Unexpected reactivity of 3-ethylsulfonyl-1,2,4-triazines with B 12H11SH?2-: First examples of the synthesis of boron-centered as-triazines and thioesters of ethyl sulfinic acid

Article abstract of DOI:10.1070/MC2003v013n06ABEH001843

The reaction of 3-ethylsulfonyl-5-methylamino-6-methylcarboxamido-1,2,4- triazine 1 with B₁₂H₁₁SH?^2- yields the boron-containing derivatives of 1,2,4-triazine 3. The interaction of 5,7-dimethyl-5,6,7,8-tetrahydropyrimido[4

Full text of DOI:10.1070/MC2003v013n06ABEH001843

,
2003, 13(6), 262–264
ù2–
Unexpected reactivity of 3-ethylsulfonyl-1,2,4-triazines with B H SH :
1
2
11
first examples of the synthesis of boron-centered as-triazines and thioesters
of ethyl sulfinic acid
Yuri Azev,*a,b Enno Lork, Thomas Duelcks and Detlef Gabel
a
a
a
a
Department of Chemistry, University of Bremen, D-28334, Germany.
Fax: +49 421 218 2871; e-mail: Gabel@chemie.uni-bremen.de
b
Ural Scientific Research Institute of Technology of Medical Preparations, 620219 Ekaterinburg, Russian Federation.
Fax: +7 3432 51 6281; e-mail: azural@dialup.utk.ru
1
0.1070/MC2003v013n06ABEH001843
2
–
The reaction of 3-ethylsulfonyl-5-methylamino-6-methylcarboxamido-1,2,4-triazine 1 with B H SHù yields the boron-con-
12
11
taining derivatives of 1,2,4-triazine 3. The interaction of 5,7-dimethyl-5,6,7,8-tetrahydropyrimido[4,5-e][1,2,4]triazine-6,8-dione
ù2–
2
with mercaptoborane B H SH gives boron-containing thiosulfinate 4 and bis(heteryl) ether 5.
12 11
Amino derivatives of 6-azalumazine may be produced by the
nucleophilic substitution of the 3-alkylthio group in 5,6,7,8-
tetrahydropyrimido[4,5-e][1,2,4]triazine-6,8-diones. Alkylsul-
O
Me
N
N
1
Na2[B12H11SH]
N
N
fonic groups possess a much higher nucleofugity than alkyl-
H
2
–4
thio groups. Thus, it was found
group in 5,7-dimethyl-5,6,7,8-tetrahydropyrimido[4,5-e]-
1,2,4]triazine-6,8-dione may be easily substituted in reactions
that the 3-alkylsulfonic
HN
SO Et
2
Me
N
Me
Me
[
1
with amines, water, sodium sulfide, sodium azide and various
C-nucleophiles.
O
2–
We studied the nucleophilic substitution of alkylsulfonic
Me
N
ù2–
N
N
derivatives of as-triazine with the mercaptoborane B H SH
2
1
2
11
H
as a nucleophile, which can be alkylated and acylated to produce
Me
N
H
Me
5
HN
N
S
sulfonium ions or thio esters.
3
-Ethylsulfonyl-5-methylamino-6-methylcarboxamido-1,2,4-
Me
triazine 1 and 3-ethylsulfonyl-5,7-dimethyl-5,6,7,8-tetrahydro-
pyrimido[4,5-e][1,2,4]triazine-6,8-dione 2 (produced by the
oxidation of corresponding alkylthio derivatives as described
3
=
B or BH
Scheme 1
earlier2 ) were used as starting heterylsulfones for reactions
,3
ù2–
with B H SH
.
1
2
11
Instead of a nucleophilic attack on the 3-carbon atom of
heterocyclic compound 2 with the substitution of the alkyl-
sulfonyl group, the boron-bonded thiol attacked the sulfur atom
of the sulfone. As a result, in this case, unknown compounds 4
and 5 were obtained.
The H NMR spectrum of 4 contains proton signals of the
Et group and of lutidine with the expected ratio 1:2 between
ù2–
We found that sulfone 1 reacted with B H SH at room
temperature in the presence of lutidine to form the boron-
containing derivatives of 1,2,4-triazine 3 (Scheme 1).
1
2
11
†
,‡
The 1H NMR spectrum of compound 3 contains proton
signals of 5-MeNH and 6-MeNH substutients of s-triazine and
the signals of protons of two molecules of lutidine. The
negative-ion fast atom bombardment (FAB) mass spectrum
shows an ion at m/z 339, which corresponds to the boron-
containing molecular anion of compound 3. In the positive-
ion FAB spectrum, an ion at m/z 108 corresponding to the
1
these groups.‡
X-ray structure analysis showed that compound 4 is the
crystalline hydrate of the salt of the doubly charged anion of
protonated lutidine (C H N) is observed.
‡
1H and 13C NMR spectra were recorded on a Bruker DPX 200
7
10
We obtained unexpected products from the reaction of sulfone
spectrometer. Chemical shifts were measured relative to DMSO as an
internal standard.
†
,‡
2
with Na [B H SH] under similar conditions (Scheme 2).
2 12 11
Mass spectra were measured on a Finnigan MAT 8200 double-focusing
mass spectrometer. Electron impact (EI) ionization conditions: electron
energy of 70 eV and ion source temperature of 200 °C. Fast atom
bombardment (FAB) mass spectra were recorded using a Xe atom gun
(beam energy of 8 keV) and 3-nitrobenzyl alcohol (NBA) as the matrix.
†
Reaction of sulfone 1 with Na [B H SH]. 0.078 g (0.3 mmol) of
2
12 11
sulfone 1 was stirred with 0.095 g (0.43 mmol) of Na [B H SH] in 2 ml
2
12 11
of acetonitrile in the presence of 0.05 ml of lutidine for 3 h at room
temperature. The reaction mixture was filtered, and the filtrate was
evaporated in vacuo. The residue was treated with 2 ml of water, and 3
was obtained as a solid. The product was recrystallised from water; yield
1
2
For 3: H NMR ([ H ]DMSO) d: 2.66 (s, 12H, 4Me lutidine), 2.71 (d,
6
3H, NMe, J 4.9 Hz), 3.01 (d, 3H, NMe, J 5.4 Hz), 7.69 (d, 4H, 2×3-H
and 2×5-H lutidine, J 7.8 Hz), 8.32 (t, 2H, 2×4-H lutidine, J 7.8 Hz),
0
.053 g (33%), mp 148–150 °C.
1
3
Reaction of sulfone 2 with Na [B H SH]. 0.470 g (1.60 mmol) of
9.11 (q, 1H, NH, J 5.4 Hz), 10.15 (q, 1H, NH, J 4.9 Hz). C NMR
2
12 11
2
sulfone 2, 0.360 g (1.63 mmol) of Na [B H SH] and 0.2 ml of lutidine
([ H ]DMSO) d: 20.11 (2Me lutidine), 26.78 (NMe), 29.23 (NHMe),
2
12 11
6
3
5
4
were stirred in 10 ml of acetonitrile for 1 h at room temperature. Crys-
tals of di(5,7-dimethylpyrimido[4,5-e][1,2,4]triazin-3-yl)ether 5 were
filtered off. Product 5 precipitated from dimethyl sulfoxide with ethanol
with a yield of 0.20 g (30%), mp > 250 °C.
125.52 (2×C ,C lutidine), 131.65 (C triazine), 146.58 (2×C lutidine),
2
6
152.32 (C triazine), 153.83 (2×C ,C lutidine), 162.80, 172.28 (C triazine).
For 4: H NMR ([ H ]DMSO) d: 1.14 (t, 3H, Me, J 7.5 Hz), 2.67 (s,
1
2
6
6H, 2Me lutidine), 2.79 (q, 2H, CH , J 7.5 Hz), 7.70 (d, 4H, 2×3-H and
2
The mother liquor was evaporated in vacuo, the residue was treated
with 2 ml of ethanol, filtered, and crystallised from 30% water/ethanol.
Compound 4 [0.250 g (32%) yield] was obtained, mp 170–171 °C.
2×5-H lutidine, J 7.8 Hz), 8.34 (t, 2H, 2×4-H lutidine, J 7.8 Hz).
1
3
2
C NMR ([ H ]DMSO) d: 8.36 (Me), 20.16 (4Me lutidine), 52.71 (CH ),
6
2
3
5
4
2
6
125.56 (2×C ,C lutidine), 146.63 (2×C lutidine), 153.80 (2×C ,C
lutidine).
For 5: H NMR ([ H ]DMSO) d: 3.20 (s, 3H, NMe), 3.26 (s, 3H,
0
.066 g (0.16 mmol) of product 5 was suspended in 8 ml of water,
.2 ml trifluoroacetic acid was added, the mixture was stirred for 3–5 min
1
2
0
6
1
3
2
and filtered. The filtrate was evaporated in vacuo, the residue was treated
with 1 ml of water and filtered to yield 0.01 g (29%) of 3-hydroxy-5,7-
dimethyl-5,6,7,8-tetrahydropyrimido[4,5-e][1,2,4]triazine-6,8-dione 6,
mp > 250 °C.
NMe). C NMR ([ H ]DMSO) d: 27.79 (Me), 28.32 (Me), 123.21,
6
152.02, 152.82, 160.34, 165.82 (Chetaryl).
1
3
2
For 6: C NMR ([ H ]DMSO) d: 29.02 (Me), 29.47 (Me), 125.14,
6
151.33, 154.40, 155.24, 157.91 (Cheteryl).
–
262 –

,
2003, 13(6), 262–264
O
C(6) C(7)
C(5)
C(11)
N(2)
Me
N
N
O(2)
N
N
C(9)
C(8)
C(12)
C(13)
C(10)
C(15)
O
N
SO Et
2
C(3) N(1)
C(4)
C(16)
B(10)
C(14)
Me
O(1)
S(2)
2
B(7)
Me
2–
C(1)
C(2)
Na [B12H11SH]
2
B(6)
B(1)
B(8)
2
O
S
B(12)
N
Me
N
H
Me
B(2)
S(1)
Me
S
B(4)
B(9)
B(11)
4
B(5)
O
O
B(3)
Me
N
N
N
Me
N
N
N
N
Figure 1 Molecular structure of compound 4. Selected bond lengths (Å):
C(1)–C(2) 1.53(1), S(1)–B(1) 1.898(8), S(1)–S(2) 2.088(3), S(2)–C(1)
1.81(1), S(2)–O(1) 1.486(5). Selected bond angles (°): B(1)–S(1)–S(2)
O
N
N
O
N
O
9
6.0(3), O(1)–S(2)–C(1) 105.0(5), O(1)–S(2)–S(1) 108.4(3), C(1)–S(2)–
Me
Me
S(1) 96.8(3), C(2)–C(1)–S(2) 110.5(8).
5
paths and products by the DADI (Direct Analysis of Daughter
Ions) technique showed that the ions at m/z 385 (M – Me), 372
O
N
(
C H N O , exp. 372.09273, theor. 372.09307, ∆ 0.9 ppm,
14 12 8 5
Me
N
N
M – N ) are formed directly from the molecular ion at m/z 400.
N
N
2
=
B or BH
Using precursor ion analysis, we found that the ion at m/z 208
O
OH
O
Me
Me
Me
O
6
N
N
N
O
Scheme 2
Me
N
N
*
– N2
N
N
N
the boron-containing thioester of ethylsulfinic acid with two
molecules of protonated lutidine {(2,6-Me C H NH) -
C14H12N O5
8
N
2
5
3
2
O
N
O
§
m/z 372.09807
[
B H SS(O)Et]·H O, Figure 1}. The thiosulfinate group of
12 11 2
the crystals of 4 is an irregular pyramide with the sulfoxide
S-atom on top and the sulfide S-atom, oxygen and CH group
forming the base of the pyramide. The bond lengths are: S–O,
Me
*
2
C14H12N10O5
1
48.6 pm; S–S, 208.8 pm; B–S, 189.8 pm; S–C, 181.2 pm.
In the H NMR spectrum of compound 5 only signals of
C H N O
7 6 5 3
m/z 400.09967
1
m/z 208.04706
the N–Me groups of the pyrimidine part of the molecule are
present. The C NMR spectrum of 5 contains seven signals
of the pyrimidotriazine fragment (5 C-atoms of the pyrimido-
triazine ring and 2 C-atoms of N–Me groups).
The molecular formula C H N O of product 5 was con-
firmed by high resolution mass spectrometry (HRMS) (theor.
‡
13
Scheme 3
‡
originates from the ions with m/z 220, 223, 287, 372 and 400.
The proof of m/z 208 (C H N O , exp. 208.04616, theor.
7
6
5
3
1
4
12 10
5
2
(
08.04706, ∆ 0.9 ppm) originating from the molecular ion
m/z 400) by this scanning technique is especially important
since this could not be confirmed by DADI due to the low
intensity of this ion.
4
00.09921, confirmed ±5 ppm). Investigation of the cleavage
§
Crystal data for 4: at 173(2) K, a crystal of C H N B OS ·H O
16
36
2
12
2
2
During crystallization of compound 5 from aqueous acid
(0.40×0.30×0.10 mm) is orthorhombic, a = 1649.1(3), b = 1661.6(3),
1
3
solutions, we isolated 3-hydroxy derivative 6. Probably, the
c = 996.1(2) pm, V = 2.7294(9) nm , space group Pna2 , Z = 4, d
=
IPDS diffractometer, q range for data collection, 2.38 to 23.49°, index
ranges, –18 £ h £ 18, –18 £ k £ 18, –11 £ l £ 11, reflections collected
=
1
calc
–
3
–1
formation of 6 is connected with easy hydrolysis of 5 under
1.179 g cm , m = 0.213 mm , l = 71.073 pm, F(000) = 1024, STOE
these conditions.
Thus, depending on the nature of the hetarylic substituent,
two different reactivities of sulfonic derivatives with B H SH
1
5151, independent reflections 4042 (Rint = 0.1537), completeness to
ù2–
12
11
q = 23.49° 100.0%, max. and min. transmissions, 0.9790 and 0.9195;
may occur:
1) a nucleophilic attack of B H SH on the C-3 atom of
2
refinement method full-matrix least-squares on F , data/restraints/
ù2–
(
1
2
11
parameters 4042/4/331, Goodness-of-fit on F2 0.853, final R indices
the triazine ring of sulfone 1, cleaving off ethylsulfonic acid
and leading to formation of undecahydrododecaboranylthio-5-
methylamino-6-methylcarboxamido-1,2,4-triazine 3;
(2) an attack of B H SH on the S-atom of the 3-sulfonic
group of pyrimidotriazine 2 leading to the formation of a boron-
containing thioester of ethylsulfinic acid 4 and bis(heteryl)
ether 5.
[
I > 2s(I)] R = 0.0665, wR = 0.1208, R indices (all data) R = 0.1490,
1
2
1
wR = 0.1448, the structure was refined as a racemic twin with a
2
fractional contribution of the main component 0.52(17), largest diff.
ù2–
–3
12 11
peak and hole 0.399 and –0.225 eÅ . The structure was solved by direct
methods, the subsequent least-squares refinement located the positions
of the remaining atoms in the electron density maps. All non-hydrogen
atoms were refined with individual anisotropic deflection parameters.
H atoms were calculated with common isotropic temperature factors.
6
All calculations were performed with the SHELX program package.
This work was supported by Deutsche Forschungsgemein-
schaft (grant no. DFG 436 RUS 17/54/02).
Figure 1 was drawn with the use of the DIAMOND program.7
Atomic coordinates, bond lengths, bond angles and thermal param-
eters have been deposited at the Cambridge Crystallographic Data Centre
References
(
CCDC). These data can be obtained free of charge via www.ccdc.cam.uk/
conts/retrieving.html (or from the CCDC, 12 Union Road, Cambridge
CB2 1EZ, UK; fax: +44 1223 336 033; or deposit@ccdc.cam.ac.uk).
Any request to the CCDC for data should quote the full literature citation
and CCDC reference number 227402. For details, see ‘Notice to Authors’,
Mendeleev Commun., Issue 1, 2003.
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2 Yu. A. Azev, I. Ya. Postovskii, E. L. Pidemskii and A. Ph. Goleneva,
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3 Yu. A. Azev, N. N. Vereshagina, I. Ya. Postovskii, E. L. Pidemskii and
A. Ph. Goleneva, Khim.-Farm. Zh., 1981, 50 (in Russian).
–
263 –

,
2003, 13(6), 262–264
4
5
6
Yu. A. Azev, D. Gabel, U. Dörfler, M.-E. El-Zaria, C. Bauer, S. V. Shorshnev
and N. A. Klyuev, Khim.-Farm. Zh., 2003, 20 (in Russian).
D. Gabel, D. Moller, S. Harfst, J. Rösler and H. Ketz, Inorg. Chem.,
7 DIAMOND – Visual Crystal Structure Information System, CRYSTAL
IMPACT, Postfah 1251, D-53002 Bonn.
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G. M. Sheldrick, SHELX Program Package, University of Götingen, 1993.
Received: 28th July 2003; Com. 03/2169
–
264 –