2-(3-acylselenoureido)benzonitriles and 2-(3-acylselenoureido)thiophene-3-carbonitriles. Preparation, structure elucidation, cyclization and retrocyclization reactions

Article abstract of DOI:10.1135/cccc19991673

Synthesis of 2-(3-acylselenoureido)benzonitriles and 2-(3-acylselenoureido)thiophene-3-carbonitriles 5a-5f by addition of 2-aminonitriles 4a-4c to benzoyl- or 2,2-dimethylpropanoylisoselenocyanate and their cycloaddition reactions are described. Structures of compounds 5a-5f were supported by CIMS, FTIR, ¹H, ¹³C, ⁷⁷Se and ¹⁵N NMR spectra. The parameters of ¹⁵N and ⁷⁷Se nuclei were obtained from inverse ¹H-X 2D HMBC and GSQMBC correlation experiments at natural abundance. Structure of compound 5b was confirmed by X-ray analysis. The geometry of 5b was optimized by ab initio RHF/DZVP quantum chemistry calculation. A very good correlation between the calculation and experimental data was found. The geometry of 5e was optimized by ab initio DFT/VWN/DZVP quantum chemistry calculation. It was found that title compounds 5a-5f do not undergo isomerization to acylisoselenoureas, in contrast to analogous ester derivatives. Fused 6-imino-6H-1,3-selenazinium salts (chlorides 6a-6f, hydrogensulfates 7a-7f and tetrafluoroborates 8a-8f) were prepared by an acid cyclization of 5a-5f. It was found that neutralization of 6a-6f, 7a-7f and 8a-8f led to their retrocyclization to 5a-5f. Selenoureas 5a-5f with equimolar amounts of methanolic potassium hydroxide afforded potassium salts 9a-9f. Only the salts 9b, 9c, 9e and 9f of the thiophene series were isolated. Their heating in methanol solution led to deacylation of isoselenoureas 10b and 10c. The in situ prepared compounds 9a and 9d cyclized and deacylated to 4-aminoquinazoline-2-selenole 11a under the same conditions. The compounds 5a-5f and 10a-10c cyclized to fused 4-aminopyrimidine-2-selenols 11a, 11b and 4-aminopyrimidine-2-selenone 12c by boiling in methanolic potassium hydroxide solution.

Full text of DOI:10.1135/cccc19991673

Benzonitriles and Carbonitriles
1673
2-(3-ACYLSELENOUREIDO)BENZONITRILES AND
2-(3-ACYLSELENOUREIDO)THIOPHENE-3-CARBONITRILES.
PREPARATION, STRUCTURE ELUCIDATION, CYCLIZATION
AND RETROCYCLIZATION REACTIONS
a
a4
Jiří ŠIBORa1, Dalimil ŽŮREK , Radek MAREKa2, Michal KUTÝa3, Otakar HUMPA
,
b1
a5,
Jaromír MAREK and Pavel PAZDERA
*
a
Department of Organic Chemistry, Faculty of Science, Masaryk University, Kotlářská 2,
611 37 Brno, Czech Republic; e-mail: sibor@chemi.muni.cz, rmarek@chemi.muni.cz,
michal@chemi.muni.cz, humpa@chemi.muni.cz, pazdera@chemi.muni.cz
Department of Inorganic Chemistry, Faculty of Science, Masaryk University, Kotlářská 2,
611 37 Brno, Czech Republic; e-mail: marek@chemi.muni.cz
1
2
3
4
5
b
Received Jan uary 25, 1999
Accepted Jun e 8, 1999
Dedicated to Professor Otto Exner on the occasion of his 75th birthday.
Syn th esis of 2-(3-acylselen oureido)ben zon itriles an d 2-(3-acylselen oureido)th ioph en e-
3-carbon itriles 5a–5f by addition of 2-am in on itriles 4a–4c to ben zoyl- or 2,2-dim eth yl-
propan oylisoselen ocyan ate an d th eir cycloaddition reaction s are described. Structures of
com poun ds 5a–5f were supported by CIMS, FTIR, 1H, 13C, 77Se an d 15N NMR spectra. Th e
param eters of 15N an d 77Se n uclei were obtain ed from in verse 1H-X 2D HMBC an d GSQMBC
correlation experim en ts at n atural abun dan ce. Structure of com poun d 5b was con firm ed by
X-ray an alysis. Th e geom etry of 5b was optim ized by ab initio RHF/DZVP quan tum ch em is-
try calculation . A very good correlation between th e calculation an d experim en tal data was
foun d. Th e geom etry of 5e was optim ized by ab initio DFT/VWN/DZVP quan tum ch em istry
calculation . It was foun d th at title com poun ds 5a–5f do n ot un dergo isom erization to
acylisoselen oureas, in con trast to an alogous ester derivatives. Fused 6-im in o-6H-1,3-
selen azin ium salts (ch lorides 6a–6f, h ydrogen sulfates 7a–7f an d tetrafluoroborates 8a–8f)
were prepared by an acid cyclization of 5a–5f. It was foun d th at n eutralization of 6a–6f,
7a–7f an d 8a–8f led to th eir retrocyclization to 5a–5f. Selen oureas 5a–5f with equim olar
am oun ts of m eth an olic potassium h ydroxide afforded potassium salts 9a–9f. On ly th e salts
9b, 9c, 9e an d 9f of th e th ioph en e series were isolated. Th eir h eatin g in m eth an ol solution
led to deacylation of isoselen oureas 10b an d 10c. Th e in situ prepared com poun ds 9a an d
9d cyclized an d deacylated to 4-am in oquin azolin e-2-selen ole 11a un der th e sam e con di-
tion s. Th e com poun ds 5a–5f an d 10a–10c cyclized to fused 4-am in opyrim idin e-2-selen ols
11a, 11b an d 4-am in opyrim idin e-2-selen on e 12c by boilin g in m eth an olic potassium h y-
droxide solution .
Key w ord s: Acylselen oureas; Fused 1,3-selen azin es; Fused pyrim idin es; 2-Am in oth ioph en e-
3-carbon itriles; 2-Am in oben zon itrile; NMR spectroscopy, m ultin uclear; Ab initio calculation s;
X-Ray diffraction ; Selen ium h eterocycles.
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

1674
Šibor et al.:
Th e in terest of our research group in th e past few years h as been focused on
th e syn th esis of fused 1,3-th iazin es, pyrim idin es, 1,3-selen azin es an d
1,3-oxazin es. Th e precursors available for th eir syn th esis are fun ction al de-
rivatives of carbon ic acid (ureas, th ioureas, selen oureas or guan idin es) de-
rived from 2-am in o substituted arom atic or h eteroarom atic n itriles or
esters. Th ese precursors cyclize to th e correspon din g azin e skeleton s un der
acid or base catalysis.
In th e literature th e syn th eses of th e title cyan o substituted acyl-
selen oureas h ave n ot been described yet. However, we publish ed th e syn -
th esis1 of an alogous eth yl esters 2a–2f an d th eir isom erization to
acylisoselen oureas 3a–3f in itiated ph otoch em ically, th erm ally or by th e ac-
tion of acid (Sch em e 1).
OEt
OEt
COOEt
NH2
R
O
O
O
C N C Se
+
H
H
N
O
N
O
1a-1c
Se
N
H
R
Se
H
N
R
2a-2f
3a-3f
R
R
1-3
a
1-3
d
e
f
t-Bu
t-Bu
t-Bu
Ph
Ph
b
S
S
S
H3C
H3C
H3C
H3C
c
Ph
S
SCHEME 1
Structure of both types of isom ers was supported by FTIR, 1H, 13C, 15N
an d 77Se NMR spectroscopies. Th e results from spectral study were sup-
ported by X-ray structural an alysis an d also by ab initio quan tum ch em istry
calculation s.
Ester an alogues1 2a–2f of title com poun ds were syn th esized by addition
of 2-am in oesters 1a–1c to carbon atom of isoselen ocyan ato group in
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Benzonitriles and Carbonitriles
1675
ben zoyl- an d 2,2-dim eth ylpropan oylisoselen ocyan ate, respectively. Th e re-
action s were carried out in aceton e solution at room tem perature. An at-
tem pt to prepare an alogous acetyl- an d (alkoxycarbon yl)selen oureas was
un successful. Nor was successful th e acylation of startin g am in es by
acylisoselen ocyan ates. In stead, com petitive attack of th e am in o group on
th e acyl carbon atom appeared.
Sim ilar isom erization h as n ot been observed with th e title cyan o com -
poun ds. However, cyclization reaction s of sulfur an alogues of title com -
poun ds in basic2–8 an d acid8–12 m edium were studied at full len gth . Th e
reactivity of ureido an alogues was studied as well13,14
.
Th e goal of th is work was preparation of th e title acylselen oureas an d
study of th eir reactivity in acid-in itiated cycloaddition givin g fused
1,3-selen azin es, cyclization by th e action of th e bases leadin g to fused
1,2-dihydropyrim idine-2-selenones, as well as their retrocyclization reactions.
RESULTS AND DISCUSSION
We h ave attem pted to prepare (acylselen oureido)n itriles 5a–5f by an addi-
tion of correspon din g am in es 4a–4c to acylisoselen ocyan ates (Sch em e 2)
an alogously to th e syn th esis1 of (acylselen oureido)esters 2a–2f. Acetyl-,
ben zoyl-, 2,2-dim eth ylpropan oyl-, eth oxycarbon yl- an d m eth oxycarbon yl-
isoselen ocyan ate prepared in situ were used in th eir aceton e solution s. In
accordan ce with th e results obtain ed with ester an alogues, we h ave ob-
CN
HSeCN
R = Me, OMe, OEt
+
NH COR
CN
R
O
C N C Se
+
NH2
CN
4a-4c
R = Ph, t-Bu
NH C NH COR
Se
Substituents for compounds a-f: see Scheme 1
5a-5f
SCHEME 2
tain ed good yields on ly with ben zoyl- an d 2,2-dim eth ylpropan oyl-
isoselen ocyan ates. Th e oth er acylisoselen ocyan ates gave eith er th e
acylation product of th e startin g am in oester (iden tified by com parison with
th e product obtain ed by acylation of th e correspon din g am in es with acyl
ch lorides) or a m ixture of th is com poun ds with acylselen ourea. Th e sam e
results were described earlier for an alogous addition reaction s1,15–18
.
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

1676
Šibor et al.:
Ben zoylselen oureas 5a–5c were also syn th esized by th e reaction of
ben zoylisoselen ocyan ate oligom er with startin g am in es 4a–4c in boilin g
toluen e solution . Th e yields of 5a–5c were about 10–15% lower th an with
ben zoylisoselen ocyan ate m on om er gen erated in situ.
Iden tification of acylselen oureas 5a–5f was based on C, H, N an d Se ele-
m en tal an alysis, m ass spectroscopy, FTIR spectra an d 1H, 13C, 77Se an d 15N
NMR spectroscopy. Th e spectral data were com pared with th e data foun d
for ester an alogues an d a good correlation between th eir spectral param e-
ters was foun d.
In m ass spectra, m olecular peak M+, peak (M + 1)+, and fragm ents of (RCO)+,
(HNCSe)+, (M – RCO)+, (M – SeH)+, (M – HseCN)+ and (NHCSeNHCOR)+ were
foun d. A sim ilar fragm en tation was observed in th e case of th e sulfur an a-
logues an d products of th eir acid cyclization , i.e. 1,3-th iazin ium salts8–10
.
In FTIR spectra of com poun ds 5a–5f, th e ban d of cyan o group, th e corre-
spon din g ban ds of –NHCO– group (am ide I an d am ide II ban ds)19 an d
selen oureido group (selen oam ide I an d III ban ds)20 as well as stretch in g vi-
bration ban ds of N–H were foun d.
1H NMR spectroscopy of com poun ds 5a–5f con firm s th e presen ce of pro-
ton s localized on th e basic skeleton s, acyl groups an d both n itrogen atom s
of th e selen oureido group. Proton sign als of th e NHCSe groups are sign ifi-
can tly desh ielded, com pared with NHCO, sim ilarly to th e ester an alogues,
due to th e h ydrogen bon din g effects. Th e sign al of NHCSe proton in
n itriles 5a–5f is sh ifted approxim ately 0.5 ppm upfield in com parison with
th e ester an alogues, probably because of a differen t electron -with drawin g
beh aviour of th e cyan o an d eth oxycarbon yl groups. Th e com parison of th e
ch em ical sh ifts at th e NHCSe group proton in th e ben zoyl an d
2,2-dim eth ylpropan oyl series in dicates stron ger in teraction of th e NHCSe
group proton with acyl oxygen atom in th e form er com poun ds.
Assign m en t of th e proton sign als was carried out on th e basis of 2D
ch em ical sh ift correlation experim en ts for selected com poun ds 5a–5f. Th e
1
sign als for oth er com poun ds were assign ed on th e basic of an alogy. H–1H
dipolar in teraction s for com poun ds 5a–5f were determ in ed by 2D NOESY
1
experim en t. For observation of h eteron uclear H–13C in teraction s (both di-
rect an d lon g-ran ge) HETCOR, COLOC, HSQC an d HMBC pulse sequen ces
were used. Th e sin gle-bon d 13C-77Se couplin g con stan ts were extracted from
th e 77Se satelites observed in 13C (1H) spectra. HMBC an d GSQMBC experi-
1
m en ts were also used for detection of H–5N an d 1H–77Se lon g-ran ge in ter-
action s. Th e detailed NMR study on h eteron uclear lon g-ran ge couplin g
con stan ts will be presen ted elsewh ere21
.
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Benzonitriles and Carbonitriles
1677
A sin gle crystal of 2-(3-ben zoylselen oureido)-4,5,6,7-tetrah ydroben zo-
[1]th ioph en e-3-carbon itrile h em ih ydrate (5b) was used for th e X-ray struc-
tural an alysis. Th e sam ple suitable for X-ray study was obtain ed by crystalli-
zation from ch loroform saturated at room tem perature with water an d th en
with com poun d 5b. Th e crystallization was carried out in a 5 m m NMR
tube at –30 °C. Preparation of a suitable sin gle crystal of an h ydrous com -
poun d 5b was un successful because th e crystals developed on ly in on e di-
m en sion as lon g n eedles an d provided diffraction in sufficien t for an alysis.
Th e foun d structural data presen ted in Tables I–III correspon d very well
with th ose calculated by ab initio DSF quan tum ch em istry calculation s.
Both th e calculated an d X-ray m olecular structures of 5b are presen ted in
Figs 1 an d 2. Crystallograp h ic d ata for th e stru ctu res rep orted in th is
p ap er h ave been d ep osited with th e Cam brid ge Crystallograp h ic Data
Cen tre as su p p lem en tary p u blication n u m ber CCDC-116 933. Cop ies
of th e data can be obtain ed free of ch arge on application to CCDC, e-m ail:
deposit@ccdc.cam .ac.uk. Sin ce we could n ot obtain suitable sin gle crystals
of 5e an d th e reported correspon den ce between th e X-ray an d ab initio RHF
data for com poun d 5b was very good, we tried to m odel an d optim ize th e
m olecular structure of 2,2-dim eth ylpropan oyl an alogues 5e by
DFT/VWN/DZVP quan tum ch em istry m eth od. Th e m olecular design of
com poun d 5e is presen ted in Fig. 3 an d som e structural data in Tables I–III.
Th e obtain ed results sh owed th at th e h ydrogen bon d between th e NHCSe
h ydrogen an d th e carbon yl oxygen is stron ger in th e case of ben zoyl deriv-
ative th an in its 2,2-dim eth ylpropan oyl an alogue. Th is observation is in
1
good accord with th e H NMR spectra.
Th e ester an alogues of title com poun ds un derwen t isom erization to
acylisoselen oureas1. In th e case of n itriles 5a–5f, th e isom erization in itiated
by ligh t or con trolled h eatin g was un successful. Th e attem pted
N13′
C15′
C14′
C12′
C4′
C22′
C19′
O11′
C20′
C23′
C21′
C3′
C2′
N6′
C16′
C10′
N8′
C5′
C17′
C7′
S1′
O24
Se9′
Se9
S1
N8
C21
C7
N6
C17
C16
C19
C2
C10
O11
C5
C4
C18
C20
FIG. 1
C23
C15
C3
C14
Molecular structure of 5b accordin g
to th e X-ray an alysis
C12
C22
N13
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

1678
Šibor et al.:
isom erization of 5a–5f by boilin g in acetic acid led to th e correspon din g
1,3-selen azin ium acetates. Th ese were separated from th e reaction m ixture
as tetrafluoroborates 8a–8f. Th e form ation of th e correspon din g
1,3-selen azin ium ch lorides usin g h ydrogen ch loride in an h ydrous m eth a-
n ol was also observed.
High er th erm odyn am ic stability of isoselen oureas is probably th e reason
for th e isom erization in ester series. However, th e n itriles are m ore stable
th an selen oureas. Th erm al an alysis also sh owed an exoth erm ic process1
durin g isom erization of ester an alogues. In th e case of n itriles 5a–5f, th is
process was n ot observed. Th e stability of both isom ers is depen den t on
two types of in tram olecular h ydrogen bon ds. Th is fact was sh own by th e
NMR studies an d ab initio quan tum ch em istry calculation s1. Th e first h y-
drogen bon d exists between th e carbon yl oxygen atom of th e ester fun ction
an d th e NHCSe group h ydrogen atom ; th e oth er type is form ed between
th e acyl oxygen atom an d Se–H h ydrogen atom . Th ese h ydrogen bon ds do
n ot exist in n itrile series (Figs 1–3). On th e oth er h an d, com poun ds 5a–5f
FIG. 2
Molecular design of 5b accordin g to th e com putation al ch em istry
FIG. 3
Molecular design of 5e accordin g to th e com putation al ch em istry
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Benzonitriles and Carbonitriles
1679
TABLE I
Selected in teratom ic distan ces (Å) in 5b an d 5e
Bon d
5b (X-ray)
5b (calculated)
5e (calculated)
C5–N6
1.39
1.33
1.37
1.38
1.50
1.81
0.86
0.86
1.21
1.72
1.37
1.43
1.13
1.39
1.33
1.36
1.38
1.49
1.83
1.02
1.04
1.22
1.72
1.38
1.44
1.17
1.38
1.33
1.36
1.38
1.30
1.81
1.15
1.02
1.23
1.72
1.38
1.44
1.15
N6–C7
C5–N6
N6–C7
C10–C18
C7–Se9
N6–NH6
N8–NH8
C10–O11
S1–C5
C4–C5
C4–C12
C12–N13
TABLE II
Selected valen cy an gles (°) in 5b an d 5e
An gle
5b (X-ray)
5b (calculated)
5e (calculated)
114.56
115.05
115.26
C5–N6–NH6
NH6–N6–C7
C5–N6–C7
114.95
130.49
115.89
125.51
118.60
127.18
117.19
121.60
121.20
123.24
177.67
114.82
131.27
116.17
127.09
119.06
128.74
117.35
123.26
122.85
124.84
178.26
114.84
132.85
116.26
124.35
119.47
128.04
117.17
123.27
124.15
122.36
179.28
N6–C7–N8
N6–C7–Se9
Se9–C7–N8
C7–N8–C10
N8–C10–C18
O11–C10–C18
O11–C10–N8
C5–C4–C12
C4–C12–N13
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

1680
Šibor et al.:
sh ow th e h ydrogen bon d between th e acyl oxygen atom an d th e NHCSe
group h ydrogen , wh ich is sh orter an d stron ger. Table IV con tain s h ydrogen
bon d distan ces of both selen ourea types an d isoselen oureas for th e
4,5,6,7-tetrah ydroben zo[1]th ioph en e skeleton as a m odel.
It is well kn own 8–12 th at in th e acidic m edium , th e sulfur an alogues of ti-
tle com poun ds 5a–5f m ay cyclize by an attack of th e sulfur on th e n itrile
carbon to form th e correspon din g 1,3-th iazin ium com poun d. Th ese reac-
tion s proceeded in con cen trated sulfuric acid at room tem perature. Wh en
TABLE III
Selected torsion an gles (°) in 5b an d 5e
An gle
5b (X-ray)
5b (calculated)
5e (calculated)
179.73
184.35
181.42
S1–C5–N6–NH6
NH6–N6–C7–Se9
Se9–C7–N8–C10
C7–N8–C10–O11
C7–N8–C10–C18
C5–N6–C7–N8
N6–C5–C4–C12
S1–C5–C4–C12
–179.40
172.00
3.75
–179.79
171.45
4.15
–179.35
176.15
3.71
–175.46
–179.81
1.67
–0.86
–174.86
–180.06
1.74
–181.63
1.78
–177.50
–178.24
–177.50
TABLE IV
Hydrogen bon d len gth s (Å) in th e 4,5,6,7-tetrah ydroben zo[1]th ioph en e skeleton
Hydrogen bon d (X-ray/calculated)
Com poun d
N6H–O=C(acyl)
N6H–O=C(ester)
SeH–O=C(acyl)
5b
2.56/2.52
–/2.63
–/2.72
2.87/2.84
–
–
–
–
5e
–
2ba
2ea
3ba
3ea
–/1.96
1.95/1.93
–/2.72
–/2.63
–
–
–/2.89
–/2.99
–
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Benzonitriles and Carbonitriles
1681
th e reaction was run at h igh er tem peratures, th e cyclization was followed
by deacylation . In th e reaction of th e th ioph en e substrates, th e correspon d-
in g 1,3-th iazin es were n ot isolated after n eutralization of reaction m ixtures;
in stead, startin g acylth ioureas were obtain ed. It was foun d th at in th e n eu-
tral m edium a retrocyclization reaction leadin g to th e th iazin ium rin g
open in g occurred. Th erefore, 2-acylam in o-4-im in o-4H-th ien o[2,3-d]-
[1,3]th iazin ium salts were separated as lower soluble perch lorates10,12
.
Ben zo-fused 2-acylam in o-4-im in o-4H-ben zo[3,1]th iazin es, prepared un -
der th e sam e con dition s from correspon din g acylth ioureas in th e
ben zon itrile series, are stable as free bases11. Th is fact is explain ed by a
h igh er strain in th e th iazin e skeleton as a con sequen ce of larger extern al
bon d an gles of th e th ioph en e rin g22.
In order to com pare properties an d reactivies of th e 1,3-th iazin e an d
1,3-selen azin e skeleton , 1,3-selen azin ium h ydrogen sulfates 7a–7f were pre-
pared by cyclization of acylselen oureas 5a–5f in con cen trated sulfuric acid
at room tem perature (Sch em e 3). We h ave observed th at title selen oureas
cyclized m ore rapidly in com parison with th eir sulfur an alogues. Th e re-
sults of kin etic study of acid cyclization of title com poun ds, th eir sulfur an d
oxygen an alogues an d th eir com parison will be publish ed later13,14
.
Hydrogen sulfates 7a–7f were soluble in water an d polar solven ts, th ough
less th an h ydrogen sulfates of an alogous 1,3-th iazin es. Th e low solubility
an d low stability of th e prepared h ydrogen sulfates were observed also in
h exadeuterodim eth yl sulfoxide in th e NMR m easurem en ts. Th erefore, we
h ave con verted th ese salts to tetrafluoroborates 8a–8f (Sch em e 3).
NH
Se
N
H
NHCOR
Y = Cl (6a-6f), HSO4 (7a-7f), BF4 (8a-8f)
H
Y
base
CN
NH
CN
N
CN
NH
O
NH C
eq. KOH, MeOH
r.t.
MeOH
C
C
NH2
C
N
C R
O
∆
R
Se
SeH
Se
5a-5f
10a-10c
9a-9f
K
∆
∆
KOH, MeOH
NH2
N
NH2
KOH, MeOH
N
N
H
Se
12a-12c
N
SeH
11a-11c
Substituents for compounds a-f:
see Scheme 1
SCHEME 3
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

1682
Šibor et al.:
Ch lorides 6a–6f were prepared by th e cyclization of 5a–5f in m eth an olic
solution of h ydrogen ch loride (Sch em e 3). For th e above-presen ted reason s,
we h ave attem pted deacylation of 6a–6f by th e action of h ydrogen ch loride
in m eth an olic solution at reflux but on ly destruction of th ese com poun ds
was observed. Selan e was elim in ated an d oxidized by th e air oxygen to red
m odification of selen ium . Selan e was iden tified by th e test with saturated
solution of silver n itrate in vapors over th e reaction m ixture.
Durin g th e n eutralization of 1,3-selen azin ium salts 6a–6f, 7a–7f an d
8a–8f in aqueous solution with bases (am m on ia, sodium h ydroxide, so-
dium carbon ate, sodium h ydrogen carbon ate an d potassium an alogues), re-
spectively, th e retrocyclization reaction to startin g acylselen oureas 5a–5f
proceeded. In con trast to sulfur an alogues, th e retrocyclization was ob-
served also with ben zo[3,1]selen azin ium derivatives 6a, 6d , 7a, 7d , 8a an d
8d .
Iden tification of salts 6a–6f, 7a–7f an d 8a–8f was supported by th e C, H,
N, Se elem en tal an alysis, m ass spectroscopy (com poun ds 6b an d 7d ), FTIR,
1H an d 13C NMR spectra an d by com parison of th e spectral data with th ose
of th e sulfur an alogues10,12. Observed ch em ical sh ifts sh owed for th e sam e
1,3-selen azin ium salts with differen t an ion an d solven t in 1H an d 13C NMR
very good accordan ce. Assign m en t of th e carbon sign als based on correla-
tion with th e sam e values obtain ed by sim ulation .
Mass spectroscopy of 6b an d 7d sh owed th at th e com poun ds durin g ion -
ization elim in ated h ydrogen ch loride an d sulfuric acid, respectively. Th e
beh aviour of 1,3-th iazin ium salts is an alogous to th at described previously8.
In th e FTIR spectra of salts 6a–6f, 7a–7f an d 8a–8f a broad ban d of th e
stretch in g N–H vibration an d am ide ban ds I–III (NHCO) were foun d. On
th e oth er h an d, in th e FTIR spectra, th e stretch in g (N+–H) vibration in th e
ran ge 2 500–2 300 cm –1 was n ot observed. Th is dem on strates th e fact th at
th e selen azin ium cation prefers on e h ydrogen atom on th e rin g N atom
an d on e on th e n itrogen atom of th e acylam in o group, th e positive ch arge
bein g delocalized aroun d C2. As a con sequen ce, th e vibration al ban d of th e
(N–C+(Se)–N) group of selen azin ium cation was observed (see Sch em e 3). In
som e cases, h owever, it was overlapped by th e am ide I ban d of th e
acylam in o group.
Due to m en tion ed low solubility an d stability of salts 6a–6f, 7a–7f an d
8a–8f in h exadeuterodim eth yl sulfoxide, NMR spectra of ch lorides 6a–6f
were m easured in deuterotrifluoroacetic acid. 13C NMR spectra supported
th e con clusion th at th e form al positive ch arge on th e C2 atom of th e
selen azin ium skeleton is delocalized. Th e value of C2 ch em ical sh ift is
sim ilar to th at of th e carbon atom in th e isoselen oureido group of
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Benzonitriles and Carbonitriles
1683
electron eutral acylisoselen ourea m olecules1. Th e bon ds C2–N1 an d C2–Se
are sh orth er as con sequen ces of positive ch arge delocalization in th e
selen azin e cation . Sim ilar situation is in stable guan idin ium cation s. In th e
case of salts 6a–6f, 7a–7f an d 8a–8f, an in volvem en t of electron den sity of
th e selen ium atom to th e π-system of selen azin ium skeleton is probably
predom in an t. Th e im plication of th is is a decrease in total en ergy of m ole-
cule caused by a decrease in in tern al ten sion of th e selen azin e rin g. We
h ave assum ed th at th e in crease in in tern al ten sion of skeleton in m olecules
6a–6f, 7a–7f an d 8a–8f is caused by th e size of selen ium atom . Th is is larger
in com parison with th e n itrogen atom in 2-acylam in o-4-im in o-3,4-dih ydro-
quin azolin es23 an d th eir th ioph en e an alogues24. Th e m en tion ed assum p-
tion m ay be supported by th e fact th at an alogous 2-acyl-4-im in o-
4H-1,3-oxazin es are stable for th e both skeleton types, i.e. for ben zo an d
th ien o system s13, as electron eutral m olecules. We h ave assum ed th at th e
ch alcogen azin ium skeleton is form ed in acidic m edia as a product of th er-
m odyn am ically con trolled reaction .
Cyclization described for acylth iourea an alogues of 5a–5f with pyrim i-
din e skeleton m ay be in itiated by th e action of a base, e.g. am m on ia, so-
dium or potassium carbon ate, alcoh olate or h ydroxide in water or
water–alcoh ol solution 5,7,8,11. In depen den ce on basicity of th e reaction
m ixture an d reaction tem perature, th e cyclization proceeds togeth er with
deacylation (un der h arder con dition s) or with out elim in ation of th e acyl
group (un der m ild con dition s an d with ben zo skeleton ). In th e secon d case,
Dim roth rearran gem en t follows th e cyclization an d 4-acylam in oquin azolin e
derivatives are form ed.
Th e action of an h ydrous m eth an olic solution of potassium h ydroxide on
5a–5f led to th e form ation of potassium salts 9a–9f (Sch em e 3). We h ave
assum ed th at deproton ation of th e n itrogen atom of acylam in o group pre-
dom in ated. Th e form ed an ion is th erm odyn am ically m ore stable th an th at
form ed by deproton ation of th e am in o group in th e h eterocyclic skeleton
as a con sequen ce of delocalization of n egative ch arge in th e [C(Se)NC(O)]–
fragm en t.
Usin g on e equivalen t of potassium h ydroxide in m eth an olic solution at
room tem perature, potassium salts of th e th ioph en e series 9b, 9c, 9e an d 9f
were isolated. Un like with th e sulfur an alogues, th eir separation was suc-
cessful due to th eir lim ited solubility.
On th e oth er h an d, potassium salts 9a an d 9d of th e ben zo series were
well soluble in th e reaction m ixture an d were n ot obtain ed in crystallin e
state. Attem pts of th eir precipitation by an addition of sm all am oun ts of
solven ts such as ben zen e, dich lorom eth an e or th eir m ixtures with petro-
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

1684
Šibor et al.:
leum eth er were un successful. Th e salts 9a an d 9d were separated as tar
products.
In FTIR spectra of 9b, 9c, 9e an d 9f correspon din g vibration al ban ds of
NHCO an d NHCSe groups were n ot foun d. On th e oth er h an d, two very in -
ten sive ban ds were observed at 1 460 an d 1 340 cm –1 an d were assign ed as
th e stretch in g vibration ban ds of th e deproton ated acylselen oureido
[C(Se)NC(O)]– group.
Stan din g at room tem perature or a sh ort reflux of m eth an olic solution
con tain in g th e in situ prepared salts 9a, 9d , caused th eir tran sform ation to
4-am in oquin azolin e-2-selen ol (11a). On th e oth er h an d, suspen sion s of 9b,
9c, 9e an d 9f in m eth an ol gave un der reflux deacylated n on -cyclic prod-
ucts, wh ich were iden tified as isoselen oureas 10b an d 10c (Sch em e 3).
We h ave assum ed th at acylselen oureas of th e ben zo series 5a an d 5d re-
act an alogously. However, due to th eir h igh er reactivity, th ey cyclize spon -
tan eously to th e quin azolin e skeleton . Sim ilar reaction was observed durin g
th e addition of am m on ia to 2-isoselen ocyan atoben zon itrile25 or its sulfur
an alogue26. Th e adducts form ed in situ already cyclized at tem perature
lower th an 0 °C. Th e correspon din g selen oureas or th ioureas were n ot iso-
lated. Th e rate of deacylation is slower an d th us th e step probably con trols
th e com plex reaction .
In FTIR spectra of 10b an d 10c, in ten sive C=N vibration s were observed,
but vibration al ban ds of th e selen oam ide group were n ot foun d. Th e ch em -
ical sh ift of th e 13C(Se) sign al with a lower value th an 170 ppm togeth er
with th e value of th e 13C-77Se couplin g sh owed th at th is carbon is bon ded
to selen ium by a sin gle bon d like in acylisoselen oureas1. Th e com poun ds
10b an d 10c exist m ain ly in th e tautom eric 3-isoselen oureido form as con -
1
firm ed by H NMR spectra as on ly on e type of proton s is observed. Th e exis-
ten ce of tautom eric 1-isoselen oures form was n ot con firm ed.
Th e lower reactivity of th e th ien o versus ben zo derivatives in cyclization
un der basic con dition s was foun d also in th e case of an alogous th ioureas22.
If th e reaction m ixture con tain in g salts 9a–9f suspen ded or dissolved in
m eth an ol was refluxed in th e presen ce of an excess of potassium h ydrox-
ide, cyclization an d deacylation proceeded un der form ation of corre-
spon din g potassium pyrim idin e-2-selen olate. After acidification of th e
reaction m ixture, fused 4-am in opyrim idin e-2-selen oles 11a an d 11b an d
4-am in o-5,6-dim eth yl-1,2-dih ydroth ien o[2,3-d]pyrim idin e-2-selon 12c, re-
spectively, crystallized as free bases.
Th e structures of fused pyrim idin es 11a–11c an d 12a–12c syn th esized by
cyclization of 5a–5f or 10a–10c in basic m edium were con firm ed by ele-
m en tal an alysis, FTIR, 1H an d 13C NMR spectroscopy. FTIR an d 13C NMR
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Benzonitriles and Carbonitriles
1685
spectra of th e products sh owed th at com poun ds 11a an d 11b are stable un -
der th e experim en tal con dition s as th e pyrim idin e-2-selen ol wh ereas com -
poun d 12c as a selen oxo com poun d. NMR spectra were m easured in
deuterotrifluoroacetic acid solution due to th eir low solubility in oth er sol-
ven ts. Th e 13C Se sign al of com poun ds 11a an d 11b was overlapped by a
sign al of carbon yl carbon usin g trifluoroacetic acid (δ 163.24–164.31 ppm )
an d its value could n ot be determ in ed.
It is well kn own th at th ioureas sim ilar to isoselen oureas 10b an d 10c by
h eatin g cyclize to pyrim idin es27. In th e case of 10b an d 10c, th e cyclization
n eed n ot be in itiated th erm ally. Th eir cycloaddition proceeded on ly by th e
action of base at h igh er tem perature. We h ave assum ed th e existen ce of
deproton ated Se–H group. A h igh er acidity of th is group in com parison
with th e term in al am in o group is given by h igh er th erm odyn am ically sta-
bility of th e form ed selen oate an ion . After redistribution of electron den -
sity, th e pyrim idin e skeleton is form ed as a product of th erm odyn am ical
con trolled reaction un der th e used con dition s.
Th e foun d results in dicate a differen t course of base-in itiated cyclization
of acylselen oureas an d th eir sulfur an alogues. Th e later can be used
preparatively8, kin etic m eth ods28 con firm ed th at deacylation proceeded af-
ter th e pyrim idin e skeleton form ation .
EXPERIMENTAL
Ch em icals an d reagen ts were purch ased from Fluka Ch em ie Co. an d used with out purifica-
tion . 2-Am in oth ioph en e-3-carbon itriles 4b an d 4c were prepared by th e m odified Gewald
m eth od29 in dim eth ylform am ide in yields 80 an d 92% (ref.29 gives 42 an d 39%), respec-
tively. Meltin g poin ts were m easured on a Boetius Rapido PHMK 79/2106 (Wägetech n ik) in -
strum en t an d are n ot corrected. CHN elem en tal an alyses were m ade on an in strum en t 1102
(Erba), selen ium was determ in ed on a spectrom eter ICP AES 7500 (Un icam ). TLC was carried
out on Silufol UV 254 plates (Kavalier, Votice) usin g UV detection or visualization with io-
din e vapors an d elution with ch loroform , dieth yl eth er or aceton itrile. Th e FTIR spectra
were taken on a spectrom eter Gen esis (Un icam ) in potassium brom ide pellets. NMR spectra
were m easured in deuterioch loroform (CDCl3), h exadeuteriodim eth yl sulfoxide ((CD3)2SO)
or in deuteriotrifluoroacetic acid (CF3COOD) on a Bruker Avan ce DRX-500 spectrom eter.
Th e 13C an d 1H NMR spectra were referen ced to tetram eth ylsilan e as an in tern al stan dard or
to th e solven t sign als of CDCl3 an d of residual CHCl3 at 77.00 (13C) an d 7.27 ppm (1H), re-
spectively. Th e 77Se NMR ch em ical sh ifts were referen ced to H2SeO3 (1 282 ppm ) or SeOCl2
(1 479 ppm ), th e 15N NMR ch em ical sh ifts were referen ced to liquid am m on ia (0 ppm ) used
as extern al stan dards. Spectral width : 9 000 Hz for 1H, 27 500 Hz for 13C an d 38 000 Hz for
77Se. HETCOR an d COLOC spectra were m easured usin g Bruker stan dard sequen ces. In th e
34
1H-15N HMBC30–33
,
1H-15N GSQMBC33,
,
1H-77Se HMBC34 an d 1H-77Se GSQMBC34 experi-
m en ts pulsed-field-gradien ts were used for coh eren ce selection . For experim en t optim iza-
tion , see refs1,30–34. Th e m easured 13C an d 1H NMR spectra were correlated with th ose
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

1686
Šibor et al.:
obtain ed by on -lin e sim ulation (Advan ced Ch em istry Developm en t, In c., Toron to, Can ada).
Th e X-ray structural data of com poun d 5b (Table V) were collected with a KUMA KM-4
kappa four-circle diffractom eter. Th e structure was solved by direct m eth ods usin g
SHELXS86 (ref.35) an d refin ed on F2 for all reflection s usin g SHELXL93 (ref.36). Crystals suit-
able for X-ray determ in ation were obtain ed by crystallization from water-saturated ch loro-
form in th e form of yellow triclin ic plates. Geom etry optim ization of structures 5b an d 5e
were perform ed at ab initio level of quan tum ch em ical calculation , RHF/DZVP an d
TABLE V
Crystal data an d structure refin em en t for com poun d 5b
Em pirical form ula
C34H32N6O3S2Se2
Molecular weigh t
794.70
Tem perature, K
288 (2)
Wavelen gth , Å
0.71073
triclin ic, P1
Crystal system , space group
Un it cell dim en sion s
a, Å; α, °
10.370(2); 102.084(13)
12.444(2); 104.444(13)
13.794(2); 94.319(14)
1 670.2(5)
b, Å; β, °
c, Å; γ, °
Volum e, Å3
Z; den sity calculated, m g m –3
Absorption coefficien t, m m –1
F(000)
2; 1.580
2.384
804
Crystal size, m m
0.80 × 0.40 × 0.20
1.57–25.05
θ ran ge for data collection , °
Ran ge of h, k, l
–12→0, –14→14, –15→16
6 204
Reflection s collected
In depen den t reflection s
Refin em en t m eth od
Data; restrain ts; param eters
Goodn ess-of-fit on F2
Fin al R in dices [I > 2σ(I)]
R in dices (all data)
Maxim um an d m in im um h eigh ts in fin al ∆ρ m ap
5 923 [R(in t) = 0.0270]
full-m atrix least-squares on F2
5 921; 0; 462
0.977
R1 = 0.0528, wR2 = 0.1411
R1 = 0.1213, wR2 = 0.1846
1.061; –0.984
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Benzonitriles and Carbonitriles
1687
DFT/VWN/DZVP, respectively. Mass spectra were taken on a spectrom eter Mat 445 (Varian )
in th e CI m ode usin g a CH4/N2O m ixture as ion izin g gas. All syn th eses m en tion ed below,
except cyclization reaction in acid m edia, were perform ed un der in ert gases (n itrogen or ar-
gon ) in order to avoid selen ium oxidation with atm osph eric oxygen .
Gen eral Procedures for Preparation of Com poun ds 5a–5f
Method A. Potassium selen ocyan ate (7.63 g, 53 m m ol) was dissolved in aceton e (50 m l,
dried 24 h with an h ydrous calcium ch loride an d distilled) un der stirrin g at room tem pera-
ture. Ben zoyl ch loride (7.45 g, 53 m m ol) or 2,2-dim eth ylpropan oyl ch loride (6.39 g, 53
m m ol) dissolved in aceton e (20 m l) was added dropwise. Th e reaction m ixture was stirred
for 10 m in , th e precipitated potassium ch loride was filtered off an d wash ed with aceton e (10
m l). An aceton e solution of th e correspon din g 2-am in on itrile (50 m m ol) was added to th e
ben zoyl- or 2,2-dim eth ylpropan oylisoselen ocyan ate solution an d th e m ixture was stirred at
room tem perature. After 15–30 m in (TLC) th e reaction m ixture was evaporated to dryn ess
an d th e crude product dissolved in ch loroform at a tem perature about 4 °C. Th e form ed sus-
pen sion was filtered with ch arcoal, th e filtrate separated from colloid selen ium an d con cen -
trated to 1/5 origin al volum e an d m ixed with an equivalen t of petroleum eth er. Th e
precipitated crystals were filtered off, wash ed with petroleum eth er an d cold m eth an ol. Th e
product was dried in vacuo.
Method B. Oligom eric ben zoylisoselen ocyan ate (4.60 g, 25 m m ol) was added to th e sus-
pen sion of am in e 4a–4c (20 m m ol) was suspen ded in toluen e (30 m l) an d th e reaction m ix-
ture was refluxed 45–60 m in (TLC con trol). After th e reaction , th e h ot m ixture was filtered
th rough silica gel, th e filtrate was cooled an d th e crude separated products (5a–5f) were pu-
rified as m en tion ed above.
2-(3-Benzoylselenoureido)benzonitrile (5a). Yield: (A) 13.7 g (83%), (B) 5.0 g (75%); m .p.
153–155 °C (m eth an ol). For C15H11N3OSe (328.2) calculated: 54.89% C, 3.38% H, 12.80% N,
24.92% Se; foun d: 54.92% C, 3.32% H, 12.74% N, 24.36% Se. MS, m/z (%): 328 (16, M+),
329 (8, (M + 1)+), 248 (98, (M – SeH)+), 226 (35, (Ph CONHCSeNH)+), 223 (10, (M – Ph CO)+),
222 (8, (M – HSeCN)+), 106 (10, (HSeCN)+), 105 (100, (Ph CO)+). FTIR: 3 325, 3 195 (NH),
2 210 (C≡N), 1 650, 1 540 (NHCO, am ide I, II), 1 515, 932 (NHCSe, selen oam ide I, III).
1H NMR (CDCl3): 7.45–8.19 m , 9 H (H-arom .); 9.66 s, 1 H (NHCO); 13.28 s, 1 H (NHCSe).
13C NMR (CDCl3): 109.63 (C-1), 115.84 (C≡N), 127.20 (C-3), 127.81 (C-2′ an d C-6′, C6H5),
127.91 (C-5), 129.28 (C-3′ an d C-5′, C6H5), 130.88 (C-1′, C6H5), 133.22 (C-6), 133.44 (C-4),
134.16 (C-4′, C6H5), 141.31 (C-2), 167.08 (C=O), 182.55 J(C,Se) = 225. 77Se NMR (CDCl3):
481.
2-(3-Benzoylselenoureido)-4,5,6,7-tetrahydrobenzo[1]thiophene-3-carbonitrile (5b ). Yield: (A)
18.1 g (93%), (B) 6.05 g (78%); m .p. 201–204 °C (m eth an ol). For C17H15N3OSSe (388.4) cal-
culated: 52.08% C, 3.89% H, 10.82% N, 20.54% Se; foun d: 51.97% C, 3.80% H, 10.70% N,
20.49% Se. MS, m/z (%): 388 (19, M+), 389 (7, (M + 1)+), 308 (95, (M – SeH)+), 283 (10, (M –
Ph CO)+), 282 (10, (M – HSeCN)+), 226 (38, (Ph CONHCSeNH)+), 106 (8, (HSeCN)+), 105 (100,
(Ph CO)+). FTIR: 3 380, 3 260 (NH), 2 200 (C≡N), 1 650, 1 560 (NHCO, am ide I, II), 1 512,
975 (NHCSe, selen oam ide I, III). 1H NMR (CDCl3): 1.85–1.86 m , 4 H (5-CH2 an d 6-CH2);
2.65 t, 2 H, J(4-CH2) = 5.0; 2.67 t, 2 H, J(7-CH2) = 6.0; 7.55–7.92 m , 5 H (C6H5); 9.53 s, 1 H
(NHCO); 14.69 s, 1 H (NHCSe). 13C NMR (CDCl3): 22.06 (C-5), 23.01 (C-6), 23.92 (C-4),
24.25 (C-7), 100.02 (C-3), 113.71 (C≡N), 127.83 (C-2′ an d C-6′, C6H5), 129.31 (C-3′ an d C-5′,
C6H5), 129.63 (C-4, th ioph en e), 130.60 (C-5, th ioph en e), 132.24 (C-1′, C6H5), 134.24 (C-4′,
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

1688
Šibor et al.:
C6H5), 147.29 (C-2, th ioph en e), 167.15 (C=O), 175.72 J(C,Se) = 223. 15N NMR (CDCl3):
151.7 (NCSe), 155.2 (C≡N), 162.3 (NCO). 77Se NMR (CDCl3): 482. For X-ray an alysis, see Re-
sults an d Discussion .
2-(3-Benzoylselenoureido)-4,5-dimethylthiophene-3-carbonitrile (5c). Yield: (A) 15.2 g (84%),
(B) 5.2 g (72%); m .p. 112–115 °C (m eth an ol). For C15H13N3OSSe (326.3) calculated: 49.73%
C, 3.62% H, 11.60% N, 22.02% Se; foun d: 49.43% C, 3.55% H, 11.40% N, 21.95% Se. MS,
m/z (%): 362 (15, M+), 282 (100, (M – SeH)+), 257 (5, (M – Ph CO) +), 256 (11, (M –
HSeCN)+), 226 (40, (Ph CONHCSeNH)+), 106 (10, (HSeCN)+), 105 (95 (Ph CO)+). FTIR: 3 273,
3 180 (NH), 2 217 (C≡N), 1 670, 1 555 (NHCO, am ide I, II), 1 519, 970 (NHCSe, selen oam ide
I, III). 1H NMR (CDCl3): 2.24 s, 3 H (CH3, C-4 th ioph en e); 2.29 s, 3 H (CH3, C-5 th ioph en e);
7.56–7.95 m , 5 H (C6H5); 9.47 s, 1 H (NHCO); 14.68 s, 1 H (NHCSe). 13C NMR (CDCl3):
12.40 (CH3, C-4 th ioph en e), 12.78 (CH3, C-5 th ioph en e), 101.95 (C-3, th ioph en e), 114.08
(C≡N), 126.50 (C-4, th ioph en e), 127.81 (C-2′an d C-6′, C6H5), 129.34 (C-3′an d C-5′, C6H5),
130.03 (C-5, th ioph en e), 130.61 (C-1′, C6H5), 134.26 (C-4′, C6H5), 146.28 (C-2, th ioph en e),
167.11 (C=O), 175.63 J(C,Se) = 222. 77Se NMR (CDCl3): 481.
2-[3-(2,2-Dimethylpropanoyl)selenoureido]benzonitrile (5d ). Yield: (A) 12.6 g (82%); m .p.
146–148 °C (m eth an ol). For C13H15N3OSe (308.2) calculated: 50.66% C, 4.90% H, 13.36% N,
25.86% Se; foun d: 50.50% C, 4.58% H, 11.40% N, 25.94% Se. MS, m/z (%): 308 (18, M+),
309 (8, (M + 1)+), 228 (100, (M – SeH)+), 235 (6, (M – (CH3)3CCO)+), 202 (11, (M –
HSeCN)+), 194 (41, ((CH3)3CCONHCSeNH)+), 106 (5, (HSeCN)+), 73 (95, ((CH3)3CCO)+).
FTIR: 3 412, 3 187 (NH), 2 229 (C≡N), 1 678, 1 550 (NHCO, am ide I, II), 1 503, 963 (NHCSe,
selen oam ide I, III). 1H NMR (CDCl3): 1.34 s, 9 H (C(CH3)3); 7.43–8.14 m , 4 H (C6H4); 9.05 s,
1 H (NHCO); 13.49 s, 1 H (NHCSe). 13C NMR (CDCl3): 28.86 (CH3, C(CH3)3), 40.05 (C(CH3)3),
109.51 (C-1), 115.73 (C≡N), 127.12 (C-3), 127.84 (C-5), 133.17 (C-6), 133.27 (C-4), 141.25
(C-2), 179.63 (C=O), 182.68 J(C,Se) = 225. 77Se NMR (CDCl3): 411.
2-[3-(2,2-Dimethylpropanoyl)selenoureido]-4,5,6,7-tetrahydrobenzo[1]thiophene-3-carbonitrile
(5e). Yield: (A) 16.4 g (89%); m .p. 178–180 °C. For C15H19N3OSSe (368.3) calculated: 48.91%
C, 5.20% H, 11.41% N, 21.66% Se; foun d: 48.78% C, 5.04% H, 11.32% N, 21.60% Se. MS,
m/z (%): 368 (16, M+), 288 (100, (M – SeH)+), 295 (10, (M – (CH3)3CCO)+), 262 (8, (M –
HSeCN)+), 194 (38, ((CH3)3CCONHCSeNH)+), 106 (6, (HSeCN)+), 73 (98, ((CH3)3CCO)+).
FTIR: 3 285, 3 190 (NH), 2 200 (C≡N), 1 675, 1 555 (NHCO, am ide I, II), 1 510, 960 (NHCSe,
selen oam ide I, III). 1H NMR (CDCl3): 1.33 s, 9 H (C(CH3)3); 1.82–1.83 m , 4 H (5-CH2 an d
6-CH2); 2.65 t, 2 H, J(4-CH2) = 5.0; 2.66 t, 2 H, J(7-CH2) = 6.0; 8.92 s, 1 H (NHCO), 14.53 s,
1 H (NHCSe). 13C NMR (CDCl3): 22.00 (C-6), 22.95 (C-5), 23.82 (C-4), 24.16 (C-7), 26.86
(CH3, C(CH3)3), 40.04 (C(CH3)3), 99.93 (C-3), 113.58 (C≡N), 129.58 (C-4, th ioph en e), 132.17
(C-5, th ioph en e), 147.24 (C-2, th ioph en e), 179.75 (C=O), 179.75 J(C,Se) = 223. 15N NMR
(CDCl3): 151.7 (NCSe), 155.2 (C≡N), 161.8 (NCO). 77Se NMR (CDCl3): 465.
2-[3-(2,2-Dimethylpropanoyl)selenoureido]-4,5-dimethylthiophene-3-carbonitrile (5f). Yield: (A)
13.1 g (77%); m .p. 163–165 °C (m eth an ol). For C13H17N3OSSe (342.3) calculated: 46.51% C,
5.01% H, 12.28% N, 23.30% Se; foun d: 46.37 % C, 4.98% H, 12.03% N, 23.37% Se. MS m/z
(%): 342 (16, M+), 262 (100, (M – SeH)+), 269 (8, M – (CH3)3CCO)+), 236 (7, (M – HSeCN)+),
194 (32, ((CH3)3CCONHCSeNH)+), 106 (8, (HSeCN)+), 73 (98, ((CH3)3CCO)+). FTIR: 3 344,
3 220 (NH), 2 211 (C≡N), 1 640, 1 567 (NHCO, am ide I, II), 1 503, 931 (NHCSe, selen oam ide
I, III). 1H NMR (CDCl3): 1.34 s, 9 H (C(CH3)3); 2.22 s, 3 H (CH3, C-4 th ioph en e); 2.27 s, 3 H
(CH3, C-5 th ioph en e); 8.93 s, 1 H (NHCO); 14.53 s, 1 H (NHCSe). 13C NMR (CDCl3): 12.24
(CH3, C-4 th ioph en e), 12.62 (CH3, C-5 th ioph en e), 26.76 (CH3, C(CH3)3), 39.93 (C(CH3)3),
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101.55 (C-3, th ioph en e), 113.84 (C≡N), 126.25 (C-4, th ioph en e), 129.76 (C-5, th ioph en e),
146.18 (C-2, th ioph en e), 179.65 (C=O), 175.70 J(C,Se) = 222. 77Se NMR (CDCl3): 466.
Gen eral Procedure for Preparation of Com poun ds 6a–6f
Nitrile 5a–5f (10 m m ol) was dissolved at th e room tem perature in a 50 m l of an h ydrous
m eth an ol solution of h ydrogen ch loride saturated at 20–25 °C. Th e reaction m ixture was
stirred at room tem perature un til crystal form ation appeared (60–120 m in ). Th en th e reac-
tion m ixture was left to crystallize in an icebox. Th e product was separated by suction ,
wash ed with m eth an ol an d dieth yl eth er an d dried in vacuo at room tem perature.
2-Benzoylamino-4-imino-4H-benzo[3,1]selenazinium chloride (6a). Yield: 3.2 g (86%); m .p.
251–252 °C (eth er). For C15H12ClN3OSe (364.6) calculated: 49.40% C, 3.32% H, 11.52% N,
21.64% Se; found: 48.95% C, 3.17% H, 11.38% N, 21.58% Se. FTIR: 3 375 (NH), 1 660 (am ide I),
1 642 (N–C+(Se)–N), 1 624 (C=N), 1 567 (am ide II), 1 277 (am ide III). 1H NMR (CF3COOD):
7.53 d, 1 H, J(C8-H) = 7.61; 7.76–7.99 m , 5 H (C6H5CO); 8.17–8.18 m , 1 H (C6-H); 8.23-8.25 m ,
1 H (C7-H); 8.50 d, 1 H, J(C5-H) = 7.63. 13C NMR (CF3COOD): 121.23 (CH), 126.81(CH),
127.21 (CH), 128.13 (CH), 132.20 (CH), 133.22 (CH), 136.20 (C), 138.92 (C), 139.41 (C),
139.78 (C), 153.80 (C=N), 160.90 J(N–C+–Se) = 161, 175.76 (C=O).
2-Benzoylamino-4-imino-5,6,7,8-tetrahydro-4H-benzo[1]thieno[2,3-d][1,3]selenazinium chloride
(6b). Yield: 4.0 g (95%); m .p. 196–198 °C (eth er). For C17H16ClN3OSSe (424.8) calculated:
48.07% C, 3.80% H, 9.89% N, 18.58% Se; foun d: 47.94% C, 3.69% H, 9.45% N, 18.53% Se.
MS, m/z (%): 388 (35, (M – HCl)+), 308 (40, (338 – SeH)+), 226 (19, (Ph CONHCSeNH)+), 105
(100 (Ph CO)+). FTIR: 3 200 (NH), 1 657 (am ide I), 1 650 (N–C+(Se)–N), 1 638 (C=N), 1 570
(am ide II), 1 260 (am ide III.). 1H NMR (CF3COOD): 2.03–2.09 m , 4 H (5-CH2 an d 6-CH2);
2.93–2.95 m , 2 H (4-CH2); 2.99–3.08 m , 2 H (7-CH2); 7.63–7.67 m , 2 H (C6H5CO); 7.79–7.82 m ,
1 H (C6H5CO); 7.97–8.08 m , 2 H (C6H5CO). 13C NMR (CF3COOD): 23.17 (CH2), 23.54
(CH2), 26.47 (CH2), 28.71 (CH2), 128.23 (CH), 130.46 (C), 131.04 (C), 131.25 (C), 132.25
(CH), 137.50 (CH), 140.88 (C), 156.76 (C=N), 156.93 J(N–C+–Se) = 171, 172.84 (C=O).
2-Benzoylamino-4-imino-5,6-dimethyl-4H-thieno[2,3-d][1,3]selenazinium chloride (6c). Yield:
2.8 g (71%); m .p. 202–205 °C (eth er). For C15H14ClN3OSSe (398.8) calculated: 45.18% C,
3.54% H, 10.54% N, 19.79% Se; foun d: 44.89% C, 3.48% H, 10.42% N, 19.74% Se. FTIR:
3 200 (NH), 1 655 (am ide I), 1 650 (N–C+(Se)–N), 1 630 (C=N), 1 575 (am ide II), 1 272
(am ide III). 1H NMR (CF3COOD): 2.72 s, 3 H (CH3); 2.82 s, 3 H (CH3); 7.75–8.25 m , 5 H
(C6H5CO). 13C NMR (CF3COOD): 13.51 (CH3), 15.51 (CH3), 126.12 (C), 126.78 (C), 129.01
(CH), 130.05 (C), 131.32 (C), 133.12 (CH), 135.65 (CH), 138.40 (C), 153.08 (C=N), 164.22
J(N–C+–Se) = 168, 177.51 (C=O).
4-Imino-2-2,2-dimethylpropanoylamino-4H-benzo[3,1]selenazinium chloride (6d ). Yield: 3.0 g
(87%); m .p. 186–189 °C (eth er). For C13H16ClN3OSe (344.7) calculated: 45.30% C, 4.68% H,
12.19% N, 22.89% Se; foun d: 45.23% C, 4.52% H, 11.97% N, 22.82% Se. FTIR: 3 315 (NH),
1 694 (am ide I), 1 652 (N–C+(Se)–N), 1 630 (C=N), 1 575 (am ide II), 1 260 (am ide III).
1H NMR (CF3COOD): 1.18 s, 9 H ((CH3)3C); 8.25 d, 1 H, J(C8-H) = 7.61; 8.31–8.34 m , 1 H
(C7-H); 8.67–8.71 m , 1 H (C6-H); 8.91 d, 1 H, J(C5-H) = 7.63. ). 13C NMR (CF3COOD): 27.62
(CH3, (CH3)3C), 41.09 (C), 127.58 (C), 132.80 (C), 141.85 (C), 142.09 (C), 157.00 (C=N),
175.83 J(N–C+–Se) = 154, 186.19 (C=O).
4-Imino-2-(2,2-dimethylpropanoyl)amino-5,6,7,8-tetrahydro-4H-benzo[1]thieno[2,3-d][1,3]selen-
azinium chloride (6e). Yield: 3.8 g (95%); m .p. 106–107 °C (eth er). For C15H20ClN3OSSe
(404.8) calculated: 44.51% C, 4.98% H, 10.38% N, 19.49% Se; foun d: 44.42% C, 4.86% H,
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10.27% N, 19.44% Se. FTIR: 3 233 (NH), 1 675 (am ide I), 1 653 (N–C+(Se)–N), 1 635 (C=N),
1 572 (am ide II), 1 266 (am ide III). 1H NMR (CF3COOD): 1.48 s, 9 H ((CH3)3C); 1.95–2.12 m ,
4 H (5-CH2 an d 6-CH2); 2.91–2.98 m , 2 H (4-CH2); 3.02-3.10 m , 2 H (7-CH2). 13C NMR
(CF3COOD): 23.47 (CH2), 24.03 (CH2), 26.41 (CH2), 27.69 (CH3, (CH3)3C), 28.63 (CH2),
42.01 (C), 130.30 (C), 130.43 (C), 133.73 (C), 140.63 (C), 156.78 (C=N), 177.72 J(N–C+–Se) =
151, 185.83 (C=O).
4-Imino-5,6-dimethyl-2-(2,2-dimethylpropanoyl)amino-4H-thieno[2,3-d][1,3]selenazinium chlo-
ride (6f). Yield: 2.9 g (77%); m .p. 137–138 °C (eth er). For C13H18ClN3OSSe (378.8) calculated:
41.22% C, 4.79% H, 11.09% N, 20.83% Se; foun d: 41.04% C, 4.73% H, 10.89% N, 20.79%
Se. FTIR: 3 315 (NH), 1 667 (am ide I), 1 650 (N–C+(Se)–N), 1 642 (C=N), 1 547 (am ide II),
1 273 (am ide III). 1H NMR (CF3COOD): 1.49 s, 9 H ((CH3)3C); 2.57 s, 3 H (CH3); 2.66 s, 3 H
(CH3). 13C NMR (CF3COOD): 13.51 (CH3), 15.51 (CH3), 27.45 (CH3, (CH3)3C), 42.11 (C),
126.05 (C), 126.55 (C), 130.05 (C), 138.40 (C), 155.05 (C=N), 176.83 J(N–C+–Se) = 159,
186.12 (C=O).
Gen eral Procedure for Preparation of Com poun ds 7a–7f
Com poun d 5a–5f (10 m m ol) was dissolved in 96% sulfuric acid (25 m l) at 5–10 °C an d th e
m ixture was left to cyclize at room tem perature. After 1 h , th e reaction m ixture was poured
on to crash ed ice (100 g). Th e in soluble portion was filtered off, wash ed successively with
m eth an ol an d dieth yl eth er, an d th en dried in vacuo at room tem perature.
2-Benzoylamino-4-imino-4H-benzo[3,1]selenazinium hydrogensulfate (7a). Yield: 3.7 g (87%);
m .p. 269–270 °C (eth er). For C15H13N3O5SSe (426.3) calculated: 42.26% C, 3.07% H, 9.89% N,
18.51% Se; foun d: 41.98% C, 2.95% H, 9.66% N, 18.43% Se. FTIR: 3 200 (NH), 1 650 (am ide I,
N–C+(Se)–N), 1 638 (C=N), 1 570 (am ide II), 1 260 (am ide III), 1 142, 1 085, 874 (HSO–4 ).
2-Benzoyla mino-4-imino-5,6,7,8-tetra hydro-4H-benzo[1]thieno[2,3-d][1,3]selena zinium
hydrogensulfate (7b). Yield: 4.2 g (86%); m .p. 265–269 °C (eth er). For C17H17N3O5S2Se (486.4)
calculated: 41.98% C, 3.52% H, 8.64% N, 16.22% Se; foun d: 41.56% C, 3.48% H, 8.53% N,
15.99% Se. FTIR: 3 200 (NH), 1 650 (am ide I, N–C+(Se)–N), 1 638 (C=N), 1 570 (am ide II),
1 260 (am ide III), 1 137, 1 073, 872 (HSO–4 ).
2-Benzoylamino-4-imino-5,6-dimethyl-4H-thieno[2,3-d][1,3]selenazinium hydrogensulfate (7c).
Yield: 3.9 (85%); m .p. 254–256 °C (eth er). For C15H15N3OSSe (460.4) calculated: 39.13% C,
3.28% H, 9.13% N, 17.14% Se; foun d: 38.12% C, 3.42% H, 8.94% N, 16.87% Se. FTIR: 3 200
(NH), 1 650 (am ide I, N–C+(Se)–N), 1 630 (C=N), 1 575 (am ide II), 1 272 (am ide III), 1 140,
1 079, 870 (HSO–4 ).
4-Imino-2-(2,2-dimethylpropanoyl)amino-4H-benzo[3,1]selenazinium hydrogensulfate (7d ).
Yield: 3.8 g (94%); m .p. 186–189 °C (eth er). For C13H17N3O5SSe (406.4) calculated: 38.43% C,
4.22% H, 10.34% N, 19.42% Se; foun d: 38.12% C, 3.99% H, 9.98% N, 19.36% Se. MS, m/z
(%): 308 (30, (M – H2SO4)+), 228 (43, (308 – SeH)+), 194 (15, ((CH3)3CCONHCSeNH)+), 73
(100, ((CH3)3CCO)+). FTIR: 3 315 (NH), 1 694 (am ide I, N–C+(Se)–N), 1 630 (C=N), 1 575
(am ide II), 1 260 (am ide III), 1 150, 1 081, 872 (HSO–4 ).
4-Imino-2-(2,2-dimethylpropanoyl)amino-5,6,7,8-tetrahydro-4H-benzo[b]thieno[2,3-d][1,3]selen-
azinium hydrogensulfate (7e). Yield: 4.0 g (86%); m .p. 162–165 °C (eth er). For C15H21N3O5S2Se
(466.4) calculated: 38.63% C, 4.54% H, 9.01% N, 16.92% Se; foun d: 38.46% C, 4.37% H,
9.06% N, 16.74% Se. FTIR: 3 233 (NH), 1 653 (am ide I, N–C+(Se)–N), 1 635 (C=N), 1 572
(am ide II), 1 266 (am ide III), 1 135, 1 075, 864 (HSO–4 ).
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4-Imino-5,6-dimethyl-2-(2,2-dimethylpropanoyl)amino-4H-thieno[2,3-d][1,3]selenazinium
hydrogensulfate (7f). Yield: 3.9 g (84%); m .p. 186–188 °C (eth er). For C13H19N3O5S2Se (440.6)
calculated: 35.46% C, 4.35% H, 9.54% N, 17.92% Se; foun d: 35.19% C, 4.06% H, 9.33% N,
17.76% Se. FTIR: 3 315 (NH), 1 667 (am ide I, N–C+(Se)–N), 1 642 (C=N), 1 547 (am ide II),
1 273 (am ide III), 1 139, 1 075, 869 (HSO–4 ).
Gen eral Procedure for Preparation of Com poun ds 8a–8f
A solution of com poun d 7a–7f (5 m m ol) in sulfuric acid was added at 5–10 °C in to a 40%
aqueous solution of tetrafluoroboric acid (25 m l). Th e products were separated as m en tion ed
above.
2-Benzoylamino-4-imino-4H-3,1-benzo[3,1]selenazinium tetrafluoroborate (8a). Yield: 1.4 g
(67%); m .p. 254–257 °C (eth er). For C15H12BF4N3OSe (416.0) calculated: 43.30% C, 2.91% H,
10.10% N, 18.97% Se; foun d: 42.98% C, 2.83% H, 10.02% N, 18.81% Se. FTIR: 3 200 (NH),
1 650 (am ide I, N–C+(Se)–N), 1 638 (C=N), 1 570 (am ide II), 1 260 (am ide III), 1 164 (BF4–).
2-Benzoyla mino-4-imino-5,6,7,8-tetra hydro-4H-benzo[1]thieno[2,3-d][1,3]selena zinium
tetrafluoroborate (8b ). Yield: 1.5g (70%); m .p. 235–240 °C (eth er). For C17H16BF4N3OSSe
(426.2) calculated: 42.88% C, 3.39% H, 8.82% N, 16.57% Se; foun d: 42.50% C, 3.24% H,
8.64% N, 16.38% Se. FTIR: 3 200 (NH), 1 650 (am ide I, N–C+(Se)–N), 1 638 (C=N), 1 570
(am ide II), 1 260 (am ide III), 1 167 (BF4–).
2-Benzoylamino-4-imino-5,6-dimethyl-4H-thieno[2,3-d][1,3]selenazinium tetrafluoroborate (8c).
Yield: 1.5 (72%); m .p. 194–195 °C (eth er). For C15H14BF4N3OSSe (450.1) calculated: 40.03% C,
3.13% H, 9.34% N, 17.53% Se; foun d: 39.63% C, 3.06% H, 9.26% N, 17.43% Se. FTIR: 3 200
(NH), 1 650 (am ide I, N–C+(Se)–N), 1 630 (C=N), 1 575 (am ide II), 1 272 (am ide III), 1 175
(BF4–).
4-Imino-2-(2,2-dimethylpropanoyl)amino-4H-benzo[3,1]selenazinium tetrafluoroborate (8d ).
Yield: 1.3 g (66%); m .p. 192–195 °C (eth er). For C13H16BF4N3OSe (396.1) calculated: 39.42% C,
4.07% H, 10.61% N, 19.92% Se; foun d: 39.06% C, 3.98% H, 10.49% N, 19.63% Se. FTIR: 3
315 (NH), 1 694 (am ide I, N–C+(Se)–N), 1 630 (C=N), 1 575 (am ide II), 1 260 (am ide III),
1 162 (BF4–).
4-Imino-2-(2,2-dimethylpropanoyl)amino-5,6,7,8-tetrahydro-4H-benzo[1]thieno[2,3-d][1,3]selen-
azinium tetrafluoroborate (8e). Yield: 1.6
g (77%); m .p. 117–120 °C (eth er). For
C
15H20BF4N3OSSe (456.2) calculated: 39.50% C, 4.42% H, 9.21% N, 17.30% Se; foun d:
39.12% C, 4.35% H, 9.16% N, 17.19% Se. FTIR: 3 233 (NH), 1 653 (am ide I, N–C+(Se)–N),
1 635 (C=N), 1 572 (am ide II), 1 266 (am ide III), 1 172 (BF4–).
4-Imino-5,6-dimethyl-2-(2,2-dimethylpropanoyl)amino-4H-thieno[2,3-d][1,3]selenazinium
tetrafluoroborate (8f). Yield: 1.4 g (65%); m .p. 141–143 °C (eth er). For C13H18BF4N3OSSe
(430.1) calculated: 36.30% C, 4.22% H, 9.77% N, 18.35% Se; foun d: 36.06% C, 3.89% H,
9.60% N, 18.21% Se. FTIR: 3 315 (NH), 1 667 (am ide I, N–C+(Se)–N), 1 642 (C=N), 1 547
(am ide II), 1 273 (am ide III), ), 1 160 (BF4–).
Retrocyclization Reaction s of 6a–6f, 7a–7f an d 8a–8f to 5a–5f. Gen eral Procedure
Com poun d 6a–6f, 7a–7f an d 8a–8f (5 m m ol) was suspen ded in water (50 m l) an d th e pH
value of th e m ixture was adjusted to 7–8 with a 5% aqueous solution of potassium carbon -
ate. After about 5 m in , th e product was extracted to ch loroform (2 × 20 m l) an d th e extract
was dried with an h ydrous sodium sulfate. Th e solution was con cen trated to 1/3 of its origi-
n al volum e an d m ixed with an equal volum e of petroleum eth er. Th e precipitated crystals
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were filtered, wash ed with petroleum eth er an d cold m eth an ol (5–10 °C). Th e pure product
was dried in vacuo. Th e yields were in th e ran ge of 90–95%. Th e obtain ed n itriles 5a–5f were
iden tical with stan dards by TLC, m .p., FTIR an d 1H NMR spectra.
Gen eral Procedure for Preparation of Com poun ds 9b, 9c, 9e an d 9f
Com poun d 5b, 5c, 5e or 5f (5 m m ol) was dissolved at room tem perature un der stirrin g in a
solution of potassium h ydroxide (340 m g, 6 m m ol) in m eth an ol (50 m l). After 30 m in , th e
correspon din g product (9b, 9c, 9e or 9f) was separated by suction , wash ed with m eth an ol,
dieth yl eth er an d dried in vacuo at room tem perature.
2-(3-Benzoylselenoureido)-4,5,6,7-tetrahydrobenzo[1]thiophene-3-carbonitrile potassium salt
(9b). Yield: 1.8 g (85%); m .p. 201–202 °C (decom p.). For C17H14N3OSSeK (462.4) calculated:
47.88% C, 3.31% H, 9.85% N, 18.50% Se; foun d: 47.43% C, 3.15% H, 9.63% N, 18.42% Se.
FTIR: 3 204, 3 165 (NH), 2 215 (C≡N), 1 460 (NCO), 1 350 (NCSe). 1H NMR ((CD3)2SO):
1.62–1.75 m , 4 H (5-CH2 an d 6-CH2); 2.14–2.15 m , 2 H (4-CH2); 2.73–2.75 m , 2 H (7-CH2);
4.30 s, 1 H (NH); 7.25–8.40 m , 5 H (C6H5). 13C NMR ((CD3)2SO): 22.46 (C-5), 23.35 (C-6),
24.00 (C-4), 24.25 (C-7), 92.82 (C-3), 114.63 (C-4, th ioph en e), 116.71 (C≡N), 127.23 (C-2′
an d C-6′, C6H5), 129.04 (C-3′ an d C-5′, C6H5), 130.72 (C-5, th ioph en e), 130.24 (C-1′, C6H5),
133.42 (C-4′, C6H5), 157.09 (C-2, th ioph en e), 160.33 (C=O), 171.95 J(C=Se) = 180.
2-(3-Benzoylselenoureido)-4,5-dimethylthiophene-3-carbonitrile potassium salt (9c). Yield:
1.65 g (84%); m .p. 292–293 °C (decom p.). For C15H12N3OSSeK (400.4) calculated: 45.00% C,
3.02% H, 10.49% N, 19.71% Se; foun d: 44.87% C, 2.97% H, 10.24% N, 19.46% Se. FTIR:
3 348, 3 318 (NH), 2 200 (C≡N), 1 458 (NCO), 1 339 (NCSe). 1H NMR ((CD3)2SO): 2.13 s, 3 H
(CH3, C-4 th ioph en e); 2.21 s, 3 H (CH3, C-5 th ioph en e); 7.39–7.88 m , 5 H (C6H5); 8.27 s,
1 H (NH).
2-[3-(2,2-Dimethylpropanoyl)selenoureido]-4,5,6,7-tetrahydrobenzo[1]thiophene-3-carbonitrile
potassium salt (9e). Yield: 1.6 g (79%); m .p. 185–188 °C (decom p.). For C15H18N3OSSeK
(406.5) calculated: 44.33% C, 4.46% H, 10.43% N, 19.42% Se; foun d: 44.19% C, 4.15% H,
10.37% N, 19.36% Se. FTIR: 3 200, 3 182 (NH), 2 225 (C≡N), 1 468 (NCO), 1 338 (NCSe).
1H NMR ((CD3)2SO): 1.16 s, 9 H (CH3, C(CH3)3); 1.17–1.24 m , 4 H (5-CH2 an d 6-CH2);
2.14–2.15 m , 2 H (4-CH2); 2.62–2.69 m , 2 H (7-CH2); 8.84 s, 1 H (NH).
2-[3-(2,2-Dimethylpropanoyl)selenoureido)-4,5-dimethylthiophene-3-carbonitrile potassium salt
(9f). Yield: 1.4 g (74%); m .p. 188–200 °C (decom p.). For C13H16N3OSSeK (380.4) calculated:
41.05% C, 4.24% H, 11.05% N, 20.74% Se; foun d: 39.98% C, 4.12% H, 11.06% N, 20.38% Se.
FTIR: 3 221, 3 060 (NH), 2 204 (C≡N), 1 459 (NCO), 1 350 (NCSe). 1H NMR ((CD3)2SO): 1.21 s,
9 H (CH3, (CH3)3C); 2.03 s, 3 H (CH3, C-4 th ioph en e); 2.16 s, (CH3, C-5 th ioph en e); 7.95 s,
1 H (NH).
Gen eral Procedure for Preparation of Com poun ds 10b an d 10c
Potassium salt 9b , 9c, 9e or 9f (2.5 m m ol) was suspen ded in an h ydrous m eth an ol
(20–30 m l) an d refluxed for 10 m in . Th e correspon din g product (10b, 10c), wh ich crystal-
lized from th e reaction m ixture after stayin g overn igh t in a freezin g box, was separated by
suction an d recrystallized from eth an ol (ch arcoal).
2-(3-Isoselenoureido)-4,5,6,7-tetrahydrobenzo[1]thiophene-3-carbonitrile (10b ). Yield: 0.5 g
(70%) (from 9b ), 0.55 g (77%) (from 9e); m .p. 202–205 °C (eth an ol). For C10H11N3SSe
(285.0) calculated: 42.26% C, 3.90% H, 14.78% N, 27.79% Se; foun d: 41.95% C, 3.81% H,
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Benzonitriles and Carbonitriles
1693
14.68% N, 27.47% Se. FTIR: 3 248, 3 188 (NH), 2 200 (C≡N), 1 650 (C=N). 1H NMR (CDCl3):
1.56 bs, 3 H (SeH an d NH2); 1.81–1.84 m , 4 H (5-CH2 an d 6-CH2); 2.73–2.94 m , 4 H (4-CH2
an d 7-CH2). 13C NMR (CDCl3): 22.96 (C-6), 24.80 (C-5), 26.21 (C-7), 27.11 (C-4), 89.38
(C-3), 122.59 (C≡N), 131.15 (C-5 th ioph en e), 131.28 (C-4 th ioph en e), 163.07 (C-2), 168.74
J(N=C–Se) = 154.
2-(3-Isoselenoureido)-4,5-dimethylthiophene-3-carbonitrile (10c). Yield: 0.6 g (84%) (from 9c),
0.6 g (84%) (from 9f); m .p. 182–186 °C (eth an ol). For C8H9N3SSe (259.0) calculated: 37.07% C,
3.50% H, 16.22% N, 30.56% Se; foun d: 36.89% C, 3.46% H, 15.97% N, 30.29% Se. FTIR: 3
249, 3 197 (NH), 2 207 (C≡N), 1 652 (C=N). 1H NMR (CDCl3): 1.58 bs, 3 H (SeH an d NH2);
2.33 s, 3 H (CH3, C-4 th ioph en e); 2.46 s, 3 H (CH3, C-5 th ioph en e). 13C NMR (CDCl3): 12.63
(CH3, C-4 th ioph en e), 14.24 (CH3, C-5 th ioph en e), 94.88 (C-3, th ioph en e), 120.56 (C≡N),
129.24 (C-5, th ioph en e), 131.71 (C-4, th ioph en e), 165.65 (C-2, th ioph en e), 169.45
J(N=C–Se) = 147.
Gen eral Procedures for Preparation of Com poun ds 11a–11c an d 12a–12c
Method A. Acylselen ourea 5a–5f (5 m m ol) was suspen ded in a 5% m eth an olic solution of
potassium h ydroxide (50 m l) an d refluxed un til a clear solution was form ed (5–10 m in ). Th e
solution was filtered with ch arcoal, un til filtrate was cooled to 5–10 °C an d n eutralized with
glacial acetic acid. Th e precipitated product (11a–11c an d 12a–12c) was filtered off, wash ed
with m eth an ol an d dried in vacuo.
Method B. Isoselen ourea 10b or 10c (2 m m ol) was suspen ded in 5% m eth an ol solution of
potassium h ydroxide (20 m l) an d refluxed (5–10 m in ). Th en th e solution was treated as de-
scribed in m eth od A.
Method C. 2-(3-Acylselen oureido)ben zon itrile 5a or 5d (5 m m ol) was dissolved in 30 m l
m eth an ol solution of potassium h ydroxide (340 m g, 6 m m ol) at room tem perature. Th e so-
lution was stirred at room tem perature for 20 m in or un der reflux for 5 m in (TLC). After
coolin g, th e precipitated 4-am in oquin azolin e-2-selen ol (11a) was filtered off, wash ed with
m eth an ol an d dried in vacuo.
4-Aminoquinazoline-2-selenol (11a). Yield: (A, from 5a) 0.9 g (80%), (A, from 5d ) 0.9 g
(80%), (C, from 5a) 0.85 g (76%), (C, from 7) 0.8 g (72%); m .p. 25–259 °C (m eth an ol). For
C8H7N3Se (224.1) calculated: 42.87% C, 3.15% H, 18.75% N, 35.21% Se; foun d: 42.46% C,
3.09% H, 18.51% N, 34.98% Se. FTIR: 3 300,
3 127 (NH2), 1
643 (C=N). 1H NMR
(CF3COOD): 7.84–8.37 m , 4 H (C6H4). 13C NMR (CF3COOD): 112.74 (C-5, pyrim idin e),
120.65 (C-5), 126.50 (C-8), 132.30 (C-6), 140.48 (C-7), 141.42 (C-6, pyrim idin e), 159.50
(C-4).
4-Amino-5,6,7,8-tetrahydrobenzo[1]thieno[2,3-d]pyrimidine-2-selenol (11b ): Yield: (A, from
5b) 1.30 g (91%), (A, from 5e) 1.20 g (84%), (B, from 10b) 0.40 g (70%); m .p. 292–295 °C
(m eth an ol). For C10H11N3SSe (285.0) calculated: 42.26% C, 3.90% H, 14.783% N, 27.76% Se;
foun d: 41.88% C, 3.76% H, 14.56% N, 27.54% Se. FTIR: 3 381, 3 212 (NH), 1 645 (C=N).
1H NMR (CF3COOD): 1.82–2.20 m , 4 H (6-CH2 an d 7-CH2); 2.85–3.09 m , 4 H (5-CH2 an d
8-CH2). 13C NMR (CF3COOD): 23.61 (C-7), 23.75 (C-6), 24.05 (C-8), 31.77 (C-5), 130.23
(C-10, cycloh exan e), 132.47 (C-9, cycloh exan e), 137.09 (C-5, pyrim idin e), 139.01 (C-6, pyri-
m idin e), 153.49 (C-4).
4-Amino-5,6-dimethylthieno[2,3-d]pyrimidine-2-(1H)-selone (12c): Yield: (A, from 5c) 1.10 g
(85%), (A, from 5f) 1.10 g (85%), (B, from 10c) 0.35 g (67%); m .p. 199–202 °C (m eth an ol).
For C8H9N3SSe (258.9) calculated: 37.07% C, 3.50% H, 16.22% N, 30.56% Se; foun d: 36.79% C,
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1694
Šibor et al.:
3.49% H, 16.16% N, 30.42% Se. FTIR: 3 440, 3 293 (NH), 1 622 (C=N), 1 527, 954 (NHCSe,
selen oam ide III, I). 1H NMR (CF3COOD): 2.82 s, 3 H (CH3); 2.83 s, 3 H (CH3). 13C NMR
(CF3COOD): 11.12 (CH3, C-5), 11.80 (CH3, C-6), 126.51 (C-5), 132.91 (C-6), 152.48 (C-5, py-
rim idin e), 155.16 (C-4), 169.71 (C-6, pyrim idin e), 181.29 J(C=Se) = 220.
This work was supported by the Grant Agency of the Czech Republic (grants No. 203/93/0715,
No. 203/96/0111 and No. 203/96/1513). We would like to thank Biosym/Molecular Simulations of
San Diego for providing us with the academic license for the InsightII and Turbomole software. We
thank the Academic Supercomputer centre in Brno for access to the computer facilities. Our thanks are
also due to Dr J. Jambor of Department of Analytical Chemistry of the Faculty for determination of se-
lenium by Inductively Coupled Plasma – Atomic Emission Spectrometry, to the Analytical department
of Lachema Co., Brno, Czech Republic for elemental analysis, MS Laboratory of Université Catholique
Louvain, Louvain-la-Neuve, Belgium for measuring mass spectra and Advanced Chemistry Develop-
ment, Inc., Toronto, Canada for the free on-line simulation of 1H and 13C NMR spectra.
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