Ефективний метод синтезу різноманітних заміщених піридин-3-тіолів
A practical and convenient method for the synthesis of pyridine-3-thiols using substituted 3-iodopyridines as starting compounds has been developed. Based on the use of thiobenzoic acid as a sulfur donor in a two-step procedure, this approach made it possible to synthesize a number of pyridine-3-thi...
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| Опубліковано в: | Журнал органічної та фармацевтичної хімії |
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| Дата: | 2025 |
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Репозитарії
Journal of Organic and Pharmaceutical Chemistry| _version_ | 1874364504709529600 |
|---|---|
| author | Borysov, Oleksandr V. Bohdan, Dmytro P. |
| author_facet | Borysov, Oleksandr V. Bohdan, Dmytro P. |
| author_institution_txt_mv | [
{
"author": "Oleksandr V. Borysov",
"institution": "Institute of Organic Chemistry of the National Academy of Sciences of Ukraine; Enamine Ltd.",
"orcid": ""
},
{
"author": "Dmytro P. Bohdan",
"institution": "Institute of Organic Chemistry of the National Academy of Sciences of Ukraine",
"orcid": ""
}
] |
| author_sort | Borysov, Oleksandr V. |
| baseUrl_str | https://ophcj.nuph.edu.ua/oai |
| collection | OJS |
| container_end_page | 48 |
| container_issue | 1 |
| container_start_page | 43 |
| container_title | Журнал органічної та фармацевтичної хімії |
| container_volume | 23 |
| datestamp_date | 2026-08-23T15:25:30Z |
| description | A practical and convenient method for the synthesis of pyridine-3-thiols using substituted 3-iodopyridines as starting compounds has been developed. Based on the use of thiobenzoic acid as a sulfur donor in a two-step procedure, this approach made it possible to synthesize a number of pyridine-3-thiols with F, Cl, Br, CH3, OCH3 substituents at various positions of the pyridine ring. The procedure presented gives high yields of the target products with a purity of 95% and is suitable for synthesis in tens of grams. |
| doi_str_mv | 10.24959/ophcj.25.324523 |
| first_indexed | 2025-07-23T04:43:41Z |
| format | Article |
| fulltext |
ISSN 2308-8303 (Print) / 2518-1548 (Online) 43
Original Research
http://ophcj.nuph.edu.ua
UDC 54.057:547.825
D. P. Bohdan1, O. V. Borysov1,2
1 Institute of Organic Chemistry of the National Academy of Sciences of Ukraine,
5, Akademik Kukhar str., 02094 Kyiv, Ukraine
2 Enamine Ltd, 78, Winston Churchill str., 02094 Kyiv, Ukraine
An Efficient Synthesis of a Variety of Substituted
Pyridine-3-Thiols
Abstract
A practical and convenient method for the synthesis of pyridine-3-thiols using substituted 3-iodopyridines as starting com-
pounds has been developed. Based on the use of thiobenzoic acid as a sulfur donor in a two-step procedure, this approach
made it possible to synthesize a number of pyridine-3-thiols with F, Cl, Br, CH3, OCH3 substituents in various positions of the
pyridine ring. The procedure presented gives high yields of the target products with a purity of 95 % and is suitable for the
synthesis in tens of grams.
Keywords: pyridine; thiols; thiobenzoic acid; chromatography; hydrolysis
Д. П. Богдан1, О. В. Борисов1,2
1 Інститут органічної хімії Національної академії наук України,
вул. Академіка Кухаря, 5, м. Київ, 02094, Україна
2 ТОВ НВП «Єнамін», вул. Вінстона Черчилля, 78, м. Київ, 02094, Україна
Ефективний метод синтезу різноманітних заміщених піридин-3-тіолів
Анотація
Розроблено практичний і зручний метод синтезу піридин-3-тіолів із використанням як вихідних сполук заміщених
3-йодопіридинів. Цей підхід, заснований на використанні тіобензойної кислоти як донора сульфуру в межах двоста-
дійної процедури, надав можливість синтезувати ряд піридин-3-тіолів із F, Cl, Br, CH3, OCH3 замісниками в різноманіт-
них положеннях піридинового циклу. Зазначена процедура дозволяє одержати цільові продукти на масштабі десятків
грам із високими виходами й чистотою 95 %.
Ключові слова: піридин; тіоли; тіобензойна кислота; хроматографія; гідроліз
Citation: Bohdan, D. P.; Borysov, O. V. An Efficient Synthesis of a Variety of Substituted Pyridin-3-Thiols. Journal of Organic
and Pharmaceutical Chemistry 2025, 23 (1), 43 – 48.
https://doi.org/10.24959/ophcj.25.324523
Received: 24 January 2025; Revised: 6 March 2025; Accepted: 10 March 2025
Copyright© 2025, D. P. Bohdan, O. V. Borysov This is an open access article under the CC BY license
(http://creativecommons.org/licenses/by/4.0).
Funding: The authors received no specific funding for this work.
Conflict of interests: The authors have no conflict of interests to declare
■ Introduction
Pyridine is a part of the body’s oxidation
systems and, in the form of nicotinic acid (vi-
tamin B3), is a component of NAD+ and NADP+
(Figure 1) [1 – 3]. Pyridines are found in plants,
for example, in alkaloids, such as nicotine.
The latter is an important biological component
and activator of nicotinic acetylcholine recep-
tors (nAChRs); it plays a significant role in the
formation of tobacco addiction [4, 5]. Anabasine,
an alkaloid related to nicotine, is the major toxin
of the Pacific hoplonemertine Paranemertes pe-
regrina, which presumably uses the alkaloid for
defense or to paralyze its prey [6].
The pyridine cycle is a pharmacophore of di-
hydropyridine calcium channel blockers [7]. Many
other biologically active compounds with a pyri-
dine cycle are known [8]. For example, huper-
zine A, an active Lycopodium alkaloid extracted
ISSN 2308-8303 (Print) / 2518-1548 (Online) 44
Журнал органічної та фармацевтичної хімії 2025, 23 (1)
from a traditional Chinese herb, is a potent, se-
lective, and reversible acetylcholinesterase (AChE)
inhibitor and has been widely used in China for
the treatment of Alzheimer’s disease [9].
Undoubtedly, pyridine derivatives play a cru-
cial role in the therapy of tuberculosis as drugs
like isoniazid [10], ethionamide, and protionami-
de [11] are the derivatives of pyridine.
Pyridinethiols are of great importance as the
parts of biologically active compounds (Figure 2).
The introduction of pyridine-4-thiol fragment hel-
ped to obtain an effective dual inhibitor of can-
cer-related cysteine isopeptidase human ubiqui-
tin-specific proteases 7 (USP7) and 47 (USP47).
This is considered to have the potential as a can-
cer therapeutic, owing to the ability to stabilize
the tumor suppressor p53 and to decrease DNA
polymerase β (Polβ). Both of them have poten-
tial antitumor effects [12].
Newly developed selective galectin-3 inhibi-
tors combining high affinity (nM) with oral bio-
availability, which reduce the profibrotic gene ex-
pression in liver myofibroblasts and display the
antifibrotic activity in CCl4-induced liver fibro-
sis and bleomycin-induced lung fibrosis mouse
models, also have 5-bromopyridine-3-thiol ga-
lactoside in their structure. Compound GB1211
was selected as the clinical candidate. It is cur-
rently in phase IIa clinical trials as a potential
therapy for liver cirrhosis and cancer [13].
Pyridine-4-thione is also a part of the fused
systems of the effective and potent BRAF inhi-
bitors bearing a novel pyridoimidazolone hinge-
binding group. They showed beneficial therapeu-
tic efficacy in mutant BRAF tumors, including
melanoma. A thiopyridine derivative was found
to be 4-fold more potent than sorafenib in inhi-
biting WM266.4 melanoma cell growth [14].
N
O
OH
nicotinic acid
N
N
Me
nicotine
N
anabsine
N
H
nifedipine
(calcium channel blocker)
N
H
CO2MeMeO2C
Me Me
NO2
N
H
O
H2N
Me
H
Me
N
NHNH2O
isoniazide
N
NH2S
N
NH2S
Me
ethionamide protionamide
Me
Figure 1. Natural pyridines and pyridine-containing medicines
N
S S
ClCl
NC
O
HN
S Me
O
O
inhibitor of the cancer-
related cysteine
isopeptidase
7 ( ),USP7 IC50 = 0.42 µM
47 ( ),USP47 IC50 = 1.0 µM N
S
N
N
H
H
O
HN
H
N OF3C
N
S
N
N
H
H
O
HN
H
N OF3C
Cl
BRAF inhibitors
IC50 = 0.028 µM IC50 = 0.4 µM
4-fold more potent than sorafenib in
inhibiting WM266.4 melanoma cell
N
S
N
N
H
H
O
H
N
H
N
O
F3C
F
IC50 = 0.029 µM
IC50 = 0.69 nM
O
HN
OH
O
S
Me
S
N
Me
potent and selective non-thiol-
containing inhibitor of protein
farnesyltransferase
N
BrS
O
OH
N
OH
OH
N N
F
F
F
GB1211
galectin-3 inhibitor combining high
in clinical trials as an oral treatment
of hepatic impairment
NP
P
OH
O
O
OH
HO
OH
S
Me
Me
Me
inhibitor of heptaprenyl
diphosphate synthase
and 200 nM against a farnesyl
diphosphate synthase
Figure 2. Biologically active compounds with a thiopyridine fragment
ISSN 2308-8303 (Print) / 2518-1548 (Online) 45
Journal of Organic and Pharmaceutical Chemistry 2025, 23 (1)
The o-tolyl biphenyl core dramatically and un-
expectedly enhanced the potency of other com-
pounds as exemplified the activity of potent and
selective non-thiol-containing inhibitors of pro-
tein farnesyltransferase playing an important role
for the Ras protein posttranslational modifica-
tions, such as the farnesylation of a cysteine re-
sidue near the C-terminus by the enzyme far-
nesyltransferase (FTase). The inhibition of this
enzyme will render Ras inactive and block the
uncontrolled mitogenic signaling pathway [15].
The compound with the antimicrobial activity
against Bacillus anthracis, Mycobacterium smegma-
tis, Bacillus subtilis, and Staphylococcus aureus
bearing pyridine-3-thione was reported. The com-
pounds from this series target the biosynthesis
of bacterial isoprenoids by inhibiting heptapre-
nyl diphosphate synthase and farnesyl diphos-
phate synthase at 200 nM [16].
Pyridine-2-thiol is a perfect ligand to stabi-
lize the complexes with metals [17, 18].
The analysis of the screening compounds
market revealed the urgent need for a variety of
pyridine-3-thiols as building blocks. The analy-
sis of the market using mathematical algo-
rithms also clearly indicates a small number of
blocks containing the SH group and the vacancy
of this market segment [19].
■ Results and discussion
There are a number of approaches to the pre-
paration of aromatic thiols that have been shown
to be promising for the synthesis of pyridinethiols.
The first reported method for obtaining pyridine-
3-thiols was the reduction of the corresponding
sulfonyl chloride [20]. In subsequent publications,
the authors used more modern reduction methods,
which made it possible to preserve a number of
functional groups, such as the double bond or Boc
protected amine [21, 22]. A number of researchers
used pyridin-3-ol as a starting compound, which,
when treated with dimethylthiocarbamoyl chlo-
ride, gave an S-aryl thiocarbamate, that could
be further thermally rearranged into the corres-
ponding S-aryl thiocarbamate according to the
Newman–Kwart rearrangement [23]. It was shown
that the hydrolysis of 3-pyridyl S-aryl thiocarba-
mate was a good way for the preparation of sodi-
um salts of pyridine-3-thiol [15, 16]. Copper (II)
sulfate catalyzed the interaction of 3-bromo py-
ridine with 1,2-ethandithiol was also reported
as the one for preparing pyridine-3-thiol, which
was alkylated in situ [24]. Some less convenient
methods where the formation of disulfides was
one of the by-processes were also reported [25].
The analysis of the above methods has shown
that most of them do not allow the isolation of
pyridine-3-thiol with a purity of more than 95 %
and have not been studied on a wide variety of
substituted pyridine derivatives. In recent years,
the appearance of 3-iodopyridines in the market
has led us to the idea of using them as starting
compounds for the synthesis of corresponding
thiols. Our attention was drawn to the possibility
of the copper-catalyzed coupling of aryl iodides
and thiobenzoic acid [26]. This reaction was pre-
viously carried out to form S-pyridin-3-yl ben-
zenecarbothioate, which was subsequently used
for the oxidative synthesis of the corresponding
sulfochlorides [27].
The authors [26] also showed the possibility
of S-phenyl benzenecarbothioate cleavage with the
formation of thiophenol under mild conditions
(K2CO3, MeOH, rt). Thus, we decided to apply
this approach and investigate it on a number of
substituted 3-iodopyridines as the starting com-
pounds.
As a result, we have found that the reaction
of a number of 3-iodopyrimidines with thioben-
zoic acid in the presence of phenanthroline and
DIPEA as an organic base readily produces the
corresponding S-pyridin-3-yl benzenecarbothio-
ate. For more thorough purification, the residue
was subjected to the flash chromatography using
a gradient (toluene/hexane 1:1 to 100 % toluene)
on silica gel. This procedure turned out to be im-
portant for a significant increase in the yield of
thiols in the next step.
Further cleavage of thiobenzoate was carried
out in a 10-fold volume of methanol and using
a 40 % excess of a dry potassium carbonate at
room temperature. For the purification of the
target pyridine-3-thiol, the salt was dissolved in
water, and non-polar impurities were extracted
with methylene chloride. To isolate the product,
the aqueous layer was acidified to pH 5, and the
product was extracted with methylene chloride.
To remove residual acid, the organic layer was
washed with saturated sodium bicarbonate solu-
tion, dried, and evaporated. This isolation proce-
dure allows obtaining a pure product 3 without
additional operations (Scheme). The use of this
procedure enabled the preparation of a variety
of substituted pyridine-3-thiols in high yields.
In the spectra of compounds 3 obtained, a
clear signal of the SH group is observed in the
range of 2.89 – 4.29 ppm in CDCl3 and at 4.73 ppm
ISSN 2308-8303 (Print) / 2518-1548 (Online) 46
Журнал органічної та фармацевтичної хімії 2025, 23 (1)
in DMSO-d6 for 2,6-dimethoxypyridine-3-thiol 3.5,
indicating, together with the HRMS spectral data,
the formation of pure compound 3 with a thione
group without disulfide impurities.
■ Conclusions
An effective and practical two-step procedure
for the preparation of pyridine-3-thiol starting
from 3-iodopyridines has been developed. The sco-
pe of the iodo derivatives that could be used for
the reaction has been studied, and as a result,
12 substituted pyridine-3-thiols have been ob-
tained with a high yield.
■ Experimental part
All of the regents were taken from “Enami-
ne” Ltd stock. Analytical TLC was performed using
Polychrom SI F254 plates. The column chroma-
tography was performed using Kieselgel Merck 60
(230 – 400 mesh) as the stationary phase. 1H NMR
spectra were recorded on a Varian Unity Plus 400
(400 MHz) or a Bruker 170 AVANCE 500 (500 MHz)
instrument; 13C NMR spectra were recorded on
a Bruker 170 AVANCE 500 (126 MHz) or an
Agilent ProPulse 600 (151 MHz) spectrometer;
19F spectra were obtained on a Varian Unity
Plus 400 (376 MHz) spectrometer. HRMS spec-
tra were acquired with an Agilent 6200 Series
TOF and 6500 Series Q-TOF LC/MS System.
The general procedure for the coupling
step (compounds 2)
The reaction was carried out in a single-necked
flask. To 0.1 mol of the corresponding 3-iodopyri-
dine 1, 150 mL of toluene was added, then 3.6 g
of phenanthroline, 2 g of CuI, 30 mL of diisopro-
pylethylamine and 14 mL of thiobenzoic acid were
added while stirring. The flask was filled with ar-
gon. The reaction mixture was heated to 80 – 100 °C
for 12 – 16 h. Then 150 ml of hexane was added
to the cool reaction mixture. The reaction mix-
ture was chromatographed on a 200 mL Schott
funnel (50 – 60°C, 100 – 150 mL of silica gel) start-
ing from the toluene/hexane 1:1 phase and pure
toluene at the end furnishing thioesters 2.
The general procedure for the hydroly-
sis step (thiols 3)
The resulting thiobenzoate 2 was added to me-
thanol (1 g per 10 mL), then 40 % excess of dry
K2CO3 was added there. The hydrolysis took 1 h
at 25°C. Then methanol was evaporated, and the
residue was dissolved in the same amount of wa-
ter. The amount of water was twice washed with
dichloromethane, then acidified to pH 5 and ex-
tracted with dichloromethane. The dichlorome-
thane extract was separated and washed with
the aqueous sodium bicarbonate saturated solu-
tion. Then methylene chloride was evaporated
leaving a residue of the pure product 3.
Pyridine-3-thiol (3.1)
A yellow powder. Yield – 40 g (76 %). M. p.
77 – 79°C dec. 1H NMR (500 MHz, CDCl3), δ, ppm:
3.26 (1H, s, SH), 7.17 (1H, dd, J = 8.1, 4.7 Hz),
7.61 (1H, dt, J = 8.1, 2.0 Hz), 8.27 – 8.45 (1H, m),
8.52 (1H, d, J = 2.4 Hz). 13C NMR (126 MHz,
CDCl3), δ, ppm: 123.1, 127.8, 136.3, 146.3, 149.3.
HRMS (ESI/TOF-Q), m/z: calcd for C5H5NS
111.0143, found 111.0143.
2-Methoxypyridine-3-thiol (3.2)
A yellow liquid. Yield – 25 g (68 %). 1H NMR
(500 MHz, CDCl3), δ, ppm: 3.76 (1H, s, SH), 4.01
N
I PhC(O)SH
PhMe, 80 100– oC, 16 h
N
S Ph
O
K2CO3, MeOH, rt
R
N
SH
1.1 1.12–
R R
N
SH
N
SH
N
SH
N
SH
3.2, 68 % 3.3, 72 % 3.4, 85 % 3.5, 83 %
N
SH
3.1, 76 %
N
SH
3.6, 80 %
N
SH
N
SH
N
SH
N
SH
3.7, 84 % 3.8, 78 % 3.9, 89 % 3.10, 62 %
N
SH
3.11, 92 %
N
SH
3.12, 95 %
OMe NMe2 Me2N MeO OMe MeO
MeO
OMe
Cl
MeO
Cl
MeO
Br
FF
Br
OMe
Me Me
Br
MeO
2.1–2.12 3 1–3.12.
Scheme. The synthesis of substituted pyridine-3-thiols
ISSN 2308-8303 (Print) / 2518-1548 (Online) 47
Journal of Organic and Pharmaceutical Chemistry 2025, 23 (1)
(3H, s), 6.79 (1H, dd, J = 7.4, 4.9 Hz), 7.51 (1H,
dd, J = 7.4, 1.7 Hz), 7.95 (1H, dd, J = 5.0, 1.7 Hz).
13C NMR (126 MHz, CDCl3), δ, ppm: 53.5, 115.6,
116.6, 136.6, 142.7, 158.8. HRMS (ESI/TOF-Q),
m/z: calcd for C6H7NOS 141.0248, found 141.0246.
2-(Dimethylamino)pyridine-3-thiol (3.3)
A yellow liquid. Yield – 20.2 g (72 %). 1H NMR
(400 MHz, CDCl3), δ, ppm: 2.89 (7H, m, 2NCH3
+ SH), 4.30 (1H, s), 6.84 (1H, ddd, J = 7.6, 4.7,
2.0 Hz), 7.55 (1H, dd, J = 7.7, 1.8 Hz), 8.10 (1H,
dd, J = 4.8, 1.8 Hz). 13C NMR (151 MHz, CDCl3),
δ, ppm: 41.7, 118.1, 122.7, 138.1, 144.2, 160.1.
HRMS (ESI/TOF-Q), m/z: calcd for C7H10N2S
154.0565, found 154.0563.
6-(dimethylamino)pyridine-3-thiol (3.4)
A yellow powder. Yield – 18 g (85 %). M. p.
65 – 68°C. 1H NMR (500 MHz, CDCl3), δ, ppm:
3.05 (7H, m, 2NCH3 + SH), 6.41 (1H, d, J = 8.8 Hz),
7.41 – 7.47 (1H, m), 8.18 (1H, d, J = 2.5 Hz).
13C NMR (126 MHz, CDCl3), δ, ppm: 37.6, 105.4,
108.7, 141.3, 150.9, 157.9. HRMS (ESI/TOF-Q),
m/z: calcd for C7H10N2S 154.0565, found 154.0562.
2,6-Dimethoxypyridine-3-thiol (3.5)
A yellow powder. Yield – 39 g (83 %). M. p.
43 – 46°C (dec.). 1H NMR (400 MHz, DMSO-d6),
δ, ppm: 3.82 (3H, d, J = 1.2 Hz), 3.90 (3H, d,
J = 1.3 Hz), 4.73 (1H, s, SH), 6.35 (1H, dd, J
= 8.1, 1.3 Hz), 7.62 (1H, dd, J = 8.1, 1.3 Hz).
13C NMR (151 MHz, CDCl3), δ, ppm: 53.4, 54.0,
101.5, 101.8, 102.8, 141.8, 158.9, 161.6. HRMS
(ESI/TOF-Q), m/z: calcd for C7H9NO2S 171.0354,
found 171.0350.
5,6-Dimethoxypyridine-3-thiol (3.6)
A white powder. Yield – 41 g (80 %). M. p.
38 – 42°C. 1H NMR (500 MHz, CDCl3), δ, ppm:
3.29 (1H, s, SH), 3.84 (3H, d, J = 2.5 Hz), 3.97
(3H, d, J = 2.5 Hz), 7.02 (1H, t, J = 2.3 Hz),
7.70 (1H, d, J = 2.3 Hz). 13C NMR (126 MHz,
CDCl3), δ, ppm: 53.2, 55.2, 116.7, 120.3, 138.3,
143.3, 153.2. HRMS (ESI/TOF-Q), m/z: calcd for
C7H9NO2S 171.0354, found 171.0352.
5-Chloro-2-methoxypyridine-3-thiol (3.7)
A gray powder. Yield – 43.8 g (84 %). M. p.
48 – 52°C (dec.). 1H NMR (500 MHz, CDCl3), δ, ppm:
3.82 (1H, s, SH), 3.98 (3H, s), 7.48 (1H, d, J =
2.3 Hz), 7.86 (1H, t, J = 2.3 Hz). 13C NMR (126 MHz,
CDCl3), δ, ppm: 53.9, 117.4, 123.5, 135.7, 140.7,
157.2. HRMS (ESI/TOF-Q), m/z: calcd for
C6H6ClNOS 174.9859, found 174.9856.
5-Chloro-6-methoxypyridine-3-thiol (3.8)
A white powder. Yield – 39.8 g (78 %). M. p.
53 – 58°C (dec.). 1H NMR (500 MHz, CDCl3), δ, ppm:
3.30 (1H, s, SH), 3.99 (3H, s), 7.65 (1H, d, J =
2.2 Hz), 8.02 (1H, d, J = 2.2 Hz). 13C NMR (126 MHz,
CDCl3), δ, ppm: 53.9, 117.6, 117.8, 140.6, 146.0,
158.0. HRMS (ESI/TOF-Q), m/z: calcd for
C6H6ClNOS 174.9859, found 174.9858.
5-Bromo-6-methoxypyridine-3-thiol (3.9)
A white powder. Yield – 41.5 g (89 %). M. p.
49 – 53°C (dec.). 1H NMR (500 MHz, CDCl3), δ, ppm:
3.30 (1H, s, SH), 3.98 (3H, s), 7.82 (1H, d, J =
2.2 Hz), 8.06 (1H, d, J = 2.1 Hz). 13C NMR (126 MHz,
CDCl3), δ, ppm: 54.1, 106.4, 117.9, 143.9, 146.8,
158.7. HRMS (ESI/TOF-Q), m/z: calcd for
C6H6BrNOS 218.9353, found 218.9353.
2,6-Difluoropyridine-3-thiol (3.10)
A yellow powder. Yield – 25 g (62 %). M. p.
39 – 44°C (dec.). 1H NMR (400 MHz, CDCl3), δ, ppm:
3.56 (1H, s, SH), 6.80 (1H, dd, J = 8.2, 3.0 Hz),
7.69 – 7.85 (1H, m). 19F NMR (376 MHz, CDCl3),
δ, ppm: -72.31, -66.11. 13C NMR (126 MHz, CDCl3),
δ, ppm: 106.3 (dd, J = 35.3, 5.9 Hz), 109.7 (dd, J =
34.1, 6.2 Hz), 144.6 (dd, J = 7.3, 3.2 Hz), 155.9
(dd, J = 14.0, 3.2 Hz), 158.8 (dd, J = 242.3, 13 Hz),
159.4 (dd, J = 246.3, 12 Hz). HRMS (ESI/TOF-Q)
m/z: calcd for C5H3FNS 146.9954, found 146.9955.
5-Bromo-2-methoxy-4-methylpyridine-3-thiol
(3.11)
A white powder. Yield – 45.3 g (92 %). M. p.
63 – 65°C (dec.). 1H NMR (400 MHz, CDCl3), δ, ppm:
2.42 (3H, s), 4.02 (3H, s), 4.29 (1H, s, SH), 8.03
(1H, s). 13C NMR (126 MHz, CDCl3), δ, ppm:
20.0, 54.0, 114.9, 117.5, 142.2, 143.5, 157.0.
HRMS (ESI/TOF-Q), m/z: calcd for C7H8BrNOS
232.9510, found 232.9506.
6-methoxy-5-Bromo-4-methylpyridine-3-thiol
(3.12)
A white powder. Yield – 44.5 g (90 %). M. p.
65 – 67°C (dec.). 1H NMR (400 MHz, CDCl3), δ, ppm:
2.52 (3H, s), 3.16 (3H, s), 3.97 (1H, s, SH), 8.04
(1H, s). 13C NMR (126 MHz, CDCl3), δ, ppm:
21.2, 54.1, 109.3, 118.9, 146.0, 149.0, 159.1.
HRMS (ESI/TOF-Q), m/z: calcd for C7H8BrNOS
232.9510, found 232.9506.
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Information about the authors:
Oleksandr V. Borysov (corresponding author), Ph.D. in Chemistry, Senior Researcher, Medicinal Chemistry Department,
Institute of Organic Chemistry of the National Academy of Sciences of Ukraine; Scientific Advisor, Enamine Ltd.;
https://orcid.org/0000-0003-0360-9295; e-mail for correspondence: boav.79@gmail.com.
Dmytro P. Bohdan, PhD student, Medicinal Chemistry Department, Institute of Organic Chemistry of the National Academy
of Sciences of Ukraine.
|
| id | oai:ojs.journals.uran.ua:article-324523 |
| institution | Journal of Organic and Pharmaceutical Chemistry |
| issn | 2518-1548 |
| keywords_txt_mv | |
| language | English |
| last_indexed | 2026-08-24T01:01:27Z |
| publishDate | 2025 |
| publisher | National University of Pharmacy |
| record_format | ojs |
| resource_txt_mv | ophcjnupheduua/76/8af22fdd37378d9ec96fbc1fcd2e6a76.pdf |
| spelling | oai:ojs.journals.uran.ua:article-3245232026-08-23T15:25:30Z An Efficient Synthesis of a Variety of Substituted Pyridine-3-Thiols Ефективний метод синтезу різноманітних заміщених піридин-3-тіолів Borysov, Oleksandr V. Bohdan, Dmytro P. піридин тіоли тіобензойна кислота хроматографія гідроліз pyridine thiols thiobenzoic acid chromatography hydrolysis A practical and convenient method for the synthesis of pyridine-3-thiols using substituted 3-iodopyridines as starting compounds has been developed. Based on the use of thiobenzoic acid as a sulfur donor in a two-step procedure, this approach made it possible to synthesize a number of pyridine-3-thiols with F, Cl, Br, CH3, OCH3 substituents at various positions of the pyridine ring. The procedure presented gives high yields of the target products with a purity of 95% and is suitable for synthesis in tens of grams. Розроблено практичний і зручний метод синтезу піридин-3-тіолів із використанням як вихідних сполук заміщених 3-йодопіридинів. Цей підхід, заснований на використанні тіобензойної кислоти як донора сульфуру в межах двостадійної процедури, надав можливість синтезувати ряд піридин-3-тіолів із F, Cl, Br, CH3, OCH3 замісниками в різноманітних положеннях піридинового циклу. Зазначена процедура дозволяє одержати цільові продукти на масштабі десятків грам із високими виходами й чистотою 95%. National University of Pharmacy 2025-03-30 Article Article application/pdf https://ophcj.nuph.edu.ua/article/view/324523 10.24959/ophcj.25.324523 Journal of Organic and Pharmaceutical Chemistry; Vol. 23 No. 1 (2025); 43-48 Журнал органической и фармацевтической химии; Том 23 № 1 (2025); 43-48 Журнал органічної та фармацевтичної хімії; Том 23 № 1 (2025); 43-48 2518-1548 2308-8303 en https://ophcj.nuph.edu.ua/article/view/324523/317736 Copyright (c) 2025 Oleksandr V. Borysov, Dmytro P. Bohdan http://creativecommons.org/licenses/by/4.0 |
| spellingShingle | піридин тіоли тіобензойна кислота хроматографія гідроліз Borysov, Oleksandr V. Bohdan, Dmytro P. Ефективний метод синтезу різноманітних заміщених піридин-3-тіолів |
| title | Ефективний метод синтезу різноманітних заміщених піридин-3-тіолів |
| title_alt | An Efficient Synthesis of a Variety of Substituted Pyridine-3-Thiols |
| title_full | Ефективний метод синтезу різноманітних заміщених піридин-3-тіолів |
| title_fullStr | Ефективний метод синтезу різноманітних заміщених піридин-3-тіолів |
| title_full_unstemmed | Ефективний метод синтезу різноманітних заміщених піридин-3-тіолів |
| title_short | Ефективний метод синтезу різноманітних заміщених піридин-3-тіолів |
| title_sort | ефективний метод синтезу різноманітних заміщених піридин-3-тіолів |
| topic | піридин тіоли тіобензойна кислота хроматографія гідроліз |
| topic_facet | піридин тіоли тіобензойна кислота хроматографія гідроліз pyridine thiols thiobenzoic acid chromatography hydrolysis |
| url | https://ophcj.nuph.edu.ua/article/view/324523 |
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