Application of bis(iminophosphorane) in heterocyclic synthesis: New entries to symmetrically or unsymmetrically substituted thieno[2,3-d:5,4-d′] dipyrimidine-4,5(3H,6H)-diones

Article abstract of DOI:10.1021/jo048691v

The bis(carbodiimides) 4, obtained from bis-aza-Wittig reactions of bis(iminophosphorane) 3 with 2 equiv of aromatic isocyanates, were reacted with secondary amine to give symmetrically substituted 2,7-diaminothieno[2,3-d:5,4- d′]dipyrimidine-4,5(3H,6H)-d

Full text of DOI:10.1021/jo048691v

Application of Bis(iminophosphorane) in Heterocyclic Synthesis:
New Entries to Symmetrically or Unsymmetrically Substituted
Thieno[2,3-d:5,4-d′]dipyrimidine-4,5(3H,6H)-diones
Ming-Wu Ding,* Sheng-Zhen Xu, and Jun-Feng Zhao
Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry,
Central China Normal University, Wuhan, 430079, P. R. China
ding5229@yahoo.com.cn
Received July 29, 2004
The bis(carbodiimides) 4, obtained from bis-aza-Wittig reactions of bis(iminophosphorane) 3 with
2 equiv of aromatic isocyanates, were reacted with secondary amine to give symmetrically
substituted 2,7-diaminothieno[2,3-d:5,4-d′]dipyrimidine-4,5(3H,6H)-dione 6 in the presence of a
catalytic amount of EtO-Na+. Reactions of 4 with phenols or ROH in the presence of a catalytic
amount of potassium carbonate or RO-Na+ gave symmetrically substituted 2,7-diaryl(alkyl)-
oxythieno[2,3-d:5,4-d′]dipyrimidine-4,5(3H,6H)-diones 6 in satisfactory yields. However, imino-
phosphoranes 9 were obtained via reaction of bis(iminophosphorane) 3 with 1 equiv of aromatic
isocyanate and subsequent reaction with an amine in the presence of a catalytic amount of EtO-Na+.
Further reaction of iminophosphoranes 9 with aromatic isocyanates and various nucleophile
generated unsymmetrically substituted thieno[2,3-d:5,4-d′]dipyrimidine-4,5(3H,6H)-diones 12 in
good yields.
Introduction
and some of them show good antitumor activity,3 there
is no report of a generally useful synthesis of thieno[2,3-
d:5,4-d′]dipyrimidine-4,5(3H,6H)-diones, compounds which
are of considerable interest as potential biologically active
compounds or pharmaceuticals.
The derivatives of fused pyrimidinones have been the
focus of great interest over many years. This is probably
due to the fact that many compounds containing a fused
pyrimidinone ring play a very important part in the
biochemistry of the living cell. Recent development of
physiologically highly potent purine analogues with
interesting antiviral, antiallergic, and specially antican-
cer activities has promoted a great current interst in
facile and general routes to these molecules in syntheti-
cally useful yields.1 The thienopyrimidine systems are
also of great importance because of their remarkable
biological properties.2 For example, some 2-alkoxy- or
2-alkyl-substituted thienopyrimidinones show significant
antifungal and antibacterial activities,2a-d whereas others
exhibited good anticonvulsant and angiotensin II or H1
receptor antagonistic activities.2e-h Although some de-
rivatives of thienodipyrimidines have been synthesized
Over the past 20 years, the aza-Wittig reactions of
iminophosphoranes have received increased attention in
view of their utility in the synthesis of nitrogen-contain-
ing heterocyclic compounds.4 Annelation of ring systems
with N-heterocycles by means of an aza-Wittig reaction
has been widely utilized because of the availability of
functionalized iminophosphoranes. However, the chem-
istry of bis(iminophosphoranes) has been studied less
extensively. Bis(iminophosphoranes) have been shown to
have synthetic potential as a result of their ability to
react with reagents bearing two functional groups or with
two separate reagents with the same or different func-
tionality. Various heterocycles have been synthesized via
bis(iminophosphoranes).5 Some of these heterocycles
include 11H-quinazolino[2,3-b]quinazolines,5a indazolo-
[2′,3′:1,5]-1,2,4-triazolo[4,3-a]-1,3,5-benzotriazepines,5b
diquino[4,3-b:3′,4′-d]pyrroles,5c benzimidazo[1,2-a]ben-
zimidazoles,5d pyrido[2,3,4-de]quinazolines,5e 1,3-diazeto-
[1′,2′-a]pyrazolo[3,4-d]-1,3-diazopines,5f and pyrido[5′′,6′′:
4,5;3′′2′′:4′,5′]dithieno[3,2-d:3′,2′-d′]dipyrimidine- 4,8-
(1) (a) Haraguchi, K.; Kubota, Y.; Tanaka, H. J. Org. Chem. 2004,
69, 1831. (b) Cushman, M.; Sambaiah, T.; Jin, G.; Illarionov, B.;
Fischer, M.; Bacher, A. J. Org. Chem. 2004, 69, 601. (c) Depecker, G.;
Patino, N.; Giorgio, C. D.; Terreux, R.; Cabrol-Bass, D.; Bailly, C.;
Aubertin, A.-M.; Condom, R. Org. Biomol. Chem. 2004, 2, 74. (d) Wnuk,
S. F.; Lewandowska, E.; Companioni, D. R.; Garcia, P. I., Jr.; Secrist,
J. A., III Org. Biomol. Chem. 2004, 2, 120.
(2) (a) Walter, H. WO 9911631, 1999 [Chem. Abstr. 1999, 130,
237580e]. (b) Walter, H. WO 9914202, 1999 [Chem. Abstr. 1999, 130,
252368k]. (c) Aboulwafa, O. M.; Ismail, K. A.; Koreish, E. A. Farmaco
1992, 47, 631. (d) Chambhare, R. V.; Khadse, B. G.; Bobde, A. S.;
Bahekar, R. H. Eur. J. Med. Chem. 2003, 38, 89. (e) Santagati, M.;
Modica, M.; Santagati, A.; Russo, F.; Spampinato, S. Pharmazie 1996,
51, 7. (f) Taguchi, M.; Ota, T.; Hatayama, K. WO 9303040, 1993 [Chem.
Abstr. 1993, 119, 160309m]. (g) Shishoo, C. J.; Shirsath, V. S.; Rathod,
I. S.; Yande, V. D. Eur. J. Med. Chem. 2000, 35, 351. (h) De Laszlo, S.
E.; Patchett, A. A.; Allen, E. E.; Greenlee, W. J. EP 502725, 1992
[Chem. Abstr. 1992, 118, 22249v].
(3) (a) Stratmann, J. Chem. Ztg. 1991, 115, 59. (b) Clark, J.; Hitiris,
G. J. Chem. Soc., Perkin Trans. 1 1984, 2005. (c) Gewald, K.; Martin,
A. J. Prakt. Chem. 1981, 323, 843.
(4) (a) Zhao, M.-X.; Wang, M.-X.; Yu, C.-Y.; Huang, Z.-T.; Fleet, G.
W. J. J. Org. Chem. 2004, 69, 997. (b) Yadav, J. S.; Srinivas, C.
Tetrahedron 2003, 59, 10325. (c) Csampai, A.; Turos, G.; Kudar, V.;
Simon, K.; Oeynhausen, H.; Wamhoff, H.; Sohar, P. Eur. J. Org. Chem.
2004, 717. (d) Kurosawa, W.; Kan, T.; Fukuyama, T. J. Am. Chem.
Soc. 2003, 125, 8112. (e). Molina, P.; Vilaplana, M. J. Synthesis 1994,
1197.
10.1021/jo048691v CCC: $27.50 © 2004 American Chemical Society
Published on Web 11/03/2004
8366
J. Org. Chem. 2004, 69, 8366-8371

Bis(iminophosphorane) in Heterocyclic Synthesis
TABLE 1. Yields of Compounds 6a-o
SCHEME 1. Preparation of
Bis(iminophosphorane) 3a
a Reagents and conditions: (a) DMF, NEt3, rt, 4 h, 35%; (b)
CH3CN, NEt3, rt, 4 h, 70%.
(3H,9H)-dione.5g Recently we have been interested in the
synthesis of quinazolinones, thienopyrimidinones, and
imidazolinones via aza-Wittig reaction of R or â ethoxy-
carbonyl iminophosphorane with aromatic isocyanate and
subsequent reaction with various nucleophiles under mild
conditions.6 Here we wish to report a fundamentally new
approach to the synthesis of symmetrically and unsym-
metrically substituted thieno[2,3-d:5,4-d′]dipyrimidine-
4,5(3H,6H)-diones from bis(iminophosphorane) 3.
SCHEME 2. Synthesis of Compounds 6a
Results and Discussion
The 2,5-diamino-3,4-(diethoxycarbonyl)thiophene 2,
easily obtained by cyclization of ethyl 2-cyanoacetate 1
with sulfur under basic condition,3c was converted to bis-
(iminophosphorane) 3 via reaction with triphenylphos-
phine, hexachloroethane, and triethylamine.7
Iminophosphorane 3 reacted with 2 equiv of aromatic
isocyanate to give bis(carbodiimide) 4, which was allowed
to react with secondary amines to provide guanidine
intermediates 5. Even in refluxing toluene, 5 did not
cyclize; however, in the presence of a catalytic amount
of sodium ethoxide, 5 were converted easily to sym-
metrically substituted 2,7-diaminothieno[2,3-d:5,4-d′]-
dipyrimidine-4,5(3H,6H)-diones 6 in satisfactory yields
at room temperature. It is noteworthy that the isolated
yield of 6 was good even when Y was a bulky diisopro-
pylamino group. The results are listed in Table 1.
The direct reaction of bis(carbodiimide) 4 with phenols
did not produce symmetrically substituted 2,7-diaryloxy-
thieno[2,3-d:5,4-d′]dipyrimidine-4,5(3H,6H)-diones 6 ei-
ther. However, when carried our in the presence of
catalytic potassium carbonate, the reaction took place to
give 6 in good yields. The formation of 6 can be rational-
ized in terms of an initial nucleophilic addition of
a Reagents and conditions: (a) CH2Cl2, 0-5 °C, 8-12 h; (b)
CH2Cl2, rt, 0.5-6 h; (c) EtOH, EtO-Na+, rt, 1-6 h; or CH3CN,
K2CO3 (s), 40-50 °C, 6-8 h.
SCHEME 3. Synthesis of Iminophosphoranes 9a
a Reagents and conditions: (a) CH2Cl2, 0-5 °C, 12 h; (b) CH2Cl2,
rt, 0.5-1 h; (c) EtOH, EtO-Na+, rt, 1-2 h.
(5) (a) Molina, P.; Conesa, C.; Velasco, M. D. Liebigs Ann./Recl.
1997, 107. (b) Molina, P.; Arques, A.; Alias, A.; Vinader, M. V.
Tetrahedron 1992, 48, 3091. (c) Molina, P.; Alajarin, M.; Vidal, A.
Tetrahedron 1995, 51, 12127. (d) Molina, P.; Lidon, M. J.; Tarraga, A.
Tetrahedron 1994, 50, 10029. (e) Molina, P.; Alajarin, M.; Vidal, A. J.
Org. Chem. 1992, 57, 6703. (f) Molina, P.; Arques, A.; Alias, A. J. Org.
Chem. 1993, 58, 5264. (g) Vilarelle, D. V.; Veira, C. P.; Lopez, J. M. Q.
Tetrahedron 2004, 60, 275.
(6) (a) Ding, M. W.; Yang, S. J.; Zhu, J. Synthesis 2004, 75. (b) Ding,
M. W.; Chen, Y. F.; Huang, N. Y. Eur. J. Org. Chem. 2004, 3872. (c)
Ding, M. W.; Sun, Y.; Yang, S. J.; Liu, X. P.; Liu, Z. J. Synth. Commun.
2003, 33, 1651. (d) Ding, M. W.; Zeng, G. P.; Wu, T. J. Synth. Commun.
2000, 30, 1599. (e) Liang, Y.; Ding, M. W.; Liu, Z. J.; Liu, X. P. Synth.
Commun. 2003, 33, 2843. (f) Ding, M. W.; Zeng, G. P.; Liu, Z. J.
Phosphorus Sulfur Silicon Relat. Elem. 2002, 177, 1315. (g) Ding, M.
W.; Shu, Y. L.; Liu, X. P.; Liu, Z. J. Acta Chim. Sin. 2002, 60, 1893.
(7) Wamhoff, H.; Herrmann, S.; Stolben, S.; Nieger, M. Tetrahedron
1993, 49, 581.
phenoxide to the bis(carbodiimide) 4 to give the inter-
mediate 5, which cyclizes to give 6. The reaction is
relatively insensitive to the presence or absence of
substituents on the phenols and the cyclization can be
completed smoothly at 40-50 °C.
The direct reaction of bis(carbodiimide) 4 with ROH
gave a complex mixture; however, when carried out in
the presence of catalytic RO-Na+, the reaction took place
smoothly and symmetrically substituted 2,7-dialkoxy-
thieno[2,3-d:5,4-d′]dipyrimidine-4,5(3H,6H)-diones 6 were
obtained in satisfactory yields.
J. Org. Chem, Vol. 69, No. 24, 2004 8367

Ding et al.
TABLE 2. Yields of Compounds 9a,b and 12a-l
SCHEME 4. Synthesis of Compounds 12a
It is interesting to note that a differentiation between
the two iminophosphorane functions appears when an
equimolar amount of aromatic isocyanate is used. In this
case, only the carbodiimide 7 is generated and monopy-
rimidinone 9 is obtained when carbodiimide 7 is further
treated with amine under basic condition. This may be
due to the lower reactivity of the second triphenylphos-
phoranylidenamino group of 7 compared with bis(imino-
phosphorane) 3.
Iminophosphorane 9 reacted further with other aro-
matic isocyanates to give carbodiimides 10, which were
allowed to react with secondary amines and subsequently
with sodium ethoxide to provide unsymmetrically sub-
stituted 2,7-diaminothieno[2,3-d:5,4-d′]dipyrimidine-4,5-
(3H,6H)-diones 12 in satisfactory yields at room temper-
ature. The results are listed in Table 2.
a Reagents and conditions: (a) CH2Cl2, 0-5 °C, 8-12 h; (b)
CH2Cl2, rt, 0.5-6 h; (c) EtOH, EtO-Na+, rt, 1-6 h; or CH3CN,
K2CO3 (s), 40-50 °C, 6-8 h.
The direct reaction of carbodiimide 10 with phenols in
the presence of catalytic potassium carbonate gave un-
symmetrically substituted 2,7-diaryloxythieno[2,3-d:5,4-
d′]dipyrimidine-4,5(3H,6H)-diones 12 in good yields. The
formation of 12 can be rationalized in terms of an initial
nucleophilic addition of phenoxides to the carbodiimides
10 to give the intermediate 11, which cyclizes to give 12.
No matter if the substituents on the phenols are electron-
withdrawing or electron-releasing groups, the cyclization
can be completed smoothly at room temperature. When
carbodiimide 10 was treated with ROH in the presence
of catalytic RO-Na+, unsymmetrically substituted 2,7-
dialkoxythieno[2,3-d:5,4-d′]dipyrimidine-4,5(3H,6H)-di-
ones 12 were obtained in satisfactory yields.
In conclusion, we have developed an efficient synthesis
of symmetrically or unsymmetrically 2,3,6,7-tetrasubsti-
tuted thieno[2,3-d:5,4-d′]dipyrimidine-4,5(3H,6H)-diones
from bis(iminophosphorane). Due to the mild reaction
condition, good yields, easily accessible starting material,
and straightforward product isolation, we think that this
new synthetic approach discussed here has potential in
8368 J. Org. Chem., Vol. 69, No. 24, 2004

Bis(iminophosphorane) in Heterocyclic Synthesis
12H), 1.08-1.26 (m, 32H), 3.00 (t, J ) 7.2 Hz, 8H), 7.26-7.42
(m, 10H). MS m/z 738 (M+, 100), 667 (20), 554 (12), 452 (38),
287 (13), 119 (49). Anal. Calcd for C44H62N6O2S: C, 71.51; H,
8.46; N, 11.37. Found: C, 71.62; H, 8.35; N, 11.39.
the synthesis of many biologically and pharmaceutically
active thienodipyrimidinone derivatives.
Experimental Section
2,7-Di(diisopropylamino)-3,6-diphenylthieno[2,3-d:5,4-
d′]dipyrimidine-4,5(3H,6H)-dione (6f). White crystals (yield
72%); mp >300 °C. IR (KBr) 1717 (CdO), 1526, 1498, 1127,
Diethyl 2,5-Bis(triphenylphosphoranylideneamino)-
thiophen-3,4-dicarboxylate (3). 3 was prepared from diethyl
2,5-diaminothiophene-3,4-carboxylate3c according to a litera-
ture report.7 Deep yellow crystals (yield 70%); mp 200-202
°C (lit.7 mp 201-203 °C).
1
698 cm-1. H NMR (CDCl3, 400 MHz) δ 1.07 (d, J ) 6.8 Hz,
24H), 3.51-3.57 (m, 4H), 7.23-7.40 (m, 10H). 13C NMR
(CDCl3, 100 MHz) δ 21.2 (8), 49.8 (4), 112.3 (2), 127.2 (2), 128.1
(4), 129.3 (4), 138.8 (2), 154.8 (2), 157.2 (2), 160.4 (2). MS m/z
570 (M+, 56), 527 (41), 470 (18), 368 (27), 250 (12), 119 (58),
43 (100). Anal. Calcd for C32H38N6O2S: C, 67.34; H, 6.71; N,
14.72. Found: C, 67.25; H, 6.83; N, 14.75.
2,7-Diaminothieno[2,3-d:5,4-d′]dipyrimidine-4,5(3H,6H)-
diones (6). To a solution of bis(iminophosphorane) 3 (2.33 g,
3 mmol) in dry methylene dichloride (15 mL) was added
aromatic isocyanate (6 mmol) under nitrogen at room tem-
perature. After the reaction mixture was left to stand for 8-12
h at 0-5 °C, the solvent was removed reduced pressure and
ether/petroleum ether (1:2, 20 mL) was added to precipitate
triphenylphosphine oxide. After filtration the solvent was
removed to give bis(carbodiimide) 4, which was used directly
without further purification. To the solution of 4 prepared
above in methylene dichloride (15 mL) was added dialkylamine
(6 mmol). After the reaction mixture was allowed to stand for
0.5-6 h, the solvent was removed and anhydrous ethanol (10
mL) with several drops of EtONa in EtOH was added. The
mixture was stirred for 1-6 h at room temperature. The
solution was then concentrated under reduced pressure and
the residual was recrystallized from ethanol to give 2,7-
diaminothieno[2,3-d:5,4-d′]dipyrimidine-4,5(3H,6H)-diones 6.
2,7-Di(diethylamino)-3,6-diphenylthieno[2,3-d:5,4-d′]-
dipyrimidine-4,5(3H,6H)-dione (6a). White crystals (yield
85%); mp >300 °C. IR (KBr) 1715 (CdO), 1536, 1508, 1286,
2,7-Di(4-morpholinyl)-3,6-di(4-methylphenyl)thieno-
[2,3-d:5,4-d′]dipyrimidine-4,5(3H,6H)-dione (6g). White
crystals (yield 87%); mp >300 °C. IR (KBr) 1717 (CdO), 1535,
1
1505, 1113, 952 cm-1. H NMR (CDCl3, 400 MHz) δ 2.38 (s,
6H), 3.13 (t, J ) 4.4 Hz, 8H), 3.43 (t, J ) 4.4 Hz, 8H), 7.21 (s,
8H). MS m/z 570 (M+, 82), 539 (10), 484 (21), 368 (34), 203
(71), 91 (100). Anal. Calcd for C30H30N6O4S: C, 63.14; H, 5.30;
N, 14.73. Found: C, 63.21; H, 5.36; N, 14.86.
3,6-Di(4-chlorophenyl)-2,7-di(1-piperidinyl)thieno[2,3-
d:5,4-d′]dipyrimidine-4,5(3H,6H)-dione (6h). White crys-
tals (yield 81%); mp >300 °C. IR (KBr) 1712 (CdO), 1535,
1489, 1251, 944 cm-1 1H NMR (CDCl3 + TFA, 400 MHz) δ
.
1.40-1.56 (m, 12H), 3.31 (t, J ) 5.6 Hz, 8H), 7.32-7.57 (m,
8H). MS m/z 608/606 (M+, 60/100), 522 (7), 467 (11), 386 (17),
221 (13), 165 (8). Anal. Calcd for C30H28Cl2N6O2S: C, 59.31;
H, 4.65; N, 13.83. Found: C, 59.25; H, 4.46; N, 13.91.
2,7-Diaryloxythieno[2,3-d:5,4-d′]dipyrimidine-4,5-
(3H,6H)-diones (6). To the solution of 4 prepared above in
CH3CN (15 mL) was added substituted phenol (6 mmol) and
solid K2CO3 (0.14 g, 1.0 mmol). The mixture was stirred for
6-8 h at 40-50 °C and filtered, the filtrate was condensed,
and the residual was recrystallized from methylene dichloride/
petroleum ether to give 2,7-diaryloxythieno[2,3-d:5,4-d′]dipy-
rimidine-4,5(3H,6H)-diones 6.
1
700 cm-1. H NMR (CDCl3, 400 MHz) δ 0.84 (t, J ) 7.2 Hz,
12H), 3.11 (q, J ) 7.2 Hz, 8H), 7.26-7.40 (m, 10H). 13C NMR
(CDCl3, 100 MHz) δ 12.5 (4), 45.0 (4), 112.4 (2), 127.7 (2), 128.6
(4), 129.1 (4), 138.1 (2), 156.0 (2), 157.0 (2), 161.1 (2). MS m/z
514 (M+, 100), 486 (11), 396 (22), 340 (35), 175 (26), 119 (38).
Anal. Calcd for C28H30N6O2S: C, 65.35; H, 5.88; N, 16.33.
Found: C, 65.27; H, 5.94; N, 16.57.
2,7-Di(4-chlorophenoxy)-3,6-diphenylthieno[2,3-d:5,4-
d′]dipyrimidine-4,5(3H,6H)-dione (6i). White crystals (yield
82%); mp >300 °C. IR (KBr) 1729 (CdO), 1561, 1484, 1211,
2,7-Di(di-n-propylamino)-3,6-diphenylthieno[2,3-d:5,4-
d′]dipyrimidine-4,5(3H,6H)-dione (6b). White crystals (yield
76%); mp 288-289 °C. IR (KBr) 1718 (CdO), 1533, 1507, 1244,
1
941 cm-1. H NMR (CDCl3, 400 MHz) δ 7.04-7.44 (m, 18H).
1
738 cm-1. H NMR (CDCl3, 400 MHz) δ 0.73 (t, J ) 7.2 Hz,
MS m/z 626/624 (M+, 76/100), 497 (88), 378 (5), 119 (29), 77
(56). Anal. Calcd for C32H18Cl2N4O4S: C, 61.45; H, 2.90; N,
8.96. Found: C, 61.49; H, 2.78; N, 8.80.
12H), 1.24-1.30 (m, 8H), 2.98 (t, J ) 7.6 Hz, 8H), 7.26-7.42
(m, 10H). 13C NMR (CDCl3, 100 MHz) δ 11.2 (4), 20.6 (4), 52.5
(4), 112.1 (2), 127.6 (2), 128.4 (4), 128.9 (4), 137.9 (2), 155.9
(2), 156.8 (2), 160.9 (2). MS m/z 570 (M+, 72), 541 (16), 470
(25), 368 (50), 203 (46), 119 (100). Anal. Calcd for C32H38-
N6O2S: C, 67.34; H, 6.71; N, 14.72. Found: C, 67.56; H, 6.88;
N, 14.64.
2,7-Di(4-bromophenoxy)-3,6-diphenylthieno[2,3-d:5,4-
d′]dipyrimidine-4,5(3H,6H)-dione (6j). White crystals (yield
73%); mp >300 °C. IR (KBr) 1730 (CdO), 1560, 1484, 1209,
1
939 cm-1. H NMR (CDCl3, 400 MHz) δ 7.00-7.45 (m, 18H).
MS m/z 716/714/712 (M+, 66/100/56), 543 (96), 514 (10), 119
(30), 77 (56). Anal. Calcd for C32H18Br2N4O4S: C, 53.80; H,
2.54; N, 7.84. Found: C, 53.93; H, 2.36; N, 7.54.
2,7-Di(di-n-butylamino)-3,6-diphenylthieno[2,3-d:5,4-
d′]dipyrimidine-4,5(3H,6H)-dione (6c). White crystals (yield
82%); mp 224-226 °C. IR (KBr) 1719 (CdO), 1532, 1507, 1229,
1
737 cm-1. H NMR (CDCl3, 400 MHz) δ 0.83 (t, J ) 7.2 Hz,
2,7-Di(4-methylthiophenoxy)-3,6-diphenylthieno[2,3-
d:5,4-d′]dipyrimidine-4,5(3H,6H)-dione (6k). White crys-
tals (yield 84%); mp >300 °C. IR (KBr) 1731 (CdO), 1560,
12H), 1.10-1.24 (m, 16H), 3.01 (t, J ) 7.2 Hz, 8H), 7.26-7.41
(m, 10H). 13C NMR (CDCl3, 100 MHz) δ 13.6 (4), 19.9 (4), 29.4
(4), 50.5 (4), 112.1 (2), 127.5 (2), 128.3 (4), 128.9 (4), 137.9 (2),
155.9 (2), 156.8 (2), 160.9 (2). MS m/z 626 (M+, 74), 570 (8),
498 (11), 396 (41), 231 (27), 119 (79), 57 (100). Anal. Calcd for
C36H46N6O2S: C, 68.98; H, 7.40; N, 13.41. Found: C, 68.85;
H, 7.16; N, 13.63.
1
1484, 1209, 939 cm-1. H NMR (CDCl3, 400 MHz) δ 2.48 (s,
6H), 7.04-7.46 (m, 18H). 13C NMR (CDCl3, 100 MHz) δ 21.3
(2), 114.7 (2), 119.2 (2), 123.3 (4), 128.0 (4), 129.9 (4), 131.9
(2), 132.6 (4), 138.8 (2), 150.6 (2), 154.1 (2), 155.7 (2), 159.7
(2). MS m/z 648 (M+, 41), 529 (14), 509 (68), 139 (45), 77 (100).
Anal. Calcd for C34H24N4O4S3: C, 62.95; H, 3.73; N, 8.64.
Found: C, 62.72; H, 3.87; N, 8.84.
2,7-Di(di-n-pentylamino)-3,6-diphenylthieno[2,3-d:5,4-
d′]dipyrimidine-4,5(3H,6H)-dione (6d). White crystals (yield
71%); mp 189-190 °C. IR (KBr) 1718 (CdO), 1532, 1508, 1458,
2,7-Di(4-bromophenoxy)-3,6-di(4-methylphenyl)thieno-
[2,3-d:5,4-d′]dipyrimidine-4,5(3H,6H)-dione (6l). White crys-
tals (yield 70%); mp >300 °C. IR (KBr) 1729 (CdO), 1562,
1
737 cm-1. H NMR (CDCl3, 400 MHz) δ 0.85 (t, J ) 7.2 Hz,
12H), 1.04-1.28 (m, 24H), 3.00 (t, J ) 7.6 Hz, 8H), 7.26-7.42
(m, 10H). MS m/z 682 (M+, 64), 625 (6), 424 (28), 354 (8), 259
(14), 119 (56), 43 (100). Anal. Calcd for C40H54N6O2S: C, 70.35;
H, 7.97; N, 12.30. Found: C, 70.18; H, 7.91; N, 12.47.
1481, 1212, 945 cm-1 1H NMR (CDCl3 + TFA, 400 MHz) δ
.
2.46 (s, 6H), 7.03-7.58 (m, 16H). MS m/z 744/742/740 (M+,
13/23/11), 571 (9), 133 (50), 39 (100). Anal. Calcd for C34H22-
Br2N4O4S: C, 55.00; H, 2.99; N, 7.55. Found: C, 55.14; H, 2.92;
N, 7.48.
2,7-Di(di-n-hexylamino)-3,6-diphenylthieno[2,3-d:5,4-
d′]dipyrimidine-4,5(3H,6H)-dione (6e). White crystals (yield
67%); mp 169-170 °C. IR (KBr) 1718 (CdO), 1534, 1508, 1466,
2,7-Di(4-methylphenoxy)-3,6-di(3-methylphenyl)thieno-
[2,3-d:5,4-d′]dipyrimidine-4,5(3H,6H)-dione (6m). White
1
737 cm-1. H NMR (CDCl3, 400 MHz) δ 0.87 (t, J ) 7.2 Hz,
J. Org. Chem, Vol. 69, No. 24, 2004 8369

Ding et al.
crystals (yield 77%); mp >300 °C. IR (KBr) 1726 (CdO), 1560,
of EtONa in EtOH was added. The mixture was stirred for 6
h at room temperature. The solution was condensed and the
residual was recrystallized from ethanol to 2-aminothieno[2,3-
d:5,4-d′]dipyrimidine- 4,5(3H,6H)-diones 12.
2-Diethylamino-3-(4-chlorophenyl)-6-phenyl-7-(1-pip-
eridinyl)thieno[2,3-d:5,4-d′]dipyrimidine-4,5(3H,6H)-di-
one (12a). White crystals (yield 82%); mp >300 °C. IR (KBr)
1716 (CdO), 1536, 1450, 1249, 946 cm-1. 1H NMR (CDCl3, 400
MHz) δ 0.88 (t, J ) 7.2 Hz, 6H), 1.24-1.42 (m, 6H), 3.06-
3.12 (m, 8H), 7.23-7.43 (m, 9H). MS m/z 560 (M+, 100), 532
(8), 408 (14), 352 (25), 209 (18), 187 (16). Anal. Calcd for C29H29-
ClN6O2S: C, 62.08; H, 5.21; N, 14.98. Found: C, 62.24; H, 5.10;
N, 14.74.
2-Diethylamino-3-(4-methylphenyl)-6-phenyl-7-(1-pip-
eridinyl)thieno[2,3-d:5,4-d′]dipyrimidine-4,5(3H,6H)-di-
one (12b). White crystals (yield 86%); mp >300 °C. IR (KBr)
1717 (CdO), 1533, 1457, 1250, 944 cm-1. 1H NMR (CDCl3, 400
MHz) δ 0.85 (t, J ) 7.2 Hz, 6H), 1.23-1.41 (m, 6H), 2.36 (s,
3H), 3.07-3.12 (m, 8H), 7.14-7.40 (m, 9H). 13C NMR (CDCl3,
100 MHz) δ 12.4 (2), 21.0, 23.8, 24.6 (2), 44.8 (2), 49.6 (2), 112.1,
112.9, 127.3, 128.1 (2), 128.7 (2), 128.9 (4), 135.2, 137.2, 137.7,
156.0, 156.3, 156.4, 156.7, 160.4, 160.9. MS m/z 540 (M+, 98),
510 (18), 407 (37), 352 (57), 189 (67), 132 (100). Anal. Calcd
for C30H32N6O2S: C, 66.64; H, 5.97; N, 15.54. Found: C, 66.31;
H, 5.85; N, 15.79.
2-(4-Morpholinyl)-3-(4-chlorophenyl)-6-phenyl-7-(1-pi-
peridinyl)thieno[2,3-d:5,4-d′]dipyrimidine-4,5(3H,6H)-di-
one (12c). White crystals (yield 81%); mp >300 °C. IR (KBr)
1718 (CdO), 1534, 1505, 1115, 950 cm-1. 1H NMR (CDCl3, 400
MHz) δ 1.22-1.43 (m, 6H), 3.05-3.13 (m, 8H), 3.42 (m, 4H),
7.26-7.44 (m, 9H). 13C NMR (CDCl3, 100 MHz) δ 24.0, 24.8
(2), 48.8 (2), 49.9 (2), 65.8 (2), 112.6, 113.4, 127.6, 128.3 (2),
128.5 (2), 129.2 (2), 130.6 (2), 133.6, 135.5, 137.7, 155.5, 155.7,
156.2, 156.9, 160.1, 161.0. MS m/z 576/574 (M+, 36/100), 540
(5), 490 (10), 388 (25), 223 (11), 77 (20). Anal. Calcd for C29H27-
ClN6O3S: C, 60.57; H, 4.73; N, 14.61. Found: C, 60.33; H, 4.93;
N, 14.48.
2-(Di-n-propylamino)-3-(4-chlorophenyl)-6-phenyl-7-
(4-morpholinyl)thieno[2,3-d:5,4-d′]dipyrimidine-4,5-
(3H,6H)-dione (12d). White crystals (yield 74%); mp >300
°C. IR (KBr) 1717 (CdO), 1536, 1506, 1245, 955 cm-1. 1H NMR
(CDCl3, 400 MHz) δ 0.76 (t, J ) 7.2 Hz, 6H), 1.23-1.36 (m,
4H), 2.98 (t, J ) 7.2 Hz, 4H), 3.08-3.10 (m, 4H), 3.40 (t, J )
4.0 Hz, 4H), 7.24-7.41 (m, 9H). MS m/z 592/590 (M+, 34/85),
561 (5), 490 (8), 77 (24), 43 (100). Anal. Calcd for C30H31-
ClN6O3S: C, 60.96; H, 5.29; N, 14.22. Found: C, 60.68; H, 5.34;
N, 14.15.
2-(Di-n-butylamino)-3-(4-chlorophenyl)-6-phenyl-7-(4-
morpholinyl)thieno[2,3-d:5,4-d′]dipyrimidine-4,5(3H,6H)-
dione (12e). White crystals (yield 72%); mp >300 °C. IR (KBr)
1717 (CdO), 1534, 1450, 1259, 955 cm-1. 1H NMR (CDCl3, 400
MHz) δ 0.85 (t, J ) 7.2 Hz, 6H), 1.14-1.27 (m, 8H), 3.01 (t, J
) 7.2 Hz, 4H), 3.09-3.11 (m, 4H), 3.39-3.41 (m, 4H), 7.24-
7.41 (m, 9H). MS m/z 620/618 (M+, 42/100), 562 (9), 490 (14),
354 (27), 77 (21). Anal. Calcd for C32H35ClN6O3S: C, 62.07; H,
5.70; N, 13.57. Found: C, 62.14; H, 5.56; N, 13.59.
2-(Diethylamino)-3-(4-methylphenyl)-6-phenyl-7-(4-mor-
pholinyl)thieno[2,3-d:5,4-d′]dipyrimidine-4,5(3H,6H)-di-
one (12f). White crystals (yield 83%); mp >300 °C. IR (KBr)
1716 (CdO), 1532, 1459, 1114, 956 cm-1. 1H NMR (CDCl3, 400
MHz) δ 0.86 (t, J ) 7.2 Hz, 6H), 2.37 (s, 3H), 3.09-3.14 (m,
8H), 3.40-3.42 (m, 4H), 7.17-7.42 (m, 9H). 13C NMR (CDCl3,
100 MHz) δ 12.5 (2), 21.1, 45.0 (2), 48.8 (2), 65.9 (2), 112.1,
113.6, 127.9, 128.4 (2), 128.8 (2), 129.0 (2), 129.1 (2), 135.3,
137.1, 137.5, 155.5, 156.1, 156.2, 156.8, 160.0, 161.3. MS m/z
542 (M+, 100), 513 (7), 470 (7), 410 (10), 354 (20), 91 (25). Anal.
Calcd for C29H30N6O3S: C, 64.19; H, 5.57; N, 15.49. Found:
C, 64.34; H, 5.31; N, 15.42.
1
1495, 1203, 940 cm-1. H NMR (CDCl3, 400 MHz) δ 2.35 (s,
6H), 2.37 (s, 6H), 7.00-7.38 (m, 16H). 13C NMR (CDCl3, 100
MHz) δ 20.8 (2), 21.2 (2), 114.4 (2), 121.0 (4), 125.1 (2), 128.8
(4), 129.5 (2), 129.9 (4), 134.6 (2), 135.6 (2), 139.0 (2), 149.3
(2), 154.3 (2), 155.8 (2), 159.9 (2). MS m/z 612 (M+, 35), 505
(49), 372 (96), 133 (23), 91 (100). Anal. Calcd for C36H28-
N4O4S: C, 70.57; H, 4.61; N, 9.14. Found: C, 70.35; H, 4.78;
N, 9.25.
2,7-Dialkoxythieno[2,3-d:5,4-d′]dipyrimidine-4,5(3H,6H)-
diones (6). To the solution of 4 prepared above in ROH (15
mL) was added several drops of RO-Na+ in ROH. The mixture
was stirred for 6 h at room temperature. The solution was
condensed and the residual was recrystallized from methylene
dichloride/petroleum ether to give 2,7-dialkoxythieno[2,3-d:5,4-
d′] dipyrimidine-4,5(3H,6H)-diones 6.
2,7-Dimethoxy-3,6-diphenylthieno[2,3-d:5,4-d′]dipyri-
midine-4,5(3H,6H)-dione (6n). White crystals (yield 73%);
mp >300 °C. IR (KBr) 1724 (CdO), 1562, 1509, 1257, 967 cm-1
.
1H NMR (CDCl3, 400 MHz) δ 3.96 (s, 6H), 7.20-7.48 (m, 10H).
MS m/z 432 (M+, 84), 313 (8), 134 (15), 119 (100). Anal. Calcd
for C22H16N4O4S: C, 61.10; H, 3.73; N, 12.96. Found: C, 61.43;
H, 3.58; N, 12.81.
2,7-Diethoxy-3,6-diphenylthieno[2,3-d:5,4-d′]dipyrimi-
dine-4,5(3H,6H)-dione (6o). White crystals (yield 75%); mp
>300 °C. IR (KBr) 1716 (CdO), 1561, 1508, 1257, 944 cm-1
.
1H NMR (CDCl3, 400 MHz) δ 1.25 (t, J ) 7.2 Hz, 6H), 4.42 (q,
J ) 7.2 Hz, 4H), 7.19-7.45 (m, 10H). 13C NMR (CDCl3, 100
MHz) δ 13.9 (2), 65.2 (2), 113.6 (2), 128.3 (2), 128.4 (4), 128.7
(4), 134.7 (2), 154.4 (2), 155.9 (2), 159.9 (2). MS m/z 460 (M+,
10), 432 (4), 119 (71), 77 (100). Anal. Calcd for C24H20N4O4S:
C, 62.60; H, 4.38; N, 12.17. Found: C, 62.47; H, 4.46; N, 12.36.
5-Ethoxycarbonyl-6-triphenylphosphoranylideneam-
inothieno[2,3-d]pyrimidin-4(3H)-ones (9). To a solution of
bis(iminophosphorane) 3 (2.33 g, 3 mmol) in dry methylene
dichloride (15 mL) was added phenyl isocyanate (0.36 g, 3
mmol) under nitrogen at room temperature. After the reaction
mixture had stood for 12 h at 0-5 °C, dialkylamine (3 mmol)
was added. After this reaction mixture had stood for 0.5-1 h
at room temperature, the solvent was removed and anhydrous
ethanol (10 mL) with several drops of EtONa in EtOH was
added. The mixture was stirred for 1-2 h at room temperature.
The solution was condensed and the residual was recrystal-
lized from ethanol to give 5-ethoxycarbonyl-6- triphenylphos-
phoranylideneaminothieno[2,3-d]pyrimidin-4(3H)-ones 9.
2-(1-Piperidinyl)-3-phenyl-5-ethoxycarbonyl-6-triph-
enylphosphoranylideneaminothieno[2,3-d]pyrimidin-
4(3H)-ones (9a). White crystals (yield 81%); mp 195-196 °C.
IR (KBr) 1705 and 1674 (CdO), 1525, 1491, 1342, 695 cm-1
.
1H NMR (CDCl3, 400 MHz) δ 1.14-1.34 (m, 9H), 2.91 (t, J )
5.2 Hz, 4H), 4.35 (q, J ) 7.2 Hz, 2H), 7.29-7.81 (m, 20H). MS
m/z 658 (M+, 51), 277 (100), 262 (73), 183 (74), 77 (44). Anal.
Calcd for C38H35N4O3PS: C, 69.28; H, 5.36; N, 8.50. Found:
C, 69.52; H, 5.42; N, 8.73.
2-(4-Morpholinyl)-3-phenyl-5-ethoxycarbonyl-6-triph-
enylphosphoranylideneaminothieno[2,3-d]pyrimidin-
4(3H)-ones (9b). White crystals (yield 77%); mp 254-255 °C.
IR (KBr) 1704 and 1684 (CdO), 1524, 1496, 1204, 695 cm-1
.
1H NMR (CDCl3, 400 MHz) δ 1.32 (t, J ) 7.2 Hz, 3H), 2.95 (t,
J ) 4.4 Hz, 4H), 3.33 (t, J ) 4.4 Hz, 4H), 4.35 (q, J ) 7.2 Hz,
2H), 7.30-7.82 (m, 20H). MS m/z 660 (M+, 94), 615 (17), 588
(20), 277 (55), 262 (100), 183 (85), 108 (72). Anal. Calcd for
C37H33N4O4PS: C, 67.26; H, 5.03; N, 8.48. Found: C, 67.18;
H, 5.25; N, 8.23.
2-Aminothieno[2,3-d:5,4-d′]dipyrimidine-4,5(3H,6H)-
diones (12). To a solution of iminophosphorane 9 (3 mmol)
in dry methylene dichloride (15 mL) was added aromatic
isocyanate (3 mmol) under nitrogen at room temperature. After
the reaction mixture had stood for 6-12 h at 0-5 °C,
dialkylamine (3 mmol) was added. After this reaction mixture
had stood for 3-6 h at room temperature, the solvent was
removed and anhydrous ethanol (10 mL) with several drops
2-(Di-n-butylamino)-3-(4-methylphenyl)-6-phenyl-7-(4-
morpholinyl)thieno[2,3-d:5,4-d′]dipyrimidine-4,5(3H,6H)-
dione (12g). White crystals (yield 74%); mp 299-300 °C. IR
(KBr) 1715 (CdO), 1536, 1454, 1114, 955 cm-1 1H NMR
.
8370 J. Org. Chem., Vol. 69, No. 24, 2004

Bis(iminophosphorane) in Heterocyclic Synthesis
(CDCl3, 400 MHz) δ 0.84 (t, J ) 7.2 Hz, 6H), 1.11-1.27 (m,
8H), 2.37 (s, 3H), 3.00-3.06 (m, 8H), 3.37-3.38 (m, 4H), 7.16-
7.39 (m, 9H). 13C NMR (CDCl3, 100 MHz) δ 13.7 (2), 20.0 (2),
20.9, 29.6 (2), 48.6 (2), 50.8 (2), 65.7 (2), 111.8, 113.4, 127.5,
128.1 (2), 128.9 (4), 129.1 (2), 135.2, 137.0, 137.2, 155.5, 155.9,
156.2, 156.3, 159.7, 160.9. MS m/z 598 (M+, 100), 555 (23), 470
(26), 354 (54), 189 (53), 77 (69). Anal. Calcd for C33H38N6O3S:
C, 66.20; H, 6.40; N, 14.04. Found: C, 66.37; H, 6.28; N, 14.21.
2-(Diethylamino)-3,6-diphenyl-7-(4-morpholinyl)thieno-
[2,3-d:5,4-d′]dipyrimidine-4,5(3H,6H)-dione (12h). White
crystals (yield 73%); mp >300 °C. IR (KBr) 1716 (CdO), 1532,
1456, 1115, 955 cm-1. 1H NMR (CDCl3, 400 MHz) δ 0.85 (t, J
) 7.2 Hz, 6H), 3.11-3.15 (m, 8H), 3.41-3.43 (m, 4H), 7.26-
7.43 (m, 10H). MS m/z 528 (M+, 100), 499 (7), 456 (5), 119 (18),
77 (72). Anal. Calcd for C28H28N6O3S: C, 63.62; H, 5.34; N,
15.90. Found: C, 63.47; H, 5.16; N, 15.98.
2-Aryloxythieno[2,3-d:5,4-d′]dipyrimidine-4,5(3H,6H)-
diones (12). To the solution of 10 prepared above in CH3CN
(15 mL) was added substituted phenol (3 mmol) and solid K2-
CO3 (0.07 g, 0.5 mmol). The mixture was stirred for 6-10 h at
40-50 °C and filtered, the filtrate was condensed, and the
residual was recrystallized from methylene dichloride/petro-
leum ether to give 2,7-diaryloxythieno[2,3-d:5,4-d′]dipyrimi-
dine-4,5(3H,6H)-diones 12.
2-(4-Methoxyphenoxy)-3,6-diphenyl-7-(1-piperidinyl)-
thieno[2,3-d:5,4-d′]dipyrimidine-4,5(3H,6H)-dione (12i).
White crystals (yield 78%); mp >300 °C. IR (KBr) 1725 (Cd
O), 1542, 1506, 1203, 942 cm-1. 1H NMR (CDCl3, 400 MHz) δ
1.24-1.42 (m, 6H), 3.13 (t, J ) 5.0 Hz, 4H), 3.81 (s, 3H), 6.88-
7.48 (m, 14H). 13C NMR (CDCl3, 100 MHz) δ 24.0, 24.8 (2),
49.8 (2), 55.5, 112.5, 114.4 (2), 114.7, 122.3 (2), 127.7, 128.3
(2), 128.4 (2), 128.7, 129.0 (4), 134.9, 137.8, 145.0, 154.2, 155.7,
156.7, 156.8, 157.3, 159.1, 161.7. MS m/z 577 (M+, 100), 454
(66), 391 (31), 288 (38), 187 (26), 77 (58). Anal. Calcd for
C32H27N5O4S: C, 66.54; H, 4.71; N, 12.12. Found: C, 66.35;
H, 4.47; N, 12.34.
288 (7), 189 (17), 77 (100). Anal. Calcd for C31H25N5O5S: C,
64.24; H, 4.35; N, 12.08. Found: C, 64.37; H, 4.41; N, 11.93.
2-Alkoxythieno[2,3-d:5,4-d′]dipyrimidine-4,5(3H,6H)-
diones (12). To the solution of 10 prepared above in ROH (15
mL) was added several drops of RO-Na+ in ROH. The mixture
was stirred for 6 h at room temperature. The solution was
condensed and the residual was recrystallized from methylene
dichloride/petroleum ether to give 2-alkoxythieno[2,3-d:5,4-d′]-
dipyrimidine-4,5(3H,6H)-diones 12.
2-Ethoxy-3,6-diphenyl-7-(4-morpholinyl)thieno[2,3-d:
5,4-d′]dipyrimidine-4,5(3H,6H)-dione (12k). White crystals
(yield 81%); mp 284-285 °C. IR (KBr) 1721 (CdO), 1537, 1507,
1260, 947 cm-1. 1H NMR (CDCl3, 400 MHz) δ 1.25 (t, J ) 7.2
Hz, 3H), 3.14 (t, J ) 4.4 Hz, 4H), 3.42 (t, J ) 4.4 Hz, 4H), 4.42
(q, J ) 7.2 Hz, 2H), 7.19-7.45 (m, 10H). MS m/z 501 (M+, 100),
473 (8), 381 (26), 313 (15), 189 (18), 77 (26). Anal. Calcd for
C26H23N5O4S: C, 62.26; H, 4.62; N, 13.96. Found: C, 62.41;
H, 4.54; N, 13.71.
2-Methoxy-3,6-diphenyl-7-(4-morpholinyl)thieno[2,3-d:
5,4-d′]dipyrimidine-4,5(3H,6H)-dione (12l). White crystals
(yield 85%); mp >300 °C. IR (KBr) 1720 (CdO), 1538, 1507,
1259, 955 cm-1. 1H NMR (CDCl3, 400 MHz) δ 3.13 (t, J ) 4.4
Hz, 4H), 3.42 (t, J ) 4.4 Hz, 4H), 3.95 (s, 3H), 7.20-7.45 (m,
10H). 13C NMR (CDCl3, 100 MHz) δ 48.9 (2), 56.1, 65.8 (2),
113.3, 113.9, 128.1, 128.4 (2), 128.6 (2), 128.8 (2), 128.9 (2),
134.7, 137.0, 155.0, 155.7, 155.9, 156.3, 159.8, 160.7. MS m/z
487 (M+, 100), 401 (17), 377 (37), 248 (28), 117 (24), 43 (60).
Anal. Calcd for C25H21N5O4S: C, 61.59; H, 4.34; N, 14.36.
Found: C, 61.85; H, 4.57; N, 14.22.
Acknowledgment. We gratefully acknowledge fi-
nancial support of this work by the National Key Project
for Basic Research (2003CB114400, 2003CB114406) and
the National Natural Science Foundation of China
(Project No.20102001).
2-(4-Methoxyphenoxy)-3,6-diphenyl-7-(4-morpholinyl)-
thieno[2,3-d:5,4-d′]dipyrimidine-4,5(3H,6H)-dione (12j).
White crystals (yield 73%); mp >300 °C. IR (KBr) 1725 (Cd
O), 1541, 1500, 1200, 945 cm-1. 1H NMR (CDCl3, 400 MHz) δ
3.08 (t, J ) 4.4 Hz, 4H), 3.38 (t, J ) 4.4 Hz, 4H), 3.82 (s, 3H),
6.87-7.47 (m, 14H). MS m/z 579 (M+, 67), 456 (48), 391 (12),
Supporting Information Available: General experimen-
1
tal procedures, copies of H NMR spectra for all compounds
and 13C NMR spectra for typical compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
JO048691V
J. Org. Chem, Vol. 69, No. 24, 2004 8371