Geminal systems: 64. N-alkoxy-N-chloroureas and N,N-dialkoxyureas

Article abstract of DOI:10.1007/s11172-015-0822-9

Molecular and crystal structures of N-alkoxy-N-chloroureas and N,N-dialkoxyureas were studied together with those of N-alkoxyureas as reference compounds. N-Alkoxy-N-chloroureas were found to have an elongated N - Cl bond and a shortened N-O(Alk) bond due to the n_O(Alk)→σ_N-Cl anomeric effect. Alcoholysis of N-alkoxy-N-chloro derivatives of urea, N′-arylureas, and carbamates in the presence of silver trifluoroacetate leads to sterically hindered N,N-dialkoxyureas, N,N-dialkoxy-N′-arylureas, and N,N-dialkoxycarbamates, respectively.

Full text of DOI:10.1007/s11172-015-0822-9

Russian Chemical Bulletin, International Edition, Vol. 64, No. 1, pp. 62—75, January, 2015
62
Geminal systems
64.* NꢀAlkoxyꢀNꢀchloroureas and N,Nꢀdialkoxyureas
V. G. Shtamburg,a R. G. Kostyanovsky,b A. V. Tsygankov,c V. V. Shtamburg,a O. V. Shishkin,d
R. I. Zubatyuk,d A. V. Mazepa,e and S. V. Kravchenkof
aUkranian State University of Chemical Technology,
8 ul. Gagarina, 49005 Dnepropetrovsk, Ukraine.
Fax: +38 (056) 473397. Eꢀmail: stamburg@gmail.com
bN. N. Semenov Institute of Chemical Physics, Russian Academy of Sciences,
4 ul. Kosygina, 119991 Moscow Russian Federation.
Fax: +7 (495) 938 2156. Eꢀmail: kost@chph.ras.ru
cKirovograd Flying Academy of the National Aircraft University,
1 ul. Dobrovol´skogo, 25005 Kirovograd, Ukraine.
Eꢀmail: geminalsystemsn@gmail.com
dInstitute of Single Crystals of the National Academy of Sciences of the Ukraine,
60 ul. Lenina, 61001 Kharkov, Ukraine.
Eꢀmail: shishkin@xray.isc.kharkov.com
eA. V. Bogatskii Physicochemical Institute of the National Academy of Sciences of the Ukraine,
86 ul. Lyustdorfskaya doroga, 65080 Odessa, Ukraine.
Eꢀmail: almazepa@rambler.ru
fDnepropetrovsk State Agrarian University,
25 ul. Voroshilova, 49600 Dnepropetrovsk, Ukraine.
Eꢀmail: svtailor@ukr.net
Molecular and crystal structures of NꢀalkoxyꢀNꢀchloroureas and N,Nꢀdialkoxyureas were
studied together with those of Nꢀalkoxyureas as reference compounds. NꢀAlkoxyꢀNꢀchloroꢀ
ureas were found to have an elongated N—Cl bond and a shortened N—O(Alk) bond due to the
nO(Alk)*N—Cl anomeric effect. Alcoholysis of NꢀalkoxyꢀNꢀchloro derivatives of urea,
N´ꢀarylureas, and carbamates in the presence of silver trifluoroacetate leads to sterically
hindered N,Nꢀdialkoxyureas, N,NꢀdialkoxyꢀN´ꢀarylureas, and N,Nꢀdialkoxycarbamates,
respectively.
Key words: NꢀalkoxyꢀNꢀchloroureas, anomeric effect, NꢀacyloxyꢀNꢀalkoxyureas, Nꢀalkoxyꢀ
Nꢀchlorocarbamates, alcoholysis, ureas, carbamates.
"Anomeric" amides bearing two electronegative heteroꢀ
Nꢀchloroureas gave N,Nꢀdialkoxyureas.15—18 NꢀAcyloxyꢀ
Nꢀalkoxybenzamides were synthesized from NꢀalkoxyꢀNꢀ
chlorobenzamides.2—5,18 NꢀAlkoxyꢀNꢀchloroureas on reꢀ
acting with sodium and potassium carboxylates selectively
transform to NꢀacyloxyꢀNꢀalkoxyureas,18—21 while Nꢀalkꢀ
oxyꢀNꢀchlorocarbamates convert to NꢀacyloxyꢀNꢀalkoxyꢀ
carbamates.18,20,22 Alcoholysis of NꢀacyloxyꢀNꢀalkoxyꢀ
ureas with primary and secondary alcohols at room temꢀ
perature selectively leads to N,Nꢀdialkoxyureas, whereas
alcoholysis of NꢀacyloxyꢀNꢀalkoxycarbamates with priꢀ
mary alcohols allows one to obtain earlier unknown
N,Nꢀdialkoxycarbamates.18,22
atoms on the nitrogen atom possess a special complex of
structural and chemical properties.2—13 The oxygen atom
of an Nꢀalkoxy group is one of such heteroatoms most
frequently encountered with.1—13 The optimization of the
electron density distribution over the N—X and N—OR
ꢀbonds in NꢀalkoxyꢀNꢀXꢀamides (X = Cl, OC(O)R,
OR´) leads to the increase in the sp3ꢀcharacter of the amide
nitrogen atom.2—13 The thus arising pyramidality of the
nitrogen atom sterically facilitates the nO(R)*N—X
orbital interaction ("anomeric effect"2), which leads to the
destabilization of the N—X bond, promoting either its
homolysis,2,6,12,14 or a nucleophilic substitution at the
amide nitrogen atom.2—13,15—18 Alcoholysis of Nꢀalkoxyꢀ
Earlier, the pyramidality of the amide nitrogen atom
was strictly confirmed by Xꢀray diffraction studies only for
NꢀacyloxyꢀNꢀalkoxybenzamides,10 and only recently this
was also established for N,Nꢀdialkoxybenzamides.13
* For Part 63, see Ref. 1.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 0062—0075, January, 2015.
1066ꢀ5285/15/6401ꢀ0062 © 2015 Springer Science+Business Media, Inc.

Anomeric amides
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 1, January, 2015
63
Table 1. Characteristic bond distances (d) in NꢀalkoxyꢀNꢀchloroureas 1—4 and Nꢀmethoxyurea (6)
Compound
d/Å
N(1)—C(=O)
N(2)—C(=O)
N—Cl
N—OMe(Alk)
123
223
3A25
3B25
4
1.4429(15)
1.4719(8)
1.447(1)
1.3202(16)
1.3536(8)
1.324(1)
1.7563(11)
1.7572(5)
1.757(1)
1.3984(13)
1.4204(7) (CMe2CO2Me)
1.383(1)(OEt)
1.447(1)
1.440(5)—1.447(5)
1.367(3)
1.324(1)
1.340(5)—1.350(4)
1.322(3)
1.670(3)
1.740(4)—1.751(3)
—
1.318(7)(OEt)
1.389(4)—1.401(4)
1.411(2)
6
In this connection, in the present work we studied the
structures of NꢀalkoxyꢀNꢀchloroureas and N,Nꢀdialkꢀ
oxyureas and considered in more details the nucleophilic
substitution reactions of the X group in NꢀalkoxyꢀNꢀXꢀ
ureas (X = Cl, OC(O)R) and NꢀalkoxyꢀNꢀchlorocarbꢀ
amates under alcoholysis conditions.*
Tables 1 and 2). There are six molecules (A—F) of comꢀ
pound 4 in the independent part of the unit cell.
The Xꢀray diffraction studies of the structure of Nꢀ
chloroꢀNꢀmethoxyurea (1) and NꢀalkoxyꢀNꢀchloroꢀN´ꢀ
(4ꢀnitrophenyl)urea (2) obtained by the chlorination of
the corresponding NꢀalkoxyꢀNꢀHꢀureas with ButOCl
showed that in both compounds the nitrogen atom of the
geminal system O—N—Cl has a pyramidal configuraꢀ
tion,23 i.e., is in the sp3ꢀhybridization state. The sum of
the bond angles at this nitrogen atom () is 328.6 (1)
and 325.8 (2). The second nitrogen atom has a trigonal
planar configuration.
Molecules E and F are disordered over two positions 1
and 2 due to the inversion of nitrogen atom N(1) with the
relative occupancies 60 : 40%. Nitrogen atom N(1) has a
trigonal pyramidal configuration. The sum of the bond
angles centered on the atom is 329.3(7)—332.4(7) in nonꢀ
disordered molecules A—D and 327(2)—335(1) in disorꢀ
dered molecules E—F, the deviation of atom N(1) from
the plane of bonded to it atoms is 0.469(4)—0.497(3) Å in
molecules A—D and 0.438(7)—0.52(1) Å in molecules E—F.
The lone pair of electrons (LP) on atom N(1) is oriented
virtually perpendicular to the carbamoyl fragment (the abꢀ
solute values of torsion angles lp(N(1))—N(1)—C(1)—N(2)
are 92—99 in molecules A—D and 67—84 in molecules
E—F, where lp(N(1)) is an idealized position of the LP on
atom N(1)). Such an orientation of the LP on atom N(1),
besides the n—ꢀconjugation, is additionally stabilized
by the formation of the intramolecular hydrogen bond
N(2)—H...O(2) (in molecules A—D: H...O is 2.04—2.10 Å,
N—H...O is 109—112; in molecules E—F: H...O is
2.12—2.34 Å, N—H...O is 100—108). The methyl group
has the scꢀorientation relative to the LP of atom N(1)
(the absolute values of torsion angles lp(N(1))—N(1)—
In the crystal structure of NꢀchloroꢀNꢀethoxyurea 3
(see Ref. 25), a disordering of molecules was observed
because of the inversion of the nitrogen atom in the gemiꢀ
nal system O—N—Cl. Two isomers 3A and 3B existing in
the crystal (the relative occupancies are 88.5 and 11.5%)
differ in the degree of pyramidality of the nitrogen atom
( 328.9 and 350.5, respectively). As a result, the N—Cl
bond distances also noticeably differ in these two isomers
(Table 1).
Cl(1)
O(1)
C(4)
C(1)
C(3)
C(2)
O(3)
N(3)
N(1)
O(2)
C(5)
N(2)
Similar disordering caused by the inversion of the niꢀ
trogen atom is also observed in the structure of Nꢀchloroꢀ
NꢀmethoxyꢀN´ꢀ(4ꢀnitrophenyl)urea 4 (see Ref. 26, Fig. 1,
C(7)
C(8)
C(6)
O(4)
Fig. 1. Structure of NꢀchloroꢀNꢀmethoxyꢀN´ꢀ(4ꢀnitrophenyl)ꢀ
urea (4).
* For preliminary communications, see Refs 20, 21, 23, and 24.

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Shtamburg et al.
Table 2. Intermolecular hydrogen bonds and angles in NꢀchloroꢀNꢀmethoxyꢀN´ꢀ(4ꢀnitroꢀ
phenyl)urea (4)
D—H...A
Bonded molecules
[operation of symmetry]
d(H...A)
/Å
D—H...A
/deg
N(2)—H...O(1)
B...D [1 – x,1 – y, –z]
D...A [–0.5 + x, 0.5 – y, –0.5 + z]
E...C [1 – x, –y, –z]
F...B [1 – x,1 – y, –z]
A...C [2 – x, 1 – y, 1 – z]
B...C [1 – x,1 – y, –z]
2.38
2.38
2.17
2.22
2.49
2.49
2.47
2.49
2.44
2.49
2.55
2.45
2.42
2.57
2.60
2.75
148
154
161
166
148
165
125
128
143
127
152
151
149
136
125
154
C(8)—H...O(4)
C(3)—H...O(4)
C(4)—H...O(3)
C(4)—H...O(1)
C(6)—H...O(3)
C(8)—H…O(3)
D...E
A...D [2.5 – x, 0.5 – y, 0.5 – z]
E...F1 [2 – x, 1 – y, –z]
F...E
C...B [0.5 – x, –0.5 + y, 0.5 – z]
E...E [–0.5 + x, 0.5 – y, –0.5 + z]
C...E [–0.5 + x, 0.5 – y, 0.5 + z]
D...A [–0.5 + x, 0.5 – y, –0.5 + z]
E...C [1 – x, –y, –z]
C(7)—H...O(1)
C(8)—H...O(1)
C(7)—H...Cl(1)
D...A [–0.5 + x, 0.5 – y, –0.5 + z]
O(2)—C(8) are 31—36 in molecules A—D and 28—37 in
molecules E—F). In all the molecules, the carbamoyl
fragment is planar (the absolute values of torsion angles
O(1)—C(1)—N(2)—C(2) are 0.9(6)—5.4(6)). In moleꢀ
cules A—D and at position 1 of molecule F, the benzene
ring lies virtually in this plane (the absolute values of torꢀ
sion angles C(1)—N(2)—C(2)—C(3) are 4.2(7)—12.3(6),
whereas in molecules D and F2 it slightly deviates from
this plane (the corresponding absolute values of torꢀ
sion angles are 27.7(9)—30.8(5)). The coplanar arrangeꢀ
ments of these fragments is stabilized by the formation in
molecules A—D and F1 of intramolecular hydrogen bond
C(3)—H...O(1) (H...O is 2.14—2.29 Å, C—H...O is 120—123).
In molecules E and F2, this interaction is noticeably weakꢀ
er and can be classified as an attractive contact (H...O is
2.43—2.46 Å, C—H...O is 111—114). The nitro group is
virtually in the plane of the benzene ring (the absolute
values of torsion angles C(4)—C(5)—N(3)—O(3) are
2.7(5)—12.5(5)).
phenylacetamides (1.71—1.72 Å),28 and Nꢀchloroimides
(1.676—1.691 Å).29—31
R = H (1), Ar (2—4)
This elongation of the N—Cl bond in NꢀalkoxyꢀNꢀ
chloroureas 1, 2, and 4 indicates its destabilization, facꢀ
ilitating the nucleophilic substitution of the chlorine
atom, and is apparently due to the anomeric effect
nO(Alk)*N—Cl2,8,9,15. This is also confirmed by the close
N—OMe bond distance values of nitrogen atom N(1)
of pyramidal configuration in compounds 1 and 4 (see
Table 1) to the N—OMe bond distance (1.396(1) Å) in
Nꢀmethoxyimide 5, the nitrogen atom in which has a comꢀ
pletely planar configuration, i.e., is in the sp2ꢀhybridizaꢀ
tion state.25 Such a shortening of the N—OMe bond in
NꢀchloroꢀNꢀmethoxyureas 1 and 4 is explained by the
domination of the anomeric effect nO(Me)*N—Cl in these
compounds.
In crystal, molecules are bonded between each other
by hydrogen bonds (see Table 2).
In NꢀalkoxyꢀNꢀchloroureas 1—4, the N(1)—C(1) and
N(2)—C(1) bonds are nonequivalent: the first is longer,
whereas the second is shorter as compared to the N—C
bond distances in urea (1.350(1) Å)27 and amides13 (1.359Å).
This indicates that the sp3ꢀhybridized nitrogen atom N(1)
of the Cl—N—O group is conjugated with the C=O bond
of the carbamoyl group to a lesser extent than the
sp2ꢀhybridized nitrogen atom N(2) of the NH2 and NHAr
groups. The N—Cl bond in NꢀalkoxyꢀNꢀchloroureas 1, 2,
and 4 is elongated as compared to the calculated
N—Cl bond distance in Nꢀchloroformamide (1.735 Å)2,
the N—Cl bond distance in substituted NꢀchloroꢀNꢀ
Earlier, it was shown that the nature of an Nꢀalkoxy
group in NꢀacyloxyꢀNꢀalkoxyureas significantly affected
the degree of pyramidality of nitrogen atom in the geminal
system O—N—O.25 Therefore, it is correctly to consider

Anomeric amides
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 1, January, 2015
65
the influence of the nature of substituent X in NꢀXꢀNꢀ
alkoxyureas on the structure of the molecule for the same
Nꢀalkoxy group.
Within the NꢀXꢀNꢀmethoxyurea family (X = Cl (1),23
H (6), OAc (7),25 OMe (8),21 OPri (9), OBut (10)), unꢀ
substituted Nꢀmethoxyurea 6, the structure of which was
studied by Xꢀray crystallography (Fig. 2, see Tables 1
and 3), was taken as a comparison reference.
C(2)
N(1)
O(2)
C(1)
N(2)
O(1)
Fig. 2. Structure of Nꢀmethoxyurea (6).
NꢀAcetoxyꢀNꢀmethoxyurea (7) was synthesized by the
reaction of NꢀchloroꢀNꢀmethoxyurea (1) with AcONa (see
Ref. 23), N,Nꢀdimethoxyurea (8) was obtained by methaꢀ
nolysis of either NꢀchloroꢀNꢀmethoxyurea (1) (see Ref. 23)
or NꢀacetoxyꢀNꢀmethoxyurea (7) (see Refs 21 and 25).
NꢀIsopropoxyꢀNꢀmethoxyurea (9) and NꢀtertꢀbutoxyꢀNꢀ
methoxyurea (10) were obtained by alcoholysis of Nꢀchloroꢀ
Nꢀmethoxyurea (1) with the corresponding alcohol in the
presence of CF3CO2Ag (Scheme 1). The structure of N,Nꢀ
dialkoxyureas 9 and 10 were also studied by Xꢀray diffracꢀ
tion analysis (Figs 3 and 4, Table 3).
We found that alcoholysis of NꢀalkoxyꢀNꢀchloroureas
in the presence of CF3CO2Ag, supposedly following the
SN1 mechanism, has proved a convenient method for the
synthesis of poorly available N,Nꢀdialkoxyureas 9 and 10.
Alternative approaches to the preparation of N,Nꢀdialkoxyꢀ
ureas 9 and 10 appeared to be ineffective. NꢀAlkoxyꢀNꢀ
chloroureas17 and NꢀacetoxyꢀNꢀalkoxyureas18 do not unꢀ
dergo tertꢀbutanolysis, probably, because of the steric hinꢀ
drance for the nucleophilic substitution at the nitrogen
atom by the SN2 mechanism.18 The reaction of Nꢀchloroꢀ
Nꢀmethoxyurea 1 with the solution of AcONa in isopropyl
alcohol leads to NꢀacetoxyꢀNꢀmethoxyurea 7, which is
C(2)
O(2)
O(3)
C(5)
N(1)
C(1)
O(1)
C(3)
C(4)
N(2)
Fig. 3. Structure of NꢀisopropoxyꢀNꢀmethoxyurea (9).
stable to isopropanolysis at room temperature (Scheme 2).
However, ethanolysis of NꢀacetoxyꢀNꢀmethoxyurea 7
gives NꢀethoxyꢀNꢀmethoxyurea (11). At the same time,
NꢀacetoxyꢀNꢀbutoxyurea (12) undergoes isopropanolysis
Scheme 1
R = Pri (9), But (10)

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Russ.Chem.Bull., Int.Ed., Vol. 64, No. 1, January, 2015
Shtamburg et al.
Table 3. Some structural parameters in Nꢀmethoxyurea (6) and NꢀXꢀNꢀmethoxyureas 1 and 7—10
Comꢀ
pound
X
N(1)/deg
d/Å

C=O/cm–1
N—OMe
Nsp3—C(=O)
Nsp2—C(=O)
C=O
123
6
Cl
H
OAc
OMe
329.0(2)
338.0
332.1(1)
331.8(2)
1.3984(13)
1.411(2)
1.401(2)
1.397(2),
1.401(2)
1.401(3),
1.408(3)
1.4429(15)
1.367(3)
1.445(2)
1.438(2)
1.3202(16)
1.322(3)
1.317(2)
1.320(3)
1.2264(15)
1.244(2)
1.2324(16)
1.220(2)
1710
1685
1708
1720
725
821
9
OPri
OBut
332.0(6)
331.6(2)
1.449(3)
1.438(3)
1.304(4)
1.322(3)
1.217(4)
1.217(2)
—
10
1.406(2),
1.408(2) (But)
1712
the nitrogen atom in NꢀacetoxyꢀNꢀmethoxyurea (7). This
causes a stronger destabilization of the N—OAc bond due
to the anomeric effect nO(Bu)*N—OAc and a stronger
sensitivity to isopropanolysis observed for NꢀacetoxyꢀNꢀ
butoxyurea (12).
N(2)
C(3)
In the molecule of Nꢀmethoxyurea (6), proceeding
from the refined coordinates of the hydrogen atoms (which
also agree with the geometry of the intermolecular hydroꢀ
gen bonds), nitrogen atom N(2) (the NHOMe group) has
almost planar configuration,  = 338, the configuration
of atom N(1) (the NH2 group) also is close to planar
( = 357). The C(2)—O(2) bond of the methoxy group
is oriented toward the LP of nitrogen atom N(2) (torsion
angle C(2)—O(2)—N(2)—lpN(2) is 23), whereas the
carbamoyl substituent is oriented virtually perpendicular
to it (torsion angle N(1)—C(1)—N(2)—lpN(2) is 96).
For Nꢀmethoxyurea (6) in crystal, the formation of the
intermolecular hydrogen bonds is observed: N(1)—
H(1a)...O(1)i [i: 1 + x, y, z] (H...O is 2.26(3) Å, N—H...O
is 138(2)), N(1)—H(1b)…O(1)ii [ii: –x, 2 – y, –z]
(H...O is 2.09(3) Å, N—H...O is 169(3)), and
N(2)—H(2)…O(1)iii [iii: –x, 1 – y, –z] (H...O is 2.11(3) Å,
N—H...O is 174(2)), which bind the molecules in layers
parallel to the plane (0 0 1).
C(1)
O(3)
C(2)
C(4)
N(1)
O(1)
O(2)
C(5)
C(6)
Fig. 4. Structure of NꢀtertꢀbutoxyꢀNꢀmethoxyurea (10).
at room temperature with the formation of NꢀbutoxyꢀNꢀ
isopropoxyurea (13).
It can be suggested that in NꢀacetoxyꢀNꢀbutoxyurea
(12), the nitrogen atom of the geminal system O—N—O
has a larger degree of pyramidality as compared to that of
Scheme 2

Anomeric amides
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 1, January, 2015
67
The structure of NꢀisopropoxyꢀNꢀmethoxyurea (9) is
similar to the structure of N,Nꢀdimethoxyurea (8) studied
earlier.21 Nitrogen atom N(1) has a trigonal pyramidal
configuration,  = 332.0(6) and deviates from the plane
of atoms bonded to itself by hN = 0.444(2) Å. The conforꢀ
mation of compound 9 is close to the conformation of
N,Nꢀdimethoxyurea 8 (see Ref. 21). The methyl and the
isopropyl groups have, respectively, the apꢀ and the
spꢀorientation relative to the LP of N(1) (torsion angle
lpN(1)—N(1)—O(2)—C(2) is 178, whereas torsion angle
lpN(1)—N(1)—O(3)—C(3) is –25). The carbamoyl group
is oriented virtually perpendicular to the LP of N(1) (torꢀ
sion angle lpN(1)—N(1)—C(1)—O(1) = 86). This conꢀ
formation is additionally stabilized by the attractive intraꢀ
molecular contact H(2b)...O(2) of 2.27 Å. The isopropyl
group is in the staggered conformation relative to the
N(1)—O(3) bond (torsion angle N(1)—O(3)—C(3)—H(3) =
= –48). In crystal, molecules of urea 9 are bonded in
double chains along the axis a by hydrogen bonds
N(2)—H(2a)...O(1)i [i: 1/2 + x, –1/2 – y, –z] (H...O is
2.10(3) Å, N—H...O is 169(4)) and N(2)—H(2b)...O(2)ii
[ii: 1 + x, y, z] (H...O is 2.25(4) Å, N—H...O is 162(3)).
In NꢀtertꢀbutoxyꢀNꢀmethoxyurea (10), nitrogen atom
N(1) (the geminal system O—N—O) has also a trigonal
pyramidal configuration. For atom N(1),  = 331.6(2),
the deviation from the plane of atoms directly bonded to
itself (hN) is equal to 0.447(2) Å. The conformation of
urea 10 is close to the conformation of urea 9. The methyl
and the tertꢀbutyl groups have, respectively, the apꢀ and
the spꢀorientation relative to the LP of atom N(1) (torsion
angle lpN(1)—N(1)—O(1)—C(1) is –178, torsion angle
lpN(1)—N(1)—O(2)—C(6) is 19). The carbamoyl group
is oriented virtually perpendicular to the LP of atom N(1)
(torsion angle lpN(1)—N(1)—C(1)—O(3) is –83), that,
besides the n—pꢀconjugation, is stabilized by the formaꢀ
tion of a shortened intramolecular attractive contact
H(2b)...O(1) of 2.21 Å, which cannot be classified as
a hydrogen bond because of the small value of the angle
N(2)—H(2b)...O(1) of 105. The tertꢀButyl group is in the
staggered conformation relative to the N(1)—O(1) bond
(torsion angle N(1)—O(1)—C(2)—C(3) is –61.3(2)).
Atom N(2) has a trigonal planar configuration, like in
N,Nꢀdimethoxyurea (8)21 and urea 9.
electronegative substituent X (X = Cl, OAc, OAlk) leads
to a sharp increase in the pyramidality of the nitrogen
atom in the geminal system X—N—O(Me). The vibration
frequencies of the carbamoyl C=O group increase in parꢀ
allel, that confirms the versatility of the Glover test on
pyramidality of the amide nitrogen atom.2,8—10,32
The N—O(Me) bond length in Nꢀmethoxyurea (6) is
significantly larger than those of the corresponding
N—O(Me) bonds in NꢀmethoxyꢀNꢀXꢀureas 1 and 7—10
(see Table 3). Since the N—O(Me) bond of the nitrogen
atom with the pyramidal configuration (compounds 1 and
7—10) cannot be shorter than a similar bond at the nitrogen
atom in almost planar configuration (Nꢀmethoxyurea 6),
a shortening of the N—O(Me) bond occurs in Nꢀmethꢀ
oxyꢀNꢀXꢀureas 1 and 7—10, probably, due to the anoꢀ
meric effect nO(Me)*N—X
.
Some nonequivalence of the N—C(=O) amide bonds
observed in Nꢀmethoxyurea (6) is much larger in Nꢀmethꢀ
oxyꢀNꢀXꢀureas 1 and 7—10 (see Tables 1 and 3). It is
probable that, like in compound 4, the LP of the sp3ꢀhyꢀ
bridized nitrogen atom N(1) has weaker conjugation with
the carbamoyl C=O bond than the LP of the sp2ꢀhybridꢀ
ized nitrogen atom N(2).
In Nꢀmethoxyurea (6), the C(1)=O(1) bond is elonꢀ
gated to 1.244(2) Å (an average value is 1.23 Å).33 In
NꢀmethoxyꢀNꢀXꢀureas 1 and 7—10, the C=O bond is
noticeably shorter (see Table 3), that is characteristic of
the anomeric amides with the sp3ꢀhybridized nitrogen
atom.2,32
Structural specific features of the NꢀmethoxyꢀNꢀXꢀ
N´ꢀ(4ꢀnitrophenyl)urea family (X = H (14), Cl (4), OMe
(15)) were studied. NꢀMethoxyꢀNꢀHꢀN´ꢀ(4ꢀnitrophenyl)ꢀ
urea (14)26 have been chosen as a structural comparison
reference with NꢀchloroꢀNꢀmethoxyꢀN´ꢀ(4ꢀnitrophenyl)ꢀ
urea (4) and N,NꢀdimethoxyꢀN´ꢀ(4ꢀnitrophenyl)urea (15).
Methanolysis of NꢀchloroꢀNꢀmethoxyꢀN´ꢀ(4ꢀnitroꢀ
phenyl)urea (4) in the presence of AcONa leads to
1ꢀmethoxyꢀ6ꢀnitroꢀ3,4ꢀdihydrobenzimidazolꢀ2ꢀone (16),34
whereas in the presence of CF3CO2Ag to N,Nꢀdimethoxyꢀ
N´ꢀ(4ꢀnitrophenyl)urea (15)24 (Scheme 3).
Similarly, NꢀalkoxyꢀN´ꢀarylꢀNꢀchloroureas (17a—e)
were converted to N,NꢀdialkoxyꢀN´ꢀarylureas (18a—e).24
According to the Xꢀray diffraction data, nitrogen
atom N(1) in NꢀmethoxyꢀNꢀHꢀN´ꢀ4ꢀnitrophenylurea (14)
(Fig. 5, Table 4) has configuration close to the planar,
 = 343.5(4).
In crystal, molecules of urea 10 are bonded in the centroꢀ
symmetric dimers by hydrogen bonds N(2)—H(2a)…O(3i)
[i: –x, 1 – y, –z] (H…O is 2.11 Å, N—H…O is 172).
Thus, the conformations of NꢀalkoxyꢀNꢀmethoxyureas
9 and 10 are close to the conformation of N,Nꢀdimethoxyꢀ
urea (8),21 whereas the degrees of pyramidality of nitrogen
atom N(1) (N,Nꢀdialkoxyamino group) and the N—OMe
bond lengths do not differ much, despite the presence
of bulky isopropoxy (9) and tertꢀbutoxy groups (10) (see
Table 3).
It should be noted that the position of the hydrogen
atom, which determines pyramidality of this nitrogen
atom, was refined independently and found to correspond
to the direction of the intermolecular hydrogen bond
N(1)—H(1)...O(2)i [i: 1 – x, 2 – y, 2 – z] (H...O is
2.092(19) Å, N—H...O is 169.8(19)), which binds the
molecules in crystal in the centrosymmetric dimers. In the
molecule of urea 14, the LP of atom N(1) is arranged
virtually perpendicular to the plane of the carbamoyl fragꢀ
As it follows from Table 3, the replacement of the
hydrogen atom in NꢀmethoxyꢀNꢀHꢀurea (6) with an

68
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 1, January, 2015
Shtamburg et al.
Scheme 3
O(2)
C(4)
C(8)
N(1)
O(1)
O(3)
C(5)
N(3)
C(3)
C(2)
C(6)
C(7)
N(2)
O(4)
C(1)
Fig. 5. Structure of NHꢀNꢀmethoxyꢀN´ꢀ(4ꢀnitrophenyl)ꢀ
urea (14).
O(4)
O(3)
N(2)
C(3)
C(8)
O(1)
N(1)
C(5)
C(6)
C(4)
C(1)
N(3)
C(2)
O(2)
O(5)
C(7)
C(9)
Fig. 6. Structure of N,NꢀdimethoxyꢀN´ꢀ(4ꢀnitrophenyl)ꢀ
urea (15).24
17, 18
Ar
R
a
b
c
d
e
4ꢀO2NC6H4
4ꢀO2NC6H4
2ꢀO2NC6H4
4ꢀClC6H4
4ꢀBrC6H4
Bn
According to the Xꢀray diffraction data,24 in N,Nꢀdiꢀ
methoxyꢀN´ꢀ(4ꢀnitrophenyl)urea (15) nitrogen atom N(1)
has a pronounced trigonal pyramidal configuration ( =
= 324.0(2), hN = 0.508(3) Å) (Fig. 6). In the unsubstitutꢀ
ed N,Nꢀdimethoxyurea (8), the degree of pyramidality of
the nitrogen atom of N,Nꢀdimethoxyamino group is conꢀ
siderably lower (see Table 3). Thus, N,NꢀdimethoxyꢀN´ꢀ
(4ꢀnitrophenyl)urea (15) in the degree of pyramidality of
its amide nitrogen atom approaches the "most pyramidal"
acyclic amides, the S. Glover´s NꢀacyloxyꢀNꢀalkoxybenzꢀ
amides ( = 323.51, hN = 0.513 Å).10
In compound 15, the LP of N(1) is arranged virtually
perpendicular to the plane of the carbamoyl fragment (torꢀ
sion angle O(3)—C(1)—N(1)—lp(N(1)) = –83.1). The
C—O bonds of two methoxy groups are oriented toward
the LP of atom N(1) (torsion angle C(8)—O(1)—N(1)—
lp(N(1)) = 7.0 and torsion angle C(9)—O(2)—N(1)—
lp(N(1)) = 32.7). The N—OMe bonds in compound 15
are slightly longer (see Table 4) than the corresponding
bonds in N,Nꢀdimethoxyurea (8)21 and N,Nꢀdialkoxyureas
9 and 10.
CH2CH2CHMe2
Et
Et
Et
ment (torsion angle N(2)—C(2)—N(1)—lpN(1) = 102).
The NO—Me bond is oriented toward the LP of N(1)
(torsion angle C(1)—O(1)—N(1)—lpN(1) = –8). Nitroꢀ
gen atom N(2) has virtually a planar configuration ( =
= 358.3(4)), that also corresponds to the direction of
the formed weak intermolecular hydrogen bond N(2)—
H(2)…O(2)ii [ii: 1 – x, 1/2 + y, 3/2 – z] (H...O is 2.43(2) Å,
N—H...O is 157.4(16)). The carbonyl group is slightly
turned relative to the plane of the benzene ring (torsion
angle C(4)—C(3)—N(2)—C(2) = 32.3(3)). But this, apꢀ
parently, does not disturb the conjugation between the
aromatic and the carbamoyl fragments, as well as provides
a possibility for the formation of a weak intramolecular
hydrogen bonds N(2)—H(2)...O(1) (H...O is 2.150(19) Å,
N—H...O is 112.6(16)) and C(4)—H(4)...O(2) (H...O is
2.43 Å, C—H...O is 112).
Table 4. Comparison of structural specific features of NꢀXꢀNꢀmethoxyꢀN´ꢀ(4ꢀnitrophenyl)ureas 4, 14, and 15
Comꢀ
pound
X
N(1)/deg
d/Å
N—OMe
N(1)—C(=O)
N(2)—C(=O)
C=O
4
14
15
Cl
H
OMe
326.6(2)—335.9(1) 1.389(4)—1.401(4) 1.440(5)—1.447(5) 1.340(5)—1.350(4) 1.203(4)—1.213(5)
343.5(4)
324.0(2)
1.4055(19)
1.418(3)
1.412(3)
1.368(2)
1.441(3)
1.355(2)
1.357(3)
1.233(2)
1.204(3)

Anomeric amides
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 1, January, 2015
69
Scheme 4
In N,Nꢀdimethoxyurea 15, the aryl substituent is coꢀ
planar to the carbamoyl fragment (torsion angle C(3)—
C(2)—N(2)—C(1) = 5.4(4)), whereas the nitro group is
slightly turned relative to the plane of the benzene ring
(torsion angle C(4)—C(5)—N(3)—O(4) = 13.4(4)). The
conformation of molecule 15, besides the conjugation efꢀ
fects, is also stabilized due to the formation of intramolecꢀ
ular hydrogen bonds N(2)—H(2)...O(2) (H...O is 2.13 Å,
N—H...O is 108) and C(3)—H(3)...O(3) (H...O is 2 24 Å,
C—H...O is 122).
In crystal, molecules 15 are bound by intermolecular
hydrogen bonds N(2)—H(2)...O(4´) [–1 + x, 0.5 – y,
–0.5 + z] (H...O is 2.27 Å, N—H...O is 155), as well as by
stacking interactions between the ꢀsystems of two moleꢀ
cules combined by the translation along the axis a (the
center of the benzene ring is placed over the middle of the
C(1)—N(2) bond at a 3.50 Å distance).
probably, due to the same reasons as for the family of
NꢀmethoxyꢀNꢀXꢀureas 1 and 7—10.
Methanolysis of NꢀalkoxyꢀNꢀchlorocarbamates 19—21
with either MeOH, or a solution of AcONa in MeOH, or
a solution of CH(OMe)3 in MeOH (to bind HCl) (Scheme 4)
leads to a mixture of NꢀalkoxyꢀNꢀHꢀcarbamates 22, 25,
26, N,N´ꢀdialkoxyꢀN,N´ꢀbis(alkoxycarbonyl)hydrazines
23, 27 (the reduction products), and carbonates 24, 28
(the fragmentation products).
However, carrying out the alcoholysis of NꢀalkoxyꢀNꢀ
chlorocarbamates 19, 20, and 29—31 in the presence of
CF3CO2Ag makes it possible to obtain N,Nꢀdialkoxycarbꢀ
amates 32—39, including sterically hindered N,Nꢀdiisoꢀ
propoxycarbamate (34) and NꢀalkoxyꢀNꢀtertꢀbutoxycarbꢀ
amates 37 and 38 (Scheme 5).
Scheme 5
For the family of NꢀmethoxyꢀNꢀXꢀN´ꢀ(4ꢀnitrophenꢀ
yl)ureas, on going from NꢀmethoxyꢀN´ꢀ(4ꢀnitrophenyl)ꢀ
urea (14) to ureas 4 and 15, i.e., replacing the H atom
(X = H (14)) with an electronegative substituent (X = Cl (4),
OMe (15)), the degree of pyramidality of the nitrogen
atom in the geminal system O—N—X sharply increases,
as does the nonequivalence of the carbamoyl N—C(=O)
bonds (see Table 4). Like in the case of the family of
NꢀmethoxyꢀNꢀXꢀureas 1 and 7—10, this phenomenon can
be explained by the fact that the sp3ꢀhybridized nitrogen
atom N(1) (of the O—N—X group) is conjugated to a lesser
extent with the C=O bond of the carbamoyl group than
the sp2ꢀhybridized nitrogen atom N(2) of the NH2 group.
On going from urea 14 to ureas 4 and 15, a noticeable
shortening of the C=O bond is observed (see Table 4),
Proꢀ
duct
32
R
R´
Yield
Starting compounds
19, 20, 29—31 (R) R´OH
Pri
Pri
Et
Pri
Bun
Octn
Me
Et
Me
Et
52
59
45
59
77
76
36
11
46
20 (Pri)
20 (Pri)
29 (Et)
MeOH
EtOH
33
Pri
Pri
Me
Me
But
But
Et
PriOH
PriOH
MeOH
MeOH
ButOH
ButOH
EtOH
34
35
36
37
38
39
20 (Pri)
30 (Bun)
31 (Octn)
19 (Me)
29 (Et)
Et
29 (Et)

70
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 1, January, 2015
Shtamburg et al.
NꢀChloroꢀNꢀmethoxyꢀN´ꢀ(4ꢀnitrophenyl)urea (4) was obꢀ
tained according to the known procedure26 by the chlorination
of NꢀmethoxyꢀN´ꢀ(4ꢀnitrophenyl)urea (6) with ButOCl. Yellowish
white crystals with m.p. 98—102 C (CH2Cl2) (Ref. 26: 120 C).
1H NMR (300 MHz, CDCl3), : 3.96 (s, 3 H, OMe); 7.71 (d, 2 H,
C(2)H, C(6)H, J = 9.3 Hz); 8.22 (br.s, 1 H, NH); 8.26 (d, 2 H,
C(3)H, C(5)H, 3J = 9.3 Hz). MS (FAB), m/z (Irel (%)): 248
[M + H]+ (15), 246 [M + H]+ (40), 119 (100).
The degree of pyramidality of the nitrogen atom in
NꢀalkoxyꢀNꢀchlorocarbamates was not determined, but it
can be expected to be lower than in NꢀalkoxyꢀNꢀchloroꢀ
ureas, similarly to carbamate and urea NꢀacyloxyꢀNꢀ
alkoxy derivatives.20 For methyl Nꢀ(4ꢀchlorobenzoyloxy)ꢀ
Nꢀmethoxycarbamate,  is 334.1 (see Ref. 20), whereas
for NꢀacetoxyꢀNꢀethoxyurea  is 333.6 (see Ref. 20);
for Nꢀ(4ꢀchlorobenzoyloxy)ꢀNꢀethoxyurea  is
329.32(8) (see Ref. 25), whereas for NꢀbutoxyꢀNꢀ(4ꢀ
chlorobenzoyloxy)urea  is 323.8 (see Ref. 21). A deꢀ
crease in the pyramidality of the nitrogen atom leads to
a decrease in the destabilization of the N—Cl bond due to
the anomeric effect nO(Alk)*N—Cl (see Refs 2 and 32).
This, in turn, hinders the nucleophilic substitution at the
nitrogen atom by the SN2ꢀlike mechanism. However, in
the case of alcoholysis in the presence of CF3CO2Ag, this
is not that significant, since the nucleophilic substitution,
obviously, follows the SN1ꢀlike mechanism through the
formation of the nitrenium cation.
In conclusion, it was found that NꢀchloroꢀNꢀmethꢀ
oxyꢀN´ꢀ(4ꢀnitrophenyl)urea (4) exists in crystal in six
forms, differing in the degree of pyramidality of the nitroꢀ
gen atom of the geminal system O—N—Cl and the bond
lengths. Replacement of the H atom in NꢀmethoxyꢀNꢀXꢀ
ureas 1 and 7—10 with the substituent X (X = Cl, OAc,
OAlk) leads to a significant increase in the degree of pyraꢀ
midality of the nitrogen atom in the geminal system
X—N—O(Me) and to the shortening of the N—O(Me)
bond. This can be regarded as a structural confirmation of
the domination of the anomeric effect nO(Me)*N—X in
compounds 1 and 7—10. Carrying out the alcoholysis of
NꢀalkoxyꢀNꢀchloro derivatives of urea, N´ꢀarylureas, and
carbamates in the presence of silver trifluoroacetate is
a convenient method for the preparation of N,Nꢀdialkꢀ
oxyureas, N,NꢀdialkoxyꢀN´ꢀarylureas, and N,Nꢀdialkoxyꢀ
carbamates, respectively.
Crystals of compound 4 are monoclinic, from CH2Cl2,
C8H8N3O4Cl, at 100 K a = 13.0232(6) Å, b = 21.0805(7) Å,
3
c = 22.4324(11) Å,  = 90.573(4), V = 6158.2(5) Å , Mr = 245.62,
Z = 24, space group P21/n, dcalc = 1.59 g cm3, (MoꢀK) =
= 0.38 mm–1, F(000) = 3024. The unit cell parameters and
intensities of 26976 reflections (13934 independent, Rint = 0.043)
were measured on a Xcalibur 3 automated fourꢀcircle diffractoꢀ
meter (MoꢀK, graphite monochromator, CCD detector, ꢀscan
technique, 2max = 57.76).
The structure was solved by the direct method using the
SHELXꢀ97 software.35 Positions of hydrogen atoms were calcuꢀ
lated geometrically and refined using a riding model with
Uiso = nUeq for the bearing atom (n = 1.5 for methyl groups and
n = 1.2 for other hydrogen atoms). The structure was refined on
F2 by the fullꢀmatrix least squares method in anisotropic approxꢀ
imation for nonhydrogen atoms to wR2 = 0.147 on 13934 reflecꢀ
tions (R1 = 0.067 on 8645 reflections with F > 4(F), S = 1.06).
In the structure refining, the limitations were imposed on the
bond distances involving disordered atoms, which were assumed
to be equal to the average distances for the corresponding bonds
in the nondisordered molecules with the 0.005 Å accuracy. The
limitations were also imposed on the equality of the tensor comꢀ
ponents of anisotropic vibrations along the bond lines involving
2
disordered atoms with the 0.01 Å accuracy, as well as on the
mutual equality of the tensor components for the disordered
2
atom C(1) of molecule F with the 0.01 Å accuracy. The code in
the Cambridge Crystallographic Data Center CCDC is 870254.
NꢀMethoxyurea (6). A cooled solution of concentrated HCl
(7 mL, 75.86 mmol) in water (10 mL) was added to a solution of
MeONH2 (2.38 g, 50.57 mmol) cooled to 0 C, the solution
obtained was allowed to stand at –10 C for 20 min, then
NaOCN (6.90 g, 106.2 mmol) was added in portions over 1 h at
–(5—10) C with stirring. The reaction mixture was allowed to
stand for 1 h at –5 C and 4 days at 17—20 C. A solid phase was
filtered off, washed with water (2 mL), a combined aqueous
filtrate was concentrated in vacuo at 20 C. The solid residue was
extracted first with boiling Pri2O (50 mL) over 30 min, then with
boiling CHCl3 (3×50 mL). The organic extracts were allowed to
stand for 24 h at 5 C, a precipitate formed was filtered off, the
filtrates were 2/3 concentrated in vacuo to obtain an additional
amount of Nꢀmethoxyurea (6). The overall yield of Nꢀmethꢀ
oxyurea (6) was 3.19 g (70%), colorless crystals, m.p. 78—81 C
(CHCl3). 1H NMR (300 MHz, (CD3)2SO), : 3.52 (s, 3 H,
NOMe); 6.39 (br.s, 2 H, NH2); 9.06 (br.s, 1 H, NHO). IR
(KBr), /cm–1: 3415 (NH); 1685 (C=O). Found (%): N, 30.95.
C2H6N2O2. Calculated (%): N, 31.10.
Experimental
1
H NMR spectra were recorded on Varian VXPꢀ300
(300 MHz), Mercuryꢀ400 (400 MHz), and Bruker Avance
DRXꢀ500 spectrometers (500 MHz) using Me4Si as an internal
standard. 13C NMR spectra were recorded on Varian VXPꢀ300
(75 MHz) and Mercuryꢀ400 (100 MHz) spectrometers in CDCl3.
IR spectra were obtained on a URꢀ20 spectrometer in KBr pelꢀ
lets or for neat samples. Mass spectra were recorded on a VG
770ꢀ70EQ mass spectrometer in the FAB mode (FAB). GLC
analysis was performed on a Tsvetꢀ5 chromatograph (a flameꢀ
ionizing detector, a 2400×3 glass column, 5% SEꢀ30 on Chromꢀ
atonꢀAW). Xꢀray diffraction studies were performed on a Xcaliꢀ
bur 3 automated fourꢀcircle diffractometer. Solvents were puriꢀ
fied according to the standard methods: MeCN and CH2Cl2
were distilled over P2O5, MeOH and EtOH over Ca, Et2O and
PhH over Na.
Crystals of compound 6 are triclinic, from CHCl3, C2H6N2O2,
at 298 K a = 4.9905(16) Å, b = 6.842(3) Å, c = 7.412(3) Å,
3
 = 77.33(4),  = 72.60(3),  = 72.07(4), V = 227.51(15) Å ,
Mr = 90.09, Z = 2, space group P1, dcalc = 1.315 g cm–3
,
(MoꢀK) = 0.115 mm–1, F(000) = 96. The unit cell parameters
and intensities of 1696 reflections (1050 independent, Rint
= 0.017) were measured on a Xcalibur 3 automated fourꢀcircle
NꢀChloroꢀNꢀmethoxyurea (1) was obtained according to the
procedure published earlier.23
=

Anomeric amides
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 1, January, 2015
71
diffractometer (MoꢀK, graphite monochromator, CCD detecꢀ
tor, ꢀscan technique, 2max = 58.32).
technique, 2
= 58.95). The structure was solved by the
max
dualꢀspace method of the SHELXD program35 and refined by
the fullꢀmatrix least squares method in anisotropic approximaꢀ
tion for nonhydrogen atoms using the SHELXL program.35 Poꢀ
sitions of hydrogen atoms were found from the difference synꢀ
thesis of electron density. The hydrogen atoms at the carbon
atoms were refined using a riding model with Uiso = nUeq for the
bearing atom (n = 1.5 for the methyl groups and n = 1.2 for the
methine hydrogen atom). Positions and isotropic thermal paraꢀ
meters for the hydrogen atoms of the amino group were refined
independently. The final Q factors are as follows: wR2 = 0.170
on all the independent reflections, R1 = 0.060 on 1463 reflecꢀ
tions with I > 2(I). The registration code in the Cambridge
Crystallographic Data Center CCDC is 989308.
The structure was solved by the direct method using the
SHELXꢀ97 software.35 Positions of hydrogen atoms of the meꢀ
thyl group were calculated geometrically and refined using
a riding model with Uiso = 1.5Ueq for the bearing atom. The
hydrogen atoms at the nitrogen atoms were refined indepenꢀ
dently in isotropic approximation. The structure was refined on
F2 by the fullꢀmatrix least squares method in anisotropic approxꢀ
imation for nonhydrogen atoms to wR2 = 0.181 on 1050 reflecꢀ
tions (R1 = 0.059 on 756 reflections with F > 4 (F), S = 1.04).
The registration code in the Cambridge Crystallographic Data
Center CCDC is 948639.
NꢀAcetoxyꢀNꢀmethoxyurea (7). NꢀChloroꢀNꢀmethoxyurea
(1) (0.305 g, 2.448 mmol) was added to a solution of AcONa
(0.250 g, 3.05 mmol) in PriOH (10 mL). The mixture was stirred
for 18 h at 17—18 C and allowed to stand for another 25 h at this
temperature. A precipitate formed was filtered off and washed
with Et2O (10 mL). A combined filtrate was concentrated
in vacuo at 7 Torr, the residue was extracted with CH2Cl2 (16 mL),
the extract was concentrated in vacuo at 10 Torr to obtain
NꢀacetoxyꢀNꢀmethoxyurea (7) (0.266 g, 73%), colorless crysꢀ
tals, m.p. 98—100 C. The product was identified by the comꢀ
parison of its 1H NMR and mass spectra with those of an authenꢀ
tic sample.25 1H NMR (300 MHz, CDCl3), : 2.22 (s, 3 H,
NOAc); 3.91 (s, 3 H, NOMe); 5.90 (br.s, 1 H, NH); 6.03 (br.s, 1 H,
NH). MS (FAB, Na+) m/z (Irel (%)): 319 [2 M + Na]+ (17),
171 [M + Na]+ (100).
NꢀtertꢀButoxyꢀNꢀmethoxyurea (10). A solution of Nꢀchloroꢀ
Nꢀmethoxyurea 1 (0.190 g, 1.523 mmol) in ButOH (3 mL) was
added to a solution of CF3CO2Ag (0.410 g, 1.856 mmol) in
a mixture of ButOH (7 mL) and Et2O (3 mL) at –24 C. The
temperature of the reaction mixture was raised to 16 C over
18 h, a precipitate of AgCl was filtered off and washed with Et2O
(8 mL). A combined filtrate was concentrated in vacuo (5 Torr),
a solution of AcONa (0.19 g, 2.32 mmol) in MeOH (5 mL) was
added to the residue. The mixture obtained was concentrated
in vacuo, the residue was extracted with CH2Cl2 (15 mL). The
extract was dried with MgSO4, filtered, and washed with CH2Cl2
(5 mL). A combined filtrate was concentrated in vacuo, the resiꢀ
due was washed with cold (5 C) hexane (2 mL), then extracted
with CH2Cl2 (15 mL). The extract was filtered through a thick
filter and concentrated in vacuo, the residue was allowed to stand
at 5 Torr to obtain product 10 (0.086 g, 35%), colorless crystals,
m.p. 115—118 C (CH2Cl2—hexane). 1H NMR (300 MHz,
CDCl3), : 1.36 (s, 9 H, NOCMe3); 3.72 (s, 3 H, NOMe); 5.50
(br.s, 1 H, NH); 5.95 (br.s, 1 H, NH). IR (KBr), /cm–1: 3427
(NH), 1712 (C=O). MS (FAB), m/z (Irel (%)): 163 [M + H]+
(10), 57 But + (100). MS (FAB, K+), m/z (Irel (%)): 201 [M + K]+
(34), 57 But+ (100). Found (%): N, 17.09. C6H14N2O3. Calcuꢀ
lated (%): N, 17.27.
Crystals of ureas 10 are monoclinic, from a mixture of
CH2Cl2—hexane, C16H14N2O3, at 298 K a = 14.429(5) Å,
b = 6.332(2) Å, c = 10.334(5) Å, V = 892.6(6) Å , Mr = 162.19,
Z = 4, space group P21/c, dcalc = 1.207 g cm–3, (MoꢀK) =
= 0.10 mm–1, F(000) = 352. The unit cell parameters and intenꢀ
sities of 6089 reflections (1761 independent, Rint = 0.059) were
measured on a Xcalibur 3 automated fourꢀcircle diffractometer
(MoꢀK, graphite monochromator, CCD detector, ꢀscan techꢀ
nique, 2max = 60.88).
The structure was solved by the direct method using the
SHELXꢀ97 software.35 Positions of hydrogen atoms were calcuꢀ
lated geometrically and refined using a riding model with
Uiso = nUeq for the bearing atom (n = 1.5 for the methyl group
and n = 1.2 for other hydrogen atoms). The structure was refined
on F2 by the fullꢀmatrix least squares method in anisotropic
approximation for nonhydrogen atoms to wR2 = 0.099 on 1761
reflections (R1 = 0.044 on 988 reflections with F > 4(F),
S = 0.97). The registration code in the Cambridge Crystalloꢀ
graphic Data Center CCDC is 885614.
NꢀEthoxyꢀNꢀmethoxyurea (11) was obtained by ethanolysis
of NꢀacetoxyꢀNꢀmethoxyurea 7 (70 h, 15 C) according to the
standard procedure18 in 88% yield and identified by the comparꢀ
ison with an authentic sample18 based on their 1H NMR spectra.
1H NMR (300 MHz, CDCl3), : 1.33 (t, 3 H, OCH2Me,
Attempted isopropanolysis of NꢀacetoxyꢀNꢀmethoxyurea (7).
A
solution of NꢀacetoxyꢀNꢀmethoxyurea 7 (0.0148 g,
0.100 mmol) in PriOH (4 mL) was allowed to stand for 90 h at
17—19 C, then concentrated in vacuo at 5 Torr to obtain the
starting NꢀacetoxyꢀNꢀmethoxyureas (7) (0.0148 g, 100%), which
1
was identified by the comparison of its H NMR spectrum with
that of an authentic sample.
NꢀIsopropoxyꢀNꢀmethoxyurea (9). A solution of Nꢀchloroꢀ
Nꢀmethoxyurea (1) (0.127 g, 1.002 mmol) in Et2O (3 mL) was
added to a solution of CF3CO2Ag (0.248 g, 1.123 mmol) in Priꢀ
OH (5 mL) at –10 C. The temperature of the reaction mixture
was raised to 15 C over 18 h, then, AcONa (0.10 g) was added,
the mixture was stirred for 15 min, PriOH was evaporated
in vacuo (5 Torr). The residue was extracted with CH2Cl2 (17 mL),
the extract was concentrated in vacuo. The residue was dissolved
in PhH (7 mL), hexane (2 mL) was added, and the mixture was
allowed to stand for 20 h at 5 C. A precipitate formed was
filtered off, washed with a mixture of PhH—hexane, a combined
filtrate was concentrated in vacuo to obtain NꢀisopropoxyꢀNꢀ
methoxyureas (9) (0.114 g, 75%), colorless crystals, m.p. 67—68 C
(CH2Cl2). 1H NMR (400 MHz, CDCl3), : 1.289 (d, 6 H,
NOCHMe2, J = 6.4 Hz); 3.781 (s, 3 H, NOMe); 4.299 (sept,
1 H, J = 6.4 Hz); 5.392 (br.s, 1 H, NH); 5.901 (br.s, 1 H, NH).
MS (FAB), m/z (Irel (%)): 149 [M + H]+ (64), 77 (100).
Found (%): N, 18.64. C5H12N2O3. Calculated (%): N, 18.91.
3
Crystals of
9 orthorhombic, from CH2Cl2—hexane,
C15H12N2O3, at 298 K, Mr = 148.17, a = 5.2528(8) Å,
3
b = 11.2347(12) Å, c = 14.108(3) Å, V = 832.6(2) Å , space group
P212121, Z = 4, dcalc = 1.182 g cm–3, (MoꢀK) = 0.097 mm–1
,
F(000) = 320. The unit cell parameters and intensities of 16840
reflections (2135 independent, Rint = 0.054) were measured on
a Xcalibur 3 automated fourꢀcircle diffractometer (MoꢀK,
graphite monochromator, Sapphireꢀ3 CCD detector, ꢀscan

72
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 1, January, 2015
Shtamburg et al.
J =6.9 Hz); 3.84 (s, 3 H, NOMe); 4.13 (q, 2 H, OCH2Me,
J = 6.9 Hz); 5.64 (br.s, 1 H, NH); 5.96 (br.s, 1 H, NH). MS
(FAB, Na+), m/z (Irel (%)): 157 [M + Na]+ (22), 137 (14), 89
(25), 72 (77), 58 (100). Found (%): C, 35.93; H, 7.80; N, 20.69.
C4H10N2O3. Calculated (%): C, 35.82; H, 7.51; N, 20.88.
NꢀButoxyꢀNꢀisopropoxyurea (13) was obtained by isoproꢀ
panolysis of NꢀacetoxyꢀNꢀbutoxyurea 12 (see Ref. 18) (138 h,
23 C) according to the standard procedure18 in 66% yield, colꢀ
orless liquid, nD22 1.4518. 1H NMR (300 MHz, CDCl3), : 0.94
(t, 3 H, O(CH2)3Me, J = 7.2 Hz); 1.29 (d, 6 H, OCHMe2,
J = 6.3 Hz); 1.42 (sext, 2 H, OCH2CH2CH2Me, J = 7.2 Hz);
1.65 (quint, 2 H, OCH2CH2CH2Me, J = 7.2 Hz); 4.01 (t, 2 H,
OCH2CH2CH2Me, J = 7.2 Hz); 4.30 (sept, 1 H, OCHMe2,
J = 6.3 Hz); 5.52 (br.s, 1 H, NH); 5.91 (br.s, 1 H, NH). IR
(KBr), /cm–1: 3360 (NH), 1720 (C=O). Found (%): N, 14.38.
C8H18N2O3. Calculated (%): N, 14.72.
8.26 (d, 2 H, C(3)H, C(5)H, J = 9.3 Hz). 13C NMR (100 MHz,
CDCl3), : 62.23 (OMe), 118.75 (C(2), C(6)), 124.84 (C(3),
C(5)), 142.25 (C(1)), 143.86 (C(4)), 156.24 (NHC(O)). MS
(FAB), m/z (Irel (%)): 242 [M + H]+ (82), 210 [M + H –
–MeOH]+ (100). Found (%): C, 44.79; H, 4.83; N, 17.25.
C9H11N3O5. Calculated (%): C, 44.82; H, 4.60; N, 17.42.
Crystals of compound 15 are monoclinic, grown at –20 C
in a mixture of CH2Cl2—hexane, C9H11N3O5, at 100 K
a = 4.8371(3) Å, b = 16.9591(11) Å, c = 12.7986(9)Å,  =92.609(7),
3
V = 1048.82(12) Å , Mr = 241.21, Z = 4, space group P21/c,
dcalc = 1.528 g cm–3, (MoꢀK) = 0.126 mm–1, F(000) = 504.
The tested crystal was a nonꢀmerohedral twin, in which the
components gave the contributions of 0.58 : 0.42 and turned with
respect to each other by 180 along the axis a. The unit cell
parameters and intensities of 9049 reflections (4131 indepenꢀ
dent, Rint = 0.072) were measured on a Xcalibur 3 automated
fourꢀcircle diffractometer (MoꢀK, graphite monochromator,
CCD detector, ꢀscan technique, 2max = 57.74).
NꢀMethoxyꢀN´ꢀ(4ꢀnitrophenyl)urea (14) was obtained from
methoxyamine and pꢀnitrophenyl isocyanate in PhH according
to the known procedure,26 yellowish crystals. m.p. 145—147 C
(Ref. 26: m.p. 152 C). 1H NMR (300 MHz, (CD3)2SO), : 3.65
(s, 3 H, OMe); 7.89 (d, 2 H, C(2)H, C(6)H, J = 9.6 Hz); 8.19
(d, 2 H, C(3)H, C(5)H, J = 9.6 Hz); 9.58 (br.s, 1 H, NH); 9.97
(br.s, 1 H, NHO). IR (KBr), /cm–1: 3224 (NH); 3215 (NH);
1664 (C=O); 1510 (NO2); 1344 (NO2).
The structure of compound 15 was solved by the direct methꢀ
od using the SHELXꢀ97 software.35 Positions of hydrogen atoms
were calculated geometrically and refined using a riding model
with Uiso = nUeq for the bearing atom (n = 1.5 for the methyl
groups and n = 1.2 for other hydrogen atoms). The structure was
refined on F2 by the fullꢀmatrix least squares method in anisotroꢀ
pic approximation for nonhydrogen atoms to wR2 = 0.145 on
4037 reflections (R1 = 0.059 on 2316 reflections with F > 4(F),
S = 0.98). The registration code in the Cambridge Crystalloꢀ
graphic Data Center CCDC is 776941.
Crystals of urea 14 are monoclinic, from PriOH, at 298 K,
C8H9N3O4, Mr = 211.18, a = 10.4233(10) Å, b = 10.2913(7) Å,
3
c = 8.9659(6) Å,  = 99.660(7), V = 948.13(12) Å , space group
P21/c, Z = 4, dcalc = 1.479 g cm–3, (MoꢀK) = 0.121 mm–1
,
F(000) = 440. The unit cell parameters and intensities of 8870
reflections (2266 independent, Rint = 0.035) were measured on
a Xcalibur 3 automated fourꢀcircle diffractometer (MoꢀK,
graphite monochromator, Sapphireꢀ3 CCD detector, ꢀscan
technique, 2max = 58.3). The structure was solved by the dualꢀ
space method of the SHELXD program35 and refined by the
fullꢀmatrix least squares method in anisotropic approximation
for nonhydrogen atoms using the SHELXL program.35 Positions
of hydrogen atoms were found from the difference synthesis of
electron density. The hydrogen atoms at the carbon atoms were
refined using a riding model with Uiso = nUeq for the bearing
atom (n = 1.5 for the methyl group and n = 1.2 for the aromatic
hydrogen atoms). Positions and isotropic thermal parameters of
the hydrogen atoms at the heteroatoms were refined indepenꢀ
dently. The final Q factors are as follows: wR2 = 0.117 on all the
independent reflections, R1 = 0.046 on 1346 reflections with
I > 2(I). The registration code in the Cambridge Crystalloꢀ
graphic Data Center CCDC is 989291.
NꢀBenzyloxyꢀNꢀchloroꢀN´ꢀ(4ꢀnitrophenyl)urea (17a) and
NꢀbenzyloxyꢀNꢀmethoxyꢀN´ꢀ(4ꢀnitrophenyl)urea (18a). A solution
of ButOCl (0.637 g, 5.67 mmol) in CH2Cl2 (5 mL) was added to
a solution of NꢀbenzyloxyꢀN´ꢀ(4´ꢀnitrophenyl)urea (0.126 g,
0.438 mmol) in CH2Cl2 (5 mL) at –20 C, the mixture was
allowed to stand for 5 min at –20 C and 5 h at 4 C, then
concentrated in vacuo. The residue was allowed to stand at
5 Torr to obtain NꢀbenzyloxyꢀNꢀchloroꢀN´ꢀ(4ꢀnitrophenyl)urea
(17a), yellow crystals with m.p. 89—91 C (with decomp.), quanꢀ
titative yield. 1H NMR (300 MHz, CDCl3), : 5.10 (s, 2 H,
NOCH2); 7.44—7.52 (m, 5 H, Ph); 7.48 (d, 2 H, C(2)H, C(6)H,
J = 9.0 Hz); 7.87 (br.s, 1 H, NH); 8.18 (d, 2H, C(3)H, C(5)H,
J = 9.0 Hz). MS (FAB), m/z (Irel (%)): 324 [M + H]+ (11), 322
[M + H]+ (28), 91 Bn+ (100). Found (%): Cl, 10.95.
C14H12ClN3O4. Calculated (%): Cl, 11.02.
NꢀBenzyloxyꢀNꢀchloroꢀN´ꢀ(4ꢀnitrophenyl)urea (17a) was
dissolved in MeOH (3 mL) at –35 C, followed by a rapid addiꢀ
tion of a solution of CF3CO2Ag (0.106 g, 0.482 mmol) in MeOH
(2.5 mL). The temperature of the reaction mixture was raised to
16 C over 20 h, a precipitate of AgCl was filtered off and washed
with MeOH (5 mL), a solution of AcONa (0.08 g) in MeOH
(4 mL) was added to the filtrate. The reaction mixture was allowed
to stand at 16 C over 2 h, then concentrated in vacuo. The
residue was extracted with CH2Cl2 (15 mL), the extract was
dried with MgSO4 and then concentrated in vacuo to obtain
NꢀbenzyloxyꢀNꢀmethoxyꢀN´ꢀ(4ꢀnitrophenyl)urea (18a) (0.138 g,
99%), a dense yellowish oil, solidifying upon a prolonged storage
at 5 C to a pale yellow solid compound with m.p. 65—67 C.
1H NMR (300 MHz, CDCl3), : 3.85 (s, 3 H, NOMe); 5.12
(s, 2 H, NOCH2); 7.40—7.50 (m, 5 H, Ph); 7.56 (d, 2 H, C(2)H,
C(6)H, J = 9.3 Hz); 7.96 (br.s, 1 H, NH); 8.20 (d, 2 H, C(3)H,
C(5)H, J = 9.3 Hz). IR (KBr), /cm–1: 3313 (NH); 1700 (C=O);
1580 (NO2); 1332 (NO2). MS (FAB), m/z (Irel (%)): 318 [M + H]+
N,NꢀDimethoxyꢀN´ꢀ(4ꢀnitrophenyl)urea (15). A solution of
NꢀchloroꢀN´ꢀmethoxyꢀNꢀ(4ꢀnitrophenyl)urea
4 (0.099 g,
0.403 mmol) in CH2Cl2 (2 mL) was added to a solution of
CF3CO2Ag (0.107 g, 0.484 mmol) in MeOH (5 mL) at –27 C,
which was accompanied by precipitation of AgCl. The reaction
mixture was slowly heated to 8 C over 16 h, then AcONa
(0.082 g, 1.00 mmol) was added, MeOH was removed in vacuo at
20 Torr. The residue was extracted with CH2Cl2 (15 mL), the
extract was concentrated in vacuo, the residue was extracted
with PhH (15 mL). The benzene extract was concentrated
in vacuo at 20 Torr, the residue was allowed to stand in vacuo at
5 Torr to obtain N,NꢀdimethoxyꢀN´ꢀ(4ꢀnitrophenyl)urea (15)
(0.091 g, 93%), pale yellow crystals, m.p. 81—83 C (PhH—hexꢀ
ane). 1H NMR (300 MHz, CDCl3), : 3.97 (s, 6 H, N(OMe)2);
7.72 (d, 2 H, C(2)H, C(6)H, J = 9.3 Hz); 8.18 (br.s, 1 H, NH);

Anomeric amides
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 1, January, 2015
73
(14), 91 Bn+ (100). Found (%): C, 56.58; H, 4.72; N, 13.02.
C15H15N3O5. Calculated (%): C, 56.78; H, 4.77; N, 13.24.
Compounds 17b,c,e were obtained similarly to compound 17a.
NꢀChloroꢀNꢀ(3ꢀmethylbutoxyꢀN´ꢀ(4ꢀnitrophenyl)urea (17b),
the yield was 94%, colorless crystals, m.p. 88—89 C (with deꢀ
comp.). 1H NMR (300 MHz, CDCl3), : 1.00 (d, 6 H, CHMe2,
J = 6.6 Hz); 1.67 (q, 2 H, OCH2CH2CH, J = 6.6 Hz); 1.74
(nonet, 1 H, CH2CHMe2, J = 6.6 Hz); 4.19 (t, 2 H, NOCH2CH2,
J = 6.6 Hz); 7.69 (d, 2 H, C(2)H, C(6)H, J = 9.3 Hz); 8.26 (d, 2 H,
C(3)H, C(5)H, J = 9.3 Hz); 8.28 (br.s, 1 H, NH). Found (%):
N, 14.05; Cl, 11.65. C12H16ClN3O4. Calculated (%): N, 13.93;
Cl, 11.75.
[M + H]+ (5), 245 [M + H]+ (13), 215 [M – MeO]+ (40),
213 [M – MeO]+ (100), 201 (8), 199 (33), 156 (18), 154 (37).
Found (%): N, 11.40. C10H13ClN2O3. Calculated (%): N, 11.45.
N´ꢀ(4ꢀBromophenyl)ꢀNꢀethoxyꢀNꢀmethoxyurea (18e), the
yield was 92%, a yellowish dense oil. 1H NMR (300 MHz,
CDCl3), : 1.39 (t, 3 H, OCH2Me, J = 7.2 Hz); 3.92 (s, 3 H,
NOMe); 4.21 (q, 2 H, OCH2Me, J = 7.2 Hz); 7.43 (d, 2 H,
C(2)H, C(6)H, J = 9.0 Hz); 7.48 (d, 2 H, C(3)H, C(5)H,
J = 9.0 Hz); 7.91 (br.s, 1 H, NH). Found (%): N, 9.78.
C10H13BrN2O3. Calculated (%): N, 9.69.
Methyl NꢀchloroꢀNꢀmethoxycarbamate (19) was obtained
according to the known procedure.14
NꢀChloroꢀNꢀethoxyꢀN´ꢀ(2ꢀnitrophenyl)urea (17c) was washed
with hexane, the yield was 67%, yellow crystals, m.p. 65—66 C
(with decomp.). H NMR (300 MHz, CDCl3), : 1.48 (t, 3 H,
OCH2Me, J = 7.2 Hz); 4.27 (q, 2 H, OCH2Me, J = 7.2 Hz);
7.29 (t, 1 H, C(4)H, J =8.4 Hz); 7.74 (t, 1 H, C(5)H, J = 8.4 Hz);
8.30 (d, 1 H, C(6)H, J = 8.4 Hz); 8.74 (d, 1 H, C(3)H, J = 8.4 Hz);
11.41 (br.s, 1 H, NH). Found (%): N, 16.08; Cl, 13.43.
C9H10ClN3O4. Calculated (%): N, 16.18; Cl, 13.65.
Methyl NꢀchloroꢀNꢀisopropoxycarbamate (20) was obtained
by chlorination of methyl Nꢀisopropoxycarbamate (25) ButOCl
according to the known procedure for the preparation of
NꢀalkoxyꢀNꢀchlorocarbamates,18 the yield was 98%, a yellow
liquid. 1H NMR (300 MHz, CDCl3), : 1.28 (d, 6 H, NOCHMe2,
J = 6.3 Hz); 3.91 (s, 3 H, CO2Me); 4.31 (sept, 1 H, NOCHMe2,
J = 6.3 Hz). IR (neat), /cm–1: 1780 (C=O). Found (%):
Cl, 21.04. C5H10ClNO3. Calculated (%): Cl, 21.15.
1
N´ꢀ(4ꢀBromophenyl)ꢀNꢀchloroꢀNꢀethoxyurea (17e), the yield
was 89%, colorless crystals, m.p. 75—75.5 C (with decomp.).
1H NMR (300 MHz, CDCl3), : 1.40 (t, 3 H, OCH2Me,
J = 6.9 Hz); 4.20 (q, 2 H, OCH2Me, J = 6.9 Hz); 7.41 (d, 2 H,
C(2)H, C(6)H, 3J = 9.3 Hz); 7.48 (d, 2 H, C(3)H, C(5)H,
J = 9.3 Hz); 7.95 (br.s, 1 H, NH). MS (EI, 70 eV), m/z (Irel (%)):
296 [M]+ (2), 294 [M]+ (8), 292 [M]+ (6), 61 (100). MS (FAB),
m/z (Irel (%)): 297 [M + H]+ (7), 295 [M + H]+ (29), 293 [M + H]+
(23), 259 (100). Found (%): C, 36.50; H, 3.62. C9H10BrClN2O2.
Calculated (%): C, 36.83; H, 3.43.
Ethyl NꢀchloroꢀNꢀmethoxycarbamate (21) was obtained acꢀ
cording to the procedure published earlier.18
Methanolysis of methyl NꢀchloroꢀNꢀmethoxycarbamate (19).
A solution of methyl NꢀchloroꢀNꢀmethoxycarbamate (19) (0.549 g,
3.938 mmol) in MeOH (5 mL) was allowed to stand at 15 C for
1 h, MeOH was distilled off in vacuo (20 Torr) and condensed in
a cooled trap. The residue was extracted with a mixture of Et2O
(7 mL) and hexane (7 mL), the extract was concentrated in vacuo
(20 Torr), the residue was fractionally distilled in vacuo (3 Torr)
to obtain methyl Nꢀmethoxycarbamate (22) (0.221 g, 53%) and
N,N´ꢀdimethoxyꢀN,N´ꢀbis(methoxycarbonyl)hydrazine (23)
(0.144 g, 35%), which were identified by the comparison of their
1H NMR spectra with the spectra of authentic samples.14
1H NMR of carbamate 22 (300 MHz, CDCl3), : 3.73 (s, 3 H,
NOMe); 3.79 (s, 3 H, CO2Me); 7.53 (br.s, 1 H, NH). 1H NMR
of hydrazine 23 (400 MHz, CDCl3), : 3.902 (s, 6 H, NOMe);
3.916 (s, 6 H, CO2Me). GLC analysis showed that the methanol
condensate contained dimethyl carbonate 24 (0.022 g, 6.23%).
Methanolysis of methyl NꢀchloroꢀNꢀisopropoxycarbamate
(20). A solution of methyl NꢀchloroꢀNꢀisopropoxycarbamate
(20) (0.570 g, 3.40 mmol) in MeOH (10 mL) was allowed to
stand at 16 C for 20 h, then concentrated in vacuo (17 Torr),
collecting the condensate in a trap. The residue was allowed to
stand at 20 C and 8 Torr for 1 h to obtain methyl Nꢀisopropoxyꢀ
NꢀChloroꢀN´ꢀ(4ꢀchlorophenyl)ꢀNꢀethoxyurea (17d) was obꢀ
tained according to the procedure published earlier.34
Compounds 18b—e were obtained similarly to compounds
15 and 18a.
NꢀMethoxyꢀNꢀ(3ꢀmethylbutoxy)ꢀN´ꢀ(4ꢀnitrophenyl)urea
(18b), the yield was 91%, a pale yellow dense oil. 1H NMR
(300 MHz, CDCl3),  1.00 (d, 6 H, CHMe2, J = 6.6 Hz); 1.67
(q, 2 H, OCH2CH2CH, J = 6.6 Hz); 1.78 (nonet, 1 H, CH2CHMe2,
J = 6.6 Hz); 3.94 (s, 3 H, NOMe); 4.19 (t, 2 H, NOCH2CH2,
J = 6.6 Hz); 7.71 (d, 2 H, C(2)H, C(6)H, J = 9.0 Hz); 8.18 (br.s,
1 H, NH); 8.26 (d, 2 H, C(3)H, C(5)H, J = 9.0 Hz). MS (FAB),
K+, m/z (Irel (%)): 336 [M + K]+ (81), 298 [M + H]+ (16),
71 (100). Found (%): C, 52.31; H, 6.68; N, 14.03. C13H19N3O5.
Calculated (%): C, 52.52; H 6.44; N, 14.13.
21
NꢀEthoxyꢀNꢀmethoxyꢀN´ꢀ(2ꢀnitrophenyl)urea (18c), the
carbamate (25) (0.137 g, 30%), a colorless liquid, nD 1.4250,
yield was 98%, a dense light yellow liquid, nD 1.5641, upon
which was identified based on the 1H NMR spectrum. 1H NMR
(300 MHz, CDCl3), : 1.15 (d, 6 H, NOCHMe2, J = 6.3 Hz);
3.68 (s, 3 H, CO2Me); 3.98 (sept, 1 H, NOCHMe2, J = 6.3 Hz);
7.33 (br.s, 1 H, NH). GLC analysis showed that the methanol
condensate contained dimethyl carbonate 24 (0.072 g, 23.5%).
Methanolysis of ethyl NꢀchloroꢀNꢀmethoxycarbamate (20) in
the presence of AcONa. A mixture of MeOH (5 mL) and AcONa
(1.85 g) was added to ethyl NꢀchloroꢀNꢀmethoxycarbamate 20
(1.23 g, 7.312 mmol). The reaction mixture was allowed to stand
at 30—31 C for 4 days, then MeOH was distilled off in vacuo
(20 Torr) and condensed in a cooled trap, the residue was exꢀ
tracted with Et2O (40 mL). The extract was concentrated in vacuo
(20 Torr), the residue was subjected to chromatography on
a column (Al2O3, Et2O—hexane). to obtain ethyl Nꢀmethoxyꢀ
carbamate (26) (0.092 g, 11%) and N,N´ꢀbis(ethoxycarbonyl)ꢀ
N,N´ꢀdimethoxyhydrazine (27) (0.124 g, 14%), which were idenꢀ
21
prolonged storage solidifies to yellow crystals. 1H NMR
(300 MHz, CDCl3), : 1.45 (t, 3 H, OCH2Me, J = 6.9 Hz); 3.96
(s, 3 H, NOMe); 4.25 (q, 2 H, OCH2Me, J = 6.9 Hz); 7.23
(t, 1 H, C(4)H, J = 8.4 Hz); 7.71 (t, 1 H, C(5)H, J =8.4 Hz);
8.28 (d, 1 H, C(6)H, J = 8.4 Hz); 8.76 (d, 1 H, C(3)H,
J = 8.4 Hz); 11.19 (br.s, 1 H, NH). IR (KBr), /cm–1: 3330
(NH); 1749 (C=O); 1510 (NO2); 1340 (NO2). MS (FAB), m/z
(Irel (%)): 256 [M + H]+ (17), 224 [M + H – MeOH]+ (100).
Found (%): N, 16.32. C10H13N3O5. Calculated (%): N, 16.46.
N´ꢀ(4ꢀChlorophenyl)ꢀNꢀethoxyꢀNꢀmethoxyurea (18d), the
yield was 62%, a yellowish dense oil. 1H NMR (300 MHz,
CDCl3), : 1.37 (t, 3 H, OCH2Me, J = 7.2 Hz); 3.90 (s, 3 H,
NOMe); 4.18 (q, 2 H, OCH2Me, J = 7.2 Hz); 7.30 (d, 2 H,
C(2)H, C(6)H, J = 9.3 Hz); 7.46 (d, 2 H, C(3)H, C(5)H,
J = 9.3 Hz); 7.90 (br.s, 1 H, NH). MS (FAB), m/z (Irel (%)): 247

74
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 1, January, 2015
Shtamburg et al.
1
tified based on the H NMR spectra (see Refs 18 and 36). GLC
analysis showed that the methanol condensate contained methyl
ethyl carbonate 28 (0.230 g, 30%).
dissolved in PriOH (2 mL) with cooling to –27 C, the solution
obtained was rapidly added to a solution of CF3CO2Ag (1.065 g,
4.821 mmol) in PriOH (5 mL) cooled to –27 C. The temperaꢀ
ture of the reaction mixture was raised to 11 C over 19 h, AcONa
(0.46 g, 5.61 mmol) was added, and the mixture was stirred for
2 h. A precipitate formed was filtered off and washed with
CH2Cl2, the filtrate was concentrated in vacuo. The residue was
twice extracted with a mixture of CH2Cl2 (7 mL) and hexane
(5 mL), the combined extracts were concentrated in vacuo, the
residue was distilled in vacuo at 2 Torr to obtained methyl N,Nꢀdiꢀ
isopropoxycarbamate (34) (0.456 g, 59%), a colorless liquid,
Methanolysis of ethyl NꢀchloroꢀNꢀmethoxycarbamate (20) in
the presence of CH(OMe)3. A solution of CH(OMe)3 (0.630 g,
5.969 mmol) in MeOH (5 mL) was added to ethyl NꢀchloroꢀNꢀ
methoxycarbamate 20 (0.611 g, 3.979 mmol) at –8 C, the mixꢀ
ture was allowed to stand at –8 C for 1 h and at 5 C for 20 h.
MeOH was distilled off in vacuo (20 Torr) and condensed in
a cooled trap, the residue was allowed to stand at 20 C and 8 Torr
for 20 min to obtain ethyl Nꢀmethoxycarbamate (26) (0.165 g,
1
35%), which was identified based on the H NMR spectrum by
nD 1.4189. 1H NMR (300 MHz, CDCl3), : 1.29 (d, 12 H,
20
the comparison with an authentic sample.36 1H NMR (300 MHz,
CDCl3), : 1.30 (t, 3 H, CO2CH2Me, J = 6.9 Hz); 3.73 (s, 3 H,
NOMe); 4.23 (q, 2 H, CO2CH2Me, J = 6.9 Hz); 7.87 (br.s, 1 H,
NH). GLC analysis showed that the methanol condensate conꢀ
tained methyl ethyl carbonate 28 (0.093 g, 22%).
NOCHMe2 J = 6.3 Hz); 3.85 (s, 3 H, CO2Me); 4.28 (sept, 2 H,
NOCHMe2, J = 6.3 Hz). Found (%): C, 50.31; H, 8.71; N, 7.08.
C8H17NO4. Calculated (%): C, 50.25; H, 8.96; N, 7.32.
Methyl NꢀbutoxyꢀNꢀmethoxycarbamate (35) was obtained
according to a similar procedure by methanolysis of methyl
NꢀbutoxyꢀNꢀchlorocarbamate (30) in the presence of CF3CO2Ag
Methyl NꢀchloroꢀNꢀethoxycarbamate (29) was obtained by
chlorination of methyl Nꢀethoxycarbamate36 with ButOCl acꢀ
cording to the known procedure,18 the yield was 98%, a yellowish
liquid. 1H NMR (300 MHz, CDCl3), : 1.31 (t, 3 H, NOCH2Me,
J = 6.9 Hz); 3.92 (s, 3 H, CO2Me); 4.07 (q, 2 H, NOCH2Me,
J = 6.9 Hz). IR (neat), /cm–1: 1795 (C=O). Found (%): Cl, 22.85.
C4H8ClNO3. Calculated (%): Cl, 23.09.
Methyl NꢀbutoxyꢀNꢀchlorocarbamate (30) and methyl
NꢀchloroꢀNꢀoctyloxycarbamate (31) were obtained according to
our procedure published earlier.18
1
in 77% yield and identified based on the H NMR spectrum by
comparison with an authentic sample.18
Methyl NꢀmethoxyꢀNꢀoctyloxycarbamate (36) was obtained
according to a similar procedure by methanolysis of methyl
NꢀchloroꢀNꢀoctyloxycarbamate (31) in the presence of CF3CO2Ag
1
in 76% yield and identified based on the H NMR spectrum by
comparison with an authentic sample.18
Methyl NꢀtertꢀbutoxyꢀNꢀmethoxycarbamate (37). A solution
of CF3CO2Ag (1.39 g, 6.06 mmol) in Et2O (3 mL) was added to
a solution of methyl NꢀchloroꢀNꢀmethoxycarbamate 19 (0.769 g,
5.510 mmol) in ButOH (9 mL) at 18 C with stirring. The reacꢀ
tion mixture was allowed to stand in dark at 18 C for 20 h, then
a precipitate of AgCl was filtered off and washed with Et2O
(9 mL), the combined filtrate was concentrated in vacuo (5 Torr).
The residue was dissolved in MeOH (3 mL) and stirred with
AcONa (0.56 g, 6.5 mmol). Then, the reaction mixture was
concentrated in vacuo, the residue was extracted with a mixture
of CH2Cl2 (7 mL) and hexane (7 mL), the extract was concenꢀ
trated in vacuo, the residue was extracted with hexane (8 mL).
The extract was concentrated in vacuo, the residue was distilled
on a collar micro distillation apparatus at 5 Torr and 65—70 C
to obtain methyl NꢀtertꢀbutoxyꢀNꢀmethoxycarbamate (37) (0.350 g,
36%), a colorless liquid. 1H NMR (500 MHz, CDCl3), : 1.322
(s, 9 H, NOBut); 3.697 (s, 3 H, NOMe); 3.865 (s, 3 H, CO2Me).
Found, (%): C, 47.62; H, 8.39; N, 7.81. C7H15NO4. Calculatꢀ
ed (%): C, 47.45; H, 8.53; N, 7.90.
Methyl NꢀtertꢀbutoxyꢀNꢀethoxycarbamate (38). A solution
of methyl NꢀchloroꢀNꢀethoxycarbamate (29) (0.641 g,
4.176 mmol) in Et2O (2 mL) was added to a mixture of ButOH
(5 mL) and Et2O (2 mL) at –20 C. The reaction mixture was
allowed to stand at –20 C for 1 h and at 4 C for 10 days, then
concentrated in vacuo by 70%, followed by the addition of
a solution of AcONa (0.41 g, 5 mmol) in MeOH (8 mL). The
mixture was allowed to stand at 4 C for 2 days, CH2Cl2 (5 mL)
was added, a precipitate was filtered off. The filtrate was conꢀ
centrated in vacuo, the residue was extracted with a mixture of
CH2Cl2 (6 mL) and hexane (16 mL). The extract was dried with
MgSO4 and filtered, the filtrate was concentrated in vacuo, the
residue was fractionally distilled on a collar micro distillation
apparatus to obtain methyl NꢀtertꢀbutoxyꢀNꢀethoxycarbamate
(38) (0.0874 g, 11%), a colorless liquid, b.p. 78—82 C (6 Torr).
1H NMR (300 MHz, CDCl3), : 1.26 (t, 3 H, NOCH2Me,
J = 7.2 Hz); 1.32 (s, 9 H, NOBut); 3.86 (s, 3 H, CO2Me); 4.01
Methyl NꢀisopropoxyꢀNꢀmethoxycarbamate (32). Methyl
NꢀchloroꢀNꢀisopropoxycarbamate (20) (1.371 g, 8.179 mmol)
was added to a solution of CF3CO2Ag (1.90 g, 8.59 mmol) in
MeOH (11 mL) at –26 C, the temperature of the reaction
mixture was raised to 14 C over 22 h. Then, AcONa (0.80 g,
9.81 mmol) was added, after 1 h a precipitate formed was filtered
off and washed with CH2Cl2 (15 mL), a combined filtrate was
concentrated in vacuo. The residue was extracted with hexane
(20 mL), the hexane extract was concentrated in vacuo, the resiꢀ
due was distilled in vacuo at 3 Torr to obtain methyl Nꢀisopropꢀ
oxyꢀNꢀmethoxycarbamate (32) (0.700 g, 52%), a colorless liqꢀ
1
uid, b.p. 50—53 C (3 Torr), nD23 1.4168. H NMR (300 MHz,
CDCl3), : 1.29 (d, 6 H, NOCHMe2, J = 6.3 Hz); 3.77 (s, 3 H,
NOMe); 3.86 (s, 3 H, CO2Me); 4.27 (sept, 1 H, NOCHMe2,
J = 6.3 Hz). 13C NMR (75 MHz, CDCl3), : 20.9 (NOCHMe2);
54.4 (CO2Me); 60.2 (NOMe); 60.4 (NOCHMe2); 159.7 (C=O).
IR (KBr), /cm–1: 1770 (C=O). MS (EI, 70 eV), m/z (Irel (%)):
163 [M]+ (3.4), 105 (5.6), 91 (14.0), 60 (21.3), 59 (54.8),
58 (24.3), 46 (16.9), 45 (36.7), 44 (21.3), 43 (100). Found (%):
C, 44.23; H, 8.17; N, 8.42. C6H13NO4. Calculated (%): C, 44.17;
H, 8.03; N, 8.58.
Methyl NꢀethoxyꢀNꢀisopropoxycarbamate (33) was obtained
according to a similar procedure by ethanolysis of methyl
NꢀchloroꢀNꢀisopropoxycarbamate (20) in the presence of
CF3CO2Ag in 59% yield and by isopropanolysis of methyl
NꢀchloroꢀNꢀethoxycarbamate (29) in the presence of CF3CO2Ag
in 45% yield, a colorless liquid, nD21 1.4200. 1H NMR (300 MHz,
CDCl3), : 1.293 (t, 3 H, NOCH2Me, J = 7.2 Hz); 1.295 (d, 6 H,
NOCHMe2, J = 6.3 Hz); 3.86 (s, 3 H, CO2Me); 4.06 (q, 2 H,
NOCH2Me, J = 7.2 Hz); 4.28 (sept, 1 H, NOCHMe2,
J = 6.3 Hz). Found (%): C, 47.19; H, 8.67; N, 7.74. C7H15NO4.
Calculated (%): C, 47.45; H, 8.53; N, 7.90.
Methyl N,Nꢀdiisopropoxycarbamate (34). Methyl Nꢀchloroꢀ
Nꢀisopropoxycarbamate (20) (0.673 g, 4.017 mmol) was rapidly

Anomeric amides
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 1, January, 2015
75
(q, 2 H, NOCH2Me, J = 7.2 Hz). MS (FAB), m/z (Irel (.%)): 192
[M + H]+ (100); 146 [M – Et]+ (60); 136 (75).
1983, 32, 2174 [Izv. Akad. Nauk SSSR, Ser. Khim.,
1983, 2411].
Methyl N,Nꢀdiethoxycarbamate (39) was obtained accordꢀ
ing to a similar procedure by ethanolysis of methyl NꢀchloroꢀNꢀ
ethoxycarbamate 29 in the presence of CF3CO2Ag in 46% yield,
a colorless liquid, b.p. 46—47 C (2 Torr), nD25 1.4139. 1H NMR
(300 MHz, CDCl3), : 1.30 (t, 6 H, NOCH2Me, J = 7.2 Hz);
3.87 (s, 3 H, CO2Me); 4.07 (q, 4 H, NOCH2Me, J = 7.2 Hz).
13C NMR (75 MHz, CDCl3), : 13.40 (OCH2Me); 54.25
(CO2Me); 69.86 (OCH2Me); 159.84 (C=O). MS (EI, 70 eV),
m/z (Irel (%)): 164 [M + H]+ (0.4); 163 [M]+ (2.0), 118 (1.7),
105 (3.1), 104 (2.7), 59 (59.8), 43 (100). Found (%): C, 44.08;
H, 8.14; N, 8.51. C6H13NO4. Calculated (%): C, 44.17; H, 8.03;
N, 8.58.
17. V. F. Rudchenko, V. I. Shevchenko, R. G. Kostyanovsky,
Bull. Acad. Sci. USSR, Div. Chem. Sci. (Engl. Transl.), 1986,
35, 543 [ Izv. Akad. Nauk SSSR, Ser. Khim., 1986, 598].
18. V. G. Shtamburg, E. A. Klots, A. P. Pleshkova, V. I. Avraꢀ
menko, S. P. Ivonin, A. V. Tsygankov, R. G. Kostyanovsky,
Russ. Chem. Bull. (Int. Ed.), 2003, 52, 2251 [Izv. Akad. Nauk,
Ser. Khim., 2003, 2132].
19. V. G. Shtamburg, A. P. Pleshkova, V. N. Serdyuk, S. P.
Ivonin, Zh. Org. Khim., 1999, 35, 1578 [Russ. J. Org. Chem.
(Engl. Transl.), 1999, 35].
20. O. V. Shiskin, R. I. Zubatyuk, V. G. Shtamburg, A. V. Tsygꢀ
ankov, E. A. Klots, A. V. Mazepa, R. G. Kostyanovsky, Menꢀ
deleev Commun., 2006, 16, 222.
This work was financially supported by the State Founꢀ
dation for Basic Research of Ukraine (Grant Fꢀ53/105ꢀ
2013) and the Russian Foundation for Basic Research
(Project No. 13ꢀ03ꢀ90460 of Program 07ꢀRFFIꢀ01).
21. V. G. Shtamburg, O. V. Shishkin, R. I. Zubatyuk, S. V.
Kravchenko, A. V. Tsygankov, V. V. Shtamburg, V. B. Disꢀ
tanov, R. G. Kostyanovsky, Mendeleev Commun., 2007,
17, 178.
22. V. G. Shtamburg, A. P. Pleshkova, V. N. Serdyuk, S. P.
Ivonin, Zh. Org. Khim., 1999, 35, 1120 [Russ. J. Org. Chem.
(Engl. Transl.), 1999, 35].
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Received February 25, 2014;
in revised form May 26, 2014