A convenient synthesis of selenocarboxamides from nitriles

Article abstract of DOI:10.1055/s-2001-15232

Aromatic and aliphatic nitriles can be conveniently converted into the corresponding selenocarboxamides with monoselenophosphate in aqueous alcohol in 50-94% yield.

Full text of DOI:10.1055/s-2001-15232

1308
SHORT PAPER
A Convenient Synthesis of Selenocarboxamides from Nitriles
S
ynthesis of Sele
a
nocarboxam
f
ides
f
ro
a
m
N
itriles l Kamiñski,a Richard S. Glass,*b Aleksandra Skowroñska*a
a
Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90–363 ód , Poland
Fax +48(42)6847126; E-mail: askow@bilbo.cbmm.lodz.pl
b
Department of Chemistry, University of Arizona, Tucson, Arizona 85721, USA
Received 5 February 2001; revised 12 March 2001
Abstract: Aromatic and aliphatic nitriles can be conveniently con-
verted into the corresponding selenocarboxamides with monosele-
nophosphate in aqueous alcohol in 50–94% yield.
Key words: monoselenophosphate, nitriles, selenocarboxamides
Equation 1
Primary selenocarboxamides have been synthesized by
the addition of the toxic and volatile hydrogen selenide to
nitriles.1 Hydrogen selenide can be generated in situ for
this reaction by the hydrolysis of aluminum selenide2 or
the reduction of elemental selenium by carbon monoxide.3
Sodium hydroselenide, prepared by the reduction of ele-
mental selenium with sodium borohydride, has also been
used to convert aryl nitriles4,5 into the corresponding sele-
nocarboxamides. Bis(trimethylsilyl)selenide6 or 4-
methylselenobenzoate7 transform aromatic and aliphatic
nitriles into selenocarboxamides but these reagents re-
quire the use of boron trifluoride diethyl etherate. Since
primary and secondary amines react with selenocarboxa-
mides unsubstituted at nitrogen to give N-mono- and N,N-
disubstituted selenocarboxamides, respectively,8 routes to
primary selenocarboxamides provide access to these de-
rivatives. This route complements the conversion of sub-
stituted amides with phosphorus pentaselenide,1 bis[1,5-
cyclooctanediylboryl]selenide9 or alkylaluminum se-
lenides,10,11 reaction of iminium ethers with hydrogen se-
lenide,12 ammonolysis of selenoesters,13 addition of
The reactions are done with aqueous solution of monose-
lenophosphate in water containing methanol or propan-2-
ol as cosolvent (Method A). Monoselenophosphate can be
also generated in situ from tris(trimethylsilyl)selenophos-
phate (Method B). The yields of the products isolated by
recrystallization or column chromatography on silica gel
are shown in Table 1.
Table 1 Synthesis of Selenocarboxamides 3 from Nitriles 1
1, R
Method and Yield a (%) Mp (oC)
Nitrile to
Lit. mp (oC)
Selenophos-
phate Ratio
Ph
A, 1
50
124
126–126.53
1252
2-MeC6H4 A, 1.2
73
107
104–1063
92–92.521
126–126.521
solid3
PhCH2
Me
A, 1
59
89
B, 10
B, 12,b 5
B, 5
79
122–124
54–55
34
amines to selenoketenes,14–17 and reaction of -amino- Et
55,b 65
54
phosphine oxide anions18 or phosphonate carbanions and
Pr
solid3
amines19 with elemental selenium.
C5H4N
B,b 1.2
70
154–156
164–1664
Monoselenophosphate phosphorylates alcohols at neutral
pH.20 In extending the scope of such phosphorylations, ac-
etonitrile was used as a cosolvent and it was converted in
good yield to selenoacetamide. Consequently, this paper
reports the use of monoselenophosphate in aqueous acid
as a convenient method for converting nitriles into prima-
ry selenocarboxamides which complements the previous-
ly reported methods.
Reaction of aromatic and aliphatic nitriles 1 with monose- c The salt of the product with H3PO4 was obtained in this reaction.
lenophosphate 2 readily available from tris(trimethylsi-
lyl)selenophosphate gives selenocarboxamides 3 as
(pyridin-
3-yl)
(dec.)
H2NC
A,b,c
1
94
195 (dec.)d
(=NH)NH
a Yields are based on monoselenophosphate and refer to analytically
pure compounds. No attempts was made to optimize the yields.
b The reaction was run under reflux.
d Anal. Calcd for C2H9N4O4PSe: C, 9.13; H, 3.45; N, 21.30; P, 11.77.
Found: C, 9.41; H, 3.52; N, 21.16; P, 11.83.
shown in Equation 1.
In analogy with the mechanism proposed22 for the reac-
tion of phosphoroselenoic acids with carbodiimides, the
mechanism for the reaction of nitriles with monoseleno-
phosphate is shown in Equation 2.
Synthesis 2001, No. 9, 29 06 2001. Article Identifier:
1437-210X,E;2001,0,09,1308,1310,ftx,en;Z01901SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

SHORT PAPER
Synthesis of Selenocarboxamides from Nitriles
1309
in organic solvents. On the basis of the kinetic data ob-
served one can predict the time and conditions for other
nitriles.
Melting points are uncorrected. IR spectra were obtained as KBr
pellets (or film) using a ATI Mattson Infinity 60 AR FTIR spectro-
photometer. 1H, 13C, 31P, and 77Se NMR spectra were measured in
the solvents shown, using tetramethylsilane as an internal standard
for the 1H and 13C, H3PO4 for the 31P and H2SeO3/D2O for the 77Se
NMR spectra at the frequency shown on Bruker AC 200 and Bruker
DRX 500 spectrometers. Mass spectra were done using a Finnigan
MAT 95 spectrometer. Ultraviolet spectra were measured with Per-
Equation 2
The UV absorption spectra of the selenocarboxyamides kin-Elmer Lambda 40 Spectrophotometer. Silica gel (240 mesh) for
column chromatography was obtained from Merck. Nitriles were
purchased from Aldrich and Fluka (benzonitrile and propionitrile)
show in protic solvents an intense band near max = 300–
330 nm (see Table 2). This absorption is due to a - *
and were used without further purification. Aqueous solution of
transition and can be used to measure the selenocarboxa-
monoselenophosphate was prepared via desilylation of tris(trimeth-
mide concentration. Several kinetic runs were performed
24
ylsilyl)selenophosphate24,25 in H2O–CHCl3 or H2O–hexane sys-
at 55°C in a H2O–MeOH (1:1 v/v) solution of HClO4
(0.01 M). The initial concentrations of reagents were
0.002 M in selenophosphate and 0.19 M in nitrile with the
exception of cyanoguanidine. On the basis of the UV ab-
sorptions at max we have determined the rates of the sele-
nocarboxamides formation (within the first half-life of the
reaction). The data are summarized in Table 2 as the rela-
tive rates of the reaction. The half-life in the case of pro-
pionitrile was ca 10 hours under the conditions of the
kinetic experiment.
tems as follows: Tris(trimethylsilyl)selenophosphate (1 mL, 2.86
mmol) was added to hexane (1 mL) and deoxygenated H2O (1 mL).
The mixture was stirred vigorously overnight at r.t. (85%).
Selenocarboxamides 3; General Procedures
Method A: To a concentrated (2 M or higher) aqueous solution (pH
1–1.5) of monoselenophosphate (2), prepared as described above
under argon, was added an equimolar amount (or 20% excess) of ni-
trile 1 (for cyanoguanidine see below) and sufficient MeOH or pro-
pan-2-ol to dissolve the reagents (at least partially). The solution
was stirred at r.t. overnight. An aqueous solution of K2CO3 equimo-
lar with the monoselenophosphate was added and the mixture was
repeatedly (2–5 times) extracted with benzene or CH2Cl2. The com-
bined extracts were dried (MgSO4), filtered, rotary evaporated, and
the residue was recrystallized or purified by column chromatogra-
phy on silica gel.
Table 2 UV Spectra of Selenocarboxamides 3 and Relative Rates
of their Formation
3, R
Solvent
max (nm)
Relative Rate
of Formation
of Product 3
(at 55°C)
max
(l mol–1
Reaction with Cyanoguanidine: Into the carefully deoxygenated
warm solution of cyanoguanidine (0.084 g, 1 mmol) in H2O (1 mL)
was added slowly (syringe, septum) a 2.4 M solution of monosele-
nophosphate (0.416 mL, 1 mmol). Colorless crystals precipitated
immediately. Deoxygenated MeOH (1 mL) was added and the
product was filtered at r.t. and washed with MeOH.
cm–1)
Ph
MeOH
MeOH
MeOH
MeOH
331 (335)23 5900
303 10300
296 (296)23 9300
3
PhCH2
Me
Et
1
Method B: Into the deoxygenated solution of the nitrile 1 in MeOH
(4 mL) at r.t. or under reflux as indicated in the Table 1 was slowly
added of O,O,O-tris(trimethylsilyl)monoselenophosphate24,25 (1
mL, 2.86 mmol) by syringe under argon. The ratio of nitrile to
monoselenophosphate is given in Table 1. A yellow color appeared
after10–60 s. The reactions were run under reflux (traces of H2Se
appeared) for 5 h or for 3–4 d at r.t. In this case conducting the re-
action in a sealed ampoule is recommended.
0.4
1
298
9800
Pr
MeOH
H2O
299
292
9600
8400
0.6
(pH = 2)a
C5H4N
(pyridin-
3-yl)
H2O
332
5200
–
(pH = 2)a
Selenobenzamide 3 (R = Ph)
IR (KBr): = 3324 (s), 3270 (s), 3144 (s), 1619 (s), 1449 (m), 1408
(w), 1308 (w), 1258 (m), 1121 (s), 1072 (s), 666 (m), 635 (m) cm–1.
H2NC
(=NH)NH H2O
MeOH
297
292
8800
5100
ca 150b
1H NMR (200 MHz, CDCl3): = 7.25–7.43 (m, 2 H), 7.49–7.57 (m,
1 H), 7.84–7.94 (m, 2 H), 7.90 (br s, 1 H), 8.82 (br s, 1 H).
(pH = 2)a
13C NMR (125.8 MHz, CDCl3): = 126.87, 128.61, 132.16, 142.02,
207.82 (C=Se).
77Se NMR (95.4 MHz, CDCl3): = 661.2.
a pH maintained with HClO4.
b Calculated from the runs at lower concentration.
MS (CI, isobutane): m/z = 104 (15), 106 (12); [M + H+]: 182 (18),
183 (223), 184 (51), 185 (23), 186 (100), 187 (32), 188 (19).
In summary, a convenient method for the synthesis of se-
lenocarboxamides from nitriles using monoselenophos-
phate has been found. This method complements the
previously reported methods since aqueous acidic condi-
tions are used as opposed to basic conditions or BF3 OEt2
2-Methylselenobenzamide 3 (R = 2-MeC6H4)
IR (KBr): = 1721, 1624–1400 (w), 1361, 1216, 912, 742 cm–1.
1H NMR (200 MHz, CDCl3): = 2.33 (s, 3 H), 7.08–7.28 (m, 4 H),
8.01 (br, 1 H), 9.12 (br, 1 H).
Synthesis 2001, No. 9, 1308–1310 ISSN 0039-7881 © Thieme Stuttgart · New York

1310
R. Kamiñski et al.
SHORT PAPER
13C NMR (50.3 MHz, CDCl3): = 19.34, 125.38, 125.67, 129,18,
130.46, 131.09, 144.59, 209.75 (C=Se).
77Se NMR (95.4 MHz, CDCl3): = 678.
MS (FAB, NBA): m/z = 186.
Anal. Calcd for C6H6N2Se: C, 38.94; H, 3.27; N, 15.14. Found: C,
39.05; H, 3.17; N, 15.11.
MS (CI, isobutane): m/z = 117 (10), 118 (100), 119 (10), 120 (11),
158 (4); [M + H+]: 196 (24), 197 (25), 198 (56), 199 (22), 200 (98),
201 (11), 202 (16).
N-Guanidylselenocarboxamide Phosphate 3 [R = H2NC(=NH)NH]
IR (KBr): = 3453 (s), 3314 (s), 3236 (m), 3104 (s), 1713 (s), 1631
(s), 1513 (w), 1402 (w), 1334 (m), 1133 (w), 1050 (s), 949 (s), 648
cm–1 (m).
Phenylselenoacetamide 3 (R = PhCH2)
IR (KBr): = 3286 (s), 3125 (s), 1632 (s), 1457 (s), 1431 (s), 1291
(w), 1253 (w), 1136 (m), 969 (m), 745 (s), 699 (s), 582 cm–1 (s).
1H NMR (200 MHz, CDCl3): = 4.07 (s, 2 H), 7.21–7.38 (m, 4 H),
7.60 (br s, 1 H), 9.25 (br s, 1 H).
13C NMR (125.8 MHz, CDCl3): = 55.58, 127.92, 128.16, 129.21,
129.32, 134.17, 212.07(C=Se).
13C NMR (50.3 MHz, DMSO-d6): = 158.33, 179.93 (C=Se).
77Se NMR (95.4 MHz, DMSO-d6): = 293.8.
31P NMR (81.0 MHz, DMSO-d6): = 1.13.
MS (CI isobutane): m/z = 85 (100); [GSA + H+ – H2Se], 97 (10), 112
(19), 113 (9), 127 (8), 129 (5); [GSA + H+]: 163 (4), 165 (9), 167
(19), 169 (4), 173 (12), 174 (12), 175 (31), 176 (5), 177 (67), 179
(11).
77Se NMR (95.4 MHz, CDCl3): = 581.8.
MS (CI, isobutane): m/z = 118 (24), 119 (3), 120 (6), 174 (6); [M +
H+]: 196 (19), 197 (20), 198 (48), 199 (15), 200 (100), 201 (16), 202
(17).
MS (FAB, glycerol): m/z = 167, 259, 351.
References
Selenoacetamide 3 (R = Me)
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IR (KBr): = 3231 (s), 3054 (s), 1652 (s), 1479 (s), 1403 (s), 1366
(w), 1288 (m), 954 (s), 767 (m), 717 (m), 615 (s) cm–1.
1H NMR (200 MHz, CDCl3): = 1.96 (s), 8.2 (br s, 1 H), 8.4 (br s,
1 H).
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(100), 125 (3), 126 (16).
Selenopropanamide 3 (R = Et)
IR (KBr): = 3435 (br, m), 3297 (s), 3155 (s), 1644 (s), 1453 (s),
1304 (w), 1281 (w), 1222 (w), 1065 (w), 1004 (w), 896 (m), 710
(m), 582 cm–1 (m).
1H NMR (200 MHz, CDCl3): = 1.31 (t, 3 H, J = 7.5 Hz), 2.70 (q, 2
H, J = 7.5 Hz), 7.73 (br s, 1 H), 8.73 (br s, 1 H).
13C NMR (125.8 MHz): = 13.55, 42.44, 217.00 (C=Se).
Selenobutanamide 3 (R = Pr)
IR (film): = 3278 (s), 3152 (s), 2962 (s), 1629 (s), 1452 (s), 1282
(m), 1207 (m), 1082 (w), 972 (w), 946 (w), 662 cm–1 (m).
1H NMR (500 MHz, CDCl3): = 0.96–0.99 (t, 3 H, J = 7.4 Hz),
1.76–1.84 (sext, 2 H, J = 7.5 Hz), 2.65–2.80 (t, 2 H, J = 7.5 Hz), 7.86
(br s, 1 H), 8.91 (br s, 1 H).
13C NMR (125.8 MHz, CDCl3): = 13.23, 22.80, 51.27, 216.01
(C=Se).
77Se NMR (95.4 MHz, CDCl3): = 557.6.
MS (CI, isobutane): m/z = 72(21), [M + H+]: 148 (18), 149 (17), 150
(47), 152 (100), 154 (17).
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1994, 113, 499.
Anal. Calcd for C4H9NSe: C, 32.01; H, 6.04; N, 9.33. Found: C,
31.97; H, 6.07; N, 9.25.
Pyridin-3-yl-selenocarboxamide 3 (R = C5H4N)
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IR (KBr): = 3450 (m), 3205 (s), 3002 (s), 2940 (s), 2805 (m), 1679
(m), 1586 (s), 1458 (s), 1402 (m), 1122 (w), 1026 (m), 867 (m), 784
(m), 697 (s), 633 cm–1 (w).
1H NMR (200 MHz, CD3OH): = 7.40–7.47 (m, 1 H), 8.24–8.30
(m, 1 H), 8.61–8.64 (m, 1 H), 9.00–9.01 (m, 1 H), 10.19 (br s, 1 H),
10.58 (br s, 1 H).
13C NMR (50 MHz, CD3OH): = 124.65, 136.50, 140.79, 148.16,
151.88, 204.70 (C=Se).
77Se (95.2 MHz, CD3OH): = 628.2.
Synthesis 2001, No. 9, 1308–1310 ISSN 0039-7881 © Thieme Stuttgart · New York