Benzamidomethylation with (benzamidomethyl)triethylammonium chloride. 2. A simple method for benzamidomethylation of thiols, amines and carboxylic acids

Article abstract of DOI:10.3390/50700927

Thiols and amines were benzamidomethylated in water solution at room temperature with (benzamidomethyl)triethylammonium chloride (1) in the presence of a small quantity of triethylamine (pH>9). Benzamidomethyl thioethers (3a-d) and (benzamidomethyl)amines or di(benzamidomethyl)amines (5) were obtained in high yields (>90%) as well as S(CH₂NHBz)₂ in a reaction of 1 with Na₂S. Benzamidomethyl esters RCOOCH ₂NHBz were obtained (60-75%) in reactions of carboxylic acids with 1 in chloroform or dioxane.

Full text of DOI:10.3390/50700927

Molecules 2000, 5, 927-936
molecules
ISSN 1420-3049
© 2000 by MDPI
http://www.mdpi.org
Benzamidomethylation with
(Benzamidomethyl)triethylammonium Chloride. 2. A Simple
Method for Benzamidomethylation of Thiols, Amines and
Carboxylic Acids*
Emil Popovski1**, Ljiljana Klisarova2 and Drazen Vikic-Topic3
1Institute of Chemistry, Faculty of Natural Sciences & Mathematics, Sts. Cyril and Methodius
University, PO Box 162, 1000 Skopje, Macedonia
E-mail: emilp@iunona.pmf.ukim.edu.mk
2Faculty of Pharmacy, Sts. Cyril and Methodius University, 1000 Skopje, Macedonia
3Rudjer Boskovic Institute, Bijenicka 54, HR-10001, Zagreb, Croatia
*For part 1, see ref. [1]
**Author to whom correspondence should be addressed.
Received:27 March 2000;revised form:22 June 2000 /Accepted:29 June 2000 /Published:7 July 2000
Abstract: Thiols and amines were benzamidomethylated in water solution at room tem-
perature with (benzamidomethyl)triethylammonium chloride (1) in the presence of a small
quantity of triethylamine (pH>9). Benzamidomethyl thioethers (3a-d) and (benzami-
domethyl)amines or di(benzamidomethyl)amines (5) were obtained in high yields (>90%) as
well as S(CH2NHBz)2 in a reaction of 1 with Na2S. Benzamidomethyl esters
RCOOCH2NHBz were obtained (60-75%) in reactions of carboxylic acids with 1 in chloro-
form or dioxane.
Keywords: Benzamidomethylation, thiols, carboxylic acids, amines.
Introduction
In the past, a large number of benzamidomethyl compounds have been synthesized which have been
used for different purposes. In the final decade, in the case of a thiol group, benzamidomethylation was
99
used for synthesis of ligands for Tc complexes, which have been utilized as radiolabels [2-4]. Also,
benzamidomethylation was used to obtain some benzamidomethyl aryl thioethers as intermediates in
the synthesis of benzothiazines [5-7]. Among the numerous S-benzamidomethyl derivatives there are

928
Molecules 2000, 5
reports of a S-benzamidomethyl-L-cysteine, which was used in peptide synthesis [8-11] and some of
them are useful for the treatment of glaucoma [12]. Also, wool proteins can be analyzed as the corre-
sponding S-amidomethyl derivatives [13]. Amidomethyl and benzamidomethyl esters were synthesized
and evaluated as potential prodrugs of carboxylic acid agents [14-17] or amide agents [18]. The ben-
zamidomethyl esters of carboxylic acids were used as a benzamidomethylation regent for compounds
with a different nucleophilic group [19, 20]. In the case of an amine group, amidomethylation was used
for synthesis of derivatives of some uracils or thiouracils that showed antitumor activity [21, 22].
Zlotin and coworkers [23] investigated some routes for the synthesis of N-benzamidomethyl deriva-
tives of functional derivatives of α-aminoacids and peptides, etc. Our good results with the benzami-
domethylation of phenols [1] using (benzamidomethyl)triethylammonium chloride (1), prompted us to
investigate the reaction of this compound with thiols, carboxylic acids and amines.
Results and Discussion
Reactions with thiols were performed in very vigorously stirred aqueous mixtures of 1 and thiols
2(a, b, c and d), in the presence of a small quantity of triethylamine (TEA) to pH>9 (Scheme 1). The
reactions with liquid thiols (2a,c,d) in the first 5-10 minutes gave yellow oils which over the next 5-10
minutes are transformed to small white solid lumps. For best results, the lumps should be ground with
a glass rod and the reaction mixture stirred over 1 hour, although in same cases the reaction is over in
30-40 minutes. The products were collected by filtration.
O
HYR
C2H5
N C2H5
C2H5
O
C
2
Cl
C
N CH2
H
TEA
Y R
N CH2
H
3
1
For a, b, c, d and f, Y = S ( only for 2f HY = NH4S); for g, h and i, Y= O
S
R =
O
a) R = Ph
f)
h)
R =
R =
C
N
C CH CH Ph
b) R = 2-naphthyl
c) R = CH2-C6H5
O
O
R =
O
C Ph
g)
C Ph
d) R = cyclohexyl
i)
C CH2 N
H
Scheme 1.

929
Molecules 2000, 5
Table 1. NMR data of compounds 3a-i.
1H-NMR (300 MHz; DMSO-d6; δ in ppm)
Com-
pound
13C-NMR (75 MHz; δ in ppm)
CONHCH2 Aromatic
NHCH2
Other
-
t, 9.33
m, 7.86-7.21
10H
d, 4.84
2H, J 5.9
166.53 C=O; 43.91 CH2;
Ar: 135.56, 134.02, 131.84, 129.9,
129.3, 128.64, 127.54, 126.68
3a
3b
1H, J 5.9
t, 9.41
1H, J 5.9
m, 8.05-7.44
12H
d, 4.97
2H, J 6.2
-
166.37 C=O; 43.63 CH2;
Ar: 133.79, 133.39, 132.85, 131.6,
131.48, 128.39, 127.78, 127.59, 127.51,
127.3, 127.1, 126.64, 125.88
t, 9.22
1H, J 5.9
m, 7.9-7.21
10H
d, 4.42
2H, J 5.9
s, 3.9 2H,
PhCH2
166.68 C=O; 41.08 CH2; 34.66 PhCH2
Ar: 139.2, 134.36, 131.73, 129.13,
128.61, 127.56, 127.01,
3c
9.13
1H
m, 7.88-7.46
5H
d, 4.46
2H, J 6.2
2.89 1H, SCH 166.27 C=O; 42.28 CH2; 39.68 SCH;
3d
broad s(quin)
33.54, 25.62, 25.41 5× CH2;
broad s(t)
Ar: 134.31, 131.65, 128.61, 127.48
m, 1.98-1.24
10H, 5 × CH2
t, 9.2
2H, J 6.2
m, 7.89-7.46
10H
d, 4.65
4H, J 6.2
-
166.6 C=O; 41.57 CH2;
Ar: 134.05, 131.91, 128.73, 127.48
3e
3f
t, 9.28
1H, J 6.0
m, 7.89-7.46
5H
d, 5.19
2H, J 6.3
t, 3.79, 2H
NCH2C
190.18 C=S; 166.74 C=O; 46.71 CH2;
54,88 and 50.70, 2 × N-CH2-C;
25.64 and 23.81, 2 × C-CH2-C;
Ar: 133.31, 131.83, 128.48, 127.44
t, 3.59, 2H
NCH2C
quin, 2.00, 2H
CCH2C
quin, 1.91, 2H
CCH2C
3ga
3hc
m, 8.08-7.41
11Hb
d, 5.73
2H, J 7.3
-
167.57 C=O; 167.48 C=O; 65.2 CH2;
Ar: 133.51, 133.22, 132.29, 129.87,
129.39, 128.70, 128.45, 127.29
t, 9.61
1H, J 6.7
m, 7.96-7.4
11Hd
d, 5.50
2H, J 6.7
d, 6.66
1H, J 16.1
=CHCOO
167.12 C=O; 166.0 C=O; 65.18 CH2;
Ar and HC=CH: 145.06, 134.01,
133.24, 132.08, 130.63, 129.0, 128.55
127.62, 117.92
t, 9.63
1H, J 6.5
m, 7.96-7.49
10H
d, 4.44
2H, J 6.5
-
170.08 C=O; 167.40 C=O; 167.1 C=O
65.62 O-CH2; 41.44 C-CH2;
3i
Ar: 133.95, 133.39, 132.36, 131.85,
128.79, 128.7, 127.85, 127. 58
t, 9.02
1H, J 5.6
d, 4.07
2H, J 5.9
a
1H-NMR (360 MHz; CDCl3), 13C-NMR (90 MHz);
bone of the 11H is from NH;
c
1H-NMR (250 MHz), 13C-NMR (63 MHz);
done of the 11H is from PhCH= .

930
Molecules 2000, 5
Table 2. Physicochemical data of compounds 3a-i and 5a-h.
Calc/found
H
FTIR (KBr) / cm-1
Com-
pound
Yield
%
M.p.
oC
C
N
νNH
Amide I
1630.0
1638.9
1638.9
1639.3
Amide II
1531.7
1542.7
1539.7
1540.0
1531.7
1507.0
1534.8
1536.5
1533.5
1536.9
1538.5
1537.4
1507.6
1538.5
Other
64e
5.4
5.7
5.8
5.6
3306.5
3242.4
3354.1
3313.4
3311.4
3397.1
3311.8
3344.6
69.1
69.3
3a
3b
3c
3d
3e
3f
99.3
98.8
93.6
94.6
96.3
95.7
73.0
62.3
74.4
97.3
90.9
91.7
100
127-30
79-80f
67-8
73.7
74.0
5.1
4.9
4.8
4.8
70.0
69.9
5.9
5.7
5.4
5.5
67.4
67.3
7.6
7.7
5.6
5.6
179
64.0
63.7
5.4
5.7
9.3
9.2
1658.6
1644.0
119-20
95-96g
111-12
171
55.7
55.4
5.7
6.0
10.0
9.8
1673.9
1655.5
1657.8
3g
3h
3i
70.6
70.7
5.1
5.4
5.5
5.4
1723.7
CH2O-C=O
72.6
72.2
5.4
5.2
5.0
5.0
1709.1
CH2O-C=O
65.4
65.1
5.2
5.2
9.0
8.9
3372.5
3320.1
1663.5
1648.1
1745.7
CH2O-C=O
5a
5b
5c
5d
5e
5f
119-21
119-20
181-3
116-7
93-4
68.7
68.8
6.4
6.4
14.1
14.1
3350.9
1645.6
1641.4
1640.7
1662.6
1636.7
70.1
69.8
7.1
7.4
12.9
12.7
3319.5
73.5
73.4
5.9
6.1
11.7
11.5
3340.5
3298.6
74.3
74.6
6.2
6.4
12.3
12.5
3418.1
3340.4
92.9
88.2
50-70
72.4
72.0
8.7
8.9
12.1
12.3
3333.8
116-7
179
79.4
79.5
6.0
6.4
9.3
9.0
3379.3
3365.3
1645.1
1636.8
1537.0
1529.5
5g
5h
67.8
67.8
6.0
6.3
14.8
14.6
3360.4
3263.9
1642.9
1551.5
191-2
69.2
69.5
5.8
6.0
13.4
13.3
3317.7
1642.3
1541.3
elit. [25], M.p. = 67oC; lit [26], M.p. = 65-6oC; flit. [25], M.p. = 82oC; glit. [27], M.p. = 92oC
The sparingly water soluble 2-thionaphtole (2b) was also benzamidomethylated with 1, but the re-
action mixture was stirred over 3 hours. Reactions of 1 with aqueous solutions of Na2S always gave
dibenzamidomethyl sulphide (3e; R = CH2NHBz, Y = S), regardless of the mole ratio of reactants
(compound 1 : Na2S = 1:0.5; 1:1; 1:2 or 1:5). An attempt to synthesize N-(sulphonylmethyl)benzamide

931
Molecules 2000, 5
(PhCONHCH2SH) at pH = 9 (where the concentration of S2- ions is minimal and concentration of SH-
ions is maximal [24]) failed. Under these conditions the reaction did not occur. An experiment with
and aqueous solution of H2S and controlled increase of pH failed, too. The reaction started and oc-
curred rapidly only when the pH of the mixture was ~10 and higher; however only 3e was obtained.
Product 3e was also obtained in the reactions of 1 with thioacetic acid and thioacetamide. However, in
a reaction of ammonium pyrroldinedithiocarbamate (2f) with 1, performed in aqueous solution (at
room temperature), benzamidomethyl pyrroldinedithiocarbamate (3f) was obtained.
The benzamidomethylation reactions of carboxylic acids with 1 did not take place in aqueous solu-
tions. Benzamidomethyl esters 3(g,h) were obtained in the reactions of carboxylic acids 2(g,h) and 1,
performed for 20 min in boiling chloroform in the presence of a small quantity of TEA. Benzami-
domethylation of 2i (which is sparingly soluble in chloroform) under the same conditions did not give
good results. But, when the reaction was performed in a dioxane suspension of 1, benzamidomethyl
hippurate (3i) was obtained in more than a 70% yield. The temperature of the mixture had to be higher
than 40oC (at lower temperatures, the reaction does not occur or is very slow) and lower than 60oC
(otherwise, a branching reaction occurs, and N,N’-methylenedibenzamide is obtained). Under the same
conditions 3f and 3g were also obtained. 1H-NMR and 13C-NMR data of compounds 3a-i are given in
Table 1, and physicochemical data are given in Table 2.
H
N R1
4e
H N
R2
R3
4
H
N R1
R3
N
1
5e
5
Ph
Ph
Ph
Ph
H N
4f
R3
5f
N
5a) R1 = CH3; R 2 = R3 = CH2NHCOPh
5b) R1 = C3H7; R 2 = R3 = CH2NHCOPh
5c) R1 = Ph;
R = R3 = CH2NHCOPh
2
5d) R1 = Ph; R 2 = H; R 3 = CH2NHCOPh
5e) R3 = CH2NHCOPh
4a) R1 = CH3
4b) R1 = C3H7
4c) R1 = Ph
5f) R3 = CH2NHCOPh
5g) R1 = H; R 2 = R3 = CH2NHCOPh
5h) R1 = R2 = R3 = CH2NHCOPh
Scheme 2.
Benzamidomethylation of amines in the aqueous solutions occurred immediately (Scheme 2). At
room temperature 1 reacts very quickly with the primary amines (4a-c) as well as with the secondary
amine (4e). Because of that, dibenzamidomethyl derivatives of primary amines (5a-c) were obtained
regardless of whether the reaction mixture had a larger quantity of primary amine than of 1. For the
synthesis of monobenzamidomethyl derivative of aniline (5d), drops of a very dispersed water solution
of 1 had to be added to a very concentrated and vigorously stirred aqueous solution of aniline (4c).
Benzamidomethylation of sparingly water soluble diphenylamine (4f) was performed in dioxane-water
mixture as a solvent.

932
Molecules 2000, 5
Table 3. NMR data of compounds 5.
1H-NMR (300 MHz; DMSO-d6; δ in ppm)
Com-
13C-NMR (75 MHz; δ in ppm)
pound
CONHCH2
Aromatic
NHCH2N
Other
5a
5b
t, 8.78
2H, J 5.7
m, 7.9-7.46
10H
d, 4.29
4H, J 6.0
s, 2.31
3H, CH3
167.12 C=O; 58.59 CH2; 37.03 CH3;
Ar: 134.25, 131.48, 128.44, 127.25
t, 8.74
2H, J 5.4
m, 7.88-7.45
10H
d, 4.36
4H, J 5.8
t, 2.54, 2H
J 7.2, NCH2C
167.1 C=O; 57.0 NCH2N;
49.94, 20.36, 11.90 propyl
Ar: 134.27, 131.49, 128.45, 127.22
sex, 1.56, 2H
J 7.2, CCH2C
t, 0.95, 3H
J 7.2, CH3
-
5c
5d
5e
t, 9.12
2H, J 4.9
m, 7.91-6.71
15H
d, 5.16
4H, J 5.2
166.83 C=O; 56.50 CH2;
Ar: 145.35, 133.99, 131.64, 129.11,
128.49, 127.31, 117.69, 112.89
t, 8.98
1H, J 4.4
m, 7.90-6.57
10H
t, 4.73
2H, J 6.0
t, 6.31, 1H
J 6.6, NHPh
166.64 C=O; 48.71 CH2;
Ar: 147.20, 134.34, 131.41, 128.97,
128.37, 127.39, 116.61, 112.65
t, 8.73
2H, J 5.7
m, 7.90-7.44
5H
d, 4.24
2H, J 5.9
t, 2.73, 4H
2 × NCH2C
166.98 C=O; 61.98 NCH2N; 52.53
NCH2C; 28.47, 26.72 CCH2C;
Ar: 134.72, 131.16, 128.26, 127.38
m, 1.57-1.53, 8H
4 × CCH2C
5f
t, 9.01
1H, J 4.9
m, 7.85-6.96
15H
d, 5.27
2H, J 5.4
-
166.87 C=O; 57.05 CH2;
Ar: 146.83, 134.25, 131.43, 129.26,
128.28, 127.54, 121.81, 121.24
5g
5h
t, 8.80
2H, J 5.4
m, 7.84-7.41
10H
d, 4.27
4H, J 5.7
broad s, 2.93, 1H 166.61 C=O; 53.10 CH2;
Ar: 134.34, 131.31, 128.31, 127.17
t, 8.82
m, 7.90-7.46
15H
d, 4.45
-
167.14 C=O; 55.56 CH2;
Ar: 134.09, 131.61, 128.50, 127.23
3H, J 5.8
6H, J 6.0
The reaction of 1 with an aqueous solution of NH3 gave a mixture of di(benzamidomethyl)amine
(5g) and tri(benzamidomethyl)amine (5h). The major component (5g; 50-70%) was obtained when
small quantities of 1 in powder form were added to a vigorously stirred large volume of 37% aqueous
solution of NH3. Compound 5h was obtained without admixture of 5g when aqueous NH3 was dropped
into a concentrated aqueous solution of 1. Also, 5g formed when a large quantity of TEA was added to
the aqueous reaction mixture of 1 or an aqueous mixture of 1 and any other nucleophilic substrate
(phenols, thiols, etc). A possible explanation for this phenomena is that pure TEA (98%) contains some
1
quantity of NH3. The physicochemical data of compounds 5a-h are given in Table 2, and their H-
NMR and 13C-NMR data are given in Table 3.

933
Molecules 2000, 5
Conclusions
In conclusion, compound 1 is an excellent benzamidomethylation agent for thiols and amines and a
good agent for carboxylic acids. Reactions of 1 with thiols and amines occurred faster and with higher
yields (>90%) than the reactions of 1 with phenols, at room temperature. The products are easily iso-
lated from reaction mixture by simple filtration.
Experimental
Compound 1 was synthesed as described previously [1].
Benzamidomethyl phenyl sulphide (3a)
A solution of 1 (2.8611 g, 10.59 mmol) in water (40 cm3) was added to the water (40 cm3) mixture
of 2a (0.538 g, 5.7 mmol) and TEA (0.3-0.5 cm3). The mixture was stirred for 1h at room temperature.
White lumps formed, which were ground with a glass rod. Colorless crystals were collected by filtra-
tion. Purification was performed by dissolving the product in cold EtOH (the smallest quantity possi-
ble) and precipitating with drops of cold water.
Dibenzamidomethyl sulphide (3e)
A solution of Na2S · 7-9H2O (3 g) in water (20 mL) was mixed with an aqueous (20 mL) solution of
1 (3.981 g, 14.7 mmol). The mixture was stirred for 30 min at room temperature and then was filtered.
Colorless crystals (from acetone).
3b, 3c, 3d and 3f were synthesized in a similar manner as 3a, and only the differences are noted for
each product.
Benzamidomethyl 2-naphthyl sulphide (3b)
Stirring time 3 h; colorless crystals; recrystallization from acetone.
Benzamidomethyl benzyl sulphide (3c)
Colorless crystals; Purification was performed by dissolving the product in cold acetone (smallest
quantity possible) and precipitating with drops of cold water.
Benzamidomethyl cyclohexyl sulphide (3d)
Colorless crystals; purification as for 3a.
Benzamidomethyl pyrroldinedithiocarbamate (3f)
Gray-white crystals; The purification was performed by dissolving the product in dioxane and pre-
cipitating with drops of cold water.

934
Molecules 2000, 5
Benzamidomethyl benzoate (3g)
Mixture of 1 (2.5633 g, 9.46 mmol), 2g (0.9758 g, 7.99 mmol) and TEA (0.2-0.4 cm3) in CHCl3 (40
cm3) was refluxed for 20-30 min. The solvent was removed under reduced pressure and theresidue was
dissolved in dioxane. After filtration, water was added to the dioxane solution until a white precipitate
appeared. Colorless crystals were filtered and purified by repeating the last procedure. Compound 3g
was also synthesized as described for 3i.
Benzamidomethyl cinnamate (3h)
Colorless crystals were obtained and purified as for 3g.
Benzamidomethyl hippurate (3i)
To a suspension of 1 (2.122 g, 7.83 mmol) in dioxane (40 mL) was added hippuric acid (2i) (1.020
g, 5.69 mmol) and TEA (0.2-0.4 cm3). The mixture was stirred and heated at 50oC for 24 h. After
cooling, water was added to the mixture until a white precipitate appeared. Colorless crystals were fil-
tered and purified as for 3g.
Di(benzamidomethyl)methylamine (5a)
To a solution of 1 (3.256 g, 12.02 mmol) in water (20 cm3) was added an aqueous (10 cm3) solution
of 4a (~ 0.16 g, 5 mmol) and TEA (0.4 cm3). The mixture was stirred for 30 min at room temperature.
Colorless crystals were collected by filtration. Purification as for 3a.
(Benzamidomethyl)phenylamine (5d)
A solution of 1 (1.328 g, 4.9 mmol) in water (50 mL) was slowly dropped into a vigorously stirred
aqueous (20 mL) solution of 4c (1.522 g, 16.3 mmol). The mixture was stirred for 30 min at room tem-
perature and then the colorless crystals were filtered. Recrystallized from toluene.
(Benzamidomethyl)diphenylamine (5f)
An aqueous (10 cm3) solution of 1 (2.03g, 7.5 mmol) was added to a dioxane (30 cm3) solution of
4f (0.956, 6.4 mmol). Water was added dropwise to the mixture until it became slightly cloudy. The
reaction was stirred for 4 h, then water was added until the product appeared as a white precipitate. Re-
crystallized from hexane : toluene (5 : 1).
Di(benzamidomethyl)amine (5g)
Powdered 1 (2.1769 g, 8.04 mmol) was added with spatula in small portions to the vigorously
stirred 37% aqueous solution of NH3 (60 cm3). After 20 min, the precipitate formed was filtered off
and dissolved in a small quantity of acetone. The solution was filtered to remove the admixture of 5h.
Colorless crystals of 5g were obtained by precipitation with water.

935
Molecules 2000, 5
5b, 5c, 5e and 5h were synthesized in a similar manner as 5a, and only the differences are presented
for each product.
Di(benzamidomethyl)propylamine (5b)
Colorless crystals. Purification as for 3c.
Di(benzamidomethyl)phenylamine (5c)
Colorless crystals. Recrystallization from toluene.
N-(Benzamidomethyl)azacycloheptane (5e)
In this synthesis the mole ratio of 1 and 4e was 1.2 : 1. Colorless crystals (from hexane).
Tri(benzamidomethyl)amine (5h)
In this synthesis the mole ratio of 1 and NH3 was 4 : 1. Colorless crystals (from acetone).
References and Notes
1. Part 1: Popovski, E.; Klisarova, Lj.; Vikic-Topic, D. Synth. Commun. 1999, 29(19), 3451-3458.
2. Okarvi, S. M.;Adriaens, P.;Verbruggen,A. J. Labelled Comp. Radiopharm.1997, 39(10), 853-874.
3. Bromans, G.; Cleynhens, B.; Adriaens, P.; Vanbilloen, H.; De Roo, M.; Verbruggen, A. Nucl.
Med. Biol. 1995, 22(3), 339-349.
4. Bryson, N.; Lister-James, J.; Jones, A. G.; Davis, W. M.; Davison, A. Inorg. Chem. 1990, 29,
2948-2951.
5. Szabo, J.; Bani-Akoto, E.; Dombi, G.; Bernáth L. Fodor, G.; Sohár, P. J. Heterocyclic Chem.
1992, 29, 1513-1517.
6. Szabo, J.; Bani-Akoto, E.; Dombi, G.; Günther, G.; Bernáth, G.; Fodor, L. J. Heterocyclic Chem.
1992, 29, 1321-1324.
7. Sohár, P.; Kövesdi, I.; Szabo, J.; Katócs, Á.; Fodor, L.; Szücs, E.; Bernáth, G.; Tamás, J. Magn.
Res. Chem. 1989, 27, 760-766.
8. Akaji, K.; Tataumi, T.; Yoshida, M.; Kimura, T.; Fujiwara, Y.; Kiso, Y. J. Chem. Soc., Chem.
Commun. 1991, 267-268.
9. Fujii, N.; Otaka, A.; Watanabe, T.; Okamachi, A.; Tamamura, H.; Yajima, H.; Inagaki, Y.; No-
mizu, M.; Asano, K. J. Chem. Soc., Chem. Commun. 1989, 283-284.
10. Chakravarty, P. K.; Olsen, R. K. J. Org. Chem. 1978, 43(6), 1270-1271.
11. Papsuevich, O. S.; Ars, G.; Miksta, O. Zh. Obshch. Khim. 1975, 6, 1384-1388.
12. Gauri, K. K.; Aasmul-Olsen, S.; Widmer, F. PCT Int. Appl. WO 92 16, 550 (CA 118: 148065a).
13. Herbert, R. B.; Woods, L. J. Electrophoresis 1994, 15(7), 972-976 (CA 121: 152593a).
14. Iley, J.; Moreira, R.; Calherios, T.; Mendes, E. Pharm. Res. 1997, 14(11), 1634-1639.
15. Moreira, R.; Calherios, T.; Cabrita, J.; Mendes, E.; Pimentel, M.; Iley, J. Pharm. Res. 1996, 13(1),
70-75 (CA 124: 241882y).

936
Molecules 2000, 5
16. Moreira, R.; Mendes, E.; Calherios, T.; Bacelo, M. J.; Iley, J. Tetrahedron Lett. 1994, 35(38),
7107-7110 (CA 121: 280586n).
17. Bundgaard, H.; Nielsen, N. M.; Buur, A. Int. J. Pharm. 1988, 44, 151-158.
18. Iley, J.; Moreira, R.; Rosa, E. J. Chem. Soc. Perkin Trans. 2 1991, 563-570.
19. Hashimoto, M.; Niwata, S.; Iwata, S.; Fukami, H. Chem. Express 1992, 7(1), 65-68 (CA 116:
128317q).
20. Ivanov, E. B.; Chichkanova, V. T.; Krokhina; S. S.; Ageeva, B. A. Izv. Akad. Nauk SSSR, Ser.
Khim. 1982, 7, 1620-1623.
21. Prikazchikova, P. L.; Khutova, M. B.; Klyuchko, V. S.; Ryhchenko, I. L.; Zhukova, S. O.; Yur-
chenko, Ya. N.; Pilipenko; V. T.; Glazkova, Yu. T. Fiziol. Akt. Veshchestva 1991, 23, 37-39 (CA
118: 224974p).
22. Khutova, M. B.; Klyuchko, V. S.; Prikazchikova, P. L.; Dracha, S. B. Dokl. Akd. Nauk Ukr. SSR,
Ser. B: Geol., Khim. Biol. Nauki 1989, 12, 42-45 (CA 114: 6423j).
23. Zlotin, G. S.; Sharova, V. I.; Luk'yanov, A. O. Izv. Akad. Nauk, Ser. Khim. 1996, 6, 1480-1488.
24. Savc, J.; Savic, M. Osnovi Analiticke Hemije; Svetlost: Sarajevo, 1989: p 118.
25. Hellmann, H.; Haas, G. Chem. Ber. 1957, 90, 444-446.
26. Branchaud, B. P.; Tsai, P. J. Org. Chem. 1987, 52, 5475-5478.
27. Bohme, H.; Tippmann, E. Arch. Pharm. (Weinheim) 1976, 309(9), 756-761.
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