Alkylation of the 2-hydroxypyridine anion in ionic liquid media

Article abstract of DOI:10.1007/s10593-008-0074-9

The alkylation reaction of the ambident 2-hydroxypyridine anion was examined in ionic liquid media. Ionic liquids increase the alkylation reaction rate in comparison with molecular liquids, as well as the level of impact on the reaction rates of the count

Full text of DOI:10.1007/s10593-008-0074-9

Chemistry of Heterocyclic Compounds, Vol. 44, No. 5, 2008
ALKYLATION OF THE 2-HYDROXYPYRIDINE
ANION IN IONIC LIQUID MEDIA
G. Vavilina, A. Zicmanis, P. Mekss, M. Klavins
The alkylation reaction of the ambident 2-hydroxypyridine anion was examined in ionic liquid media.
Ionic liquids increase the alkylation reaction rate in comparison with molecular liquids, as well as the
level of impact on the reaction rates of the counter ion and/or additives, and the distribution of isomers
of the reaction products in trans- formations of the ambident 2-hydroxypyridine anion.
Keywords: ambident anion, 2-hydroxypyridine, ionic liquids, alkylation.
Ionic liquids (ILs) have become an increasingly popular medium for transformations of organic
compounds during the last decade and replace step-by-step molecular liquids – conventional organic solvents
[1-17]. Among the numerous organic reactions performed in ionic liquids little attention is paid to
transformations of ambident ions in ILs. A few published communications [18-26] signalize the increase in the
reaction rates in ILs but do not allow us to foresee at present whether the selectivity of the reactions of ambident
anions would change in the media of ILs as compared with that in molecular liquids.
In the course of the systematic investigation of ambident ions concerning their benefits in media of ILs
[23-26], regularities of the alkylation reaction of the ambident 2-hydroxypyridine anion 2 are discussed in the
present communication considering different alkylation reagents 3 and various ILs 6, 7.
Scheme 1
MY
_
_
ionic liquid
N
O
N
OH
R
N
O
M+
M+
2B
2A
1
X
3a–c
2
+
ionic liquid
N
R
O
N
5a–c
OR
4a–c
2–
M = K, Na, Li, Ag; Y= H, Bu, OH, OMe, CO3
;
3 a1 X = Cl, a2 X = Br, a3 X = I, a4 X = Ts; 3– 5 a R= n-Bu, b R = PhCH2, c R = CH2=CHCH2
__________________________________________________________________________________________
Faculty of Chemistry, University of Latvia, Riga LV-1586, Latvia; e-mail: zicmanis@latnet.lv.
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 699-710, May, 2008. Original article
submitted December 10, 2007.
0009-3122/08/4405-0549©2008 Springer Science+Business Media, Inc.
549

2-Hydroxypyridine anion 2 forms two isomeric products in its reactions with electrophilic reagents –
N-substituted (4) and O-substituted (5) derivatives [27-30]. Particularities of the chosen solvent, the impact of the
cation connected with the substrate anion, and other factors influencing the transformation rates, as well as the
regioselectivity of reactions in these alkylation reactions performed in non-conventional solvents, ILs, are discussed.
In order to assess the rate and regioselectivity of the alkylation of 2-hydroxypyridine anion in ILs, the
following imidazolium 6a–c and pyridinium 7a,b salts with alkyl groups of various length were used.
+
N
+
N
N
R1
Me
–
Y
–
Br
6a–c
R
7a,b
6 a R1 = Me, Y = Ts; b R1 = Bu, Y = Br; c R1 = Bu, Y = Ts;
7 a R = C7H15, b R = n-Bu
We have alkylated 2-hydroxypyridine salts by n-butyl halides, 3-chloro-1-propene (allyl chloride), and
benzyl chloride. The reaction pathway was followed by gas chromatography (GC). Joint gas chromatography –
1
mass spectrometry (GC/MS), together with the characterization of isolated individual compounds by H NMR
spectra and the data of elemental analyses, have served to prove the structures of the alkylation products
obtained.
Substance, %
a
time, h
Substance, %
b
time, h
Fig. 1. Alkylation of 2-hydroxypyridine potassium salt with 1-iodobutane in (7a) at:
a − 25°C; b − 80°C: 1 – 1-iodobutane; 2 – 1-butyl-2-pyridone; 3 – 2-butoxypyridine.
550

1-Iodobutane, %
time, h
Fig. 2. Alkylation of 2-hydroxypyridine potassium salt with 1-iodobutane at 65°C in:
1 – N,N-dimethylformamide; 2 – tetrahydrofuran; 3 – 7a.
Alkylation of 2-hydroxypyridine potassium salt in IL media proceeds rapidly (Fig. 1a, b). A good
conversion degree (73%) is reached in the medium of 1-heptylpyridinium bromide (7a) at 80°C for 0.5 h, a
conversion of 80% being obtained during 5 h at room temperature. 1-Butyl-2-pyridone (4a) and
2-butoxypyridine (5a) were formed in both cases; the yield and reaction rate increased with temperature
(Fig. 1a, b)
ILs as a solvent cause the augmentation of the reaction rates in these transformations in comparison with
molecular liquids. The results of such a comparison are presented in Fig. 2, where the reaction rate in the IL 7a
is compared with the rates in solvents most frequently used for similar alkylation reactions – N,N-dimethyl-
formamide and tetrahydrofuran. These results look very promising for ILs.
Alkali metal salts (K, Na, Li) of 2-hydroxypyridine enter the alkylation reactions mainly at the nitrogen
atom, resulting in the formation of 1-alkyl-2-pyridones (4), the alkylation rates of Li salts being considerably
lower than those of sodium or potassium salts. The alkylation reaction of the silver salt results in the formation
of a larger fraction of 2-alkoxypyridines (5) – the product of O-alkylation. All the reaction mixtures of the
mentioned silver salts are heterogeneous at the beginning, and they turn homogeneous during the reaction course
(~ 15 min). Four different ILs were examined in order to obtain some information on the impact of the structure
of ILs themselves on the pathway of the alkylation reactions (Table 1).
The data presented above (Table 1) confirm that IL solvents affect both the alkylation reaction rates
(conversion) of 2-hydroxypyridine anion and the distribution of isomers in the product mixture.
The type of substrate cation in IL media, the alkyl group and leaving group of the alkylating reagent,
and the type of cation and anion of the used IL itself all affect the substrate conversion rate. The last decreases in
the row of substrate cations K > Na > Li (Table 1, entries 1–3, 5–7, 9–11, 15–17, 19–21, 23–25, 27–29, 35–37,
39–41, 45–47, 49–51, 57–59, 61–63). Hence, a weaker electrostatic interaction between a cation and anion in
the substrate molecule facilitates alkylation of the ambident anion – the harder lithium cation hinders the
alkylation rate more than the softer potassium cation. The silver cation does not fall within the mentioned row
because the specific interaction between it and the alkylating reagent (alkyl halide or tosylate) becomes
predominant. Its impact on the substrate conversion becomes especially favorable in the case of butyl iodide or
butyl tosylate (Table 1, entries 26, 34, 48, 56). It was noticed that the alkylation of the 2-hydroxypyridine silver
salt proceeds only slightly, if at all, in ionic liquids having tosylate or other sulfonate anion (Table 1, entries 4,
8, 12, 18, 44).
551

The type of the alkyl group and the leaving group influence the reagent conversion rate. Reagents with
benzyl or allyl groups have higher conversion than those with saturated alkyl groups without any possible
conjugation, as it is shown by comparison of the conversion of benzyl, allyl, and butyl chlorides (Table 1,
entries 15-17 and 19-21 vs 9-11; entries 35-37 and 39-41 vs 31; entries 57-59 and 61-63 vs 53). This
phenomenon can be seen even better if registered in time (Fig. 3).
TABLE 1. Ratio of Isomers in the Alkylation Reactions of 2-Hydroxypyri-
dine Salts 2 in Different Ionic Liquids
Compound in the product
mixture after alkylation, %*
Conversion
of the
substrate 3, %*
Reaction conditions
Entry
1
M
IL
2
Reagent 3
4
5
in the salt 2
3
4
5
6
7
1
6a
BuI
K
Na
Li
62.8
38.1
5.7
85.9
87.9
80.2
6.0
14.1
12.1
19.8
94.0
9.4
2
3
4
Ag
K
Na
Li
6.5
5
6
BuBr
BuCl
42.1
23.1
1.6
90.6
94.4
100.0
0.0
92.4
88.8
100.0
0.0
5.6
7
0.0
8
9
Ag
K
0.0
11.4
9.4
0.0
7.6
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
Na
Li
Ag
K
11.2
0.0
0.0
1.4
0.0
BuOTs
92.9
18.1
25.8
19.0
8.1
83.1
10.3
59.4
53.8
70.3
0.0
16.9
89.7
40.6
46.2
29.7
100.0
2.7
Ag
K
PhCH2Cl
Na
Li
Ag
K
5.0
CH2=CHCH2Cl
90.8
81.1
2.1
97.3
96.5
100.0
0.0
Na
Li
3.5
0.0
Ag
K
23.4
28.4
33.2
0.5
100.0
16.5
10.4
100.0
80.5
29.5
22.4
100.0
84.4
16.5
0.0
6b
BuI
83.5
89.6
0.0
Na
Li
Ag
K
20.6
63.3
25.3
0.3
19.5
70.5
77.6
0.0
BuBr
Na
Li
Ag
K
45.1
22.9
0.0
15.6
83.5
0.0
BuCl
Ag
K
BuOTs
PhCH2Cl
84.2
43.8
70.7
28.2
4.3
79.8
20.6
90.8
88.8
73.5
14.5
95.2
94.3
0.0
20.2
79.4
9.2
Ag
K
Na
Li
11.2
26.5
85.5
4.8
Ag
K
47.2
89.2
76.7
14.0
65.7
48.1
1.1
CH2=CHCH2Cl
BuBr
Na
Li
5.7
100.0
76.3
12.6
100.0
Ag
K
23.7
87.4
0.0
6c
Ag
552

TABLE 1. (continued)
1
2
3
4
5
6
7
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
7a
BuI
K
Na
Li
82.5
54.6
0.6
91.0
76.5
100.0
20.9
80.1
57.6
100.0
48.0
88.3
87.4
81.3
11.1
94.0
92.3
24.3
68.9
96.4
92.5
51.8
51.0
9.0
23.5
0.0
Ag
K
96.4
17.1
7.6
79.1
19.9
42.4
0.0
BuBr
Na
Li
6.5
Ag
K
34.7
6.4
52.0
11.7
12.6
18.7
88.9
6.0
BuCl
Ag
K
0.8
BuOTs
PhCH2Cl
47.0
60.1
87.3
81.4
4.7
Ag
K
Na
Li
7.7
75.7
31.1
3.6
Ag
K
92.0
85.1
76.3
15.1
96.0
CH2=CHCH2Cl
Na
Li
7.5
48.2
49.0
Ag
_______
* After stirring at 25°C for 5 h, and determined by GC, with accuracy ±5%.
Alkylhalide, %
time, h
Fig. 3. Alkylation of 2-hydroxypyridine silver salt with different alkylating reagents
(in 7a at 25°C): 1 – 1-chlorobutane; 2 – 1-bromobutane; 3 – 1-iodobutane;
4 – benzyl chloride; 5 – allyl chloride.
The observation alludes that the ionization of the C–X bond following SN1 substitution is more favorable
than the bimolecular (SN2) pathway in IL media. The auspicious influence of the leaving group corresponds to the
row Bu–I > > Bu–Br > Bu–Cl in every separate IL, albeit the conversion values hardly differ between various
ILs. This fact drives one to the assumption that sufficiently strong hydrogen bonds might exist between ILs and
reagent molecules in the investigated reactions similar to those existing in protic solvents.
553

The possibility of IL to form hydrogen bonds is discussed in the literature and has been experimentally proved,
at least between the C(2)–H bond and a substrate molecule in solutions of 1,3-dialkyl imidazolium salts. The
contributory influence of the silver ion on the ionization of the R–X bond can be observed only with butyl
iodide and butyl bromide, provided that the ILs used do not contain a sulfonate anion. In the latter case, the
conversion of the silver salt takes place only slightly, if at all (Table 1, entries 4, 8, 26, 30, 44, 48, 52). The
tosylate anion seems to be a better leaving group than the bromide anion in the reagent molecule Bu–X in some
cases (Table 1, entry 13 vs 5; 33 vs 27; 55 vs 49) and worse in others (Table 1, entry 43 vs 27). Accordingly, in
the examples observed, the influence is less significant by comparison with the dominance of the IL structure.
Regarding the structure of ILs, it should be mentioned that the conversion of the 2-hydroxypyridine
anion is higher in ILs with 1-alkylpyridinium cation than with the 1,3-dialkylimidazolium cation (for example,
Table 1, entry 45 vs 1 and 23 or 57 vs 15 and 35). The difference can be seen more convincingly when the
comparison is made in time (Fig. 4).
The difference observed might be caused hydrogen bonding between the C(2)–H bond of imidazolium
cycle and the ambident anion, as mentioned above, which could decrease the reactivity of the latter. To prove
this hypothesis, further experiments are in progress in our laboratory using ILs with a substituted C(2) atom. The
impact of the IL anion manifests itself in the disturbing influence of the sulfonate anion on the conversion of the
silver salt as well as in higher conversion rates in the medium of 1,3-dialkyl- imidazolium tosylate by
comparison with the same in 1,3-dialkylimidazolium bromide (Table 1, entries 1–22 vs 23–42), the tosylate
anion influence being more favorable.
The distribution of isomers in the mixture of reaction products in ILs markedly favors the N-alkylation
direction. Always more N-alkylpyridones (4) than the products of O-alkylation – 2-alkoxypyridines (5) – were
formed in IL media than in molecular solvents. The formation of O-alkylated products (5) in the examined ILs is
substantially promoted by the silver ion and slightly promoted by the lithium ion in the substrate molecule.
Benzyl and allyl groups in the reagent molecule are also advantageous for O-alkylation in comparison with the
butyl group; the iodide anion as a leaving group is much more favorable than the bromide, chloride, or tosylate
anion. As to the structure of the ILs, more O-alkylation product forms in ILs with the 1-alkylpyridinium cation
than with the 1,3-dialkylimidazolium one. It was difficult to find any effect of the IL anion on the ratio of
isomers in the product mixture.
1-Bromobutane, %
time, h
Fig. 4. Alkylation of 2-hydroxypyridine potassium salt with 1-bromobutane in different
ionic liquids (at 25°C) in: 1 – 7a; 2 – 6a; 3 – 6c; 4 – 6b.
554

ILs are quaternary ammonium salts and therefore they might also serve as alkylating reagents in the
reactions investigated, as formerly noticed in the alkylation reactions of indole or nitrite anions [24–26]. Such a
parasitic reaction takes place slowly at room temperature, the N-alkylation product being the dominant one. The
latter is also the major product in the alkylation reaction at elevated temperature (65°C), and the fraction of the
O-alkylation product diminishes sharply in this case (Table 2). Fortunately, the fraction of the alkylation
products created by ILs themselves is quite small in the general mixture of products and does not exceed 3%.
Scheme 2
6b, 7a,b
+
–
N
O
N
OR
N
R
O
K+
5a,d
4a,d
6b, 7a, b – ionic liquids; 4, 5 a R = n-Bu; d R = C7H15
As quaternary ammonium salts, ILs quite are frequently highly hygroscopic materials. We have
performed special experiments to clarify the influence of the presence of protic solvents in ILs on the course of
the alkylation reactions investigated. Small amounts of water or methanol were purposely added to the
alkylation reaction mixture. The presence of water decreased the conversion rate, and its influence increased
with rising concentration of water in the reaction mixture. One can presume that water might induce the
hydrolysis of the 2-hydroxypyridine salt into 2-hydroxypyridine, which cannot enter the alkylation reaction any
more. This appears possible because the molar concentration of water exceeds that of the mentioned salt by
1.5 times. The addition of methanol (weaker acid) does not lead to such a disastrous aftereffect, the conversion
degree remaining practically the same in the presence or absence of methanol. It is worth mentioning that the
presence of protic solvents in the reaction mixture in ILs does not change the ratio of product isomers (Table 3).
One can presume, therefore, that ILs have a dominant role on the regioselectivity of alkylation reactions in the
mixtures with molecular liquids.
The unexpected decreased influence of the substrate cation (M) on the distribution of N- vs O-alky-
lation products in comparison with the situation in molecular liquids (organic solvents) [27–29] could be
explained by the ILs leveling effect. An exchange reaction might take place between the substrate cation (M)
and the bulky hard cation of the IL. As a result, a loose ion pair is formed between the ambident 2-hydroxy-
pyridine anion and the bulky IL cation, and any specific cation−anion interaction between the substrate ions is
diminished or even fully abolished, which explains the IL leveling effect.
TABLE 2. Ratio of alkylation products of the 2-hydroxypyridine
potassium salt by ionic liquids themselves
Content of the substance in the product
mixture, %*
Alkyl group
R in ILs and
in products
Entry
IL
Temp., °C
4
5
1
2
3
4
5
6
6b
6b
7a
7a
7b
7b
Bu
25
80
25
80
25
80
87.4
93.2
89.8
97.8
66.4
98.9
12.6
6.8
Bu
C7H15
C7H15
Bu
10.2
2.2
33.6
1.1
Bu
_______
* Without any other alkylating reagent after 6 h.
555

TABLE 3. Influence of protic solvents on the ratio of alkylation products of
2-hydroxypyridine sodium salt
Compound in the product
Conversion
of iodobutane
3a, %*2
Sodium salt 2
preparation procedure*
Entry
mixture after alkylation, %*2
4a
5a
1
2
3
4
5
6
NaH
54.6
19.9
12.0
92.2
99.7
96.5
76.5
87.7
87.4
90.6
90.6
91.2
23.5
12.3
12.6
9.4
NaH + H2O
NaH + H2O
NaOCH3
NaOCH3 + CH3OH
NaOCH3 + CH3OH
9.4
8.8
_______
* Entry 2 − 0.46; 3 − 1.58, 5 − 0.083, 6 − 0.26 mmol / 1 mmol IL.
*2 In the reaction of 2-hydroxypyridine sodium salt with 1-iodobutane in IL 7a at 25°C.
The mentioned ion exchange causes a decrease in the specific interaction even of the silver cation with
the 2-hydroxypyridine anion, wich makes the well-known effect of the silver ion very much less powerful in ILs
in comparison with molecular liquids such as N,N-dimethylformamide [28, 29].
Scheme 3
+
N
–
M+
X
–
N
–
N
+
+
+
N
–
O
O
X
M+
2B
2C
EXPERIMENTAL
1H NMR spectra were registered on a Varian Mercury BB (200 MHz) instrument in DMSO-d6, internal
standard TMS.
Gas chromatographic (GC) analyses were carried out on a Hewlett Packard 5890 instrument using a
flame ionization detector with a hydrogen flow rate of 30 ml/min, air flow rate of 300 ml/min, and helium flow
rate of 25 ml/min. A DB-5MS (30 m × 0.25 mm) column was used, injection temperature was 250°C, and the
temperature regime of analyses was as follows: starting temperature 50°C (1 min), then 10°C/min up to 250°C,
and final temperature 250°C (for 10 min). GC/MS analyses were performed with a Shimadzu GC 2010 gas
chromatograph connected with Shimadzu QP 2010 mass spectrometer, EI ionization with energy 70 eV,
distribution in splitless injector 1:30, and using automatic injector OAC 20i. The sample volume for all the
analyses was 1 µl.
Ionic liquids 1,3-dimethylimidazolium para-toluenesulfonate (6a), 1-butyl-3-methylimidazolium
bromide (6b), 1-butyl-3-methylimidazolium para-toluenesulfonate (6c), N-heptylpyridinium bromide (7a), and
N-butylpyridinium bromide (7b) were prepared according to the procedures described [30, 31]. Other reagents
were purchased from Aldrich and used without further purification. Solvents were purchased from Aldrich and
also used without further purification. 1-Butyl-2-pyridone (4a), 2-butoxypyridine (5a), 1-benzyl-2-pyridone
(4b), and 2-benzyloxypyridine (5b) were prepared according to [32], and 1-allyl-2-pyridone (4c), and 2-allyl-
oxypyridine (5c) – according to [33, 34].
556

1-Butyl-2-pyridone (4a) and 2-Butoxypyridine (5a). A. Alkylation in ionic liquids. 2-Hydroxy-
pyridine (200 mg, 2.10 mmol), IL 6b (920 mg, 4.20 mmol), and KOH (236 mg, 4.20 mmol) were mixed
together under argon and stirred for 0.5 h at room temperature. 1-Bromobutane (575 mg, 4.20 mmol) was added
to the stirred mixture. Samples (~ 1 mg) were taken from the mixture after definite time intervals (0.25, 0.5, 1, 3,
and 5 h), treated with diluted (1:1) HCl, and extracted with ether (3 × 5 ml). The joint extract was analyzed by
GC, 1-butyl-2-pyridone and 2-butoxypyridine being used as reference materials (Table 1 and Figs. 1, 3, 4).
Other 2-hydroxypyridine derivatives 4, 5 (Table 1 and Figs. 1, 3, 4) were obtained and other experiments
were performed in a similar way. Bases KOH, MeONa, NaH, BuLi, and Ag2CO3 were used for preparation of the
corresponding salts of 2-hyd-roxypyridine. The alkylating reagents 1-chlorobutane, 1-bromobutane, 1-iodobutane,
benzyl chloride, and 3-chloro-1-propene (allyl chloride) were used for 2-hydroxy- pyridine alkylation at room
1
1
temperature (25°C) and at 80°C. Structures of the products were initially confirmed by H NMR analyses. H
NMR analyses for 4a,b, 5a,b correspond to the literature data [32]; for 4c, 5c − to [33, 34]. 1-Heptyl-2-pyridone
(4d) and 2-heptyloxypyridine (5d) were obtained in a way similar to the described one [32]. 1H NMR spectrum,
δ, ppm (J, Hz) for 4d: 7.63 (1H, dd, J = 2.0, J = 6.6, H-4); 7.34 (1H, ddd, J = 1.9, J = 6.6, J = 9.9, H-6); 6.33 (1H,
d, J = 9.9, H-3); 6.16 (1H, td, J = 1.6, J = 6.6, H-5); 3.85 (2H, t, J = 7.5, NCH2); 1.69 (2H, m, NCH2–CH2); 1.19
(8H, s, (CH2)4); 0.82 (3H, t, J = 7.5, CH3); for 5d: 8.15 (1H, ddd, J = 0.9, J = 2.1, J = 5.1, H-6); 7.68 (1H, ddd,
J = 2.1, J = 7.1, J = 8.4, H-4); 6.90 (1H, ddd, J = 1.0, J = 5.1, J = 7.1, H-5); 6.75 (1H, d, J = 8.3, H-3); 4.25 (2H, t,
J = 7.5, OCH2); 1.75 (2H, m, OCH2–CH2); 1.35 (8H, s, (CH2)4); 0.92 (3H, t, J = 7.3, CH3). The experiments
were subsequently followed by GC analyses, the GC/MS being used for further confirmation of signals of
chromatography. Every measurement was repeated 3–5 times.
B. Alkylation in organic solvents. 2-Hydroxypyridine (200 mg, 2.10 mmol) was dissolved in anhydrous
THF (9 ml). The solution was slowly added to a KOH suspension (236 mg) in THF (5 ml) at room temperature.
After that the mixture was stirred at 65°C for 15 min. A solution of butyl iodide (773 mg, 4.20 mmol) in
anhydrous THF (5 ml) was added to the 2-hydroxypyridine potassium salt solution at room temperature, and the
mixture was stirred at 65°C. The samples (~ 1 mg) were taken from the mixture after definite time intervals
(0.25, 0.5, 1, 3, 5 h), treated with aqueous ammonium chloride, and extracted with diethyl ether (3 × 5 ml). Each
joint extract was analyzed by GC.
The reaction was run also in N,N-dimethylformamide solution in a very similar way. All the results
obtained were presented in Fig. 2.
C. Alkylation by ionic liquids themselves. 2-Hydroxypyridine (200 mg, 2.10 mmol), KOH (236 mg,
4.20 mmol), and N-butylpyridinium bromide (7b, 903 mg, 4.20 mmol) were stirred at 25°C for 6 h. Samples
(~ 1 mg) were taken from the mixture and extracted with ether (3 × 5 ml). The joint extract was analyzed by GC,
the 1-butyl-2-pyridone and 2-butoxypyridine being used as reference materials. The results obtained are
compiled in Table 2, entry 5.
The experiments with other ILs at 25 and 80°C and analyses of the results were made in a similar way,
the results being presented in Table 2.
D. Alkylation in ionic liquids in the presence of protic solvents. 2-Hydroxypyridine (200 mg,
2.10 mmol), N-heptylpyridinium bromide (7a, 1.08 g, 4.20 mmol), and NaH (168 mg of 60% dispersion in
mineral oil; 4.20 mmol) were stirred at 25°C for 15 min. Butyl iodide (773 mg, 4.20 mmol) and water (120 mg,
6.65 mmol) were added, and the mixture was stirred at 25°C for 5 h. A sample (~ 1 mg) was taken from the
mixture and extracted with ether (3 × 5 ml). The joint extract was analyzed by GC 1-butyl-2-pyridone and
2-butoxypyridine being used as reference materials. The results obtained are compiled in Table 3, entry 3.
The experiment with a different amount of water (Table 3, entry 2) was made in a similar way. Sodium
ethoxide was used for sodium salt preparation (Table 3, entries 4–6) in three other experiments, and methanol was
added instead of water (Table 3, entries 5, 6) in these experiments, the isolation procedure and GC analyses being
the same as mentioned above.
557

This research project was financially supported by the Latvian Research Council. G. V. would like to
thank the European Social Foundation for her research fellowship.
REFERENCES
1.
D. R. MacFarlane, J. M. Pringle, K. M. Johansson, S. A. Forsyth, and M. Forsyth, Chem. Commun.,
1905 (2006).
2.
3.
4.
5.
6.
7.
J. Dupont, C. S. Consorti, and J. Spencer, J. Brazil. Chem. Soc., 11, 580 (2000).
S. T. Handy, Curr. Org. Chem., 9, 959 (2005).
N. Jain, A. Kumar, S. Chauhan, and S. M. S. Chauhan, Tetrahedron, 61, 1015 (2005).
Z.-B. Zhou, H. Matsumoto, and K. Tatsumi, Chem. Eur. J., 11, 752 (2005).
G. W. Meindersma, A. J. G. Podt, and A. B. De Haan, Fuel Processing Technology, 87, 59 (2005).
C. Baudequin, D. Bregeon, J. Levillain, F. Guillen, J.-C. Plaquevent, and A.-C. Gaumont, Tetrahedron.
Asymmetry, 16, 3921 (2005).
8.
9.
K. N. Marsh, J. A. Boxall, and R. Lichtenthaler, Fluid Phase Equilibria, 219, 93 (2004).
C. F. Poole, J. Chromatogr. A., 1037, 49 (2004).
10.
11.
12.
13.
P. Kubisa, Progr. Polym. Sci., 29, 3 (2004).
C. E. Song, Chem. Commun., 1033 (2004).
P. Wasserscheid and T. Welton, Ionic Liquids in Synthesis, VCH, Weinheim, 2003.
M. A. Abraham and L. Moens, Clean Solvents: Alternative Media for Chemical Reactions and
Processing, ACS Symposium Series 819, ACS, Washington DC, 2002.
R. Sheldon, Chem. Commun., 2399 (2001).
P. Wasserscheid and W. Keim, Angew. Chem., Int. Ed. Engl, 39, 3772 (2000).
R. D. Rogers and K. R. Seddon, Ionic Liquids: Industrial Application to Green Chemistry, ACS
Symposium Series 818, ACS, Washington DC, 2002.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
T. Welton, Chem. Rev., 99, 2071 (1999).
G. Shao, Hecheng Huaxue, 11, 6 (2003); Chem. Abstr., 139, 116960 (2003).
G. V. Kryshtal, G. M. Zhdankina, and S. G. Zlotin, Mendeleev Commun., 57 (2002).
M. J. Earle, P. B. McCormac, and K. R. Seddon, Green Chem., 2, 261 (2000).
M. J. Earle, P. B. McCormac, and K. R. Seddon, Chem. Commun., 2245 (1998).
Y. R. Jorapur, J. M. Jeong, and D.Y. Chi, Tetrahedron Lett., 47, 2435 (2006).
A. Zicmanis, A. Ozolina, P. Mekss, and M. Klavins, Latv. J. Chem., 141 (2006).
A. Zicmanis, G. Vavilina, S. Drozdova, M. Klavins, and P. Mekss, Latv. J. Chem., 301 (2006).
A. Zicmanis, G. Vavilina, M. Klavins, and P. Mekss, Latv. J. Chem., 172 (2007).
A. Zicmanis, G. Vavilina, S. Drozdova, P. Mekss, and M. Klavins, Central Eur. J. Chem., 5, 156 (2007).
N. Kornblum, R. A. Smiley, R. K. Blackwood, and D. C. Iffland, J. Am. Chem. Soc., 77, 6269 (1955).
G. G. Hopkins, J. P. Jonak, H. J. Minnemeyer, and H. Tieckelmann, J. Org. Chem., 32, 4040 (1967).
N. M. Chung and H. Tieckelmann, J. Org. Chem., 35, 2517 (1970).
J. G. Huddleston, H. D. Willauer, R. P. Swatloski, A. E. Visser, and R. D. Rogers, Chem. Commun.,
1765 (1998).
31.
32.
33.
T. Nishida, Y. Tashiro, and M. Yamamoto, J. Fluorine Chem., 120, 135 (2003).
I. Almena, E. Diez-Barra, and A. de la Hoz, Synth. Commun., 24, 1057 (1994).
B. I. Mikhent’ev, E. I. Fedorov, A. I. Kucherova, and V. P. Potapova, Zhurn. Obshch. Khim., 29, 1874
(1959).
34.
F. J. Dinan and H. Tieckelmann, J. Org. Chem., 29, 892 (1964).
558