DOI 10.

1007/s10593-014-1628-7
Chemistry of Heterocyclic Compounds, Vol. 50, No. 11, February, 2015 (Russian Original Vol. 50, No. 11, November, 2014)

ADAMANTYLATION OF PYRIDINE DERIVATIVES

V. A. Shadrikova1*, E. V. Golovin1, and Yu. N. Klimochkin1

The reaction of isomeric hydroxypyridines with 1-bromoadamantane under various conditions led to
mono- and disubstituted С-, О-, and N-adamantylation products. Hydroxypyridines and 4-dimethyl-
aminopyridine were found to have catalytic effect on the quaternization of pyridine with adamantyl
bromide. A method was developed for the preparation of quaternary 1-(adamant-1-yl)pyridinium salts
under mild conditions.

Keywords: 1-(adamant-1-yl)pyridinium bromide, 1-bromoadamantane, 4-dimethylaminopyridine,

hydroxypyridine, 1Н-pyridone, adamantylation, alkylation, quaternization.

Quaternary pyridinium salts are frequently used as alkylating agents, phase transfer catalysts, broad
spectrum antimicrobial agents, ionic liquids, surfactants, and corrosion inhibitors [1-9]. Despite the large
number of publications devoted to preparation of pyridinium salts [1, 4, 9, 10], reactions of pyridines with
sterically crowded alkyl halides according to SN1 mechanism have not been thoroughly studied with respect to
the effects of various factors on the course of reaction. Very limited information is available about pyridinium
salts with tert-alkyl substituents at the nitrogen atom [11-13]. Functionalized pyridines have been studied the
least in such processes.
The introduction of adamantane substituent into organic compounds often results in a broadened
spectrum of useful properties. These effects are due to specific features of the adamantane framework, such as
conformational rigidity, lipophilicity, and the approximately spherical shape [14, 15]. 1-(Adamant-1-yl)-
pyridinium bromide is used as a standard guest molecule for building supramolecular ensembles [16, 17]. This
motivated several attempts at preparation of pyridinium salts containing the bulky adamantyl substituent at
nitrogen atom.
1-(Adamant-1-yl)pyridinium salts were synthesized by heating a sealed ampoule with 1-bromo- or
1-iodoadamantane solution in excess pyridine, β-picoline, or γ-picoline at 180°С [18]. The authors note that the
reaction was sensitive to steric factors, because 2-substituted pyridines and quinoline did not form
quaternization products. Another method for obtaining adamantylpyridinium halides is the reaction of pyridine
with 1,3-dehydroadamantane in the presence of iodine or alkyl halides [19]. This approach was used for the
preparation of quaternary pyridinium salts from α-picoline and quinoline. The synthesis of 1-(adamant-1-yl)-
pyridinium perchlorate from pyridine, 1-bromoadamantane, and silver perchlorate in nitromethane solution was
described by Katritzky [20].

_______
*To whom correspondence should be addressed, e-mail: shadricova@yandex.ru.

1
Samara State Technical University, 244 Molodogvardeiskaya St., Samara 443100, Russia.
_________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1725-1734, November, 2014.
Original article submitted June 4, 2014.

1586 0009-3122/15/5011-1586©2015 Springer Science+Business Media New York

 We continued the study of cationic transformations in adamantane series [21-23] by investigating the
reactivity of alkyl-, hydroxy-, and amino derivatives of pyridine in adamantylation reaction under various
conditions in order to evaluate the effect of substituent in pyridine ring on the reaction direction.
The interaction of isomeric 2-, 3-, and 4-hydroxypyridines (1-3) with 1-bromoadamantane was studied.
The presence of hydroxyl group in the pyridine ring decreased the π-deficient character of the aromatic system,
thus increasing the reactivity [24].
It is known that 2- and 4-hydroxypyridines (1, 3) exist mainly in the form of pyridones and their dimers
[25-29] (compounds 1, 3 will be further considered as pyridones), and 3-hydroxypyridine (2) can transform into
the zwitterionic form [29, 30]. The direction of hydroxypyridine adamantylation may be variable, leading to
different products depending on the nature of reaction medium.
Heating 2-pyridone (1) with 1-bromoadamantane in decane resulted in a mixture of С-adamantylation
products, which were separated by column chromatography. Compounds 4-6 were obtained as a result, in 12,
19, and 20% yields, respectively, while no products of the possible О- and N-alkylation were identified.
Ad Ad Ad Ad
AdBr, C10H22
+ +
, 8 h
N O N O N O N O
H H H H
1 4 (12%) 5 (19%) 6 (20%)
Ad = adamant-1-yl

The main direction of electrophilic substitution in 2-pyridone (1) was apparently due to the thermal
lability of 2-adamantyloxypyridine. 2-Alkoxypyridines are known to eliminate the respective alkene upon
heating, converting to 2-pyridone (1) [31]. The transformation to С-adamantylation products apparently was
caused by the impossibility of 1-adamantyl cation stabilization through proton elimination (Bredt's rule) [32].
The IR spectra of the obtained compounds contained characteristic amide absorption bands at 1670-
1647 cm-1. The 1Н spectrum of compound 6 had two aromatic proton signals as doublets with 4J = 2.3 Hz at 7.40
and 7.58 ppm, confirming the adamantylation at positions 3 and 5. The 13С NMR signals of carbonyl carbon atoms
were observed at 160.4-164.1 ppm. The quaternary carbon atom of adamantyl fragment in pyridone 4 gave a 13C
NMR signal at 36.9 ppm, and in the case of pyridone 5 – at 34.1 ppm, which was characteristic for a tert-butyl
group bonded to a pyridine ring carbon atom [33].
The N- and O-adamantylation products 7 and 8 were isolated as individual compounds in 9 and 59%
yields, respectively, after reaction of 3-hydroxypyridine (2) with 1-bromoadamantane in decane.
OH OAd OH
AdBr, C10H22
+
, 8 h + Br–
N N N
2 7 (9%) Ad
8 (59%)

The IR spectrum of 3-(adamant-1-yloxy)pyridine (7) contained an absorption band at 1230 cm-1, which
is characteristic of alkoxypyridines [34]. Four aromatic proton signals were present in the 1Н NMR spectrum at
7.17-8.31 ppm. The 13С NMR spectrum contained a signal of quaternary carbon atom of adamantane fragment
at 79.0 ppm, confirming the occurrence of O-adamantylation [35].
The 1Н NMR spectrum of compound 8 featured four aromatic proton signals in the region of 7.88-
8.80 ppm. The chemical shift of quaternary adamantane carbon in the 13С NMR spectrum was 69.7 ppm,
indicating the formation of quaternization product of 3-hydroxypyridine [36].
The interaction of 4-pyridone (3) with 1-bromoadamantane in decane allowed to obtain a mixture of О-,
С-, and N-substitution products 9-12, which were separated by column chromatography. The major products
were 1-(adamant-1-yl)-1Н-pyridone-4 (10) and 3-(adamant-1-yl)-1Н-pyridone-4 (11).

1587
 O OAd O O O
Ad Ad
AdBr, C10H22
+ + +
, 8 h
N N N N N
H H
Ad Ad
3
9 (9%) 10 (35%) 11 (29%) 12 (1%)

The IR spectra of compounds 10-12 contained the characteristic carbonyl group absorption band at 1639
cm-1, which was absent in the IR spectrum of compound 9. The 13С NMR spectra of compounds 10-12
contained carbonyl carbon signals in the region of 171.1-178.8 ppm, while the quaternary aromatic carbon atom
in compound 9 gave 13C NMR signal at 162.1 ppm. The 1Н NMR spectra of compounds 9 and 10 contained two
signals of four aromatic ring protons with integrals of 2Н, while the 13С NMR spectra contained three signals of
aromatic carbon atoms. The quaternary carbon of adamantyl fragment in pyridine 9 produced 13С NMR signal at
79.8 ppm, while in the case of pyridone 10 – at 60.8 ppm. The 13С NMR spectrum of compound 11 contained a
signal of quaternary adamantyl carbon at 36.8 ppm, the spectrum of compound 12 showed quaternary carbon
atoms of two adamantyl fragments at 36.6 and 61.6 ppm. The structure of compounds 11 and 12 was proved
unequivocally by spectral data set including DEPT, HMBC, and HMQC experiments. The signals of protons at
С-5 carbon atoms in pyridones 11, 12 were found at 7.30 and 6.56 ppm, respectively, while the chemical shifts
of protons bonded to С-2 and С-6 carbon atoms were located downfield (8.21-8.25 ppm for compound 11, 7.54
and 7.65 ppm for compound 12). The HMBC spectrum of pyridone 11 featured a cross peak of proton at the С-5
atom of pyridone fragment (7.30 ppm) with the carbon signal at 137.6 ppm, which was assigned from HMBC
data as the quaternary С-3 atom bonded to adamantane fragment. The HMBC spectrum of pyridone 12
confirmed the substitution at С-3 position, manifested by cross peak of adamantane methylene protons
(2.05 ppm) with the quaternary С-3 carbon atom at 137.0 ppm. The proton at the С-2 atom (7.54 ppm) was
coupled to the quaternary carbon atom of adamantane fragment, bonded to the С-3 atom (36.6 ppm). This
proton also gave cross peaks with signals of С-4 and С-6 carbon atoms. The proton at С-6 atom was coupled to
the С-2 and С-4 carbon atoms.
The reaction of 2-pyridone (1) with 1-bromoadamantane in pyridine produced unseparated mixture of
compounds 4-6 (less that 5%). The major product was a complex of 1-(adamant-1-yl)pyridinium bromide and
2-pyridone (13) (56% yield). Its 1Н and 13С NMR spectra were practically a superposition of 2-pyridone (1) [37]
and 1-(adamant-1-yl)pyridinium bromide spectra [18] in 1:1 ratio.

AdBr, Py
·
, 27 h +
N O N N O
H Br– H
Ad
1 13 (56%)

The cocrystals 13 were found to be stable, with ratio of components and melting points unchanged after
recrystallization from chloroform.
As in the case of reaction in decane, performing the reaction in pyridine did not form products of
2-pyridone О-adamantylation.
Reaction of 3-hydroxypyridine with 1-bromoadamantane in pyridine was accompanied to a significant
degree by the competing reaction with the solvent, and 1-(adamant-1-yl)pyridinium bromide (14а) was obtained
in 60% yield. 1-(Adamant-1-yl)-3-hydroxypyridinium bromide (8) was isolated as individual compound in 5%
yield. The product 7 expected from О-adamantylation was not isolated, even though it was identified in trace
amounts by TLC and GC-MS.

1588
 OH OH
AdBr, Py
+
, 27 h + +
N N Br– N Br–
2 Ad Ad
8 (5%) 14a (60%)

The reaction of 4-pyridone (3) with 1-bromoadamantane in pyridine yielded 1-(adamant-1-yl)-4(1Н)-

pyridone (10) in 38% yield. The competing product of pyridine quaternization, compound 14а, was isolated in
19% yield.
O O O
Ad
AdBr, Py
+ +
, 27 h +
N N N N Br–
H H
Ad Ad
3
10 (38%) 11 (4%) 14a (19%)

The observed low degree of alkylation of oxo(hydroxy)pyridines 1 and 2 in pyridine medium provided
evidence of their participation in this reaction not only as substrates, but rather as catalysts of pyridine
adamantylation. This proposition was confirmed by the impossibility of obtaining quaternary pyridinium salts
with adamantyl bromide in open system at 115°С when compounds 1-3 were absent in the reaction mixture
[18].
We perfomed the reaction of О- and N-adamantylation products of 3-hydroxypyridine (compounds 7, 8)
with pyridine for 20 h. In the case of 3-(adamant-1-yloxy)pyridine (7), the reaction mixture remained
unchanged, while only trace amounts of the salt 14a could be found after the reaction with 1-(adamant-1-yl)-
3-hydroxypyridinium bromide (8). This indicated that the reaction route in the presence of oxo(hydroxy)-
pyridines 1-3, leading to the formation of 1-(adamant-1-yl)pyridinium bromide (14а), was more complicated,
and the presence of pyridines having electron-donating group clearly facilitated the adamantylation of pyridine.
For these reasons, we used 4-dimethylaminopyridine (DMAP) as catalyst for the quaternization of
pyridines 15а-е with 1-bromoadamantane. Compounds 14a-e were thus obtained in 69-80% yields, while the
product from N-adamantylation of 4-dimethylaminopyridine was not detected.

1 1 R1 R2 R3 Yield, %
R R
2 AdBr 2 a H H H 69
R R
5 mol% DMAP Br– b Me H H 70
+
N , 60 h N c H Me H 75
3 3
R R Ad d Me Me H 80
15a–e 14a–e e Me H Me 78

1-(Adamant-1-yl)-4-(dimethylamino)pyridinium bromide (16) was obtained in practically quantitative

yield by refluxing equimolar amounts of 4-dimethylaminopyridine and 1-bromoadamantane in decane.

Me2N Me2N O
AdBr, C10H22 Br– NaOH, H2O
+
N , 30 h N , 21 h N
Ad Ad
16 (96%) 11 (88%)

The 13С NMR spectrum of compound 16 contained a signal for the quaternary carbon atom in
adamantane fragment at 64.7 ppm, indicating a bond with quaternary nitrogen atom of pyridine ring [36].

1589
 1-Substituted quaternary 4-dimethylaminopyridinium salts are known to undergo nucleophilic
substitution upon treatment with dilute alkali, leading to the formation of 1-R-4(1Н)-pyridones [38]. In order to
unequivocally confirm the adamantylation of nitrogen atom in the pyridine ring of 4-dimethylaminopyridine, we
treated the obtained salt 16 with 11% solution of NaOH and obtained 1-(adamant-1-yl)-4(1Н)-pyridone (11) in
88% yield as a result.
Thus, due to the specific properties of adamantane system in reactions of 2-pyridone, 3-hydroxypyridine,
and 4-pyridone with 1-bromoadamantane, products from adamantylation at carbon atoms were observed along
with the products of О- and N-adamantylation. The rate of pyridine quaternization with 1-bromoadamantane
noticeably increased in the presence of electron-rich pyridine derivatives.

EXPERIMENTAL

IR spectra were recorded for KBr pellets on a Shimadzu IRAffinity-1 FT-IR spectrometer. 1Н and 13С
NMR spectra (400 and 100 MHz, respectively), as well as 2D NMR spectra (DEPT, HMBC, and HMQC) were
acquired on a JEOL JNM-ESCX400 spectrometer in DMSO-d6 (compounds 8, 13, 14а-е), CF3COOH
(compound 11), and CDCl3 (the rest of compounds), with TMS as internal standard. Elemental analysis was
performed on a EuroVector EA-3000 automated CHNS-analyzer. Melting points were determined on a PTP-M
apparatus (Russia) by capillary method. Column chromatography was performed on Silica 60 stationary phase
(0.063-0.200 mm) obtained from Macherey-Nagel, thin-layer chromatography was performed on Sorbfil plates,
visualization with iodine vapor.
Adamantylation of Oxo(hydroxy)pyridines 1-3 in Decane (General Method). A mixture of
oxo(hydroxy)pyridine 1-3 (1.00 g, 10.5 mmol) and 1-bromoadamantane (2.26 g, 10.5 mmol) in decane (10 ml)
was refluxed with stirring for 8 h. The liquid layer was decanted from the reaction mixture, solvent was
evaporated under vacuum, the obtained residue was separated by column chromatography. The residual material
in the flask after decantation was purified by recrystallization or column chromatography.
Adamantylation of 2-Pyridone (1) in Decane. Column chromatography of the residue after
evaporation of decane allowed to recover the starting 1-bromoadamantane (0.20 g, 8%) upon elution with
petroleum ether, then compound 4 (0.03 g, 1%) upon elution with CHCl3. The residue after decantation was
separated by column chromatography (eluent 10:1 CCl4–MeOH), yielding the main crop of compound 4
(0.26 g, 11%), as well as compounds 5, 6.
3-(Adamant-1-yl)-2(1Н)-pyridone (4). Total yield 0.29 g (12%), white powder, mp 244-246°С
(acetone). Identical samples of compound 4 were obtained from the evaporated solvent and from the residue
after decantation. IR spectrum, ν, cm-1: 2900 (C–H Ad), 2848 (C–H Ad), 1653 (C=O), 1608, 1552, 1477, 1170,
752, 557. 1Н NMR spectrum, δ, ppm (J, Hz): 1.76 (6Н, br. s, 3СН2 Ad); 2.06 (9H, s, 3СН Ad, 3CH2 Ad); 6.28
(1H, dd, 3J = 6.4, 3J = 7.1, H-5); 7.30 (1H, dd, 4J = 1.3, 3J = 6.4, H-4); 7.34 (1H, dd, 4J = 1.3, 3J = 7.1, H-6).
13
C NMR spectrum, δ, ppm: 28.8 (CH Ad); 36.9 (C Ad); 37.0 (CH2 Ad); 39.5 (CH2 Ad); 107.3 (С-5); 132.2
(С-4); 136.3 (C-6); 140.1 (C-3); 163.7 (C=O). Found, %: С 78.61; H 8.39; N 6.18. C15H19NО. Calculated, %:
С 78.56; H 8.35; N 6.11.
5-(Adamant-1-yl)-2(1Н)-pyridone (5). Yield 0.48 g (19%), pale-pink crystals, mp 228-230°С
(acetone). IR spectrum, ν, cm-1: 2906 (C–H Ad), 2845 (C–H Ad), 1670 (С=О), 1624, 1544, 1473, 1340, 1269,
839, 597, 555, 511. 1Н NMR spectrum, δ, ppm (J, Hz): 1.69-1.75 (12Н, m, 6CH2 Ad); 2.05 (3Н, s, 3CH Ad);
6.60 (1Н, dd, 5J = 0.5, 3J = 9.6, Н-3); 7.26 (1Н, dd, 5J = 0.5, 4J = 2.8, Н-6); 7.61 (1Н, dd, 4J = 2.8, 3J = 9.6,
Н-4); 12.85 (1Н, br. s, NH). 13C NMR spectrum, δ, ppm: 28.6 (CH Ad); 34.1 (C Ad); 36.5 (CH2 Ad); 42.4 (CH2
Ad); 119.2 (С-3); 130.3 (С-6); 130.9 (C-5); 140.7 (С-4); 164.1 (C=O). Found, %: С 78.63; H 8.30; N 6.21.
C15H19NО. Calculated, %: С 78.56; H 8.35; N 6.11.
3,5-Di(adamant-1-yl)-2(1Н)-pyridone (6). Yield 0.80 g (20%), white powder, mp >330°С (acetone).
IR spectrum, ν, cm-1: 3433, 2902 (C–H Ad), 2848 (C–H Ad), 1647 (C=O), 1627, 866, 605, 574. 1Н NMR

1590
spectrum, δ, ppm (J, Hz): 1.69-1.81 (18Н, m, 9СН2 Ad); 2.08 (12H, br. s, 6СН Ad, 3CH2 Ad); 7.40 (1H, d,
4
J = 2.3, H-6); 7.58 (1H, d, 4J = 2.3, H-4). 13C NMR spectrum, δ, ppm: 28.6 (CH Ad); 28.7 (CH Ad); 34.7
(C Ad); 36.4 (CH2 Ad); 36.8 (CH2 Ad); 37.1 (C Ad); 39.6 (CH2 Ad); 42.5 (CH2 Ad); 128.5 (С-6); 134.9
(C-3(5)); 137.6 (С-4); 137.9 (C-5(3)); 160.4 (C=O). Found, %: С 82.63; H 9.13; N 3.80. C25H33NО. Calculated,
%: С 82.60; H 9.15; N 3.85.
Adamantylation of 3-Hydroxypyridine (2) in Decane. The residue from evaporation of decane was
separated chromatographically by eluting with petroleum ether, resulting in recovery of the starting 1-bromo-
adamantane (0.60 g, 27%), then compound 7 was eluted with CHCl3. The residue after decantation was purified
by recrystallization from EtOH, yielding compound 8. The starting 3-hydroxypyridine (2) (0.35 g, 35%) was
isolated from filtrate.
3-(Adamant-1-yloxy)pyridine (7). Yield 0.20 g (9%), light-yellow needles, mp 48-50°С (CCl4).
IR spectrum, ν, cm-1: 2908 (C–H Ad), 2854 (C–H Ad), 1570, 1470, 1412, 1354, 1230, 1060, 921, 717. 1Н NMR
spectrum, δ, ppm (J, Hz): 1.57-1.63 (6Н, m, 3СН2 Ad); 1.83 (6Н, s, 3CH2 Ad); 2.16 (3Н, s, 3CH Ad); 7.17 (1Н,
dd, 3J = 8.2, 4J = 4.6, H-5); 7.27 (1Н, ddd, 5J = 1.4, 4J = 2.5, 3J = 8.2, H-4); 8.29-8.31 (2Н, m, H-2,6). 13C NMR
spectrum, δ, ppm: 30.9 (CH Ad); 36.0 (CH2 Ad); 42.7 (CH2 Ad); 79.0 (C Ad); 123.5 (C-5); 132.0 (C-4); 144.8
(C-2); 146.8 (C-6); 150.3 (C-3). Found, %: С 78.61; H 8.32; N 6.06. C15H19NО. Calculated, %: С 78.56;
H 8.35; N 6.11.
1-(Adamant-1-yl)-3-hydroxypyridinium Bromide (8). Yield 1.86 g (59%), colorless crystals,
mp 281-282°С (EtOH). IR spectrum, ν, cm-1: 2916 (C–H Ad), 2850 (C–H Ad), 1585, 1500, 1303, 1253, 1126,
813, 682. 1Н NMR spectrum, δ, ppm (J, Hz): 1.69 (6Н, br. s, 3СН2 Ad); 2.23 (9Н, s, 3CH Ad, 3CH2 Ad);
7.88-7.94 (2Н, m, H-4,5); 8.73 (1Н, s, H-2); 8.80 (1Н, dd, 3J = 5.1, 4J = 1.3, H-6). 13C NMR spectrum, δ, ppm:
30.1 (CH Ad); 35.0 (CH2 Ad); 41.6 (CH2 Ad); 69.7 (C Ad); 128.8 (C-5); 130.4 (C-4); 131.5 (C-6); 132.9 (C-2);
157.4 (C-3). Found, %: С 58.15; H 6.52; N 4.48. C15H20BrNО. Calculated, %: С 58.07; H 6.50; N 4.51.
Adamantylation of 4-Pyridone (3) in Decane. Chromatographic separation of residue after
evaporation of decane with petroleum ether as eluent allowed to recover 1.00 g (44%) of the starting 1-bromo-
adamantane, then compound 9 was eluted with CHCl3. The residue after decantation was separated by column
chromatography with 1:1 CCl4–CHCl3 as eluent, yielding compounds 11 and 12, then compound 10 was eluted
with 1:1 CHCl3–MeOH.
4-(Adamant-1-yloxy)pyridine (9). Yield 0.20 g (9%), light-yellow needles, mp 59-60°С (CCl4).
IR spectrum, ν, cm-1: 2912 (C–H Ad), 2854 (C–H Ad), 1589, 1558, 1280, 1261, 1060 (С–O–C), 933, 820, 536.
1
Н NMR spectrum, δ, ppm (J, Hz): 1.60-1.67 (6Н, m, 3CH2 Ad); 1.96 (6Н, s, 3CH2 Ad); 2.20 (3Н, s, 3CH Ad);
6.88 (2Н, d, 3J = 5.7, H-3,5); 8.40 (2Н, d, 3J = 5.7, H-2,6). 13C NMR spectrum, δ, ppm: 30.9 (CH Ad); 36.1
(CH2 Ad); 42.5 (CH2 Ad); 79.8 (C Ad); 118.3 (C-3,5); 150.8 (C-2,6); 162.1 (C-4). Found, %: С 78.59; H 8.38;
N 6.07. C15H19NО. Calculated, %: С 78.56; H 8.35; N 6.11.
1-(Adamant-1-yl)-4(1Н)-pyridone (10). Yield 0.88 g (35%), light-yellow powder, mp 170-172°С
(acetone). IR spectrum, ν, cm-1: 2908 (C–H Ad), 2847 (C–H Ad), 1639 (C=O), 1562, 1153, 848. 1Н NMR
spectrum, δ, ppm (J, Hz): 1.66-1.78 (6Н, m, 3СН2 Ad); 2.01 (6H, s, 3СН2 Ad); 2.27 (3H, br. s, 3СН Ad); 6.37
(2H, d, 3J = 7.8, H-3,5); 7.59 (2H, d, 3J = 7.8, H-2,6). 13C NMR spectrum, δ, ppm: 29.7 (CH Ad); 35.5 (CH2
Ad); 42.4 (CH2 Ad); 60.8 (C Ad); 118.4 (С-3,5); 135.4 (С-2,6); 178.8 (C=O). Found, %: С 78.63; H 8.34;
N 6.08. C15H19NО. Calculated, %: С 78.56; H 8.35; N 6.11.
3-(Adamant-1-yl)-4(1Н)-pyridone (11). Yield 0.72 g (29%), colorless crystals, mp >320°С (MeOH).
IR spectrum, ν, cm-1: 2900 (C–H Ad), 2846 (C–H Ad), 1639 (С=О), 1496 (С=С Ar). 1Н NMR spectrum, δ, ppm
(J, Hz): 1.81-1.90 (6Н, m, 3CH2 Ad); 2.15 (9Н, s, 3CH Ad, 3CH2 Ad); 7.30 (1Н, d, 3J = 6.6, H-5); 8.21-8.25
(2Н, m, H-2,6). 13C NMR spectrum, δ, ppm: 28.2 (CH Ad); 36.0 (CH2 Ad); 36.8 (C Ad); 38.9 (CH2 Ad); 114.3
(C-5); 137.6 (C-3); 139.1 (C-2); 139.2 (C-6); 171.1 (C=O). Found, %: С 78.51; H 8.40; N 6.02. C15H19NО.
Calculated, %: С 78.56; H 8.35; N 6.11.
1,3-Di(adamant-1-yl)-4(1Н)-pyridone (12). Yield 0.04 g (1%), colorless crystals, mp 260-262°С
(CHCl3). IR spectrum, ν, cm-1: 3417, 2900 (C–H Ad), 2846 (C–H Ad), 1639 (C=O), 1566 (С=С Ar), 1184, 825.

1591
1
Н NMR spectrum, δ, ppm (J, Hz): 1.69-1.79 (12H, br. s, 6CH2 Ad); 2.05 (15H, s, 3CH Ad, 6CH2 Ad); 2.29
(3Н, s, 3CH Ad); 6.56 (1Н, d, 3J = 7.4, H-5); 7.54 (1Н, d, 4J = 2.3, H-2); 7.65 (1Н, dd, 4J = 2.3, 3J = 7.4, H-6).
13
C NMR spectrum, δ, ppm: 28.8 (CH Ad); 29.8 (CH Ad); 35.6 (CH2 Ad); 36.6 (C 3-Ad); 37.0 (CH2 Ad); 39.5
(CH2 Ad); 42.5 (CH2 Ad); 61.6 (C 1-Ad); 117.9 (C-5); 132.3 (C-2); 133.9 (C-6); 137.0 (C-3); 176.9 (C=O).
Found, %: С 82.53; H 9.18; N 3.82. C25H33NО. Calculated, %: С 82.60; H 9.15; N 3.85.
Adamantylation of Oxo(hydroxy)pyridines 1-3 in Pyridine (General Method). A solution of
oxo(hydroxy)pyridine 1-3 (1.00 g, 10.5 mmol) and 1-bromoadamantane (2.26 g, 10.5 mmol) in pyridine (5 ml)
was refluxed for 27 h. Pyridine was removed from the reaction mixture by evaporation in vacuum. The residue
was purified by recrystallization or column chromatography.
Adamantylation of 2-pyridone (1). The obtained mixture of reaction products (3.60 g) was diluted
with acetone, the precipitate was filtered off and then purified by recrystallization from CHCl3, giving
compound 13. The filtrate contained a part of reaction mixture and was evaporated, the residue was purified by
column chromatography (eluent 10:1 CCl4–MeOH), resulting in isolation of unreacted 1-bromoadamantane (0.90 g,
41%) and 2-pyridone (1) (0.35 g, 35%) as well as 0.15 g (5%) of product mixture from adamantylation of
2-pyridone, compounds 4-6.
Product of 1-(Adamant-1-yl)pyridinium Bromide and 2-Pyridone (13) Cocrystallization. Yield
2.30 g (56%), colorless crystals, mp 164-166°С (CHCl3). IR spectrum, ν, cm-1: 3406, 3049, 2922 (C–H Ad),
2854 (C–H Ad), 1649 (С=О), 1627, 1600. 1Н NMR spectrum, δ, ppm (J, Hz): 1.70 (6Н, s, 3CH2 Ad); 2.20 (9H,
s, 3CH Ad, 3CH2 Ad); 6.35 (1H, td, 3J = 6.6, 5J = 0.8, H-5); 6.46 (1H, dt, 3J = 9.2, 5J = 0.8, H-3); 7.50 (1H, ddd,
3
J = 6.6, 4J = 2.2, 5J = 0.8, H-6); 7.55 (1H, ddd, 3J = 9.2, 3J = 6.6, 4J = 2.2, H-4); 8.12 (2Н, t, 3J = 7.0, Н-3,5 Py);
8.57 (1H, t, 3J = 7.0, Н-4 Py); 9.34 (2H, d, 3J = 7.0, Н-2,6 Py). 13C NMR spectrum, δ, ppm: 30.0 (CH Ad); 35.0
(CH2 Ad); 41.6 (CH2 Ad); 69.8 (C Ad); 107.8 (C-5); 119.2 (C-3); 128.5 (C-3,5 Py); 136.5 (C-6); 142.3 (C-4
Py); 142.9 (С-2,6 Py); 145.9 (C-4); 162.5 (C=O). Found, %: С 61.68; H 6.50; N 7.23. C20H25BrN2О.
Calculated, %: С 61.70; H 6.47; N 7.20.
Adamantylation of 3-Hydroxypyridine (2). The obtained reaction product mixture (3.15 g) was
separated by column chromatography. Elution with CHCl3 gave 1-(adamant-1-yl)-3-hydroxypyridinium
bromide (8) (0.20 g, 5%) as well as unreacted 1-bromoadamantane (0.30 g, 13%) and 3-hydroxypyridine (0.65 g,
65%). Compound 14a was subsequently isolated by elution with EtOH.
1-(Adamant-1-yl)pyridinium Bromide (14а). Yield 1.90 g (60%), colorless crystals, mp 244-246°С
(mp 246-248°С [18]). 13C NMR spectrum, δ, ppm: 30.0 (CH Ad); 35.0 (CH2 Ad); 41.6 (CH2 Ad); 69.8 (C Ad);
128.5 (Н-3,5); 142.3 (Н-4); 145.9 (Н-2,6).
Adamantylation of 4-Pyridone (3). The obtained mixture of reaction products (2.80 g) was separated
by column chromatography. Elution with 1:1 mixture of CCl4–CHCl3 gave products 10 and 11 in 38 and 4%
yields. Further elution with 1:1 mixture of CHCl3–MeOH gave salt 14а in 19% yield.
Preparation of 1-(Adamant-1-yl)pyridinium Bromides 14а-е in the Presence of 4-Dimethylamino-
pyridine (General Method). A mixture of pyridine 15а-е (50 mmol), 1-bromoadamantane (2.15 g, 10 mmol),
and 4-(dimethylamino)pyridine (0.06 g, 0.5 mmol) was refluxed for 60 h. The excess of pyridine 15а-е was
evaporated from the reaction mixture at reduced pressure, the residue containing quaternary salt was washed
with EtOAc, then recrystallized from CHCl3.
1-(Adamant-1-yl)pyridinium Bromide (14а). Yield 2.00 g (69%), colorless crystals, mp 244-246°С
(mp 246-248°С [18]).
1-(Adamant-1-yl)-3-methylpyridinium Bromide (14b). Yield 2.20 g (70%), colorless crystals,
mp 184-186°С (mp 187-189°С [18]). 13C NMR spectrum, δ, ppm: 18.6 (CH3); 30.0 (CH Ad); 35.0 (CH2 Ad); 41.6
(CH2 Ad); 69.6 (C Ad); 127.7 (CН Ar); 139.3 (CН Ar); 139.5 (CН Ar); 141.6 (CН Ar); 146.2 (C-3).
1-(Adamant-1-yl)-4-methylpyridinium Bromide (14c). Yield 2.30 g (75%), colorless crystals,
mp 224-225°С (mp 223-224°С [18]). 13C NMR spectrum, δ, ppm: 21.6 (CH3); 30.0 (CH Ad); 35.0 (CH2 Ad); 41.6
(CH2 Ad); 68.7 (C Ad); 128.8 (C-3,5); 141.1 (C-2,6); 159.2 (C-4).

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 1-(Adamant-1-yl)-3,4-dimethylpyridinium Bromide (14d). Yield 2.60 g (80%), colorless crystals, mp
230-234°С (CHCl3). IR spectrum, ν, cm-1: 3406, 3078, 3005, 2978, 2912 (C–H Ad), 2850 (C–H Ad). 1Н NMR
spectrum, δ, ppm (J, Hz): 1.70 (6Н, br. s, 3CH2 Ad); 2.25 (9H, br. s, 3CH Ad, 3CH2 Ad); 2.43 (3Н, s, 4-СН3);
2.51 (3Н, s, 3-СН3); 7.91 (1Н, d, 3J = 6.4, Н-5); 9.03 (1H, d, 3J = 6.4, Н-6); 9.14 (1H, s, Н-2). 13C NMR
spectrum, δ, ppm: 16.8 (CH3); 19.9 (CH3); 30.0 (CH Ad); 35.0 (CH2 Ad); 41.6 (CH2 Ad); 68.6 (C Ad); 128.3
(CH Ar); 138.3 (CH Ar); 138.9 (CH Ar); 140.2 (C-3(4)); 158.1 (C-4(3)). Found, %: С 63.41; H 7.47; N 4.40.
C17H24BrN. Calculated, %: С 63.36; H 7.51; N 4.35.
1-(Adamant-1-yl)-3,5-dimethylpyridinium Bromide (14e). Yield 2.50 g (78%), colorless crystals, mp
266-270°С (CHCl3). IR spectrum, ν, cm-1: 3406, 3028, 2931, 2908, 2878 (C–H Ad), 2850 (C–H Ad), 1624,
1600, 1477, 1215, 1168, 690, 513. 1Н NMR spectrum, δ, ppm (J, Hz): 1.70 (6Н, br. s, 3CH2 Ad); 2.25 (9H,
br. s, 3CH Ad, 3CH2 Ad); 2.47 (6Н, s, 2СН3); 8.25 (1Н, s, Н-4); 9.05 (2H, s, Н-2,6). 13C NMR spectrum,
δ, ppm: 18.4 (CH3); 30.1 (CH Ad); 35.1 (CH2 Ad); 41.7 (CH2 Ad); 69.4 (C Ad); 138.4 (C-2,6); 138.9 (C-4);
146.6 (C-3,5). Found, %: С 63.38; H 7.54; N 4.29. C17H24BrN. Calculated, %: С 63.36; H 7.51; N 4.35.
1-(Adamant-1-yl)-4-(dimethylamino)pyridinium Bromide (16). A solution of 4-(dimethylamino)-
pyridine (1.88 g, 15.3 mmol) and 1-bromoadamantane (3.30 g, 15.3 mmol) in decane (15 ml) was refluxed for
30 h. After cooling, the solution was decanted, the residue was washed with petroleum ether. The obtained
precipitate was refluxed in water with activated carbon, then water was evaporated, the dry residue was purified
by recrystallization from CHCl3. Yield 4.70 g (96%), colorless crystals, mp 229-230°С (CHCl3). IR spectrum, ν,
cm-1: 3396, 2918 (C–H Ad), 2850 (C–H Ad), 1643, 1571, 1404, 1230, 1136, 1124, 1103, 830, 780, 500.
1
Н NMR spectrum, δ, ppm (J, Hz): 1.72 (6Н, s, 3СН2 Ad); 2.15 (6H, s, 3СН2 Ad); 2.28 (3H, s, 3СН Ad); 3.23
(6H, s, 2CH3); 7.14 (2H, d, 3J = 7.8, H-3,5); 8.59 (2H, d, 3J = 7.8, H-2,6). 13C NMR spectrum, δ, ppm: 29.9 (CH
Ad); 35.2 (CH2 Ad); 40.6 (CH3); 42.3 (CH2 Ad); 64.7 (C Ad); 108.7 (C-3,5); 138.8 (C-2,6); 156.0 (C-4). Found,
%: С 60.49; H 7.49; N 8.34. C17H25BrN2. Calculated, %: С 60.54; H 7.47; N 8.31.
Hydrolysis of Bromide 16. A solution of NaOH (1.8 g, 45.0 mmol) in Н2О (15 ml) was added with
stirring to salt 16 (3.0 g, 8.8 mmol); the obtained mixture was stirred and refluxed for 21 h. The reaction mixture
was then cooled and neutralized with 5% HCl to pH 6.5-7. The product was extracted with CHCl3 (3×15 ml),
the collected fractions were combined and dried over Na2SO4. After removal of the solvent and recrystallization
from acetone, compound 11 (1.8 g, 88%) was isolated. The obtained product was identical to a sample of
compound 11 obtained by adamantylation of 4-pyridone (3).

This work received financial support from the Ministry of Education and Science of the Russian
Federation within the framework of baseline of the State Assignment for scientific activity (2014/199-1078)
using the scientific equipment of Samara State Technical University Collective Use Center "Physicochemical
Investigation of Substances and Materials".

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