 68.1% and 47.0%, respectively. However, so many sorts that EHEH became the main product, showing that oxidation,
of by-products were formed that poor selectivities of EHN were hydrolysis and esterification took place together with Lewis
achieved (entries 8 and 9). In contrast, lanthanide(III) triflates acid Eu(OTf)3. In the cyclic polar solvents dioxane and tetra-
displayed better catalytic performances, and La, Pr, Sm, Eu, hydrofuran, the reactions occurred in a disorderly manner,
where ring decompositions were observed (entries 8 and 9,
Table 2). So, cyclohexane was chosen as the solvent in the
further optimal tests. It was not unexpected to find that the
more loading amounts of Eu(OTf)3 resulted in faster rates of
Table 1 Screening of metal triflates by 2-ethylhexanol nitrationa
nitrations (entries 10–13, Table 2). In the course of 10 h,
10 mol% Eu(OTf)3 realized 88.2% conversion. Prolonging the
time to 15 h increased the conversion to 91.0% (entry 14,
Table 2). Increasing the temperature increased the reaction
rate, and 95 °C seemed to be the preferable temperature for
the nitration of 2-ethylhexanol to EHN (entries 15–18, Table 2).
Select. b (%)
Temperatures of 100 °C and above could result in the oxidation
of HNO3. The loading amount of the stabilizer urea showed an
obvious influence on the nitration. More urea would slow
down the reaction, and less urea would lead to the occurrence
of side reactions (entries 19–21, Table 2). The preferable
amount was 3 mol% (based on HNO3), which provided a
98.5% yield of EHN.
For nitration, the complete consumption of HNO3 will lead
to a simple separation of products and avoid the generation of
acidic waste. Table 3 presents the results of the nitration of
2-ethylhexanol with different amounts of HNO3. As can be
seen, the more the HNO3 used, the faster the reaction (entries
1–5, Table 3). Employing 0.95 equivalents of HNO3 as the
nitrating reagent was intended to investigate whether HNO3
could be consumed completely. The method was surveying the
pH value of the reaction mixture. When the pH increased to 2,
HNO3 was deemed to be nearly exhausted. When the nitration
with 0.95 equivalents of HNO3 proceeded for 12 h, the conver-
sion reached 92.1% and the pH less than 1 (entry 6). This
meant that at the later stage of nitration the rate slowed down.
The presumable causes could be that the residual HNO3
became so little that the nitration hardly ever took place. The
Entry
M(OTf)n
Conv. b (%)
EHN
EHA
IOA
EHEH
1c
—
—
86.6
4.9
9.0
9.3
>99
>99
>99
>99
>99
>99
35.9
11.3
>99
13.2
>99
>99
>99
>99
6.5
41.3
0
0
0
0
0
0
6.0
47.5
0
13.0
0
0
0
0
27.3
0
0
0
0
38.6
0
0
0
0
0
0
50.9
10.1
0
66.4
0
0
0
0
54.7
0
0
0
0
5.4
0
0
0
0
0
0
7.2
31.0
0
7.4
0
0
0
0
4.8
0
0
0
0
2d
3
Na
Mg
Ca
Ba
Bi
Cu
Fe
La
Ce
Pr
Sm
Eu
Er
4
5
6
7
8
9
10
11
12
13
14
15
16e
17f
18f
19f
20f
18.6
23.7
22.9
21.2
68.1
47.0
28.2
64.7
25.7
30.2
36.3
25.2
94.4
56.3
47.2
36.4
31.6
Eu
Eu
Sm
Ca
Bi
>99
>99
>99
>99
a Reaction conditions: 2-ethylhexanol (2.5 mmol), M(OTf)n (5 mol%
based on 2-ethylhexanol), HNO3 (1.4 equiv.), urea (5 mol%, based on
HNO3 loading), 2 mL of DCE, 90 °C, and 5 h. b GC yields. c M(OTf)n
and urea free. d M(OTf)n free. e Urea free. f For 10 h.
Org. Biomol. Chem.
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