Reaction of N-alkylglycolurils with electrophilic reagents

Article abstract of DOI:10.1007/s10593-006-0094-2

The N-hydroxymethylation, N-acetylation, and N-acetoxymethylation of mono-, di-, and trialkylglycolurils by reaction with the electrophilic reagents formaldehyde and acetaldehyde have been studied. General methods have been developed for the preparation of mono-, di-, and tri-N-hydroxymethylglycolurils by treatment of differently substituted N-alkylglycolurils with formaldehyde (as hemiformal in methanol) and the synthesis of di-N-and tri-N-acetyl-or N-acetoxymethylglycolurils via the electrophilic substitution of hydrogen atoms for an acetyl group at the nitrogen or oxygen atoms in the hydroxymethyl groups of glycolurils using acetic anhydride. The regioselectivity of the reaction of the 2-t-Bu-and 2-c-C₆H₁₁-glycolurils with formaldehyde has been shown to yield a 4,6-di(hydroxymethyl) derivative. It was found that the hydroxymethylation of 2,4-and 2,6-dialkylglycolurils occurs regioselectively with a stoichiometric ratio of glycoluril to hemiformal and permits preparation of their mono-and dihydroxymethyl derivatives. The enantiomeric analysis of the obtained compounds has been carried out for the first time using HPLC on chiral phases. X-ray analysis has been carried out on the previously unreported racemic 2,6-diacetoxymethyl-4,8-dimethylglycoluril. 2006 Springer Science+Business Media, Inc.

Full text of DOI:10.1007/s10593-006-0094-2

Chemistry of Heterocyclic Compounds, Vol. 42, No. 3, 2006
REACTION OF N-ALKYLGLYCOLURILS
WITH ELECTROPHILIC REAGENTS
1
1
1
1
1
A. N. Kravchenko , A. S. Sigachev , G. A. Gazieva , E. Yu. Maksareva , N. S. Trunova ,
1
2
2
1
2
K. A. Chegaev , K. A. Lyssenko , D. V. Lyubetsky , M. I. Struchkova , M. M. Il'in ,
2
1
1
1
V. A. Davankov , O. V. Lebedev , N. N. Makhova , and V. A. Tartakovsky
The N-hydroxymethylation, N-acetylation, and N-acetoxymethylation of mono-, di-, and
trialkylglycolurils by reaction with the electrophilic reagents formaldehyde and acetaldehyde have been
studied. General methods have been developed for the preparation of mono-, di-, and tri-N-
hydroxymethylglycolurils by treatment of differently substituted N-alkylglycolurils with formaldehyde (as
hemiformal in methanol) and the synthesis of di-N- and tri-N-acetyl- or N-acetoxymethylglycolurils via
the electrophilic substitution of hydrogen atoms for an acetyl group at the nitrogen or oxygen atoms in
the hydroxymethyl groups of glycolurils using acetic anhydride. The regioselectivity of the reaction of
the 2-t-Bu- and 2-c-C H -glycolurils with formaldehyde has been shown to yield
a
6
11
4
2
,6-di(hydroxymethyl) derivative. It was found that the hydroxymethylation of 2,4- and
,6-dialkylglycolurils occurs regioselectively with a stoichiometric ratio of glycoluril to hemiformal and
permits preparation of their mono- and dihydroxymethyl derivatives. The enantiomeric analysis of the
obtained compounds has been carried out for the first time using HPLC on chiral phases. X-ray analysis
has been carried out on the previously unreported racemic 2,6-diacetoxymethyl-4,8-dimethylglycoluril.
Keywords: N-Hydroxymethyl(acetyl, acetoxymethyl)glycolurils, acetic anhydride, formaldehyde,
electrophilic reagents, hydroxymethylation and electrophilic substitution of N-alkylglycolurils,
regioselectivity, regiospecificity, X-ray analysis, enantiomeric analysis.
The preparation of enantiomerically pure biologically active compounds is an important goal in organic
and medicinal chemistry. In recent years this problem has being resolved by us in the case of glycoluril
(
2,4,6,8-tetraazabicyclo[3.3.0]octane-3,7-dione) derivatives which are a promising class of neurotropic
compounds [1-4]. For access to enantiomers of glycolurils we have developed two basic methods, viz. the
diastereoselective and diastereospecific synthesis using optically pure precursors (asymmetric induction) [5, 6]
and the separation of racemates via spontaneous crystallization [7-11]. A necessary condition for the
spontaneous separation into enantiomers is the ability of the racemates to form conglomerates (crystallization as
a mixture of homochiral crystals). Both N-alkyl- [7, 8, 11], N-carboxy- [9, 11], and N-hydroxyalkylglycolurils
[10] show this property. However, N-alkylglycolurils are basically finely dispersed powders [8, 10] while
glycolurils with functional groups in the substituent generally form coarser crystals fully suited to X-ray
_
_________________________________________________________________________________________
1
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 117913;
2
e-mail: kani@ioc.ac.ru. A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of
Sciences, Moscow 119991; e-mail: kostya@xray.ineos.ac.ru. Translated from Khimiya Geterotsiklicheskikh
Soedinenii, No. 3, pp. 411-423, March, 2006. Original article submitted July 15, 2005.
0
009-3122/06/4203-0365©2006 Springer Science+Business Media, Inc.
365

analytical investigation [9, 12]. In particular, it has been shown that 2-carboxypropyl- and 2-(2-hydroxy-1,1-
dimethylethyl)glycolurils among this type of derivative crystallize as conglomerates [9, 11, 12]. In addition we
have developed an enantiomeric analysis of chiral N-alkyl (carboxyalkyl-, hydroxylalkyl)glycolurils by HPLC
on chiral phases [10-13].
In a continuation of our study of the synthesis of racemic functionally substituted glycolurils the aims of
this work were to develop general methods for preparation of previously unrecorded racemic N-acetyl- and
N-hydroxymethylglycolurils and their O-acetyl derivatives, the enantiomeric analysis of the compounds
obtained by HPLC, and an investigation of their crystallization processes from different solvents. The
preparation of conglomerates might be expected in this series because it has previously been shown that
2
,6-diacetyl-4,8-dinitroglycoluril crystallizes in a noncentrosymmetric space group P2 2 2 [14] which is most
1 1 1
typical of glycolurils forming conglomerates [7-9, 11].
The reactions of glycolurils with different electrophilic reagents in N-hydroxymethylation, acylation,
chlorination, and nitration processes has only been described for glycoluril and isolated N-alkylglycolurils
[15-51]. The processes of chlorination [17-32] and nitration [33-35] have been known for a long time and mostly
reported in the patent literature [17, 19, 22-32, 34, 35]. It is known that the synthesis of N-hydroxymethyl
derivatives of glycolurils occurs by treatment of glycolurils with formaldehyde [36-45]. This reaction is only
known in some detail for glycoluril. Thus the synthesis of 2,4,6,8-tetra-(hydroxymethyl)glycoluril (1a) occurs in
8
0% yield by condensation of the glycoluril 2a in a suspension of paraformaldehyde in aqueous base solution at
pH 10-12 and a temperature of 50-60°C, the length of the process not being reported [45]. Compound 1a was
separated and characterized by melting point. In another example the reaction occurs over 2 h at pH 9-10 and
temperature of 50°C with the formaldehyde being used as a 40% solution in water (Scheme 1). A 50% solution
of the glycoluril 1a was obtained and was used in a subsequent reaction without separation [15].
Scheme 1
R1
N
R
3
R1
N
R3
N
N
4CH O
2
O
O
O
O
N
N
H
N
N
2
2
R
R
CH OH
2
2
a
1a
1
2
3
1
2
3
1
a R = R = R = CH
2
OH; 2a R = R = R = H
The N-acylation of glycolurils is carried out using acid chlorides or acetic anhydride and with either
BuLi in absolute solvents or HClO [15, 16, 46-51] as catalysts. Examples of the O-acylation of the
4
hydroxymethylglycolurils are absent in the literature.
As targets for the study we chose the mono- (2b-e), di- (2f-k), and tri-N-alkylglycolurils (2l-o)
(
Scheme 2). The synthesis of the starting glycolurils 2b-o was carried out by methods developed by us before
[10, 52]. Mono- (2b-e), 2,4-di- (2i), and 2,4,6-trialkylglycolurils (2l-o) were prepared by the α-ureidoalkylation
of mono- and 1,3-dialkylureas and using as ureidoalkylating agents the corresponding
,5-dihydroxyimidazolidin-2-ones [10, 52]. The 2,6- (2f-h), and 2,8-dialkyl derivatives (2j,k) were prepared by
4
condensation of the corresponding monoalkylureas with glyoxal [10].
It is known that 2-mono-, 2,4-, 2,6-, and 2,8-dialkylglycolurils 2b-k are poorly soluble in water [10] and
hence their complete hydroxymethylation in conditions similar to the literature method will also occur in
3
66

Scheme 2
1
l–o
1
b,c
R1
N
R3
N
1
d,e
O
O
1j,k + 3b,c
N
R2
N
H
R1
N
R3
N
2
a–o
1
f–h
1i + O
O
N
N
Me
CH OH(Me)
2
3
a
1
2
3
1
2
3
1
2
1
b R = Me, R = R = CH
2
OH; c R = Et, R = R = CH
2
OH; d R = t-Bu, R = CH
2
OH,
3
1
2
3
1
2
3
1
R = H; e R = c-C H , R = CH OH, R = H; f R = CH OH, R = R = Me; g R = CH OH,
R = R = Et; h R = CH OH, R = R = Pr; i R = R = Me, R = CH OH; j R = R = Me,
R = CH OH; k R = R = Et, R = CH OH; l R = R = Me, R = Et; m R = R = R = Me;
n R = R = R = Et; o R = R = Et, R = Me; 2 a R = R = R = H; b R = Me, R = R = H;
6
11
2
2
2
2
3
1
2
3
1
2
3
1
3
2
2
2
1
3
2
1
2
3
1
2
3
2
2
2
1
3
1
2
3
1
2
3
1
2
3
1
2
3
1
2
3
1
2
3
c R = Et, R = R = H; d R = t-Bu, R = R = H; e R = c-C H , R = R = H;
6
3
11
1
2
3
1
2
3
1
2
1
2
f R = H, R = R = Me; g R = H, R = R = Et; h R = H, R = R = Pr; i R = R = Me,
3
1
3
2
1
3
2
1
2
3
R = H; j R = R = Me, R = H; k R = R = Et, R = H; l R = R = Me, R = Et;
1
2
3
1
2
3
1
2
3
m R = R = R = Me; n R = R = R = Et; o R = R = Et, R = Me;
1
3
1
3
1
3
3
a R = Me, R = H; b R = R = Me; c R = R = Et
suspension complicating the method of carrying out the TLC monitoring and thus the optimization of the
process. We therefore studied the possible hydroxymethylation of these compounds using hemiformal as a
methanol solution prepared from paraformaldehyde in the presence of K CO .
2
3
Development of the method for the hydroxymethylation of compounds 2b-k was carried out in the case
of 2-methylglycoluril 2b and a methanol solution of hemiformal taken in stoichiometric amounts at 60°C over
1
-2 h in two different pH ranges (8-9 and 10-12). TLC analysis showed that the optimum time for the reaction
was 1 h. After separation in the pure state (crystallization from methanol) the yield of the target glycoluril 1b in
the pH 10-12 experiment was 70-75% and in the range 8-9 it was 82-85%. Hence the hydroxymethylation
processes were carried out subsequently at pH 8-9.
We carried out the targeted full hydroxymethylation of the glycolurils 2c-j in the optimum conditions
(
2
pH 8-9, 1 h, 60°C) and the yields of the glycolurils were 65-95%. The hydroxymethylation of the 2-t-Bu- and
-cyclohexylglycolurils 2d,e gave the products of partial hydroxymethylation 2-alkyl-4,6-
di(hydroxymethyl)glycolurils 1d,e* independently of the molar ratio of 2d,e to formaldehyde (1:3 or 1:2). The
regiospecific substitution of only the cis-related hydrogen atoms on atoms N(4) and N(6) in compounds 2d,e and
the absence of hydroxymethyl groups on atom N infers steric hindrance to hydroxymethylation at the N atom
(
8)
(8)
due to the bulky t-Bu and c-C H substituents in the starting glycolurils 2d,e.
6
11
1
The presence of products of incomplete substitution was observed in the H NMR spectra of the
unpurified products of hydroxymethylation of the glycolurils 2i-k. Fractional crystallization from methanol gave
the pure achiral compounds 1i-k in 65-70% yield and compounds 3a-c (20-25% yield) as the products of
incomplete hydroxymethylation of the starting 2i-k. The ratio of the products of full 1i-k and partial
_
*
______
The structure of the compounds prepared was confirmed by us by a chemical route through their use in the
8
.10
synthesis of tricyclic glycoluril derivatives 3-Alk-7-t-Bu-(c-C H )-1,3,5,7,9-pentaazatricyclo[5.3.1.0 ]-
6
11
dodecane-6,10-diones which will be reported later on.
3
67

hydroxymethylation 3a-c was 2.4:1 or 3.25:1 which shows the regioselectivity of this reaction. In the reaction of
i with hemiformal the glycoluril 3a could not be separated but the methyl ether 3a' was obtained, evidently
2
formed via etherification of the hydroxymethyl group by methanol in the prolonged crystallization process.
With the aim of studying a possible regioselectivity in the hydroxymethylation of one of the nitrogen
atoms in 2,4- and 2,8-dimethylglycolurils 2i and 2j,k we have looked at their reaction with 1 mol of
1
formaldehyde under these conditions. From the H NMR analysis in the region for the NH group proton signals
(
6.5-7.5 ppm) and CH groups (4.0-4.7 ppm) of the reaction mass evaporated to dryness it is evident that the
2
signals for three products appear in each: the starting glycolurils 2i or 2j,k, the products of incomplete
substitution 3a and 3b,c, and the fully substituted products 1i and 1j,k. The starting glycolurils 2i and 2j,k
precipitate from the reaction mixtures. The di- (1i and 1j,k) and monohydroxymethylglycolurils (3a and 3b,c)
were prepared in the pure state by fractional crystallization from methanol. The separated products 1i (j,k), 2i
(
j,k), and 3a (b,c) show that a change in the ratio of glycoluril 2i (j,k) to hemiformal does not lead to
regiospecificity in their N-hydroxymethylation processes.
Hydroxymethylation of the readily water soluble 2,4,6-trialkylglycolurils 2l-o was studied by us for two
variants using a methanol solution of hemiformal according to the developed method (Method A) or using
formaldehyde as a 37% aqueous solution (formalin) (Method B).
Method B was developed in the case of the reaction of 6-ethyl-2,4-dimethylglycoluril 2l with formalin.
The reaction was carried out in formalin at pH 8-9 and pH 10-12 and a temperature of 60°C over 1-3 h. TLC was
used to monitor the process. It was found that the optimal reaction time was 1 h. At pH 10-12 the reaction mass
darkened and the separation of product 1l was hindered by the need to carry out the extraction with CHCl , the
3
yield being 70%* The hydroxymethylated derivatives 1m-o were synthesized from the trialkylglycolurils 2m-o
.
in 79-97% yields by a similar method.
The hydroxymethylation of 2l-o using hemiformal as a methanol solution (pH 8-9, 1 h, 60°C, Method 1)
gives compounds 1l-o in similar yields. For the separation of the products 1l-o it was not necessary to use CHCl3
extraction hence the glycolurils 1l-o were separated as oily residues (after evaporation of methanol) giving solid
products upon trituration with ether.
The N-acetylation of the racemic 2-methyl(ethyl)- and 2,6-dialkyl(dimethyl and diethyl)glycolurils 2b,c
ad 2f,g respectively were optimized by us using a method based on their reaction with acetic anhydride (as
reagent and solvent) in the presence of a ten-fold excess of NaOAc. The reaction was performed by refluxing for
0
.5-1.5 h (Scheme 3). The dependence of the yields of 4a-d on the duration of the acetylation was evaluated
after separation of the final products 4a-d in the pure state. The N-acetyl derivatives 4a-d were obtained in
1-78% yields with a reaction time of 1.5 h. The yields of the compounds synthesized by us 2,4,6-triacetyl-2-
6
methyl- (4a) (75-78%) or 2,6-diacetyl-4,8-dimethylglycolurils (4c) (64-66%) were comparable or greater than
those reported in the literature [46] for preparation of these compounds (4a – 45%, 4c – 65%) from 2-methyl- or
2
,6-dimethylglycolurils using acetic anhydride in the presence of HClO4.
Scheme 3
R1
N
R5
Ac O
N
2
2
b,c,f,g
O
O
NaOAc
N
N
R 4
Ac
4
a–d
1
4
5
1
4
5
1
4
5
4
a R =Me, R = R = Ac; b R = Et, R = R = Ac; c R = Ac, R = R = Me;
1
4
5
d R = Ac, R = R = Et
_
*
______
Here and subsequently averaged product yields are given.
3
68

However, the introduction of an acetyl group at the N(8) atom of 2,4,6-trialkylglycolurils 2l-o was
unsuccessful either with the use of acetic anhydride in the presence of HClO or NaOAc or with acetyl chloride
4
in the presence of triethylamine and this may be related to steric factors.
To investigate the O-acetylation we have chosen the most readily available chiral N-hydroxymethylated
derivatives 1b,c,f,g. O-Acetylation was carried out using acetic anhydride in pyridine at room temperature over
1
13
2
4 h. On the basis of the H and C NMR spectroscopic data it was found that all of the hydroxymethyl groups
had undergone acetylation. The yields of the N-acetoxymethylglycolurils 5a-d were 54-70% (Scheme 4).
Scheme 4
1
R
N
R7
N
Ac O, pyridine
2
1
b,c,f,g
O
O
7
-14 h, room temp.
N
N
R6
CH OAc
2
5
a–d
1
6
7
1
6
7
1
5
a R = Me, R = R = CH
2
OAc; b R = Et, R = R = CH
2
OAc; c R = CH
2
OAc,
6
7
1
6
7
2
R = R = Me; d R = CH OAc, R = R = Et
With the aim of clarifying the ability of the synthesized glycolurils 1, 4, 5 to crystallize as conglomerates
we have studied their crystallization processes from 50% aqueous methanol, methanol, chloroform and ethyl
acetate. The hydroxymethylated glycolurils 1 are finely dispersed powders and the N-acetyl derivatives 4 and O-
acetylglycolurils 5 crystallize as very fine, needle-like crystals thus it was not possible to evaluate the ability of
the obtained compounds to form conglomerates at this stage. Crystals suitable for X-ray analysis were prepared
only in the crystallization of the glycoluril 5c from methanol. X-ray analysis showed that compound 5c
crystallizes in a centrosymmetric space group C2/c, i.e. it is a racemate.
The crystal 5c is characterised overall as having C2 symmetry in this molecule, the second order axis
passing through the center of the C –C bond. The basic bond lengths in the 5c molecule are close to those
(
1)
(1A)
expected for this class of compounds (Table 1). The conformation of the 5-membered ring (Fig. 1) is a flattened
Fig. 1. Overall view of the molecule of compound 5c
(
atoms are shown with thermal vibration ellipsoids having 50% probability).
3
69

TABLE 1. Basic Bond Lengths (l) and Valence Angles (ω) in the Molecule
of Compound 5c
Bond
O(1)−C(3)
l, Å
Angle
ω, deg.
1.219(2)
1.386(2)
1.426(2)
1.453(2)
1.356(2)
1.438(2)
1.446(2)
1.555(3)
C(3)−N(2)−C(4)
C(3)−N(2)−C(1)
C(4)−N(2)−C(1)
C(3)−N(6)−C(7)
C(3)−N(6)−C(1А)
C(7)−N(6)−C(1А)
N(6А)−C(1)−N(2)
N(6А)−C(1)−C(1А)
N(2)−C(1)−C(1А)
O(1)−C(3)−N(6)
O(1)−C(3)−N(2)
N(6)−C(3)−N(2)
120.3(1)
111.7(1)
124.8(1)
123.4(1)
113.7(1)
122.7(1)
112.9(1)
102.7(1)
103.7(1)
126.4(1)
125.5(1)
108.0(1)
N(2)−C(3)
N(2)−C(4)
N(2)−C(1)
N(6)−C(3)
N(6)−C(7)
N(6)−C(1А)
C(1)−C(1А)
"
envelope" with the atom C(1A) deviating from the plane of the C , N , C , N atoms by 0.06 Å (which are
(1) (2) (3) (6)
coplanar with 0.003 Å). The acetyl groups in the molecule are placed to one side of the mean plane of the ring
and are characterized by a cis-orientation relative to the bridging hydrogen atoms.
The atoms N(2) and N(6) in the molecule 5c are somewhat different (the deviation of the N(2) and N(6)
atoms from the plane formed by atoms linked with these atoms are 0.15 and 0.03 Å respectively). The difference
in degree of pyramidalization of the nitrogen atoms in turn leads to a lengthening of the N –C (1.386(2)) bond
(
2)
(3)
when compared with N –C (1.356(2) Å) bond.
(
6)
(3)
Analysis of the crystal packing has shown that, beside a series of weak C–H···O interactions of all the
remaining intermolecular distances correspond to conventional van der Waal contacts.
The synthesized racemic compounds 1f-h, 4b, 5c were subjected to chromatography on several chiral
HPLC columns (OJ-H, OD, AD, ChirobioticTAG, β-CD) and on a C18 ligand exchange column modified by
C -L-Hyp. However, only when using the OJ-H HPLC column, elution with a mixture of hexane and i-PrOH,
1
0
and UV detection at 210 nm were the enantiomeric peaks for the compounds 1g and 1h base line separated after
-9 min with good resolution. These conditions were fully suited to a rapid enantiomeric analysis of the given
compounds.
Hence a study of the N-acylation, N-hydroxymethylation, and N-acetoxymethylation of mono-, di-, and
6
trialkylglycolurils has shown that the use of a methanol solution of hemiformal in condensation reactions with
N-glycolurils or acetic anhydride in the electrophilic substitution at the nitrogen or oxygen atoms of the
hydroxymethyl groups of N-glycolurils give this process applicability to differently substituted at the nitrogen
atom N-glycolurils.
The regioselectivity of the reaction of 2-t-Bu- and 2-c-C H -glycolurils with formaldehyde giving the
6
11
4
2
,6-di(hydroxymethyl) derivative was found. It was shown that hydroxymethylation of 2,4- and
,6-dialkylglycolurils occurs regioselectively with a stoichiometric ratio of glycoluril to hemiformal and leads to
formation of monohydroxy- and dihydroxymethylglycolurils. The possibility of carrying out the enantiomeric
analysis of racemates of these synthesized compounds using HPLC on chiral phases has been shown for the first
time. Using X-ray analysis it was found that the previously unrecorded 2,6-diacetoxymethyl-4,8-
dimethylglycoluril is a racemate.
3
70

TABLE 2. Characteristics of the Synthesized Compounds 1b-o, 3a', 3b,c,
4
a-d, 5a-d
Found, %
Calculated, %
H
Com-
pound
Empirical
formula
——————
mp, °С
Yield, %
C
N
1
1
1
1
1
1
1
1
1
1
1
1
1
1
3
3
3
4
4
4
4
5
5
5
5
b
c
С
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
С
C
C
C
C
C
C
C
C
8
9
H
14
16
N
4
4
O
5
5
38.92
5.79
5.73
6.18
6.20
7.08
7.02
7.14
7.09
6.19
6.13
6.95
7.02
7.77
7.74
6.09
6.13
6.17
6.13
7.06
7.02
6.98
7.07
6.61
6.59
7.91
7.87
7.53
7.49
6.61
6.59
6.01
6.04
6.99
7.07
4.93
5.00
5.29
5.44
5.58
5.55
6.38
6.43
5.44
5.41
5.79
5.74
5.85
5.77
22.81
22.75
21.47
21.53
21.64
21.69
19.65
19.71
24.21
24.34
21.61
21.69
19.52
19.57
24.28
24.34
24.38
24.34
21.62
21.69
24.69
24.55
26.09
26.15
21.93
21.86
23.03
23.13
26.19
26.15
27.17
27.99
24.44
24.55
19.95
19.85
19.06
18.91
22.07
22.04
19.84
19.85
15.03
15.05
14.47
14.50
17.81
17.83
130-132
114-116
198-200
170-172
159-161
119-121
89-91
80-82
70-73
78-80
70-72
82-85
88-90
75-78
62-65
85-87
89-91
93-95
90-92
89-91
83-85
20-22
23-25
21-22
75-78
63-65
64-66
61-62
68-70
57-58
65-67
54-56
3
9.02
H
N
O
41.65
1.54
4
d
e
10
12
H
18
N
4
4
О
4
4
46.48
6.50
4
H
20
N
О
50.75
0.69
5
f
8
H
14
N
4
O
4
41.67
1.74
46.59
6.50
4
g
h
i
10
12
H
H
18
22
N
4
O
O
4
4
N
4
4
50.29
0.34
41.78
1.74
5
8
8
H
14
N
4
O
O
4
163-165
135-137
124-126
108-110
132-134
97-99
4
j
H
14
N
4
4
41.69
1.74
46.55
6.50
4
k
l
10
H
18
N
4
O
4
4
9
8
H
16
N
4
O
3
3
47.32
7.36
44.92
4.85
4
m
n
o
a'
b
c
H
14
N
4
O
4
11
10
H
20
N
4
4
O
3
3
51.49
1.55
49.72
9.58
5
H
18
N
O
106-108
181-183
151-153
143-145
172-174
165-167
159-161
144-146
169-171
133-135
162-164
120-122
4
8
7
9
H
14
N
4
4
4
O
3
O
3
O
3
44.82
4.85
42.02
2.00
4
H
12
16
N
N
4
Н
47.33
7.36
46.92
6.81
4
a
b
c
11
12
10
12
14
15
12
14
H
14
16
14
18
20
22
18
22
N
N
N
N
N
N
N
N
4
4
4
4
4
4
4
4
O
O
O
O
O
O
O
O
5
5
4
4
8
8
6
6
4
H
H
H
H
H
H
H
48.81
8.65
47.19
7.24
4
4
d
a
b
c
51.11
1.06
45.58
5.61
5
4
46.66
6.63
45.98
5.86
4
4
d
49.04
9.12
6.52
6.48
16.41
16.37
4
EXPERIMENTAL
1
H NMR spectra were recorded on a Bruker AM-300 instrument (300 MHz) using DMSO-d
spectroscopic investigation was carried out using an MS-30 mass spectrometer.
6
. Mass
3
71

1
TABLE 3. H NMR Spectra of the Synthesized Glycolurils 1b-o, 3a', 3b,c, 4a-d, 5a-d
Glycoluril
1
Chemical shifts, δ, ppm (J, Hz)
2
2
8
,4,6-Tri(hydroxymethyl)-
-methylglycoluril (1b)
2.85 (3H, s, СН
and 5.49 (each 1Н, both d, J = 8.5, 2СН); 5.92 (3H, m, 3ОН)
1.08 (3H, t, J = 6.7, СН ); 3.20 (2H, m, NCH ); 4.60 (6H, m,
3NCH ); 5.44 (2H, m, СНСН); 5.95 (3H, br. s, 3ОН)
1.31 (9Н, s, 3СН ); 4.65 (4Н, m, 2СН );
3 2
); 4.69 (6H, m, 3NCH ); 5.29
8
-Ethyl-2,4,6-tri(hydroxymethyl)-
3
2
glycoluril (1c)
-tert-Butyl-4,6-
di(hydroxymethyl)glycoluril (1d)
2
2
3
2
5.36 and 5.43 (each 1Н, both d, J = 8.6, 2СН); 5.78 (2Н,
br. s, 2ОН); 7.70 (1Н, br. s, NH)
2
-Cyclohexyl-4,6-di(hydroxy-
1.17 (4H, m, 2СН
СН); 4.55 (4H, m, 2СН
J = 8.0, 2СН); 5.78 (2H, br. s, 2ОН); 7.48 (1H, s, NH)
2.83 (6H, s, 2NСН ); 4.37 (4H, m, 2NCH ); 5.24 (2H, s,
СНСН); 5.94 (1H, t, J = 5.0, ОН)
1.11 (6H, t, J = 6.62, 2СН ); 3.23 (2H, m, NCH
m, NCH ); 4.59 and 4.71 (each 1Н, both d, J = 11.0, 2NCH
.46 (2H, s, 2СН); 5.95 (2H, br. s, 2ОН)
0.85 (6H, t, J = 7.4, 2СН ); 1.48 (4H, m, 2СН
NCH ); 3.35 (2H, m, NCH ); 4.58 and 4.72 (each 1Н, both d,
J = 11.0, 2NCH ); 5.41 (2H, br. s, 2СН);
.05 (2H, br. s, 2ОН)
2.82 (6H, s, 2NСН ); 4.66 (4H, m, 2NCH
2СН); 6.05 (2H, br. s, 2ОН)
2.81 (6H, s, 2NСН ); 4.38 (4H, m, 2NСН
2
); 1.62 (8Н, 6Н, m, 3СН
2
); 3.43 (1H, m,
methyl)glycoluril (1e)
2
); 5.25 and 5.67 (each 1Н, both d,
2
4
,6-Di(hydroxymethyl)-
,8-dimethylglycoluril (1f).
3
2
4
,8-Diethyl-2,6-di(hydroxy-
3
2
); 3.38 (2H,
);
methyl)glycoluril (1g)
2
2
5
2
4
,6-Di(hydroxymethyl)-
,8-dipropylglycoluril (1h)
3
2
); 3.17 (2H, m,
2
2
2
6
2
4
2
4
,4-Di(hydroxymethyl)-
,8-dimethylglycoluril (1i)
,8-Di(hydroxymethyl)-
,6-dimethylglycoluril (1j)
3
2
2
); 5.46 (2H, br. s,
); 5.11
3
and 5.49 (each 1H, d, J = 7.9, 2CH); 5.82 (2H, m, 2ОН)
1.7 (6H, m, 2CСН ); 3.07 (4H, m, 2CCH ); 4.56 (4H, m,
2NСН ); 5.21 and 5.48 (each 1Н, both d, J = 7.0, 2СН);
.87 (2H, m, ОН)
1.00 (3H, t, J = 7.3, СН
NСН ); 3.16 (2H, m, NCH
.20 and 5.26 (each 1Н, both d, J =8.5, 2СН); 5.90 (1H, t,
4
,6-Diethyl-2,8-di(hydroxy-
3
2
methyl)glycoluril (1k)
2
5
4
6
-Ethyl-2-hydroxymethyl-
,8-dimethylglycoluril (1l)
3
); 2.81 (3H, s, NСН
3
); 2.83 (3H, s,
);
3
2
); 4.67 (2H, d, J = 6.7, NCH
2
5
J = 6.5, ОН)
2
4
4
-Hydroxymethyl-
3 2
2.81 (9H, m, 3СН ); 4.66 (2H, m, NCH O); 5.09
and 5.26 (each 1Н, both d, J = 8.1, СН); 5.73 (1H, br. s, ОН)
0.91 (3H, br. s, СН ); 1.02 (3Н, br. s, СН ); 1.08 (3Н, br. s,
СН ); 3.02 (6Н, m, 3NCH ); 5.04 (2H, br. s, NCH O); 5.07
and 5.19 (each 1Н, both d, J = 7.9, 2СН); 7.42 (1H, br. s, ОН)
,6,8-trimethylglycoluril (1m)
,6,8-Triethyl-2-hydroxymethyl-
3
3
glycoluril (1n)
3
2
2
1
2
.11 (6Н, m, 2СН
3
); 2.85 (3Н, s, NСН
3
); 2.00 (4H, m,
6
4
,8-Diethyl-2-hydroxymethyl-
-methylglycoluril (1o)
NCH ); 4.68 (2Н, br. s, NCH
2
2
O); 5.16 and 5.28 (each 1Н,
both d, J = 8.5, 2СН); 5.91 (1H, br. s, ОН)
6
-Methoxymethyl-2,4-dimethyl-
2.67 (3H, s, NСН ); 2.78 (3H, s, NСН ); 3.18 (3H, s, ОСН );
3
3
3
glycoluril (3a')*
2
4.53 and 4.67 (each 1Н, both d, J = 11.0, NСН ); 5.18 (2H,
m, СНСН); 7.98 (1H, s, NH)
2
4
-Hydroxymethyl-
,6-dimethylglycoluril (3b)
2.67 (3H, s, NСН
4.75 (each 1Н, both d, J = 9.0, NСН
3
); 2.78 (3H, s, NСН
3
); 4.43 and
2
); 5.12 and
5
7
.22 (each 1Н, both d, J = 7.5, 2СН); 5.55 (1Н, br. s, ОН);
.49 (1H, s, NH)
4
,6-Diethyl-2-hydroxymethyl-
1.12 (6H, m, 2СН
4.65 (each 1Н, both d, J = 9.1, NСН
5
7
3
); 3.32 (4H, m, 2NCH
); 5.02 and
.21 (each 1Н, both d, J = 7. 0, СН); 5.59 (1H, br. s, ОН);
.51 (1H, s, NH)
2
); 4.40 and
glycoluril (3c)
2
2
,4,6-Triacetyl-8-methylglycoluril 2.33 (3H, s, С(О)СН
3
3
); 2.40 (3H, s, С(О)СН ); 2.47 (3Н, s,
(
4a) С(О)СН ); 2.79 (3Н, s, NСН
3
3
); 5.81 and 6.39 (each 1Н,
both d, J = 4.5, СНСН)
1.07 (3H, t, J = 6.64, СН
2
,4,6-Triacetyl-8-ethylglycoluril
3
); 2.31 (3H, s, С(О)СН
); 3.10 (1H, m,
); 5.93 and 6.37 (each 1Н,
3
);
(4b)
2.39 (3H, s, С(О)СН
NCH ); 3.40 (1H, m, NCH
both d, J = 7.4, 2СН)
,6-Diacetyl-4,8-dimethylglycoluril 2.41 (6H, s, 2СОСН ); 2.80 (6H, s, 2NCH
4c)
CH−CH)
3 3
); 2.47 (3H, s, С(О)СН
2
2
2
(
3
3
); 5.75 (2H, s,
3
72

TABLE 3 (continued)
1
2
2
,6-Diacetyl-4,8-diethylglycoluril
1.07 (6H, t, J = 6.6, 2СН
m, NCH
1.98 (3H, s, СОСН
NСН ); 4.56–5.12 (6H, m, 3NСН
both d, J = 7.5, СНСН)
.10 (3H, t, J = 7.3, ССН
s, СОСН ); 3.33 (2H, m, СН
.20 and 5.45 (each 1Н, both d, J = 11.8, 2CH)
2.03 (6H, s, 2СОСН ); 2.85 (6H, s, 2NСН ); 5.28 (2H, d,
3
3
); 2.40 (6H, s, 2COCH ); 3.22 (2H,
(4d)
2
); 3.40 (2H, m, NCH
); 2.03 (6H, s, 2СОСН
); 5.28 and 5.36 (2H,
2
); 5.56 (2H, s, 2СН)
2
8
,4,6-Triacetoxymethyl-
-methylglycoluril (5a)
3
3
); 2.75 (3H, s,
3
2
2
,4,6-Triacetoxymethyl-8-
1
3
); 2.04 (6H, s, СОСН
3
); 2.08 (3H,
);
ethylglycoluril (5b)
3
2
); 4.81 (6H, m, 3NCH
2
5
2
4
,6-Diacetoxymethyl-
,8-dimethylglycoluril (5c)
3
3
J = 11.6, NСН
J = 11.6, NСН
2
); 5.36 (2H, s, 2СН); 5.47 (2H, d,
)
2
2
4
,6-Diacetoxymethyl-
,8-diethylglycoluril (5d)
1.10 (3H, t, J = 7.3, С-СН
3.44 (each 2Н, both m, 2СН
both d, J = 11.8, 2СН ); 5.47 (2H, s, 2СН)
3
); 2.04 (6H, s, СОСН
3
); 3.22 and
2
); 5.20 and 5.45 (each 2Н,
2
_
*
1
______
Mass spectrum, m/z (I, %): 214 (5), 183 (29), 182 (100), 154 (44),
40 (33), 139 (36), 113 (39), 112 (96), 111 (28), 98 (26), 97 (36), 84 (28), 82
(
39), 69 (25), 45 (48), 43 (56), 42 (64).
X-ray Diffraction Experiment for Compound 5c (C H N O ) was carried out at temperature of
1
4
18
4
8
1
20 K on a Smart CCD 1000K three circle automatic diffractometer (MoKα irradiation, graphite
monochromator, ω-scanning to 2θmax ≤ 56°). The crystals are monoclinic at 120 K: a = 18.238(3), b = 9.397(1), c
3
3
-1
=
=
8.387(1) Å; β = 96.810(5)°; V = 1427.3(3) Å ; dcalc = 1.723 g/cm ; M = 242.20; F(000) =776; µ = 1.43 cm ; Z
4 (Z' = 0.5); space group C2/c. Of the overall number of 6482 reflections, 1742 independent reflections (R =
int
0
.0567) were used in subsequent calculations and refinement. The structure was solved by a direct method and
2
refined using a least squares analysis in an anisotropic, full matrix approximation for F hkl. Hydrogen atoms were
localized from difference electron density Fourier synthesis and refined using the "riding" model. The final
difference factors were 0.0485 for 1460 reflections with I > 2σ (I), wR = 0.1217 and GOF = 1.081 for all
2
reflections. All calculations were performed using the SHELXTL PLUS program package [53].
N-Hydroxymethylation of Glycolurils 2a-o (General Method). A. K CO on the tip of a spatula and
2
3
methanol (5 ml) were added to a solution containing the calculated amount of paraformaldehyde (0.005 mol for
each NH group) heating until complete solution of the paraformaldehyde. The stoichiometric amount of 2-alkyl-
(
2a-e), 2,4- (2i), 2,6- (2f-h), 2,8-dialkyl- (2j,k) or 2,4,6-trialkylglycolurils 2l-o and water (1 ml) (pH 8-9) was
added and the product was refluxed for 1 h, cooled, evaporated in vacuo, and the residue was triturated with
ether or acetone, filtered, and crystallized from methanol. When the mixture of precipitates formed from the
N-hydroxymethylation of the glycolurils 2i,j,k was crystallized from methanol 3a-c initially precipitated and
then 1i,j,k. Recrystallization of 3a from methanol gave 3a' (Tables 2 and 3).
The course of the reaction of 2b was monitored every 15 min using TLC on Silufol plates in the system
CHCl –MeOH (9:1); R 0.42 for the starting glycoluril 2b and 0.85 for compound 1b. At the end of 1 h at both
3
f
pH 8-9 and also at pH 10-12 the reaction mixture contained virtually no starting glycoluril 2b while at pH 10-12
traces of contaminant products appeared. At the end of 2 h the picture had not changed but the reaction mixture
showed contaminants with R 0.36-0.25 in the experiment at pH 8-9 and at 0.32-0.15 at pH 10-12 and this can be
f
explained by partial oligomerization of the products 1b.
B. Potassium carbonate was added in small portions to an aqueous solution (37%, d = 1.083) of formalin
(
0.005 mol) to pH 8-9 followed by the corresponding compound 2l-o (0.005 mol). The reaction mixture was
heated to 60°C for 1 h. Solvent was distilled off on a rotary evaporator to half volume and the product was
3
73

3
extracted with CHCl (5 × 5 ml). Solvent was distilled off and the product was precipitated from the oily residue
by ether. The precipitated 1l-o was filtered off and recrystallized from methanol.
In the case of the reaction of glycoluril 2l with formalin the course of the reaction was monitored by
TLC on Silufol plates using the system CHCl –MeOH (10:1); R 0.58 for the starting glycoluril 2l and 0.75 for
3
f
compound 1l. At the end of 1 h the reaction mixture contained virtually no remaining glycoluril and after 2 h the
picture was unchanged. At the end of 3 h hydrolysis of the hydroxymethylation product 1l to the starting
glycoluril 2l had begun.
N-Acetylation of 2-Alkyl- (2b,c) and 2,6-Dialkylglycolurils (2f,g) (General Method). The 2-alkyl,
2
,4-, 2,6-, or 2,8-dialkylglycoluril (0.005 mol), anhydrous sodium acetate (a 3-fold excess for each amino
group), and acetic anhydride (10 ml) were placed in a round bottomed flask. The suspension was stirred at
00-110°C for 1.5 h, cooled, the solvent distilled off, and the residue was extracted with chloroform (2 × 15 ml).
1
The chloroform extracts were evaporated to give the N-acetylglycolurils 4a-d which were recrystallized from
methanol (Tables 2 and 3).
O-Acetylation
di(hydroxymethyl)glycolurils (1f,g) (General Method). Acetic anhydride (5 ml) and the hydroxy derivative
0.005 mol) were added to dry pyridine (5 ml) and the product was stirred to complete solution at 20°C and held
of
2-Alkyl-4,6,8-tri(hydroxymethyl)-
(1b,c)
and
2,6-Dialkyl-4,8-
(
at this temperature for 1 day. The solvent was distilled off and the residue was triturated with ether of give the
precipitated 5a (5b-d) which was filtered off and recrystallized from methanol (Tables 2 and 3).
This work was carried out with the support of the Chemistry Division program OKh-10 of the Russian
Academy of Sciences.
REFERENCES
1
2
3
.
.
.
M. D. Mashkovskii, Drugs [in Russian], Vol. 1, Novaya Volna, Moscow (2000), p. 86.
S. S. Novikov, Izv. Akad. Nauk SSSR. Ser. Khim., 2261 (1979).
O. V. Lebedev, L. I. Khmel'nitskii, L. V. Epishina, L. I. Suvorova, I. V. Zaikonnikova, I. E. Zimakova,
S. V. Kirshin, A. M. Karpov, V. S. Chudnovskii, M. V. Povstyanoi, and V. A. Eres'ko, in Targeted
Search for Novel Neurotropic Preparations [in Russian], Zinatne, Riga (1983), p. 81.
Yu. V. Vicharev, L. V. Anikina, I. E. Chikunov, Yu. V. Shklyaev, and A. N. Kravchenko, in Abstracts
4
.
th
Book of the 7 International Seminar "Scientific Advances in Chemistry: Heterocycles, Catalysis and
Polymers as Driving Forces" [in Russian], Yekaterinburg (2004), p. 129.
5.
6.
7.
8.
9.
A. N. Kravchenko, K. Yu. Chegaev, I. E. Chikunov, P. A. Belyakov, E. Yu. Maksareva, K. A. Lyssenko,
O. V. Lebedev, and N. N. Makhova, Mendeleev Commun., 269 (2003).
I. E. Chikunov, A. N. Kravchenko, P. A. Belyakov, K. A. Lyssenko, V. V. Baranov, O. V. Lebedev, and
N. N. Makhova, Mendeleev Commun., 253 (2004).
R. G. Kostyanovsky, K. A. Lyssenko, G. K. Kadorkina, O. V. Lebedev, A. N. Kravchenko, I. I. Chervin,
and V. R. Kostyanovsky, Mendeleev Commun., 231 (1998).
R. G. Kostyanovsky, K. A. Lyssenko, A. N. Kravchenko, O. V. Lebedev, G. K. Kadorkina, and V. R.
Kostyanovsky, Mendeleev Commun., 134 (2001).
K. A. Lyssenko, D. G. Golovanov, A. N. Kravchenko, I. E. Chikunov, O. V. Lebedev, and
N. N. Makhova, Mendeleev Commun., 105 (2004).
1
3
0.
A. N. Kravchenko, A. S. Sigachev, E. Yu. Maksareva, G. A. Gazieva, N. S. Trunova, B. V. Lozhkin,
T. S. Pivina, M. M. Il'in, K. A. Lyssenko, Yu. V. Nelyubina, V. A. Davankov, O. V. Lebedev,
N. N. Makhova, and V. A. Tartakovsky, Izv. Akad. Nauk, Ser. Khim., 680 (2005).
74

1
1.
N. N. Makhova, A. N. Kravchenko, I. E. Chikunov, A. V. Shevtsov, V. Yu. Petukhova, A. S. Sigachev,
O. V. Lebedev, and G. A. Gazieva, in Plenary Lectures and Proceedings of the 7 International Seminar
th
"
Scientific Advances in Chemistry: Heterocycles, Catalysis and Polymers as Driving Forces" [in
Russian], Yekaterinburg (2004), p. 127.
1
1
2.
3.
A. S. Sigachev, B. V. Lozhkin, and A. N. Kravchenko in: Abstracts of VII Youth Science-School
Conference of Organic Chemistry [in Russian], Yekaterinburg (2004), p. 166.
M. M. Il'in, V. A. Davankov, O. V. Lebedev, A. N. Kravchenko, A. S. Sigachev, and E. Yu. Maksareva,
in Russian Symposium “Chromatography and Chromatographic Equipment” [in Russian], Moscow
(
2004), p. 243.
1
1
1
4.
5.
6.
P. J. Boileau, E. Wimmer, M. Pierrot, A. Baldy, and R. Gallo, Acta Crystallogr., C41, 1680 (1978).
H. Petersen, Synthesis, 273 (1973).
A. A. Bakibaeva (editor), Progress in the Chemistry in the Design of Novel Biologically Active
Compounds [in Russian], Tomsk (1998), p. 72.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
43.
F. B. Slesak, P. Bluestone, and H. H. Bluestone, US Pat. 3187005; Chem. Abstr., 63, 11570 (1965).
F. B. Slezak, A. Hirach, and J. Rosen, J. Org. Chem., 25, 660 (1960).
H. B. Adkins, US Pat. 2654763; Chem. Abstr., 48, 10778 (1954).
D. F. Kutepov and D. N. Khokhlov, Zh. Obshch. Khim., 31, 793 (1961).
Ch. Hasee and D. Kuchling, Liebigs Ann. Chem., 95 (1975).
G. Laurene and O. Petersen, US Pat. 2779764; Chem. Abstr., 58, 7947 (1963).
J. W. Williams, US Pat. 2649389; Chem. Abstr., 48, 8267 (1954).
L. Gandon and P. H. Williame, Fr. Patent 1345699; Chem. Abstr., 60, 14513 (1964).
A. J. Stokes, US Pat. 2777856; Chem. Abstr., 52, 9705 (1958).
I. Rosen and F. Slezak, US Pat. 3019075; Chem. Abstr., 57, 3461 (1962).
K. Yagimoto, Y. Zhimizu, and M. Mitomi, Jpn. Patent 7495992; Chem. Abstr., 82, 156298 (1975).
F. B. Slezak, I. Rosen, and C. A. Neros, Fr. Patent 1360998; Chem. Abstr., 61, 13333 (1964).
P. Palitzsch, East Ger. Patent 123467; Chem. Abstr., 87, 135329 (1977).
H. Ulrid, East Ger. Patent 99788; Chem. Abstr., 80, 26782 (1974).
T. Inoi, K. Shoji, and T. Takahashi, Jpn. Patent 7040291; Chem. Abstr., 74, 112053 (1971).
K. Nonaka and K. Shoji, Jpn. Patent 6928871; Chem. Abstr., 72, 101818 (1970).
A. Franchimont and E. A. Rlobbie, Rec. Trav. Chim., 7, 236 (1887).
J. Boileau, J. M. Emeury, and J. P. Kehren, Ger. Patent 2462330; Chem. Abstr., 86, 75499 (1976).
J. Boileau, J. M. Emeury, and J. P. Kehren, Ger. Patent 2435651; Chem. Abstr., 83, 30483 (1975).
H. Petersen and H. Bille, Ger. Patent 2027203; Chem. Abstr., 76, 114770 (1979).
J. Boileau, J. M. Emeury, and J. P. Kehren, US Pat. 4487938; Chem. Abstr., 73, 46604 (1984).
W. R. Hausch, US Pat. 4435456; Chem. Abstr., 100, 193372 (1984).
R. Toepfl, H. Abel, and A. Maeder, Ger. Patent 1954358; Chem. Abstr., 73, 46604 (1970).
H. Rongzu, L. Yanjun, F. Yingao, and W. Jinsheng, J. Therm. Analysis, 46, 1283 (1996).
H. Rongzu, D. Yang. H. Zhao, Sh. Gao, and Q. Shi, Thermochimica Acta,, 389, 65 (2002).
Y. Fang and G. Wu, Hanneng Cailiao, 5, 9 (1997); Chem. Abstr., 126, 295252 (1997).
G. A. Gazieva, A. N. Kravchenko, K. Y. Chegaev, Yu. A. Strelenko, and O. V. Lebedev, Mendeleev
Commun., 28 (2000).
4
4
4
4
4.
5.
6.
7.
H. Gattner and K. Wagner, Eur. Patent 60471; Chem. Abstr., 98, 1663 (1983).
H. G. Goodman, US Pat. 2697714; Chem. Abstr., 49, 73683 (1955).
D. Kuhling, Liebigs Ann. Chem., 263 (1973).
S. Sun, L. Edwards, and P. Harrison, J. Chem. Soc., Perkin Trans 1, 437 (1998).
3
75

4
4
5
5
5
5
8.
9.
0.
1.
2.
3.
C. F. Matta, C. C. Cow, S. Sun, J. F. Dritten, and P. H. M. Yarrison, J. Mol. Struct., 523, 241 (2000).
D. Kuehling, Ger. Patent 19966502; Chem. Abstr., 78, 97655 (1973).
J. Boileau, E. Wimmer, M. Carail, and R. Gallo, Bull. Soc. Chim. Fr., 465 (1986).
Henkel and Cie GmbH, Ger. Patent 1909876; Chem. Abstr., 70, 33002 (1969).
A. N. Kravchenko, O. V. Lebedev, and E. Yu. Maksareva, Mendeleev Commun., 27 (2000).
G. M. Sheldrick, SHELXTL-97. Version 5.10, Bruker AXS Inc., Madison, WI-53719, USA.
3
76