Synthesis of 5-(functionalized acyl)-1,3-dialkyl- substituted barbituric and 2-thiobarbituric acids

Article abstract of DOI:10.1002/jhet.5570380207

A sodium derivative of 1,3-dimethylbarbituric acid or 1,3-diethyl-2-thiobarbituric acid undergoes an efficient monoacylation at C5 by the reaction with ω-chloroalkanoyl chloride or diacid dichloride in the presence of pyridine in tetrahydrofuran. A nucleophilic displacement of the chlorine in a 5-chloroacetyl-bartiburate can be accomplished by using a one-pot procedure. By contrast, a similar transformation of a 5-(chlorobutanoyl)barbituric acid requires intramolecular cyclization in the presence of a nonnucleophilic base followed by treatment with a nucleophile of the resultant 5-[4,5-dihydro(3H)-2-furylidene]barbiturate.

Full text of DOI:10.1002/jhet.5570380207

Mar-Apr 2001
Synthesis of 5-(Functionalized acyl)-1,3-dialkyl-
Substituted Barbituric and 2-Thiobarbituric Acids
Hanafi H. Zoorob and Mohamed A. Ismail
359
Chemistry Department, Faculty of Science, Al-Mansoura University
Al-Mansoura, Egypt
Lucjan Strekowski*
Department of Chemistry, Georgia State University, Atlanta, Georgia 30303, USA
Received September 12, 2000
A sodium derivative of 1,3-dimethylbarbituric acid or 1,3-diethyl-2-thiobarbituric acid undergoes an
efficient monoacylation at C5 by the reaction with ω-chloroalkanoyl chloride or diacid dichloride in the
presence of pyridine in tetrahydrofuran. A nucleophilic displacement of the chlorine in a 5-chloroacetyl-
bartiburate can be accomplished by using a one-pot procedure. By contrast, a similar transformation of a
5-(chlorobutanoyl)barbituric acid requires intramolecular cyclization in the presence of a nonnucleophilic
base followed by treatment with a nucleophile of the resultant 5-[4,5-dihydro(3H)-2-furylidene]barbiturate.
J. Heterocyclic Chem., 38, 359 (2001).
C5-Substituted barbituric and 2-thiobarbituric acids
approximately equimolar amounts. In a subsequent report
[11] we described a limited number of transformations of
5-(ω-chloroalkanoyl)-1,3-dimethylbarbituric acids 3 and
4. In this paper we present a full account of the above
mentioned chemistry that includes complete experimental
details and a detailed characterization of all products
mentioned previously [10, 11]. More importantly,
additional examples of the successful derivatization of 1
and 2 are described.
The highest efficiency of the acylation reaction of 1 and 2
to give the corresponding product 3-6 is observed when one
equivalent of a sodium derivative of 1 or 2 and one
equivalent of pyridine are used. This implies the formation
exhibit a wide spectrum of biological activity, and some of
them are useful drugs or agrochemicals [1-5]. The major
synthetic routes to these compounds involve ring
construction because few efficient substitution reactions of
the parent barbituric acids are available [1]. In particular,
we have reported recently an improved procedure for a
selective introduction of either one or two benzyl groups at
C5 of 1,3-dimethylbarbituric acid (1) [6]. Benzoylation [4]
of 1 can be accomplished by treatment with benzoyl
chloride in the presence of Et N and Zn(CN) or by the
3
2
reaction of its sodium derivative with benzoyl chloride [7].
Compound 1 can also be acetylated by treatment under
forcing conditions with a large excess of acetic anhydride
[8], but similar preparations of higher alkanoyl derivatives
have not been reported. Indeed, our attempted reactions of
1 and 1,3-diethyl-2-thiobarbituric acid (2) with either
butyric chloride or butyric anhydride under the conditions
indicated above produced only traces of the substituted
product. On the other hand, compound 1 is efficiently
acylated by reaction with an alkanoyl chloride when
conducted in pyridine [9]. It appears that pyridine
undergoes a reaction with the acid chloride to generate an
intermediate N-acylpyridinium cation that is more reactive
than the starting acid chloride [9, 10]. Unfortunately, this
method is not suitable for the preparation of nucleophile-
sensitive compounds such as 3-6 (Scheme 1). In our hands,
the treatment of 1 with either chloroacetyl chloride or
4-chlorobutanoyl chloride in pyridine produced an
inseparable mixture of products.
In a preliminary report [10] we showed that the desired
compounds 3-6 are efficiently synthesized by the reaction
of the corresponding sodium derivative of 1 and 2 with an
alkanoyl chloride in the presence of pyridine under
conditions that all three reagents (a sodium derivative of 1
or 2, an alkanoyl chloride, and pyridine) are present in

360
Vol. 38
H. H. Zoorob, M. A. Ismail and L. Strekowski
18.1 ± 0.2. The suggested enolization of the carbonyl group
at position 6 of the pyrimidine is in excellent agreement
with the observed (δ 94.6-96.8) chemical shifts for C5 in
13
the C nmr spectra and the corresponding computer
simulated values (δ 94.5-96.7) using an ACD/Labs™
program [12]. By comparison, the calculated chemical shift
for C5 in the alternative tautomer with the acyl carbonyl
enolized is δ 107±2 and the predicted value for the all-
carbonyl tautomer is δ 80±3 for all compounds 3-6.
The synthesis of bis-barbituryl derivatives 7-10 is given
in Scheme 1. Although these compounds can be obtained
by conducting the reaction in pyridine, the modified
method as described above greatly facilitates workup and
isolation of these relatively water-soluble products. Again,
compounds 7-10 exist in a single enol form as shown.
Since many substituted azoles exhibit potent biological
activity [13-17], it was of interest to substitute the
ω-chloro atom in 3-6 with the azole functionality. The
reactions of 3 and 5 with sodium derivatives of indole,
benzimidazole, imidazole, and 1,2,4-triazole furnished the
corresponding products 11, 12, 15-18 in good yields
(Scheme 2). A gc-ms analysis revealed that the 1,2,4-
triazoles 16, 18 were not accompanied by isomeric 1,3,4-
triazoles. On the other hand, the treatment of 3, 5 with tri-
ethylamine resulted in cyclization and gave the respective
furanouracils 13, 14. These structures were derived from
spectral data and then confirmed by an x-ray crystallo-
graphic analysis of 13. The furan subsystem of 13, 14
undergoes a facile ring opening in the presence of a nucle-
ophile, as exemplified in Scheme 2 by the reaction of 13
with imidazole.
of an enolate of 3-6. After quenching the mixture with acid
the product 3-6 also exists in an enol form. Thus, the H
1
In contrast to the facile nucleophilic displacement of
chlorine of the chloroacetyl group in 3, 5, the ω-chloro-
butanoyl-substituted barbituric acids 4, 6 undergo deacyl-
ation under similar conditions to give 1, 2 in nearly
quantitative yields (Scheme 3). The facile loss of the acyl
group from 4, 6 can be explained in terms of a nucleophile
addition to the acyl carbonyl group followed by retro
aldol-type fragmentation of the resultant adduct.
nmr spectra of 3-6 taken in anhydrous deuteriochloroform
show the presence of a single enol form that absorbs at δ
The desired compound 21 was obtained by cyclization
of 4 in the presence of potassium carbonate and then
opening of the furylidene subunit in the resultant product
19 by treatment with imidazole. The 2-thio analog 6
undergoes a similar cyclization to 20. Since on the basis of
spectral data alone the structures of 19 and its 2-thioxo
analog 20 could not be determined unambiguously, the
molecular structure of the selected compound 19 was
solved by x-ray crystallographic analysis.
In summary, we have described a simple method for the
introduction of an ω-chloroalkanoyl group at C5 of
1,3-dialkyl-substituted barbituric and 2-thiobarbituric
acids. While chlorine in chloroacetyl-substituted products
can be displaced by nucleophiles in a one-pot reaction, a
similar transformation of ω-chlorobutanoyl derivatives
requires a two-step procedure. It is important to note that
no chromatography was involved and analytically pure

Mar-Apr 2001
361
5-(Functionalized acyl)-1,3-dialkyl-Substituted Barbituric and 2-Thiobarbituric Acids
5-(4-Chlorobutanoyl)-1,3-diethyl-2-thiobarbituric Acid (6).
products were obtained by crystallization in all cases
studied. Several substituted azoles obtained as part of this
work were screened by DuPont and were shown to be
insecticides against southern corn rootworm, two-spotted
spider mite, green peach aphid or corn planthopper [18].
The biological results will be published in due course.
1
This compound was obtained in 57% yield, mp 48-49°; H nmr: δ
1.30 (m, 6H), 2.20 (m, 2H), 3.35 (t, J = 7.5 Hz, 2H), 3.65 (t, J = 6.6
Hz, 2H), 4.50 (m, 4H), 18.1 (br s, exchangeable with deuterium
13
oxide, 1H); C nmr: δ 11.8, 12.2, 27.7, 35.1, 43.1, 43.3, 44.1, 96.7,
+
158.0, 167.0, 177.0, 200.1; ms: m/z 69 (100), 268 (60, M -HCl).
Anal. Calcd. for C H ClN O S: C, 47.29; H, 5.62; N, 9.19.
12 17
2 3
Found: C, 47.24; H, 5.53; N, 9.17.
EXPERIMENTAL
5-Acylbarbiturates, 7-10.
Tetrahydrofuran was distilled from sodium benzophenone
ketyl immediately before use. All reactions were conducted
under a nitrogen atmosphere. The progress of the reactions was
monitored, and mass spectra of pure products were obtained on a
gc-ms instrument equipped with an on-column injector, a
poly(dimethylsiloxane)-coated capillary column, and a mass
selective detector operating at 70 eV. The lack of mass spectral
data indicates a nonvolatile compound. Melting points are not
In the procedure described above a diacid dichloride
(6 mmoles) was substituted for the acid chloride under otherwise
identical conditions including workup. The product 7-10 was
crystallized from ethanol/chloroform (1:1).
1,5-Bis(1,3-dimethyl-5-barbituryl)pentane-1,5-dione (7).
1
This compound was obtained in 75% yield, mp 181-182°; H
nmr: δ 2.10 (m, 2H), 3.28 (t, J = 7.8 Hz, 4H), 3.32 (s, 6H), 3.37
1
13
corrected. H and C nmr spectra were obtained at 400 MHz and
100 MHz, respectively. Unless otherwise indicated the nmr
spectra were taken in deuteriochloroform at 25°.
13
(s, 6H), 17.90 (br s, exchangeable with deuterium oxide, 2H);
C
nmr: δ 20.9, 27.9, 28.0, 36.1, 95.4, 150.3, 160.8, 169.7, 198.4.
Anal. Calcd. for C H N O : C, 50.00; H, 4.94; N, 13.72.
17 20
4 8
Found: C, 49.87; H, 4.86; N, 13.54.
5-Acylbarbiturates, 3-6.
1,5-Bis-(1,3-dimethyl-5-barbituryl)octane-1,8-dione (8).
A solution of 1 or 2 (10 mmoles) in tetrahydrofuran (10 ml)
was added to a suspension of sodium hydride (0.3 g, 95%,
12 mmoles) in tetrahydrofuran (50 ml) and the mixture was
heated under reflux for 2.5 hours. After cooling the mixture was
treated with pyridine (1 ml, 12 mmoles) followed by addition of
an acid chloride (12 mmoles) and stirring at 40° for 24 hours.
After concentration under reduced pressure the residue was
extracted with chloroform (3 x 20 ml). The extract was dried with
magnesium sulfate and concentrated, and the resultant product
was crystallized from ethanol (3) or ether/pentanes (1:1, 4-6).
1
This compound was obtained in 72% yield, mp 157-158°; H
nmr: δ 1.47 (m, 4H), 1.71 (m, 4H), 3.14 (t, J = 7.8 Hz, 4H), 3.32
(s, 6H), 3.37 (s, 6H), 17.80 (br s, exchangeable with deuterium
13
oxide, 2H); C nmr: δ 25.6, 27.8, 28.0, 29.1, 36.6, 95.2, 150.3,
160.8, 169.7, 199.6.
Anal. Calcd. for C H N O : C, 53.33; H, 5.82; N, 12.44.
20 26
4 8
Found: C, 53.20; H, 5.71; N, 12.41.
1,5-Bis-[1,3-diethyl-5-(2-thiobarbituryl)]pentane-1,5-dione (9).
1
This compound was obtained in 59% yield, mp 133-134°; H
5-Chloroacetyl-1,3-dimethylbarbituric Acid (3).
nmr: δ 1.29 (m, 12H), 2.22 (m, 2H), 3.30 (t, J = 7.5 Hz, 4H), 4.54
(m, 8H), 18.10 (br s, exchangeable with deuterium oxide, 2H);
C nmr: δ 11.9, 12.2, 20.2, 36.9, 43.0, 43.3, 96.8, 158.4, 167.9,
1
This compound was obtained in 82% yield, mp 101-102°; H
nmr: δ 3.33 (s, 3H), 3.40 (s, 3H), 4.96 (s, 2H), 17.91 (br s,
13
13
exchangeable with deuterium oxide, 1H); C nmr: δ 28.1, 28.2,
177.1, 200.4.
44.1, 94.6, 149.8, 160.3, 169.7, 190.9; ms: m/z 81 (100), 196
Anal. Calcd. for C H N O S : C, 50.79; H, 5.68; N, 11.28.
21 28
4 6 2
+
(80, M -HCl).
Found: C, 50.63; H, 5.81; N, 11.16.
Anal. Calcd. for C H ClN O : C, 41.31; H, 3.90; N, 12.04.
8
9
2 4
1,5-Bis-[1,3-diethyl-5-(2-thiobarbituryl)]octane-1,8-dione (10).
Found: C, 41.29; H, 3.75; N, 11.91.
1
This compound was obtained in 51% yield, mp 123-124°; H
5-(4-Chlorobutanoyl)-1,3-dimethylbarbituric Acid (4).
nmr: δ 1.27 (m, 12H), 1.48 (m, 4H), 1.73 (m, 4H), 3.15 (t, J = 7.8
Hz, 4H), 4.53 (m, 8H), 18.02 (br s, exchangeable with deuterium
oxide, 2H); C nmr: δ 11.9,12.2, 25.2, 29.0, 37.5, 43.0, 43.3,
1
This compound was obtained in 67% yield, mp 56-57°; H
nmr: δ 2.17 (m, 2H), 3.32 (t, J = 8 Hz, 2H), 3.37 (s, 6H), 3.63
(t, J = 6.8 Hz, 2H), 17.87 (br s, exchangeable with deuterium
13
96.7, 158.4, 167.9, 177.2, 201.5.
13
oxide, 1H); C nmr: δ 27.8, 28.0, 28.1, 34.2, 44.1, 95.3, 150.2,
Anal. Calcd. for C H N O S : C, 53.51; H, 6.36; N, 10.40.
24 34
4 6 2
+
160.7, 169.7, 198.0; ms: m/z 42 (100), 224 (80, M -HCl).
Found: C, 53.47; H, 6.52; N, 10.30.
Anal. Calcd. for C H ClN O : C, 46.08; H, 5.03; N, 10.75.
10 13
2 4
5-(Azolylacetyl)barbiturates, 11, 12, 15-18.
Found: C, 46.29; H, 5.12; N, 10.47.
A mixture of sodium hydride (95%, 38 mg, 1.5 mmoles) and an
azole (1.5 mmoles) in N,N-dimethylformamide (10 ml) was stirred
at 23° for 1 hour and then treated with 3,5 (1 mmole). The stirring
was continued at 80° for 16 hours. Following concentration on a
rotary evaporator, the residue was dissolved in water (10 ml) and
the solution was neutralized by dropwise addition of 2 M
hydrochloric acid. The resulting precipitate was filtered, washed
with water, dried, and crystallized from ethanol (11), chloroform/-
methanol (12), water (15) or ethanol/methanol (16-18).
5-Chloroacetyl-1,3-diethyl-2-thiobarbituric Acid (5).
1
This compound was obtained in 65% yield, mp 91-92°; H
nmr: δ 1.40 (m, 6H), 4.60 (m, 4H), 5.00 (s, 2H), 18.20 (br s,
13
exchangeable with deuterium oxide, 1H); C nmr: δ 11.7, 12.1,
43.5, 45.4, 95.8, 158.0, 167.9, 176.5, 193.1; ms: m/z 42 (100),
+
240 (90, M -HCl).
Anal. Calcd. for C H ClN O S: C, 43.40; H, 4.73; N, 10.12.
10 13
2 3
Found: C, 43.13; H, 4.57; N, 9.95.

362
Vol. 38
H. H. Zoorob, M. A. Ismail and L. Strekowski
5-(Indol-1-ylacetyl)-1,3-dimethylbarbituric Acid (11).
1,3-Dimethylfurano[3,2-e]pyrimidine-2,4,5(1H,3H,6H)-trione (13).
1
1
This compound was obtained in 57% yield, mp 206-207°; H
nmr: δ 3.35 (s, 3H), 3.38 (s, 3H), 5.74 (s, 2H), 6.59 (d, J = 3.3
Hz, 1H), 7.16 (m, 4H), 7.64 (d, J = 3.3 Hz, 1H), 17.90 (br s,
This compound was obtained in 89% yield, mp 205-206°; H
13
nmr: δ 3.25 (s, 3H), 3.50 (s, 3H), 4.80 (s, 2H); C nmr: δ 27.9,
28.8, 77.6, 92.1, 150.1, 155.6, 176.9, 187.7; ms: m/z 81 (100),
13
+
exchangeable with deuterium oxide, 1H); C nmr: δ 28.0, 28.1,
196 (90, M ).
50.1, 94.3, 102.4, 108.9, 119.9, 121.1, 122.0, 128.4, 128.8, 136.7,
149.9, 160.8, 169.5, 193.4; ms: m/z 130 (100), 313 (70, M ).
Anal. Calcd. for C H N O : C, 48.98; H, 4.11; N, 14.28.
Found: C, 49.09; H, 3.95; N, 14.01.
8
8 2 4
+
Anal. Calcd. for C H N O : C, 61.34; H, 4.83; N, 13.41.
16 15
3 4
1,3-Diethylfurano[3,2-e]pyrimidine-2(1H)-thione-4,5(3H,6H)-
dione (14).
Found: C, 61.31; H, 4.64; N, 13.40.
5-(Benzimidazol-1-ylacetyl)-1,3-diethyl-2-thiobarbituric acid
(12).
1
This compound was obtained in 72% yield, mp 199-200°; H
nmr: δ 1.20 (t, J = 7.5 Hz, 3H), 1.40 (t, J = 7.5 Hz, 3H), 4.50
This compound was obtained in 54% yield, mp 274-276°
13
(m, 4H), 4.80 (s, 2H); C nmr: δ 11.3, 12.6, 43.1, 43.6, 76.9,
1
(dec); H nmr: δ 1.41 (t, J = 6.6 Hz, 6H), 4.70 (q, J = 6.6 Hz, 4H),
+
94.3, 153.8, 175.5, 176.0, 188.0; ms: m/z 42 (100), 240 (90, M ).
5.79 (s, 2H), 7.70 (m, 4H), 8.90 (s, 1H), no signal for the enol
Anal. Calcd. for C H N O S: C, 49.99; H, 5.03; N, 11.66.
10 12
2 3
+
proton is observed; ms: m/z 132 (100), 358 (80, M ). High-
Found: C, 49.72; H, 4.99; N, 11.56.
resolution ms: Calcd. for C H N O S m/z 358.1100; observed
17 18
4 3
Furylidenebarbiturates, 19 and 20.
m/z 358.1110.
Anal. Calcd. for C H N O S•H O: C, 54.24; H, 5.36; N,
17 18
4
3
2
A mixture of 4 or 6 (5 mmoles) and anhydrous potassium
carbonate (2 g, 15 mmoles) in tetrahydrofuran (50 ml) was stirred
at 23° for 8 hours, filtered, and the solution was concentrated.
The residue was treated with water (30 ml) and extracted with
chloroform (3 x 20 ml). The extract was dried with magnesium
sulfate, concentrated, and the solid residue was crystallized from
toluene/hexanes.
14.88. Found: C, 54.41; H, 5.28; N, 14.86.
5-(Imidazol-1-ylacetyl)-1,3-dimethylbarbituric Acid (15).
1
This compound was obtained in 77% yield, mp 255-256°; H
nmr: (deuterium oxide, 50°) δ 2.99 (s, 6H), 5.32 (s, 2H), 7.23
(d, J = 1.5 Hz, 1H), 7.28 (d, J = 1.5 Hz, 1H), 8.49 (s, 1H); ms: m/z
+
82 (100), 264 (80, M ).
Anal. Calcd. for C H N O •H O: C, 46.80; H, 4.96; N,
5-[4,5-Dihydro(3H)-2-furylidene]-1,3-dimethylbarbituric Acid (19).
11 12
4
4
2
19.86. Found: C, 46.49; H, 4.88; N, 19.74.
1
This compound was obtained in 51% yield, mp 178-179°; H
1,3-Dimethyl-5-(1,2,4-triazol-1-ylacetyl)barbituric Acid, (16).
nmr: δ 2.23 (m, 2H), 3.32 (s, 6H), 3.58 (t, J = 8.0 Hz, 2H), 4.75
13
(t, J = 8.0 Hz, 2H); C nmr: δ 21.9, 27.9, 28.1, 36.6, 76.9, 97.0,
This compound was obtained in 74% yield, mp 211-212°
+
151.5, 160.4, 163.0, 190.0; ms: m/z 42 (100), 224 (80, M ).
1
(dec); H nmr: (dimethyl sulfoxide-d , 30°): δ 3.20 (s, 6H), 5.84
6
Anal. Calcd. for C H N O : C, 53.57; H, 5.39; N, 12.49.
+
10 12
2 4
(s, 2H), 8.10 (s, 1H), 8.66 (s, 1H); ms: m/z 265 (100, M ). High
Found: C, 53.55; H, 5.38; N, 12.40.
resolution ms:. Calcd. for C H N O m/z 265.0811, observed
10 11
5 4
m/z 265.0812.
Anal. Calcd. for C H N O •0.5 H O: C, 43.79; H, 4.37; N,
1,3-Diethyl-5-[4,5-dihydro(3H)-2-furylidene]-2-thiobarbituric
Acid (20).
10 11
5
4
2
25.54. Found: C, 43.82; H, 4.25; N, 25.41.
1
This compound was obtained in 43% yield, mp 140-141°; H
1,3-Diethyl-5-(imidazol-1-ylacetyl)-2-thiobarbituric Acid, (17).
nmr: δ 1.28 (t, J = 7.0 Hz, 6H), 2.24 (m, 2H), 3.59 (t, J = 7.8 Hz,
13
2H), 4.53 (q, J = 7.0 Hz, 4H), 4.79 (t, J = 7.5 Hz, 2H); C nmr: δ
1
This compound was obtained in 68% yield, mp 249-250°; H
12.2, 12.4, 21.9, 37.1, 43.1, 43.2, 77.3, 98.4, 158.3, 161.0, 178.8,
nmr: δ 1.33 (t, J = 6.9 Hz, 6H), 4.62 (q, J = 6.9 Hz, 4H), 5.60
+
191.5; ms: m/z 69 (100), 268 (60, M ).
(s, 2H), 7.06 (d, J = 1.1 Hz, 1H), 7.22 (d, J = 1.1 Hz, 1H), 8.60
Anal. Calcd. for C H N O S: C, 53.71; H, 6.01; N, 10.44.
12 16
2 3
(s, 1H), 15.80 (br s, exchangeable with deuterium oxide, 1H); ms:
Found: C, 53.55; H, 6.26; N, 10.38.
+
m/z 308 (100, M ). High resolution ms: Calcd. for C H N O S
13 16
4 3
m/z 308.0943, observed m/z 308.0943.
Anal. Calcd. for C H N O S: C, 50.64; H, 5.23; N, 18.17.
Found: C, 50.66; H, 5.43; N, 18.11.
Fusion of 13 or 19 with Imidazole.
13 16
4 3
Heating a mixture of a furanouracil 13 (0.2 g, 1 mmole) or a
furylidenebarbituric acid 19 (0.22 g, 1 mmole) and imidazole
(0.1 g, 1.5 mmoles) to 125° for 2 hours followed by trituration
with ethanol and crystallization of the resultant solid from water
gave the respective products 15 (yield 72%) and 21.
1,3-Diethyl-5-(1,2,4-triazol-1-ylacetyl)-2-thiobarbituric Acid (18).
1
This compound was obtained in 71% yield, mp 206-208°; H
nmr: (dimethyl sulfoxide-d , 30°) δ 1.16 (t, J = 6.6 Hz, 6H), 4.41
6
(q, J = 6.6 Hz, 4H), 5.63 (s, 2H), 8.59 (s, 1H), 9.26 (s, 1H).
5-[4-(1-Imidazolyl)butanoyl]-1,3-dimethylbarbituric Acid (21).
Anal. Calcd. for C H N O S: C, 46.59; H, 4.89; N, 22.65.
12 15
5 3
1
This compound was obtained in 60% yield, mp 203-205°; H
Found: C, 46.63; H, 4.89; N, 22.88.
nmr: (deuterium oxide, 50°) δ 2.02 (m, 2H), 2.71 (t, J = 8.0
Hz, 2H), 3.03 (s, 6H), 4.12 (t, J = 8.0 Hz, 2H), 7.29 (d, J = 1.1 Hz,
1H), 7.37 (d, J = 1.1 Hz, 1H), 8.57 (s, 1H); ms: m/z 183 (100),
Furanouracils, 13 and 14.
A solution of 3 or 5 (10 mmoles) and triethylamine (1 ml) in
absolute ethanol (50 ml) was heated to 50° for 8 hours. After
cooling the resultant precipitate was filtered and crystallized
from ethanol.
+
292 (70, M ).
Anal. Calcd. for C H N O : C, 53.42; H, 5.52; N, 19.17.
13 16
4 4
Found: C, 53.11; H, 5.59; N, 18.84.

Mar-Apr 2001
363
5-(Functionalized acyl)-1,3-dialkyl-Substituted Barbituric and 2-Thiobarbituric Acids
[3] D. Getova and V. Georgiev, Acta Physiol. Pharmacol. Bulg.,
15, 83 (1989).
X-ray Structural Data for 13.
The molecular formula is C H N O , M = 196.16, the crystal
is orthorhombic, space group fold 2, crystal size = 0.187 x 0.034
8
8 2 4
[4] D. Lee and C. Carter (Stauffer Chemical Co.), U.S. Patent
4,797,147 (1989), Chem. Abstr., 111, 148889c (1989).
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[12] The ACD/Labs™ program is available from Advanced
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x 0.034 mm, unit cell dimensions, a = 28.333 (2) Å, α = β = γ =
3
90°, v = 3409.2 (4) Å , refinement by full-matrix least-squares on
F , F (000) = 1632, no. of reflections collected = 4365, no. of
2
independent reflections = 1449 [R (int) = 0.1090]. The complete
crystallographic data for 13 have been deposited at the
Cambridge Crystallographic Data Centre.
X-ray Structural Data for 19.
The molecular formula is C
H N O , M = 224.22, the
10 12 2 4
crystal is monoclinic, space group P2 (1)/C, crystal size = 0.612 x
0.374 x 0.255 mm, unit cell dimensions, a = 12.8616 (11) Å, b =
11.0200 (9) Å, c = 7.2909 (6) Å, α = 90, β = 102.8980 (10) °, γ =
3
90°, v = 1007.3 (2) Å , refinement by full-matrix least-squares on
F , F (000) = 472, no. of reflections collected = 6277, no. of
2
independent reflections = 2354 [R (int) = 0.0494]. The complete
crystallographic data for 21 have been deposited at the
Cambridge Crystallographic Data Centre.
[14] M. Abel, R. Hewgill, K. Malczyk, R. Micetich and M.
Daneshtalab, J. Heterocyclic Chem., 35, 193 (1998).
[15] J. Pesti, J. Downard, M. Lauritsen, G. Kauffman, W. Bryant
III, G. Huhn, J. Arnett, R. Yule, J. Segretario, K. Nelson, E. Gorko, G.
Page, L. Lloyd, R. Olson, C. Barnum and J. Mrowca, J. Heterocyclic
Chem., 35, 249 (1998).
Acknowledgment.
The experimental work was conducted by M.A. Ismail at
Georgia State University thanks to financial assistance by the
CHANNEL program of the government of Egypt.
[16] K. Walker, A. Braemer, S. Hitt, R. Jones and T. Matthews, J.
Med. Chem., 21, 840 (1997).
REFERENCES AND NOTES
[17] H. Bossche, G. Willemsens, D. Bellens, I. Roels and P.
Janssen, J. Biochem. Soc. Trans., 18, 10 (1990).
[18] The biological assays were conducted at DuPont Agricultural
Products, Stine-Haskell Research Center, P.O. Box 30, Elkton Road,
Newark, Delaware 19714-0030, USA.
[1] For a review, see: D. J. Brown, The Pyrimidines, Interscience,
New York, NY, 1994.
[2] H. Zoorob, M. Abou-Elzahab, M. Abdel-Mogib, M. A. Ismail
and M. Abdel-Hamid, Arzneim. Forsch./Drug Res., 47, 958 (1997).