Acyloxy group exchange in N-acyloxy-N-alkoxyamides

Article abstract of DOI:10.1070/MC2004v014n05ABEH001908

Acyloxy group exchange at the nitrogen atom proceeds in the interaction of N-acyloxy-N-alkoxyureas, N-acyloxy-N-alkoxybenzamides and N-acyloxy-N- alkoxycarbamates with Na and K carboxylates in MeCN.

Full text of DOI:10.1070/MC2004v014n05ABEH001908

, 2004, 14(5), 208–210
Acyloxy group exchange in N-acyloxy-N-alkoxyamides†
Vasiliy G. Shtamburg,a Alexandr V. Tsygankov,a Evgeniy A. Klotsa and Remir G. Kostyanovsky*b
a Department of Chemistry, Dnepropetrovsk National University, 49050 Dnepropetrovsk, Ukraine.
Fax:+ 38 056 776 5833; e-mail: heterosycle@ff.dsu.dp.ua
b N. N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, 119991 Moscow, Russian Federation.
Fax: +7 095 651 2191; e-mail: kost@chph.ras.ru
DOI: 10.1070/MC2004v014n05ABEH001908
Acyloxy group exchange at the nitrogen atom proceeds in the interaction of N-acyloxy-N-alkoxyureas, N-acyloxy-N-alkoxy-
benzamides and N-acyloxy-N-alkoxycarbamates with Na and K carboxylates in MeCN.
proceeds under the action of amines,3,4 NaN3 and alkaline
hydrolysis,7 but the initially formed products are unstable and
undergo decomposition. N-Acyloxy-N-alkoxysubstituted ureas
and carbamates afford corresponding stable N,N-dialkoxy
derivatives under alcoholysis.2 The possibility of selective
nucleophilic substitution at the nitrogen atom in these N-acyl-
oxy-N-alkoxyamides under the action of different nucleophiles
is ambiguous because of both competitive nucleophilic attacks
5,6
The first N-acyloxy-N-alkoxy-N-tert-alkylamine has been syn-
thesised earlier.1 In N-acyloxy-N-alkoxyureas, N-acyloxy-
N-alkoxycarbamates and N-acyloxy-N-alkoxybenzamides, the
acyloxy group is an anionic leaving group, and nucleophilic
substitution can take place.2–4 In N-acyloxy-N-alkoxybenz-
amides, the nucleophilic substitution of the acyloxy group
†
Geminal systems, part 51. Previous communication see ref. 2.
208 Mendeleev Commun. 2004

, 2004, 14(5), 208–210
at other electrophilic centres and redox reactions.2 In this con-
nection, the search of nucleophiles that selectively attack the
nitrogen atom and yield relatively stable initial products of the
nucleophilic substitution is needed. In this work, the carboxylate
anions were choosen as such selective nucleophiles. It should
be mentioned that the acyloxy group substitution by another
acyloxy group is discussed in our article for the first time.
We found that the acyloxy group exchange at the nitrogen
atom occurs when N-acyloxy-N-alkoxy-substituted ureas, benz-
amides and carbamates react with Na and K carboxylates in
MeCN (18–23 °C) and, as a rule, it is not accompanied by
competitive processes.‡
In the case of N-acyloxy-N-alkoxyureas, when Na carboxylates
were used, the reaction did not proceed to the end, and a mixture
of starting and final ureas was obtained. Probably, it is a con-
sequence of the reversibility of this reaction. The separation of
the mixture of both Na carboxylates and the repeating treatment
by a new portion of Na carboxylate increases the yield of the
product. Thus, the successive treatment of N-benzoyloxy-N-
butyloxyurea 1 by two portions of AcONa yields the mixture
of urea 1 and N-acetoxy-N-butyloxyurea 3 in a ratio of 70:30.
The mixture of ureas 2 and 3 in a ratio of 27:73 was obtained
from N-p-chlorobenzoyloxy-N-butyloxyurea 2 after stirring with
AcONa for 80 h (Scheme 1).
The repeated treatment of this mixture by a fresh portion of
AcONa (104 h) yielded pure N-acetoxy-N-butyloxyurea 3 in
42% yield. The more complete N-acyloxy group exchange was
achieved by the interaction of N-benzoyloxy-N-alkoxyureas
with K carboxylates. By the twofold treatment with EtCO2K,
ureas 1 and 5 were fully converted into corresponding
N-propionyloxy-N-alkoxyureas 4† and 6, respectively (Scheme 2).
OBz
O2CEt
EtCO2K
– BzOK
H2N
N
H2N
N
OBu
OBu
O
O
O
O
1
4, 66.9%
OBz
N
O2CEt
EtCO2K
– BzOK
MeHN
MeHN
N
OPr
OPr
5
6
, 87.1%
Scheme 2 Reagents and conditions: for 4, 7.8 equiv. EtCO2K, MeCN,
18–20 °C, (a) 37 h, (b) 83 h; for 6, 5.3 equiv. EtCO2K, MeCN, 22 °C,
(a) 61 h, (b) 12 h.
The interaction of ethyl N-chlorobenzoyloxy-N-methoxy-
carbamate 7 with two portions of AcONa yielded ethyl
N-acetoxy-N-methoxycarbamate 8. The ratio of carbamates 7
and 8 in the reaction mixture was 71:29 (Scheme 3).
O2C–C6H4X-p
OAc
N
AcONa
– p-XC6H4CO2Na
H2N
N
H2N
OBu
OBu
O2CC6H4Cl-p
OAc
AcOM
– p-ClC6H4CO2M
O
O
RO2C
N
RO2C
N
1 X = H
3
OMe
OMe
X = Cl
2
7
8
R = Et
R = Et
Scheme 1 Reagents and conditions: for 1, 3 equiv. AcONa, MeCN, 20–
23 °C, (a) 30 h, (b) 20 h; for 2, 4.5 equiv. AcONa, MeCN, 20 °C, (a) 80 h,
(b) 104 h.
9 R = Me
10 R = Me
Scheme 3 Reagents and conditions: for R = Et, 3.6 equiv. AcONa, MeCN,
20 °C, (a) 32 h, (b) 41 h; 5.5 equiv. AcOK, MeCN, 20 °C, (a) 55 h, (b) 65 h,
(c) 86 h; for R = Me, 3 equiv. AcOK, MeCN, 20 °C, (a) 44 h, (b) 165 h.
‡
The standard method of the acyloxy group exchange in N-acyloxy-
N-alkoxyamides. (A). A solution of N-benzoyloxy-N-butyloxyurea 1
(0.452 g, 1.793 mmol) in MeCN (30 ml) and EtCO2K (1.57 g, 14 mmol)
was stirred for 37 h at 18–20 °C; the solid was filtered off and washed
with Et2O (15 ml); the filtrate was concentrated in vacuo; the residue
was extracted with Et2O (20 ml); the extract was evaporated in vacuo. The
residue was dissolved in MeCN (25 ml); the solution was stirred with
EtCO2K (1.57 g, 14 mmol) for 83 h; the solid was filtered off and washed
with Et2O (20 ml). The filtrate was evaporated in vacuo; the residue was
extracted with Et2O (20 ml); the ether was removed in vacuo, yielding
0.245 g (66.9%) of N-propionyloxy-N-butyloxyurea 4 as a colourless
liquid. 1H NMR (300 MHz, CDCl3) d: 0.95 [t, 3H, NO(CH2)3Me, 3J 7 Hz],
The replacement of AcONa by AcOK also results in more
complete exchange of acyloxy group: the ratio of compounds
7 and 8 is 42:58.‡ An additional treatment by two portions of
AcOK followed by distillation of the reaction mixture gives pure
carbamate 8 in 53% yield. By analogy, methyl N-p-chloro-
benzoyloxy-N-methoxycarbamate 9 is converted into methyl
N-acetoxy-N-methoxycarbamate 10 with a 75% yield by treat-
ment with two portions of AcOK.
N-p-Chlorobenzoyloxy-N-ethoxybenzamide 11 reacts more
actively than carbamate 7, and after stirring with two portions
of AcONa, compound 11 is converted into N-acetoxy-N-ethoxy-
benzamide 12 (Scheme 4).
3
1.22 (t, 3H, O2CCH2Me, J 7.2 Hz), 1.39 [t qu, 2H, NO(CH2)2CH2Me,
3
3J 7 Hz], 1.68 (quint, 2H, NOCH2CH2CH2Me, J 7 Hz), 2.46 (qu, 2H,
3
3
O2CCH2Me, J 7.2 Hz), 4.09 (t, 2H, NOCH2, J 7 Hz), 5.64 (br. s, 1H,
NH), 5.97 (br. s, 1H, NH). Found (%): C, 46.93; H, 8.02; N, 13.94. Calc.
for C8H16N2O4 (%): C, 47.05; H, 7.90; N, 13.72. According to Scheme 5,
compound 4 was obtained in 82% yield.
O2CC6H4Cl-p
OAc
AcONa
– p-ClC6H4CO2Na
Bz
N
Bz
N
OEt
OEt
(B). A solution of compound 7 (0.5 g, 1.82 mmol) in MeCN (23 ml) and
AcOK (0.98 g, 10 mmol) were stirred for 55 h at 20 °C; the solid was
filtered off and washed with CH2Cl2 (7 ml). The filtrate was evaporated
in vacuo; the residue was extracted with CH2Cl2 (10 ml); the extract,
was evaporated in vacuo. 0.38 g of a colourless liquid was obtained.
According to 1H NMR spectrum, it is a mixture of N-acyloxy-
N-methoxycarbamates 7 and 8 in a molar ratio of 42:58. An additional
treatment with two portions of AcOK followed by distillation in vacuo
yielded pure N-acetoxy-N-methoxycarbamate 8 (0.17 g, 53%).2
Standard method for the synthesis of N-acyloxy-N-alkoxyamides. A
solution of N-chloro-N-ethoxyurethane 152 (1.12 g, 7.3 mmol) in MeCN
(40 ml) and p-ClC6H4CO2Na (2.6 g, 14.6 mmol) were stirred for 55 h at
18–20 °C; the solid was filtered off and washed with CH2Cl2 (30 ml).
The filtrate was evaporated in vacuo; the residue was extracted with
CH2Cl2 (10 ml). The extract was evaporated in vacuo; hexane (4 ml) was
added. The mixture was kept at –2 °C; the precipitate was filtered and
washed with hexane (3 ml). 1.27 g (63.6%) of ethyl N-p-chlorobenzoyloxy-
N-methoxycarbamate 7 was obtained as colourless crystals, mp 25–27 °C.
1H NMR (300 MHz, CDCl3) d: 1.35 (t, 3H, CO2CH2Me, 3J 7.2 Hz),
3.97 (s, 3H, OMe), 4.36 (qu, 2H, CO 2CH2Me, 3J 7.2 Hz), 7.47 (d, 2H,
C6H4, 3J 8.4 Hz), 8.03 (d, 2H, C6H4, 3J 8.4 Hz). IR (n/cm–1): 1790
(C=O), 1780 (C=O). Found (%): C, 48.11; H, 4.62; N 5.02. Calc. for
C11H12ClNO5 (%): C, 48.28; H, 4.42; N, 5.12.
11
12
, 86.5%
Scheme 4 Reagents and conditions: 5.7 equiv. AcONa, MeCN, 20 °C,
(a) 48 h, (b) 73 h.
Compounds 3, 5, 8, 10 and 12 were described earlier;2 new
compounds 1, 2, 7,‡ 9 and 11 were obtained by the reactions
Cl
N
O2CR2
N
R2CO2M
– MCl
X
X
OR1
OR1
O
O
13 X = NH2, R1 = Bu
14 X = NHMe, R1 = Pr
15 X = OEt, R1 = Me
16 X = OMe, R1 = Me
17 X = Ph, R1 = Et
1 X = NH2, R1 = Bu, R2 = Ph
2 X = NH2, R1 = Bu, R2 = p-ClC6H4
4 X = NH2, R1 = Bu, R2 = Et
6 X = NHMe, R1 = Pr, R2 = Et;
7 X = OEt, R1 = Me, R2 = p-ClC6H4
9 X = OMe, R1 = Me, R2 = p-ClC6H4
11 X = Ph, R1 = Et, R2 = p-ClC6H4
Scheme 5 Reagents and conditions: 2.5 equiv. R2CO2M, M = Na, K,
MeCN, 20 °C, 25–55 h.
Mendeleev Commun. 2004 209

, 2004, 14(5), 208–210
of corresponding N-chloro-N-alkoxyamides 13–172 with Na
and K carboxylates. Analogously, the counter synthesis of
N-propionyloxy-N-alkoxyureas 4, 6 was performed by the
reactions of N-chloro-N-alkoxyureas 13, 14 with EtCO2K
(Scheme 5).
Thus, the acyloxy group exchange in N-acyloxy-N-alkoxy-
amides was performed for the first time.
This work was supported by the Russian Academy of
Sciences and the Russian Foundation for Basic Research (grant
no. 03-03-32019).
Thus, the following compounds were obtained.
N-Benzoyloxy-N-butyloxyurea 1: yield 90.9%, viscous colourless oil,
mp 18–20 °C. 1H NMR (200 MHz, CDCl3) d: 0.93 [t, 3H, O(CH2)3Me,
3J 7 Hz], 1.40 [t qu, 2H, O( CH 2)2CH2Me, 3J 7 Hz], 1.72 ( quint, 2H,
References
1 V. G. Shtamburg, V. F. Rudchenko, Sh. S. Nasibov, I. I. Chervin, A. P.
Pleshkova and R. G. Kostyanovsky, Izv. Akad. Nauk SSSR, Ser. Khim.,
1981, 2320 (Bull. Acad. Sci. USSR, Div. Chem. Sci., 1981, 30, 4907).
2 V. G. Shtamburg, E. A. Klots, A. P. Pleshkova, V. I. Avramenko, S. P.
Ivonin, A. V. Tsygankov and R. G. Kostyanovsky, Izv. Akad. Nauk, Ser.
Khim., 2003, 2132 (Russ. Chem. Bull., Int. Ed., 2003, 52, 2251).
3 J. J. Campbell and S. A. Glover, J. Chem. Soc., Perkin Trans. 2, 1992,
1661.
4 (a) J. J. Campbell and S. A. Glover, Chem. Res. (S), 1999, 8, 474;
(b) J. J. Campbell and S. A. Glover, Chem. Res. (M), 1999, 8, 2075.
5 S. A. Glover and G. Mo, J. Chem. Soc., Perkin Trans. 2, 2002, 1728.
6 S. A. Glover and A. Rauk, J. Chem. Soc., Perkin Trans. 2, 2002, 1740.
7 A. M. Bonin, S. A. Glover and G. P. Hammond, J. Org. Chem., 1998,
63, 9684.
3
3
OCH2CH2CH2Me, J 7 Hz), 4.19 (t, 2H, NOCH 2, J 7 Hz), 5.80 (br. s,
3
2H, NH2), 7.47 (t, 2H, Ph, J 7.2 Hz), 7.58 (t, 1H, Ph, 3J 7.2 Hz), 8.10
(d, 2H, Ph, 3J 7.2 Hz). Found (%): C, 57.07; H, 6.28; N, 11.34. Calc. for
C12H16N2O4 (%): C, 57.13; H, 6.39; N, 11.10.
N-p-Chlorobenzoyloxy-N-butyloxyurea 2: yield 75%, colourless crystals,
mp 79–80 °C. 1H NMR (300 MHz, CDCl3) d: 0.93 [t, 3H, NO(CH2)Me,
3J 7.2 Hz], 1.39 [t qu, 2H, NO(CH2)2CH2Me, 3J 7.2 Hz], 1.71 (quint,
2H, NOCH2CH2CH2Me, 3J 7.2 Hz), 4.17 (t, 2H, NOCH
,
3J 7.2 Hz),
2
6.10 (br. s, 2H, NH2), 7.46 (d, 2H, C6H4, 3J 8.4 Hz), 8.03 (d, 2H, C6H4,
3J 8.4 Hz). 13C NMR (75 MHz, CDCl3) d: 13.7 (Me), 19.0, 30.0 (CH2),
75.6 (CH2O), 125.9 [C(4)], 129.0 [C(3), C(5)], 131.4 [C(2), C(6)], 140.5
[C(1)], 160.3 (H2NC=O), 163.9 (C=O). Found (%): C, 50.14; H, 5.42;
N, 9.61. Calc. for C12H15ClN2O4 (%): C, 50.27; H, 5.27; N, 9.77.
N-Propionyloxy-N-propyloxy-N'-methylurea 6: yield 77%, colourless
liquid. 1H NMR (300 MHz, CDCl3) d: 0.95 (t, 3H, NOCH2CH2Me,
3J 6.9 Hz), 1.21 (t, 3H, NO2CCH2Me, 3J 7.5 Hz), 1.71 ( t qu, 2H,
NOCH2CH2Me, 3J 6.9 Hz), 2.45 (qu, 2H, NO2CCH2Me, 3J 7.5 Hz),
3
3
2.90 (d, 3H, NH Me, J 5.1 Hz), 4.03 (t, 2H, NOCH2, J 6.9 Hz), 6.42
( br. s, 1H, NH). Found ( %): C, 47.22; H, 8.15; N, 13.48. Calc. fo
r
C8H16N2O4 (%): C, 47.05; H, 7.90; N 13.72.
Methyl N-p-chlorobenzoyloxy-N-methoxycarbamate 9: yield 77%,
1
colourless crystals, mp 33–34 °C. H NMR (300 MHz, CDCl3) d: 3.92
(s, 3H, NOMe), 3.97 (s, 3H, CO2Me), 7.47 [d, 2H, C(3)H, C(5)H,
3
3J 8.4 Hz], 8.03 [d, 2H, C(2)H, C(6)H, J 8.4 Hz]. 13C NMR (75 MHz,
CDCl3) d: 55.3 (NOMe), 63.4 (CO2Me), 125.6 [C(4)], 129.2 [C(3),
C(5)], 131.5 [C(2), C(6)], 140.8 [C(1)], 158.5 (CO2Me), 163.7 (C=O).
Found (%): C, 46.11; H, 3.92; N, 5.20. Calc. for C 10H10ClNO5 (%): C,
46.26; H, 3.88; N, 5.39.
N-p-Chlorobenzoyloxy-N-ethoxybenzamide 11: yield 90%, colourless
viscous oil. 1H NMR ( 300 MHz, CDCl 3) d: 1.31 (t, 3H, NOCH2Me,
3J 7 Hz), 4.34 (qu, 2H, NOCH2Me, 3J 7 Hz), 7.41 (t, 2H, Ph, 3J 7.5 Hz),
3
7.42 (d, 2H, C6H4, J 8.7 Hz), 7.53 (t, 1H, Ph, 3J 7.5 Hz), 7.84 (d, 2H,
3
3
Ph, J 7.5 Hz), 7.94 (d, 2H, C 6H4, J 8.7 Hz). Found (%): C, 59.87; H,
4.63; N, 4.16. Calc. for C16H14ClNO4 (%): C, 60.10; H, 4.41; N, 4.38.
Received: 19th February 2004; Com. 04/2234
210 Mendeleev Commun. 2004