Full text of DOI:10.1002/jhet.5570380120

Jan-Feb 2001
Oxidation of 7,8-Diaminotheophylline with Lead Tetraacetate and
Reaction of the Oxidation Product, 6-Cyanoimino-5-diazo-1,3-
dimethylpyrimidine-2,4-dione with Alcohols or Amines
141
Taisei Ueda*, Naoyoshi Yatsuzuka, Shin-ichi Nagai, Kumiko Okada, Emi Takeichi,
Hiromi Segi, and Jinsaku Sakakibara
Faculty of Pharmaceutical Sciences, Nagoya City University, Tanabe-dori, Mizuho-ku, Nagoya 467-0027, Japan
Received January 18, 2000
Oxidation of 7,8-diaminotheophylline (1) with lead tetraacetate in refluxing toluene gave a mixture of
3-amino-5,7-dimethylpyrimido[4,5-e][1,2,4]triazine-6,8-dione (2) and 6-cyanoimino-5-diazo-1,3-
dimethylpyrimidine-2,4-dione (4). The latter was transformed to 2 by the reaction with 1-propanethiol in
quantitative yield. The reaction of 4 with methanol, ethanol and 1-propanol in the presence of rhodium (II)
acetate gave 5-alkoxy-6-(2-alkyl-3-isoureido)-1,3-dimethylpyrimidine-2,4-diones (7a-c). A similar reac-
tion of 4 with alkylamines such as n-propylamine, n-butylamine, isobutylamine and n-hexylamine gave a
mixture of 7-alkyl-8-aminotheophyllines (8a-d) and (5-alkylamino-1,3-dimethyl-2,4-dioxopyrimidin-6-
yl)cyanamides (9a-d).
J. Heterocyclic Chem., 38, 141 (2001).
Theophylline is an important drug with diuretic, cardiac
N,N-dimethylformamide did not give the expected
products, but rather provided 2 [6] in 17% yield. The
structural confirmation of 2 was carried out by proton
nuclear magnetic resonance and mass spectra. Moreover,
acetylation of 2 with acetic anhydride in pyridine gave
3-acetylamino-5,7-dimethylpyrimido[4,5-e][1,2,4]-
triazine-6,8-dione (3a) and 3-diacetylamino-5,7-
dimethylpyrimido[4,5-e][1,2,4]triazine-6,8-dione (3b).
Because 2 seemed to be formed via nitrene [7] which
was generated during the reaction of 1 with sodium
hydride and/or air in N,N-dimethylformamide, we exam-
ined the nitrene reaction of 1 with lead tetraacetate [8] as
the oxidizing agent (Table 1). The yield of 2 is increased
stimulant and smooth muscle relaxant activities [1]. In the
course of medicinal and chemical studies of theophylline
derivatives we previously synthesized 7,8-diaminotheo-
phylline (1) [2] and examined its reactivity [3]. During the
examination of the alkylation of 1 with alkyl halide in the
presence of sodium hydride, the nitrene reaction product
3-amino-5,7-dimethylpyrimido[4,5-e][1,2,4]triazine-6,8-
dione (2) was found to be formed. This paper reports on
the oxidation of 1 and the reaction of the oxidation prod-
uct, 6-cyanoimino-5-diazo-1,3-dimethylpyrimidine-2,4-
dione (4) with alcohols or amines.
Our finding that tricyclic fused purines [4] were formed
by the reaction of 8-aminotheophylline [5] with
α ,ω-dibromoalkanes induced us to examine facile
synthesis of fused tricycles from 1. However, to our
surprise the reaction of 1 with alkyl halides such as
1,2-dibromoethane, ethyl bromoacetate, and ethyl bromo-
propionate in the presence of sodium hydride in
Table 1
Yields of 2 and 4 by the Oxidation of 1 with Lead Tetraacetate.[a]
Solvent Pb(OAc) (eq)[b] Temperature
2(%) 4(%)
1(%)
4
benzene
benzene
benzene
benzene
benzene
benzene
toluene
1
1
1
1.5
1.5
1.5
1.5
2.0
2.0
rt
6
46
41
30
69
64
45
27
92
85
48
46
24
20
11
0
0
0
0
40°C
reflux
rt
40°C
reflux
reflux
rt
12
36
10
24
48
65
4
benzene
benzene
40°C
12
[a] All reactions were carried out with 1 (0.5 mmol) in 20 ml of benzene
or toluene for 20 hours.
[b] Molar equivalent to compound 1.
as the reaction temperature is increased, and the best yield
was obtained by refluxing toluene with 1.5 molar equiva-
lent of lead tetraacetate to give 2 (65%) along with 4 in
27% yield. By contrast, the reaction at room temperature
gave better yield of 4. When two molar equivalents of
lead tetraacetate were used in benzene at room temper-
ature, the yield of 4 was remarkably increased to 92% and
that of 2 was decreased to 4%. In this way either 2 or 4

Vol. 38
T. Ueda, N. Yatsuzuka, S. Nagai, K. Okada, E. Takeichi, H. Segi, and J. Sakakibara
142
can be synthesized at our option. The infrared spectra of 4
indicated the presence of a cyano group. For the confir-
mation of the unique structure of 4, hydrolysis with
concentrated hydrochloric acid in ethanol (1:5) was
carried out by refluxing for 6 hours to give 6-imino-5-
diazo-1,3-dimethylpyrimidine-2,4-dione (5) in 60% yield
and 5-diazo-1,3-dimethylbarbituric acid (6) [9] in 33%
yield. The reaction of 4 with refluxing concentrated
hydrochloric acid gave 5 as the sole product in 95% yield.
These experiments proved the presence of the cyanoimino
group in 4.
obtained previously by us [12] during the reaction of
8-aminotheophylline with propyl bromide or butyl
bromide.
Consequently we could synthesize 2 or 4 by the nitrene
reaction of 7,8-diaminotheophylline at our option. Since 4
is easily transformed to 2 in excellent yield, our method
makes a facile synthesis of 2 from 1. The carbenoid reac-
tion of 4 with alcohols or amines gave new pyrimidinones
(7a-c, 9a-d).
EXPERIMENTAL
All melting points were determined with a Yanagimoto micro
melting point apparatus and are uncorrected. The infrared spectra
were measured with a JASCO IR-810 spectraphotometer. Mass
spectra were measured with a JEOL JMS-DX 300 mass spectro-
meter. Proton nuclear magnetic resonance spectra were recorded
with a JEOL JNM-LA-400 and JNM-EX-270 spectrometer using
tetramethylsilane as internal standard. Abbreviations are as
follows: s, singlet; d, doublet; q, quartet; br, broad; m, multiplet.
Similar ring expansion of N-aminoimidazoles to
triazines by the nitrene reaction has been reported [10].
However, the formation of the cyanoiminouracil type
compounds like that of 4 is unknown. To further examine
the unique structure of 4 the rhodium carbenoid OH inser-
tion reaction [11] was employed. The reaction of the diazo
compound 4 in alcohol in the presence of rhodium (II)
acetate gave 5-alkoxy-6-(2-alkyl-3-isoureido)-1,3-
dimethylpyrimidine-2,4-diones (7a-c). Among the reac-
tions of 4 with methanol, ethanol and propanol, the reac-
tion with propanol gave the better yield (55%) of the
insertion product 7c. However, the carbenoid reaction
with butanol or 2-bromoethanol did not proceed at all.
Since the carbenoid reaction with propanol gave the better
yield of 7c, the reaction of 4 with 1-propanethiol was
tried. But, to our surprise this reaction gave 2 in 97%
yield, and no carbenoid reaction was observed. Thus the
formation of 2 from 4 appears to arise from the addition
of propanethiol to a cyanoimino group.
3-Amino-5,7-dimethylpyrimido[4,5-e][1,2,4]triazine-6,8-dione (2).
To a solution of 7,8-diaminotheophylline (1) (2.1 g, 10 mmol)
in N,N-dimethyl formamide (130 ml) was added sodium hydride
(60% dispersion in mineral oil 840 mg) at 100° and the reaction
mixture was stirred for 8 hours. After being cooled to room
temperature, the reaction mixture was concentrated under
reduced pressure, diluted with water (10 ml) and neutralized
with 5% aqueous hydrochloric acid. The mixture was extracted
with ethyl acetate (5x30 ml). The organic layer was washed with
water (30 ml), dried over anhydrous sodium sulfate and concen-
trated under reduced pressure. The residue was chromato-
graphed on silica gel with a mixture of chloroform:methanol
(10:1) as eluent to give compound 2 (0.36 g, 17%), fine crystals,
1
mp>300° (from methanol); H nmr (deuteriochloroform): δ 3.27
We next examined the carbenoid reaction with alkyl-
amines. The reaction of 4 with alkylamines, such as
n-propylamine, n-butylamine, isobutylamine, and
n-hexylamine in the presence of rhodium (II) acetate gave
7-alkyl-8-aminotheophyllines (8a-d) and (5-alkyl-1,3-
dimethyl-2,4-dioxopyrimidin-6-yl)cyanamides (9a-d).
These reactions even proceeded in the absence of rhodium
(II) acetate, though the yields of 8a-d and 9a-d were poor.
7-Propyl-8-aminotheophylline (8a) and 7-butyl-8-
aminotheophylline (8b) were identical with those
(3H, s, Me), 3.38 (3H, s, Me), 8.30 (2H, br, NH ); ir (potassium
2
-1
-1
bromide): ν max 3350 and 3330 cm (NH ), 1690 cm (C=O);
2
+
ms: m/z 208 (M ).
Anal. Calcd. for C H N O : C, 40.37; H, 3.88; N, 40.38.
7
8 6 2
Found: C, 40.29; H, 4.08; N, 40.15.
3-Acetylamino-5,7-dimethylpyrimido[4,5-e][1,2,4]triazine-6,8-
dione (3a) and 3-Diacetylamino-5,7-dimethylpyrimido[4,5-e]-
[1,2,4]triazine-6,8-dione (3b).
To a solution of compound 2 (208 mg, 1 mmol) in pyridine
(3 ml) was added acetic anhydride (3 ml) at 100° and stirred for

Jan-Feb 2001
Oxidation of 7,8-Diaminotheophylline with Lead Tetraacetate
143
12 hours. The reaction mixture was concentrated under reduced
pressure and the residue was chromatographed on silica gel with
a mixture of chloroform:methanol (15:1) to give compound 3a
(138 mg 55%) and 3b (26 mg, 9%).
Compound 3a: mp 244-246° (from ethanol); H nmr
(deuteriochloroform): δ 2.28 (3H, s, C-Me), 3.31 (3H, s, N-Me),
Method b: A solution of compound 4 (618 mg, 3 mmol) in
concentrated hydrochloric acid (36 ml) was refluxed for 3 hours.
The reaction mixture was evaporated to dryness and the residue
was chromatographed on silica gel with a mixture of chloro-
form:methanol (15:1) as eluent to give compound 5 (514 mg,
95%).
1
3.45 (3H, s, N-Me), 8.31 (1H, br, NH); ir (potassium bromide):
General Procedure for the Reaction of Compound 4 with
Alcohols: Synthesis of 5-Alkoxy-6-(2-alkyl-3-isoureido)-1,3-
dimethylpyrimidine-2,4-diones (7a-c).
-1
-1
ν max 3210 cm (NH), 1740 and 1680 cm (C=O); ms: m/z
+
250 (M ).
Anal. Calcd. for C H N O : C, 43.20; H, 4.03; N, 33.59.
9
10 6 3
To a solution of compound 4 (0.49 mmol) in alcohol (30 ml)
was added rhodium(II) acetate (4.4 mg, 0.0098 mmol) at room
temperature and stirred at 65° for 15 hours. The reaction mixture
was concentrated under reduced pressure and the residue was
chromatographed on silica gel with a mixture of chloroform:-
methanol (20:1) as eluent.
Found: C, 43.16; H, 4.03; N, 33.60.
1
Compound 3b: mp 158-160°C (from ethanol); Η nmr
(deuteriochloroform): δ 2.39 (6H, s, C-Me x 2), 3.59 (3H, s,
N-Me), 3.66 (3H, s, N-Me); ir (potassium bromide): ν max 1740
-1
+
and 1680 cm (C=O); ms: m/z 292 (M ).
Reaction of 7,8-Diaminotheophylline with Lead Tetraacetate
(Synthesis of 2 and 4).
5-Methoxy-6-(2-methyl-3-isoureido)-1,3-dimethylpyrimidine-
2,4-dione (7a).
Method a: To a solution of 7,8-diaminotheophylline (105 mg,
0.5 mmol) in refluxing toluene (20 ml) was added lead tetra-
acetate (332 mg 0.75 mmol) and the solution was stirred for 20
hours. The reaction mixture was concentrated under reduced
pressure. The residue was chromatographed on silica gel with a
mixture of chloroform:methanol (50:1) as eluent to give
compound 2 (64 mg, 65%) and compound 4 (26 mg, 27%).
Compound 7a was obtained in 19% yield as colorless prisms,
mp 209-211° (from methanol); H nmr (deuteriochloroform): δ
3.37 (3H, s, N-Me), 3.38 (3H, s, N-Me), 3.66 (3H, s, O-Me),
1
3.87 (3H, s, O-Me), 4.87 (2H, br, NH ); ir (potassium bromide):
2
-1
-1
ν max 3380 and 3320 cm (NH ), 1695 cm (C=O); ms: m/z
2
+
242 (M ).
Anal. Calcd. for C H N O : C, 44.63; H, 5.83; N, 23.13.
9
14 4 4
1
Compound 4: mp 197-199°C (from ethanol); H nmr
(deuteriochloroform): δ 3.35 (3H, s, N-Me), 3.43 (3H, s, N-Me);
Found: C, 44.34; H, 5.64; N, 23.18.
5-Ethoxy-6-(2-ethyl-3-isoureido)-1,3-dimethylpyrimidine-2,4-
dione (7b).
-1
-1
ir (potassium bromide): ν max 2190 cm (CN), 2145 cm
-1
+
(C=N=N), 1720 and 1670 cm (C=O); ms:m/z 206 (M ).
Anal. Calcd. for C H N O : C, 40.78; H, 2.93; N, 40.77.
Compound 7b was obtained in 37% yield as colorless prisms,
7
6 6 2
1
mp 140-141° (from chloroform); H nmr (deuteriochloroform):
Found: C, 40.75; H, 3.05; N, 40.78.
δ 1.24 (3H, t, J = 7.1 Hz, CH CH ), 1.35 (3H, t, J = 7.1 Hz,
Method b : To a solution of 7,8-diaminotheophylline (105 mg,
0.5 mmol) in refluxing benzene (20 ml) was added lead tetra-
acetate (443 mg, 1 mmol) and the solution was stirred for 20
hours. The reaction mixture was concentrated under reduced
pressure. The residue was chromatographed on silica gel with a
mixture of chloroform:methanol (50:1) as eluent to give
compound 2 (4 mg, 4%) and compound 4 (95 mg, 92 %).
2
3
CH CH ), 3.35 (3H, s, N-Me), 3.37 (3H, s, N-Me), 3.88 (2H, q,
2
3
J = 7.1 Hz, CH CH ), 4.30 (2H, q, J = 7.1 Hz, CH CH ), 4.99
2
3
2
3
(2H, br, NH ); ir (potassium bromide): ν max 3395 and 3315
2
-1
-1
+
cm (NH ), 1690 cm (C=O); ms: m/z 270 (M ).
2
Anal. Calcd. for C H N O : C, 48.88; H, 6.71; N, 20.73.
11 18
4 4
Found: C, 48.73; H, 6.69; N, 20.78.
5-Propoxy-6-(2-propyl-3-isoureido)-1,3-dimethylpyrimidine-
2,4-dione (7c).
Hydrolysis of Compound 4: Synthesis of 6-Imino-5-diazo-1,3-
dimethylpyrimidine-2,4-dione (5) and 5-Diazo-1,3-
dimethylpyrimidine-2,4,6-trione (6).
Compound 7c was obtained in 55% yield as colorless prisms,
1
mp 110-111°(from chloroform); H nmr (deuteriochloroform): δ
Method a: To a solution of compound 4 (206 mg, 1 mmol) in
ethanol (30 ml) was added concentrated hydrochloric acid
(6 ml) and the mixture was refluxed for 6 hours. The reaction
mixture was concentrated under reduced pressure and the
residue was chromatographed on silica gel with a mixture of
chloroform:methanol (15:1) as eluent to give 5 (109 mg, 65%)
and 6 (64 mg, 35%).
0.92 (3H, t, J = 7.3 Hz, CH CH CH ), 1.00 (3H, t, J = 7.3 Hz,
2
2
3
CH CH CH ), 1.59-1.68 (2H, m, CH CH CH ), 1.69 (2H, m,
2
2
3
2
2
3
CH CH CH ), 3.33 (3H, s, N-Me), 3.36 (3H, s, N-Me), 3.75
2
2
3
(2H, t, J = 6.6 Hz, CH CH CH ), 4.19 (2H, t, J = 6.6 Hz,
2
2
3
CH CH CH ), 5.10 (2H, br, NH ); ir (potassium bromide): ν
2
2
3
2
-1
-1
max 3400 and 3350 cm (NH ), 1700 cm (C=O); ms: m/z 298
2
+
(M ).
Compound 5; colorless crystalline powder, mp 259-261 °C
Anal. Calcd. for C
H N O : C, 52.34; H, 7.43; N, 18.78.
13 22 4 4
1
(from methanol); H nmr (deuteriochloroform): δ 3.21 (3H, s,
Found: C, 52.58; H, 7.40; N, 18.78.
N-Me), 3.44 (3H, s, N-Me), 8.26 (1H, br, NH); ir (potassium
-1
-1
Reaction of Compound 4 with 1-Propanethiol.
bromide): ν max 3450 cm (NH), 1720 cm (C=O); ms: m/z
181 (M ).
+
To a solution of compound 4 (51.5 mg, 0.25 mmol) in
chloroform (5 ml) was added 1-propanethiol (380 mg, 5
mmol) at room temperature and the mixture was refluxed for
2 hours. The reaction mixture was evaporated under reduced
pressure, and the residue was chromatographed on silica gel
with chloroform:methanol (15:1) as eluent to give compound
2 (46 mg, 92%).
Anal. Calcd. for C H N O : C, 39.78; H, 3.89; N, 38.66.
6
7 5 2
Found: C, 40.16; H, 4.22; N, 38.30.
Compound 6; colorless prisms, mp 162-163 °C (from
1
methanol); H nmr (deuteriochloroform): δ 3.35 (s, 6H, N-Me
-1
x 2); ir (potassium bromide): ν max 2150 cm (C=N=N), 1710
-1
+
and 1660 cm (C=O); ms: m/z 182 (M ).

Vol. 38
T. Ueda, N. Yatsuzuka, S. Nagai, K. Okada, E. Takeichi, H. Segi, and J. Sakakibara
144
General Procedure for the Reaction of 4 with Alkylamines:
Synthesis of 7-Alkyl-8-aminotheophyllines (8a-d) and
(5-Alkylamino-1,3-dimethyl-2,4-dioxopyrimidin-6-yl)carbodi-
imides (9a-d).
chloroform): δ 0.98 (3H, t, J = 7.3Hz, -CH CH CH ), 1.59-1.68
2 2 3
(2H, m, -CH CH CH ), 3.32 (3H, t, J = 7.1 Hz, -CH CH CH ),
2
2
3
2
2
3
3.37 (3H, s, N-Me), 3.52 (3H, s, N-Me), 5.71 (1H, br, NH),
-1
10.88 (1H, br, NH); ir (potassium bromide) ν max 3325 cm
-1
-1
+
(NH), 3150 cm (NH), 1700 cm (C=O); ms: m/z 237 (M ).
Anal. Calcd. for C N O : C, 50.61; H, 6.38; N, 29.53.
To a solution of alkylamine (49 mmol) in chloroform (135
ml), rhodium (II) acetate (22 mg, 0.49 mmol) was added. A
solution of 4 in chloroform (15 ml) was added dropwise over 10
minutes to the above mixture. The reaction mixture was concen-
trated under reduced pressure and the residue was chromato-
graphed on silica gel with chloroform:methanol (20:1) as eluent.
H
10 15
5 2
Found: C, 50.57; H, 6.32; N, 29.31.
(5-Butylamino-1,3-dimethyl-2,4-dioxopyrimidin-6-yl)-
cyanamide (9b).
This compound was obtained in 25% yield as colorless
prisms, mp 227-229° (from chloroform): δ 0.95 (3H, t, J = 7.1
7-Propyl-8-aminotheophylline (8a).
Hz, -CH CH CH CH ), 1.34-1.45 (2H, m, -CH CH CH CH ),
2
2
2
3
2
2
2
3
This compound was obtained in 57% yield as colorless
prisms, mp 233-234° (from ethanol); H nmr (deuterio-
chloroform): δ 0.98 (3H, t, J = 7.3 Hz, -CH CH CH ), 1.77-1.90
1.51-1.62 (2H, m, -CH CH CH CH ), 3.36 (2H, t, J = 7.3 Hz,
2
2
2
3
1
-CH CH CH CH ), 3.37 (3H, s, N-Me), 3.51 (3H, s, N-Me),
2
2
2
3
2
2
3
5.56 (1H, br, NH), 7.59 (1H, br, NH); ir (potassium bromide): ν
(2H, m, -CH CH CH ), 3.50 (3H, s, N-Me), 3.38 (3H, s, N-Me),
-1
-1
-1
2
2
3
max 3500 cm (NH), 3300 cm (NH), 1695 cm (C=O); ms:
4.04 (2H, t, J = 7.3 Hz, -CH CH CH ), 4.59 (2H, br, NH ); ir
+
2
2
3
2
m/z 251 (M ).
-1
(potassium bromide): ν max 3390 and 3340 cm (NH ), 1700
2
Anal. Calcd. for C H N O : C, 52.58; H, 6.82; N, 27.87.
11 17
5 2
-1
+
cm (C=O); ms: m/z 237 (M ). This compound was identical
with that obtained by the reaction of 8-aminotheophylline with
propyl bromide [12].
Found: C, 52.33; H, 6.91; N, 27.84.
(1,3-Dimethyl-5-(2-methylpropylamino)-2,4-dioxopyrimidin-6-
yl)cyanamide (9c).
7-Butyl-8-aminotheophylline (8b).
This compound was obtained in 26% yield as colorless
prisms, mp 254-256° (from ethanol): δ 1.00 (6H, d, J = 6.9 Hz,
This compound was obtained in 53% yield as colorless
prisms, mp 202-203° (from chloroform); H nmr (deuterio-
chloroform): δ 0.95 (3H, t, J = 7.3 Hz, -CH CH CH CH ),
1
-CH CH(CH ) ), 1.84-1.96 (1H, m, -CH CH(CH ) ), 3.27 (2H,
2
3 2
2
3 2
d, J = 6.6 Hz, -CH CH(CH ) ), 3.42 (3H, s, N-Me), 3.55 (3H, s,
2
2
2
3
2
3 2
1.34-1.45 (2H, m, -CH CH CH CH ), 1.68-1.79 (2H, m,
N-Me), 5.12 (1H, br, NH), 11.36 (1H, br, NH); ir (potassium
2
2
2
3
-1
-1
-1
-CH CH CH CH ), 3.36 (3H, s, N-Me), 3.48 (3H, s, N-Me),
bromide): ν max 3280 cm (NH), 3170 cm (NH), 1695 cm
2
2
2
3
+
(C=O); ms: m/z 251 (M ).
4.08 (2H, t, J = 7.3 Hz, -CH CH CH CH ), 5.63 (2H, br, NH );
2
2
2
3
2
-1
Anal. Calcd. for C H N O : C, 52.58; H, 6.82; N, 27.87.
ir (potassium bromide): ν max 3350 and 3420 cm (NH ), 1690
11 17
5 2
2
-1
+
Found: C, 52.29; H, 6.59; N, 27.61.
cm (C=O); ms: m/z 251 (M ). This compound was identical
with that obtained by the reaction of 8-aminotheophylline with
butyl bromide [12].
(5-Hexylamino-1,3-dimethyl-2,4-dioxopyrimidin-6-yl)-
cyanamide (9d).
7-(2-Methylpropyl)-8-aminotheophylline (8c).
This compound was obtained in 33% yield as colorless
prisms, mp 223-225° (from ethanol): δ 0.89 (3H, t, J = 7.1 Hz,
This compound was obtained in 38% yield as colorless
1
-CH (CH ) CH ), 1.25-1.49 (6H, m, -CH CH (CH ) CH ),
prisms, mp 172-174° (from ethanol), H nmr (deuterio-
chloroform): δ 0.98 (6H, d, J = 6.6 Hz, (Me) CHCH -),
2 2 4 3 2 2 2 3 3
1.60-1.72 (2H, m, -CH CH (CH ) CH ), 3.41 (3H, s, N-Me),
2
2
2 3
3
2
2
3.46 (2H, t, J = 7.1 Hz, -CH (CH ) CH ), 3.55 (3H, s, N-Me),
2
2 4
3
2.17-2.27 (1H, m, (Me) CHCH -), 3.38 (3H, s, N-Me), 3.50
2
2
4.99 (1H, br, NH), 11.56 (1H, br, NH); ir (potassium bromide): ν
(3H, s, N-Me), 3.85 (2H, d, J = 7.6 Hz, (Me) CHCH -), 4.66
2
2
-1
-1
-1
max 3270 cm (NH), 3130 cm (NH), 1695 cm (C=O); ms:
(2H, br, NH ); ir (potassium bromide): ν max 3460 and 3420
2
+
m/z 279 (M ).
-1
-1
+
cm (NH ), 1700 cm (C=O); ms: m/z 251 (M ).
2
Anal. Calcd. for C
H N O : C, 55.88; H, 7.58; N, 25.08.
13 21 5 2
Anal. Calcd. for C H N O : C, 52.58; H, 6.82; N, 27.87.
11 17
5 2
Found: C, 55.65; H, 7.42; N, 25.00.
Found: C, 52.36; H, 6.75; N, 27.64.
Acknowledgement.
7-Hexyl-8-aminotheophylline (8d).
This compound was obtained in 43% yield as colorless
prisms, mp 176-177° (from methanol); H nmr (deuterio-
We are grateful to Misses T. Naito, S. Kato and K. Takahashi
of this Faculty for elemental analyses, H NMR and MS
measurements.
1
1
chloroform): δ 0.87 (3H, t, J = 7.1 Hz, CH (CH ) CH ),
2
2 4
3
1.26-1.34 (6H, m, CH CH (CH ) CH ), 1.74-1.82 (2H, m,
2
2
2 3
3
CH CH (CH ) CH ), 3.38 (3H, s, N-Me), 3.49 (3H, s, N-Me),
2
2
2 3
3
REFERENCES
4.07 (2H, t, J = 7.3 Hz, CH (CH ) CH ), 4.97 (2H, br, NH ); ir
2
2 4
3
2
-1
(potassium bromide): ν max 3400 and 3350 cm (NH ), 1700
cm (C=O); ms: m/z 279 (M ).
Anal. Calcd. for C N O : C, 55.88; H, 7.58; N, 25.08.
2
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-1
+
H
13 21
5 2
Found: C, 55.81; H, 7.58; N, 25.34.
(1,3-Dimethyl-2,4-dioxo-5-propylaminopyrimidin-6-yl)-
cyanamide (9a).
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1

Jan-Feb 2001
Oxidation of 7,8-Diaminotheophylline with Lead Tetraacetate
145
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