Short access to 6-substituted pyrimidine derivatives by the SRN1 mechanism. Synthesis of 6-substituted uracils through a one-pot procedure

Article abstract of DOI:10.1021/jo101064e

(Figure presented) The synthesis of 6-substituted 2,4-dimethoxypyrimidines with different nucleophiles was accomplished with good to excellent yields (50-95%) through S_RN1 reactions, starting from commercially available 6-chloro-2,4-dimethoxypy

Full text of DOI:10.1021/jo101064e

pubs.acs.org/joc
Short Access to 6-Substituted Pyrimidine Derivatives by the SRN1
Mechanism. Synthesis of 6-Substituted Uracils through
a One-Pot Procedure
Javier I. Bardagı and Roberto A. Rossi*
´
ꢀ
´
INFIQC, Departamento de Quımica Organica, Facultad de Ciencias Quımicas, Universidad Nacional de
Coꢀrdoba, Ciudad Universitaria, 5000 Coꢀrdoba, Argentina
rossi@fcq.unc.edu.ar
Received June 1, 2010
The synthesis of 6-substituted 2,4-dimethoxypyrimidines with different nucleophiles was accomplished
with good to excellent yields (50-95%) through SRN1 reactions, starting from commercially available
6-chloro-2,4-dimethoxypyrimidine (1). Hydrolysis of these derivatives gave access to 6-substituted
uracils with good yields and short times by the use of microwave irradiation. The preparation of uracils
from 1 without the isolation of 2,4-dimethoxypyrimidine derivatives affords a rapid access to these
compounds in good yields and excellent purity by avoiding an unnecessary step of purification.
Introduction
Uracils are considered privileged structures in drug discov-
ery and their functionalization at positions N1, N3, C5, and C6
is of major synthetic importance.4 In particular, there is a
renewed interest in the synthesis of new C6 derivates to be
applied to the treatment of cancer or as antiviral compounds.5
There are three main synthetic strategies to prepare uracil
derivatives: (a) building of the uracil nucleus from acyclic
precursors with appropriate substituents; (b) modification of
the structure of functionalized uracils or uracil itself by
reaction with different reagents; and (c) functionalization
of masked uracil moieties with reactions incompatible with
the nucleus.6 The combination of these approaches is often
found in the synthesis of target compounds with potential
biological activity.7
The uracil unit is one of the most important structures in
life, being part of the building blocks of RNA and other
natural products. Therefore, it is not surprising that uracil
derivatives have important biological activity. Actions as
antiviral and antitumoral agents are probably among the
most widely reported activities;1 however, uracil derivatives,
including herbicides, insecticides, bactericides, and acari-
cides, among others, have also been synthesized.2 In addi-
tion, uracil units can be found in the chemistry of peptide
nucleic acid (PNA) or as part of other fused systems with
antiallergic, antihypertensive, cardiotonic, bronchodilator,
or antibronchitis activity.3
An interesting example has illustrated the first preparation of
boron analogues of uracils (borauracils) starting from acyclic
precursors.8 A series of reports have described the synthesis of
uracils fused to different heterocycles. Recent examples involve
(1) (a) Parker, W. B. Chem. Rev. 2009, 109, 2880. (b) Pathak, T. Chem.
Rev. 2002, 102, 1623 and references cited therein.
(2) (a) Saladino, R.; Crestini, C.; Palamara, A. T.; Danti, M. C.; Manetti,
F.; Corelli, F.; Garaci, E.; Botta, M. J. Med. Chem. 2001, 44, 4554. (b) Zhi,
C.; Long, Z.; Manikowski, A.; Brown, N. C.; Tarantino, P. M.; Holm, K.;
Dix, E. J.; Wright, G. E.; Foster, K. A.; Butler, M. M.; LaMarr, W. A.; Skow,
D. J.; Motorina, I.; Lamothe, S.; Storer, R. J. Med. Chem. 2005, 48, 7063.
(4) Newkome, G. R.; Pandler, W. W. Contemporary Heterocyclic Chem-
istry; Wiley: New York, 1982.
ꢀ
(c) Fustero, S.; Piera, J.; Sanz-Cervera, J. F.; Catalan, S.; Ramırez de
(5) Hopkins, A. L.; Ren, J.; Tanaka, H.; Baba, M.; Okamato, M.; Stuart,
D. I.; Stammers, D. K. J. Med. Chem. 1999, 42, 4500.
Arellano, C. Org. Lett. 2004, 6, 1417. (d) Lagoja, M. Chem. Biodiversity
2005, 2, 1. (e) Jain, K. S.; Chitre, T. S.; Minutosiyar, P. B.; Kathiravan,
M. K.; Bendre, V. S.; Veer, V. S.; Shahane, S. R.; Shishoo, C. J. Curr. Sci.
2006, 793 and references cited therein.
(3) Palasz, A.; Monatsh. Chem. 2008, 139, 1397 and references cited
therein.
(6) For one example of each one see: (a) Reference 2c. (b) Uraguchi, D.;
Yamamoto, K.; Ohtsuka, Y.; Tokuhisa, K.; Yamakawa, T. Appl. Catal., A
2008, 348, 137. (c) Reese, C. B.; Wu, Q. Org. Biomol. Chem. 2003, 1, 3160.
(7) Bardagı, J. I.; Rossi, R. A. Org. Prep. Proced. Int. 2009, 41, 479–514.
(8) Ruman, T.; Dzugopolska, K.; Rode, W. Bioorg. Chem. 2010, 38, 33.
DOI: 10.1021/jo101064e
r
Published on Web 06/30/2010
J. Org. Chem. 2010, 75, 5271–5277 5271
2010 American Chemical Society

Bardagı and Rossi
JOCArticle
a multicomponent approximation used to prepare pyrido[2,3-
d:6,5-d ]dipyrimidines, tetrahydropyrimido[4,5-b]quinolines,
and pyrazolo[40,30:5,6]pyrido[2,3-d]pyrimidine-diones in good
yields, starting from barbituric acids, aldehydes, and different
amines in water as solvents.9 The same reactions were per-
formed in short reaction times with ultrasonic irradiations.10
Likewise, the synthesis of pyrimido[4,5-c]pyridazine-5,7(1H,
6H )-diones,11 pyrido[2,3-d ]pyrimidines,12 and azocine-pyri-
midines13 has been achieved through condensation, hetero-
Diels-Alder, and radical cyclization reactions, respectively.
6-Substituted thymines have been prepared recently via
lithiation of a N1-sulfonamide and by reaction with alde-
hydes.14 Substitutions at positions five and six by nucleophiles
have been accomplished by reaction of tosyl and halouracils
(or activated uracils) with different species like amines, alco-
hols, and anions derived from tiols and selenols.15 However, as
can be inferred, this strategy is limited to nucleophiles with
basicity similar to uracil, or in the synthesis of N1-substituted
ones.16
Recently we studied the reaction of 6-chloro-2,4-di-
methoxypyrimidine (1) with trimethylstannyl anions by the
SRN1 mechanism and obtained excellent yields of the corre-
sponding stannane 2 (95%, eq 1). This stannane reacted with
electrophiles EX (EX=ArI and ArCOCl) in cross-coupling
reactions catalyzed by Pd(0) to obtain 6-aryl and 6-acylpyri-
midines 3 that afforded 6-substituted uracil derivatives 4
after hydrolysis with good global yields (eq 2).17
(ET) from the nucleophile to the substrate to afford a radical
anion. In some systems, the ET step is spontaneous, but in
others, light is required to induce the reaction. The propaga-
tion steps consist of fragmentation of the radical anion to
afford a radical and the leaving group (eq 3), coupling of the
radical with the nucleophile to afford a radical anion (eq 4),
followed by ET to the substrate (eq 5) forming the inter-
mediate necessary to continue the propagation cycle.
-
-
3
ðArXÞ f Ar þ X
ð3Þ
ð4Þ
ð5Þ
-
-
3
3
Ar þ Nu f ðArNuÞ
-
-
3
3
ðArNuÞ þ ArX f ArNu þ ðArXÞ
We report now the synthesis of uracil derivatives through a
sequence of SRN1-hydrolysis reactions from commercially
available 1. We have studied and optimized the two steps
separately to obtain the best result. In addition, we examined
the possibility of performing the two reactions in a “one-pot”
approximation to gain rapid access to the different families
of 6-substituted uracils.
Results and Discussion
Some years ago, Wolfe et al. performed the reaction of 1
with pinacolone enolate anion 5 in liquid ammonia and
obtained excellent yields of the substitution product after
15 min of irradiation by the SRN1 mechanism (eq 6).19
We repeated the reaction of 1 and 5 and obtained an
excellent yield of the substitution product 6, in the same
experimental conditions (Table 1, expt 1).
TABLE 1. Photostimulated Reactions of Anions from Aliphatic
Ketones with 1.a
expt
Nu-
solvent (time)
product (%)b
Cl-,c %
The radical nucleophilic substitution, or SRN1 reaction, is
a process through which an aromatic nucleophilic substitu-
tion is achieved. The scope of this process has increased
considerably and it nowadays serves as an important syn-
thetic strategy.18 The initiation step is an electron transfer
1
2
3
4
5
6
5
5
7
9
9
9
NH3 (15 min)
DMSO (15 min)
NH3 (30 min)
NH3 (30 min)
DMSO (20 min)
MeCN (15 min)
6 (95%)
100
<5
e
77
68
6 (traces)
8 (69%)d
10 (50%)d
10 (traces)
10 (traces)
<5
aAll the photostimulated reactions were performed with 0.25 ꢀ 10-3
mol of 1 as substrate and 1.0 ꢀ 10-3 mol of nucleophile (Nu-). Photo-
stimulated reactions were performed with two water-cooled metallic
(9) Bazgir, A.; Khanaposhtani, M. M.; Ghahremanzadeh, R.; Soorki,
A. A. C. R. Chim. 2009, 12, 1287.
(10) Mosslemin, M. H.; Nateghi, M. R. Ultrason. Sonochem. 2010, 17, 162.
(11) Turbiak, A. J.; Kampf, J. W.; Hollis Showalter, H. D. Tetrahedron
Lett. 2010, 51, 1326.
(12) Deb, M. L.; Bhuyan, P. J. Beil. J. Org. Chem 2010, 6, 11.
(13) Majumdar, K. C.; Mondal, S.; Ghosh, D. Tetrahedron Lett. 2010, 51,
348.
c
iodure lamps. bYield. Determined potentiometrically. dReduced sub-
strate was detected but not quantified. eNot quantified.
It is proposed that rigid polycyclic moieties like adamantyl
or norbornyl could increase the biological activity of com-
pounds; including these moieties in the structure increases
the lipophilic properties of drugs. In addition, many com-
pounds containing these polycyclic moieties have biological
activity.20 With the anion derived from 1-adamantylmethyl
(14) Loksha, Y. M.; Pedersen, E. B.; Bond, A. D.; La Colla, P.; Secci, B.;
Loddo, R. Synthesis 2009, 21, 3589.
(15) (a) Benhida, R.; Aubertin, A.-M.; Grierson, D. S.; Monneret, C.
Tetrahedron Lett. 1996, 37, 1031. (b) Fang, W.-P.; Cheng, Y. T.; Cheng,
Y.-R.; Cherng, Y. J. Tetrahedron 2005, 61, 3107.
(16) See for example: (a) Saladino, R.; Stasi, L.; Crestini, C.; Nicoletti, R.;
Botta, M. Tetrahedron 1997, 53, 7045. (b) Saladino, R.; Stasi, L.; Nicoletti,
R.; Crestini, C.; Botta, M. Eur. J. Org. Chem. 1999, 2751.
(17) Bardagı, J. I.; Rossi, R. A. J. Org. Chem. 2008, 73, 4491.
~ꢀ~
(18) For reviews, see: (a) Rossi, R. A.; Pierini, A. B.; Penenory, A. B.
(19) Carver, D. R.; Komin, A. P.; Hubbarda, J. S.; Wolfe, J. F. J. Org.
Chem. 1981, 46, 294.
(20) See for example: (a) Webster, S. P.; Ward, P.; Binnie, M.; Craigie, E.;
McConnell, K. M. M.; Sooy, K.; Vinter, A.; Seckl, J. R.; Walker, B. R.
Bioorg. Med. Chem. Lett. 2007, 17, 2838. (b) Rho, H. S.; Baek, H. S.; Lee, B.;
Kim, J. H.; Kim, D. H.; Chang, I. S. Bull. Korean Chem. Soc. 2006, 27, 115.
Chem. Rev. 2003, 103, 71–167. (b) Rossi, R. A.; Pierini, A. B.; Santiago, A. N.
In Organic Reactions; Paquette, L. A., Bittman, R., Eds.; Wiley & Sons: New
York, 1999; pp 1-271. (c) Rossi, R. A. In Synthetic Organic Photochemistry;
Griesberck, A. G., Mattay, J., Eds.; Marcel Dekker: New York, 2005; Vol.
12, Chapter 15, pp 495-527.
5272 J. Org. Chem. Vol. 75, No. 15, 2010

Bardagı and Rossi
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TABLE 2. Hydrolysis of 6-Substituted-2,4-dimethoxypyrimidines
expt
substrate, 10-3 M
conditions
product (%)
heatinga
1
2
3
4
5
6
7
8
9
6, 16.7
6, 6.0 (17%)c,d
8, 12.0
18, 10.7
6, 16.7
6, 16.7
6, 16.7
6, 6.0 (85%)c,d
6, 16.7
0.2 M HCl, reflux 48 h
19 (85)b
19 (37)d
20 (75)b
21 (69)b
19 (78)e
19 (81)e
19 (85)e
CH
CH
CH
CH
MW
MW
MW
MW
MW
0.2 M HCl, 120 °C, 80 min, sealed tube
0.2 M HCl, reflux 48 h
0.2 M HCl, reflux 48 h
0.1 M HCl, 120 °C, 40 min, sealed tube
0.1 M HCl, 120 °C, 10 min, sealed tube
0.01 MHCl, 120 °C, 1 h, sealed tube
water, 120 °C, 80 min, sealed tube
f
-
0.1 M HCl, constant power 70 W (100-103 °C), 20 min, open tube
19 (∼12)e
aCH: conventional heating. MW: microwave irradiation. bYield. cRemaining substrate. dQuantified by 1H NMR. eQuantified by HPLC. fNo product
detected.
ketone (7), we obtained the corresponding pyrimidine 1-ada-
With nucleophiles derived from arsenic and phosphorus it
has been possible to prepare arsanes and phosphanes with good
yields. We performed the reactions of 1 and diphenylphospha-
nide (14) or diphenylarsenide (15) anions, as representative of
this type of nucleophiles, and prepared the corresponding pyri-
midines with good yields (eq 10). With 14 as a nucleophile, it was
possible to obtain phosphane 1622 and phosphane oxide 17.
mantyl-2-(2,6-dimethoxypyrimidin-4-yl)-1-oxoethane (8) with
good yields after 30 min of irradiation (eq 7, Table 1, expt 3);
reduced substrate 2,4-dimethoxypyrimidine was detected but
not quantified. The low solubility of this anion in liquid
ammonia might be responsible for the lower yield found.
The anion of camphor (9) allows us to prepare the inter-
esting substituted compound 10 in 50% yield (eq 8). Again,
the low solubility and the greater steric demand of the anion
may be the cause of the lower yields obtained.
Hydrolysis of 2,4-Dimethoxypyrimidines. Uracils can be
obtained by treating dialkoxypyrimidines with concentrated
acids at reflux; good yields have been obtained.23 However, reac-
tion times are generally high and the conditions are very drastic.
Some caution is also needed concerning the concentration
of pyrimidine to avoid undesirable isomerization reactions.24
Seeking better conditions to obtain uracils from 6-sub-
tituted-2,4-dimethoxypyrimidines synthesized, we studied
this reaction in different conditions, using compound 6 as a
model substrate to afford uracil 19 (eq 11, Table 2).25
We tried the synthesis in other solvents. However, it was
not possible to obtain the products with all anions studied
(Table 1, expts 2, 5, and 6). On the basis of GC and CG/MS
analysis we estimated that polar addition reactions with the
activated nucleus of pyrimidine are faster than electron
transfer reactions at room temperature because of the
appearance of products of pyrimidine decomposition.
The photostimulated reaction of 1 with acetophenone
enolate anion (11), a nucleophile representative of aromatic
ketones, gave only ca. 9% of chloride anion in liquid ammo-
nia. We changed the leaving group chlorine to bromine (12)
since, in the photostimulated reaction, it is more reactive.
However, in liquid ammonia and after 3 h of irradiation, only
15% of the substitution product 13 was obtained (eq 9).
We found that the best choice was to perform the hydro-
lysis in a solution of HCl without cosolvent, synthesizing
85% yield of 19 after 48 h at reflux (Table 2, expt 1). This
condition worked well even for other substrates, in which we
obtained good yields of 6-(2-oxo-2-(1-adamantyl)ethyl)-
uracil (20) and 6-(diphenylarsanyl)uracil (21) starting from
8 and 18 (Table 2, expts 3 and 4).
(22) This product was identified only by GC/MS. The purity was deter-
mined by GC.
(23) See for example: (a) Reference 8. (b) Boudet, N.; Knochel, P. Org.
Lett. 2006, 8, 3737. (c) Ismail, M. A.; Zoorob, H. H.; Strekowski, L. Arkivoc;
ARKAT Foundation, 2002; Part x, p 1.
(24) Wong, J. L.; Fuchs, D. S. J. Org. Chem. 1970, 35, 3786.
(25) A list of all conditions examined can be seen in the Supporting
Information (Table S2).
It was not possible to obtain a good yield of 13 in DMSO
or in any other solvent.21 Probably in the case of 13,
competitive polar reactions are responsible for the high
number of unidentified byproduct.
(21) See Table S1 in the Supporting Information for details.
J. Org. Chem. Vol. 75, No. 15, 2010 5273

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TABLE 3. “One-Pot” Synthesis of 6-Substituted Uracilsa
yield (%)
“one-pot”b
step-by-step
expt
nucleophile, 10-3 mol
1st step conditions (hv)
2nd step conditions
product
CH
MW
CH
MW
76
1
2
3
4
5
6
5, 1.0
8, 1.0
18, 0.26
9, 1.0
15 min
20 min
5 min
30 min
15 min
10 min
48 h (CH); 10 min (MW)
56 h (CH); 10 min (MW)
48 h (CH); 40 min (MW)
48 h (CH); 40 min (MW)
48 h (CH); 10 min (MW)
48 h (CH); 20 min (MW)
19
20
21
22
24
25
84
45
69
82
42
56
80
52
48
25
CH3COCH2- (23), 1.0
14, 0.27
90
55
44
aAll reactions were performed with 0.25 ꢀ 10-3 mol of substrate 1. CH: conventional heating. MW: microwave irradiation. bThe purity of products
was determined by HPLC and was >96% in all cases.
To explore the scope of the present “one-pot” approach,
we performed the reactions with different nucleophiles and 1
in the conditions described above (Scheme 1, Table 3). It was
possible to obtain, excepting one case, the pure isolated
product through the “one-pot” approach. Even when the
yields of product were less satisfactory with MW, it should be
noted that the experimental conditions were not optimized.
The only case where the product could not be obtained was
when anion 9 was used, due to the large quantity of by-
product which made impossible the purification through a
simple procedure. However, working with the step-by-step
approximation we could prepare compound 22 in 25%
global yield, which is acceptable if we consider the interesting
structure of this uracil.
In view of the long reaction times required, we decided to per-
form the reaction under microwave irradiation (MW) instead
of conventional heating (CH). We studied the reaction in
solutions of chlorohydric acid under different conditions, using
6 as a model substrate (Table 2, expts 5-9 and Table S2, expts
8-17 in the Supporting Information). The results show some
advantage of MW in comparison with CH, allowing us to pre-
pare good yields of 19 after having worked 10-60 min in sealed
tubes at 120 °C. As seen, temperature and type of heating are
responsible for the short reaction times, because changing only
one variable, such as temperature (Table 2, expt 1 vs 2) or type
of heating (expt 1 vs 9), has not produced better results.
Synthesis of 6-Substituted Uracils. In our synthetic strat-
egy we studied the two steps and synthesized uracils 19-21 in
good yields. We then decided to explore the possibility of
synthesizing the target compounds without the isolation of
2,4-dimethoxypyrimidines, to avoid an instance of purifica-
tion and a possible loss of yield.17,26
Conclusions
The preparation of 6-substituted pyrimidines by reaction
with nuclephiles by SRN1 reactions was possible in good to
excellent yields and short reaction times. In addition, the
syntheses of 6-substituted uracils were successful through a
“one-pot” SRN1-hydrolysis sequence, obtaining good yields
and purity of products in a simplified procedure. The use of
MW also allowed us to prepare the same product in shorter
times but with fewer yields in some cases.
SCHEME 1. Synthesis of 6-Substituted Uracils through a
One-Pot Procedure
These results together with those obtained in the three-step
“one-pot” synthesis of substituted uracils with different
electrophiles17 highlight the fact that the SRN1 reactions
could be useful to prepare different pyrimidines in good
yields.
We performed the reaction of 1 and pinacolone enolate ion
5 in liquid ammonia under photostimulation for 15 min. We
allowed the ammonia to evaporate and added a solution of
HCl. Finally, we heated the mixture at reflux and obtained 19
in an excellent yield (Scheme 1, Table 3, expt 1).27 CH and
MW irradiation was used, obtaining with the latter short
reaction times in less severe conditions. If we compare the
step-by-step synthesis with the “one-pot” procedure in the
synthesis of 19-21 the results are satisfactory: similar yields
could be obtained in less time through a simplified “one-pot”
procedure.
Experimental Section
General Methods. High Pressure Liquid Chromatographic
(HPLC) analyses were performed on an instrument with a UV
detector (diode array) equipped with a C18 column. Gas
Chromatographic (GC) analyses were performed on an instru-
ment with a flame ionization detector equipped with a VF-5 ms
column (15 m ꢀ 0.25 mm ꢀ 0.25 μm). Gas Chromatographic-
Mass Spectrometer analyses were carried out on an instrument
equipped with a quadrupole detector and a VF-5 ms column
(30 m ꢀ 0.25 mm ꢀ 0.25 μm). High Resolution Mass Spectra
were done in a MS/MS instrument over the pure products.
(26) Boudet, N.; Knochel, P. Org. Lett. 2006, 8, 3737.
(27) See the Experimental Section for details.
5274 J. Org. Chem. Vol. 75, No. 15, 2010

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1H NMR (400.16 MHz), 31P NMR (162 MHz), and 13C NMR
(100.62 MHz) data are shown in ppm. Irradiation was con-
ducted in a reactor equipped with two 400-W lamps of metal
iodide28 refrigerated with air and water. MW reactions were
performed in a single mode instrument equipped with a noncon-
tact infrared sensor to measure the temperature. Potentiometric
titrations of halide ions were performed in a pH meter with an
Ag/Agþ electrode. Melting points were performed with an ele-
ctronic air-heating instrument and are uncorrected. Quantifica-
tion by GC was performed by the Internal Standard Method
with a standard deviation e5%. Quantification by HPLC was
performed by the External Standard Method with a standard
deviation e7%. Quantification by 1H NMR was performed by
adding a Standard to the crude in D2O as solvent.
Materials. 6-Chloro-2,4-dimethoxypyrimidine, potassium tert-
butoxide, pinacolone, 1-adamantyl methyl ketone, camphor,
acetophenone, triphenylphosphane, triphenylarsane, trifluoroce-
tic acid, tetrachloromethane, and hydrochloric acid were commer-
cially available and used as received from the supplier. DMSO was
dried with molecular sieves. All solvents were analytical grade and
used as received from the supplier. Silica gel (0.063-0.200 mm)
was used in column chromatography. Silica gel (60 PF254) plates
(1 mm and 2 mm) were employed in radial thin-layer chromato-
graphy purification. 6-Bromo-2,4-dimethoxypyrimidine was pre-
pared has previously indicated.29
1-(2,6-Dimethoxypyrimidin-4-yl)-3,3-dimethylbutan-2-one (6):
Reactions of 1 with Enolate Anions in Liquid Ammonia (Typical
Procedure). Ammonia (150 mL), previously dried with Na metal
under nitrogen, was condensed into a three-necked, 250-mL
round-bottomed flask equipped with a coldfinger condenser
charged with ethanol, a nitrogen inlet, and a magnetic stirrer.
Potassium tert-butoxide (117.0 mg, 1.04 mmol) was then added
and stirred for 5 min. Pinacolone was later added (125 μL, 1.00
mmol) andthe mixturewas stirredfor 15 min. The irradiationwas
started and then 6-chloro-2,4-dimethoxypyrimidine (43.6 mg,
0.25 mmol) was added to the solution dissolved in 1 mL of dried
ethyl ether and the reaction mixture was irradiated for 15 min
with two metal iodide lamps of 400 W. Ammonium nitrate was
added in excess to eliminate any remaining anions; the ammonia
was allowed to evaporate. Water (50 mL) was added and the
aqueous phase was extracted with ethyl acetate. The organic
phase was dried (magnesium sulfate) and filtered, and the solvent
was evaporated under vacuum. The product was isolated as a
brown oil in 95% yield (59.4 mg, >97% purity). The product was
extra purified by column chromatography on silica gel eluting
with dichloromethane/methanol (100:0 to 96:4), yielding a color-
less oil (54.0 mg, 86%). The spectroscopic data (1H and 13C
NMR) are in agreement with those previously reported.19 1H
NMR (400 MHz, CCl3D):δ 13.91 (s, 1H, enol), 6.30 (s, 1H, keto),
5.95 (s, 1H, enol), 5.29 (s, 1H, enol), 4.00 (s, 3H, enol), 3.96 (s, 6H,
keto), 3.94 (s, 3H, enol), 3.81 (s, 2H, keto), 1.22-1.20 (s super-
imposed, 9H, keto-enol). 13C NMR (100.62 MHz, CCl3D)
keto-enol: δ 211.0, 178.7, 171.9, 171.6, 166.7, 166.0, 165.2,
101.7, 95.0, 91.4, 54.7, 54.6, 53.8, 45.1, 44.9, 36.7, 27.9, 26.2.
GC/MS (m/z): 238 (Mþ; 4), 181 (52), 155 (15), 154 (60), 153 (28),
96 (13), 72 (25), 58 (13), 57 (100), 55 (13), 41 (37).
NMR (400 MHz, CCl3D): δ 13.88 (s, 1H, enol), 6.28 (s, 1H, keto),
5.94 (s, 1H, enol), 5.22 (s, 1H, enol), 4.00-3.94 (s, 6H, keto-enol
mixture), 3.78 (s, 2H, keto), 2.08 (br s, 3H, keto-enol mixture),
1.88 (m, 6H, keto-enol mixture), 1.79-1.69 (m, 6H, keto-enol
mixture). 13CNMR(400MHz, CCl3D) keto-enol:δ210.7, 178.4,
171.8, 171.6, 166.8, 166.1, 165.2, 163.3, 101.7, 95.0, 91.4, 54.7, 53.8,
47.2, 44.6, 39.6, 38.0, 36.8, 36.5, 28.2, 27.9. 1H-1H COSY NMR
(CCl3D): δH/δH 13.88/13.88, 6.28/6.28, 5.94/5.94, 5.22/5.22, 4.00/
4.01, 3.96/3.97, 3.78/3.78, 2.08/1.78, 2.08/2.08, 2.08/1.89, 1.88/
1.72, 1.88/2.08, 1.88/1.89, 1.76/2.10, 1.76/1.77, 1.72/1.74, 1.71/
1.89. 1H-13C HSQC NMR (CCl3D): δH/δC 6.28/101.7, 5.94/95.0,
5.22/91.4, 4.00/54.7, 3.96/54.7, 3.95/53.8, 3.78/44.6, 2.12/27.9,
2.04/27.9, 1.88/38.0, 1.87/39.6, 1.75/36.5, 1.73/36.8. GC/MS (m/z):
317 (Mþ þ 1; 3), 316 (Mþ; 16), 181 (59), 154 (17), 136 (12), 135
(100), 107 (10), 93 (18), 79 (22). ESI/APCI-HRMS Anal. Calcd for
C18H25N2O3 (M þ Hþ) 317.1860, found 317.1872.
3-(2,6-Dimethoxypyrimidin-4-yl)-1,7,7-trimethylbicyclo[2.2.1]-
heptan-2-one (10). Camphor (152.2 mg, 1.0 mmol) was added
dissolved in 1 mL of diethyl ether and the mixture was stirred for
30 min; some precipitate of the enolate anion appeared. The
product was purified by radial thin-layer chromatography on
silica gel eluting with dichloromethane/methanol (99:1) yielding
a yellow oil (36.0 mg, 50%). In the NMR data the keto and enol
1
tautomers are observed. H NMR (400 MHz, CCl3D): δ 6.84
(d, J = 1.15, 1H, enol), 6.37 (s, 1H, keto), 5.29 (s, 1H, enol),
4.00-3.96 (m, 6H, keto-enol mixture), 3.68 (d, J = 4.74, 1H,
keto), 2.57-2.55 (m, 1H, keto-enol mixture), 1.74-1.72 (m, 2H,
keto-enol mixture), 1.51-1.43 (m, 1H, keto-enol mixture),
1.31-1.26 (m, 1H, keto-enol mixture), 1.05 (s, 3H, keto-enol
mixture), 0.99 (s, 6H, keto-enol mixture). GC/MS (m/z): 291
(Mþ þ 1, 2), 290 (Mþ, 11), 275 (10), 247 (37), 182 (10), 181 (76),
180 (17), 179 (11), 167 (47), 155 (14), 154 (100), 72 (12), 55 (16), 41
(21). ESI/APCI-HRMS Anal. Calcd for C16H23N2O3 (M þ Hþ)
291.1703, found 291.1699.
2-(2,6-Dimethoxypyrimidin-4-yl)-1-phenylethanone (13). Aceto-
phenone (117 μL, 1.0 mmol) and pinacolone (32 μL,, 0.25 mmol)
were added. The product was purified by radial thin-layer chro-
matography on silica gel eluting with dichloromethane/methanol
(100:0 to 96:4) yielding a brown oil. Inthe NMR data the keto and
1
enol tautomers are observed. H NMR (400 MHz, CCl3D): δ
14.23 (s, 1H enol), 8.07-8.05 (m, 2H), 7.84-7.82 (m, 2H), 7.61-
7.57 (m, 1H), 7.50-7.43 (m, 5H), 6.38 (s, 1H keto), 6.10 (s, 1H
enol), 5.97 (s, 1H, enol), 4.29 (s, 2H, keto), 4.07 (s, 3H), 3.99
(s, 3H), 3.96 (s superimposed, 6H). GC/MS (m/z): 259 (Mþþ1, 2),
258 (Mþ,15), 230 (34), 229 (44), 105 (100), 77 (54), 51 (11). ESI/
APCI-HRMS Anal. Calcd for C14H15N2O3 (M þ Hþ) 259.1077,
found 259.1080.
Diphenyl(2,4-dimethoxy-6-pyrimidyl)phosphane Oxide (17):
Reactions of Ph2P-Naþ (or Ph2As-Naþ) in Liquid Ammonia
(Typical Procedure). Ammonia (150 mL), previously dried with
Na metal under nitrogen, was condensed into a three-necked,
250-mL round-bottomed flask equipped with a coldfinger con-
denser charged with ethanol, a nitrogen inlet, and a magnetic
stirrer. PPh3 (68.8 mg, 0.26 mmol) was then added, and Na metal
was introduced in small pieces; total discoloration between
each addition was expected. Addition was continued until the
solution maintained its dark brown for at least 5 min. After the
1-(1-Adamantyl)-2-(2,6-dimethoxypyrimidin-4-yl)ethanone (8).
1-Adamantylmethyl ketone (178.0 mg, 1.0 mmol) instead of pina-
colone was added dissolved in 1 mL of diethyl ether and the mixture
was stirred for 30 min; some precipitate of the enolate anion
appeared. The product was purified by radial thin-layer chroma-
tography on silica gel eluting with dichloromethane/methanol
(99:1) yielding a white solid (51.4 mg, 69%) with mp 97-100 C.
In the NMR data the keto and enol tautomers are observed. 1H
-
color became red, tert-butanol was added to eliminate the NH2
anions formed. An orange solution of Ph2P- ions is obtained.
The irradiation was started and then 6-chloro-2,4-dimethoxy-
pyrimidine 1 (43.6 mg, 0.25 mmol) was added to the solu-
tion dissolved in 1 mL of dried ethyl ether. The reaction mixture
was irradiated for 10 min. Ammonium nitrate was added
in excess to eliminate any remaining anions; the ammonia
was allowed to evaporate. Hydrogen peroxide 20 vol (2 mL)
and water (50 mL) were added and the mixture was stirred for
30 min. The aqueous phase was extracted with ethyl acetate, the
organic phase was dried (magnesium sulfate), and the solvent was
(28) A spectrum of the lamp can be seen in www.luz.philips.com.ar/
archives/lamps_hid_hpiplus.pdf.
(29) White, J. D.; Hansen, J. D. J. Org. Chem. 2005, 66, 1963.
J. Org. Chem. Vol. 75, No. 15, 2010 5275

Bardagı and Rossi
JOCArticle
evaporated under vacuum. The product was purified by radial
thin-layer chromatography on silica gel eluting with dichloro-
methane/methanol (100:0 to 96:4) yielding a white solid (57.2 mg,
67%) with mp 143.5-146 C. 1H NMR (400 MHz, CCl3D):
δ 7.95-7.9 (m, 4H), 7.57-7.54 (m, 2H), 7.5-7.46 (m, 4H), 7.39
(d, H-PJ = 7.28 Hz, 1H), 4.01 (s, 3H), 3.96 (s, 3H). 13C NMR (400
MHz, CCl3D): δ 172.1 (d, C-PJ= 13.22 Hz), 166.1 (d, C-PJ=
124.74 Hz), 165.1 (d, C-PJ=22.08 Hz), 132.3 (d, C-PJ =2.83
Hz), 132.1 (d, C-PJ = 9.56 Hz), 130.9 (d, C-PJ = 105.44 Hz),
128.4 (d, C-PJ = 12.33 Hz), 107.7 (d, C-PJ = 18.61 Hz), 55.2,
54.3. 1H-13CHSQCNMR(CCl3D): δH/δC 132.3/7.54, 132.3/7.52,
132.2/7.93, 132.2/7.88, 132.2/7.91, 128.5/7.44, 128.5/7.48, 128.5/
7.46, 107.8/7.37, 107.6/7.35, 55.0/3.94, 54.1/3.99. 1H-13C HMBC
NMR (CCl3D): δH/δC 172.0/4.01, 172.2/4.01, 165.0/7.40, 165.3/
7.38, 165.5/3.96, 166.8/3.96, 132.0/7.95-7.9, 132.1/7.95-7.9 132.2/
7.95-7.9, 132.3/7.95-7.9, 132.0/7.57-7.54, 132.1/7.57-7.54,
132.2/7.57-7.54, 132.3/7.57-7.54, 132.0/7.5-7.46, 132.1/7.5-
7.46, 132.2/7.5-7.46, 132.3/7.5-7.46, 130.4/7.95-7.9, 131.5/
7.95-7.9, 130.4/7.5-7.46, 131.5/7.5-7.46, 128.3/7.5-7.46, 128.5/
7.5-7.46. GC/MS (m/z): 341 (Mþ þ 1, 8), 340 (Mþ, 37), 339 (100),
325(19), 263 (40), 201 (20), 199(14), 183 (15), 77 (33), 51 (14). ESI/
APCI-HRMS Anal. Calcd for C18H18N2O3P (M þ Hþ) 341.1045,
found 341.1061.
Diphenyl(2,4-dimethoxy-6-pyrimidyl)phosphane (16). After
the irradiation time, ammonium nitrate was added in excess to
eliminate any remaining anions; the ammonia was allowed to
evaporate under nitrogen. Deoxygenated water (50 mL) was
added and the aqueous phase was extracted with ethyl acetate,
the organic phase was dried (magnesium sulfate), and the
solvent was evaporated under vacuum. The product was puri-
fied by radial thin-layer chromatography on silica gel eluting
with dichloromethane/methanol (98:2 to 96:4) yielding a white
solid (46.1 mg, 57%). GC/MS (m/z): 325 (Mþ þ 1, 14), 324 (Mþ,
73), 323 (100), 247 (11), 183 (46), 107 (15).
mmol) and methanol (5 mL) were mixed. HCl 0.2 M (10 mL)
was later introduced and the solution was heated at reflux for
48 h. A solid was formed. The mixture was concentrated to eva-
porate methanol and the product was filtered from the crude
yielding a white solid (34.5 mg, 75%) with mp (methanol) 290 °C
1
dec. H NMR (400 MHz, DMSO-d6): δ 10.95 (s, 1H), 10.74
(s, 1H), 5.32 (s, 1H), 3.67 (s, 2H), 2.01 (s, 3H), 1.79 (m, 6H), 1.68
2
3
(dd, J = 21.5 Hz, J = 12.2 Hz, 6H). 13C NMR (400 MHz,
DMSO-d6): δ 209.5. 164.5. 152.0. 151.3. 101.2. 46.3. 40.5. 38.0.
36.4. 27.8. ESI/APCI-HRMS Anal. Calcd for C16H21N2O3
(M þ Hþ) 289.1547, found 289.1550.
6-(Diphenylarsanyl)uracil (21). Diphenyl(2,4-dimethoxy-
6-pyrimidyl)arsano (18) (58.7 mg, 0.16 mmol) was treated as in
the case of compound 20 yielding a white solid (37.4 mg, 69%)
1
with mp (methanol/water) 244-247 °C. H NMR (400 MHz,
DMSO-d6): δ 11.28 (s, 1H), 11.09 (s, 1H), 7.49-7.46 (m, 6H),
7.41-7.38 (m, 4H), 4.78 (t, J = 1.66, 1H). 13C NMR (400 MHz,
DMSO-d6): δ 163.2, 159.0, 152.0, 136.0, 134.1, 130.1, 129.7,
106.3. GC/MS (m/z): 341 (Mþþ1, 7), 340 (Mþ, 39), 262 (16),
229 (22), 227 (51), 154 (63), 153 (17), 152 (100), 151 (24), 68 (23).
ESI/APCI-HRMS Anal. Calcd for C16H14AsN2O2 (M þ Hþ)
341.0266, found 341.0265.
6-(4,7,7-Trimethyl-3-oxobicyclo[2.2.1]heptan-2-yl)uracil (22).
10 (36.0 mg, 0.12 mmol) and methanol (5 mL) were mixed. HCl
(0.2 M, 10 mL) was later introduced and the solution was heated
at reflux for 48 h. The solution was neutralized with NaOH and
extracted with ethyl acetate. The organic phase was dried (magne-
sium sulfate), and the solvent was evaporated under vacuum yield-
ing a white solid (16.5 mg, 50%) with mp (methanol) 230 °C dec.
1H NMR (400 MHz, DMSO-d6): δ 11.04 (s, 1H), 10.74 (s, 1H),
5.12 (s, 1H), 3.51 (d, J = 4.47 Hz, 1H), 2.53 (br s, 1H), 1.74-1.72
(m, 2H), 1.26-1.21 (m, 2H), 0.98 (s, 3H), 0.85 (s, 6H). 13C NMR
(400MHz, DMSO-d6):δ213.7, 164.3, 152.7, 151.9, 99.0, 58.9, 52.2,
47.1, 45.8, 29.6, 21.2, 19.5, 19.4, 9.8. ESI/APCI-HRMS Anal.
Calcd for C14H19N2O3 (M þ Hþ) 263.1390, found 263.1395.
Typical Procedure for the Hydrolysis with MW Heating. Into a
5-mL tube equipped with a magnetic stirrer were added sub-
strate and HCl (aq). The tube was sealed and irradiated with
MW at 120 °C for the time indicated. The temperature was
measured with a noncontact infrared sensor. After the irradia-
tion time the mixture was treated as indicated for the hydrolysis
with conventional heating for each compound.
Diphenyl(2,4-dimethoxy-6-pyrimidyl)arsane (18). AsPh3 (80.4
mg, 0.26 mmol) was added instead of Ph3P. The ammonia was
allowed to evaporate. Water (50 mL) was added, the aqueous
phase was extracted with ethyl acetate, the organic phase was
dried (magnesium sulfate), and the solvent was evaporated
under vacuum. The product was purified by radial thin-layer
chromatography on silica gel eluting with dichloromethane/
methanol (100:0 to 99:1) yielding a yellow oil (64.6 mg, 70%).
1H NMR (400 MHz, CCl3D): δ 7.46-7.44 (m, 4H), 7.39-7.35
(m, 4H), 6.26 (s, 1H), 4.96 (s, 3H), 3.93 (s, 3H). 13C NMR (400
MHz, CCl3D): δ 178.3, 171.1, 164.6, 138.0, 134.1, 128.9, 128.8,
106.8, 55.0, 53.7. GC/MS (m/z): 369 (Mþþ1; 18), 368 (Mþ; 100),
367 (48), 291 (12), 227 (29), 214 (12), 153 (12), 152 (33),
151 (18). ESI/APCI-HRMS Anal. Calcd for C18H18AsN2O2
(M þ Hþ) 369.0579, found 369.0594.
“One-Pot” Reactions: 6-(2-Oxopropyl)uracil (24): Typical
Procedure for “One-Pot” Reactions (Hydrolysis with Conven-
tional Heating). After distillation of ammonia (50 mL), potas-
sium tert-butoxide (121.0 mg, 1.05 mmol) and acetone (73 μL,
1.00 mmol) were added as previously described in the synthesis
of 6. The irradiation was started and then 1 (43.6 mg, 0.25 mmol)
was added to the solution dissolved in 1 mL of dried ethyl ether.
The reaction mixture was irradiated for 15 min. Ammonium
nitrate was added (84 mg, 1.0 mmol) and the ammonia was
allowed to evaporate. HCl 0.2 M was added (15 mL) and the
coldfinger condenser was changed for a condenser. The mixture
was heated at reflux for 48 h. The reaction was allowed to cool to
rt, the solution was neutralized with NaOH (1 M), and the
solvent was evaporated under vacuum. Acetone was added to
the residue and the solution was filtered to eliminate the
inorganic salts. The filtrate was evaporated under vacuum and
the residue was analyzed for HPLC; yielding a yellow solid (37.7
mg, 90%, 95% purity). The solid was recrystallized from
6-(3,3-Dimethyl-2-oxobutyl)uracil (19): Hydrolysis (Typical
Procedure). Into a 50-mL round-bottomed flask equipped with
a condenser and a magnetic stirrer were added1-(2,6-dimethoxy-
pyrimidin-4-yl)-3,3-dimethylbutan-2-one (6) (47.1 mg, 0.20
mmol) and HCl 0.2 M (12 mL) then the solution was heated
at reflux for 48 h. The reaction was allowed to cool to rt, the
solution was neutralized with NaOH (1 M), and the solvent was
evaporated under vacuum. Acetone was added to the residue
and the solution was filtered to eliminate the inorganic salts. The
filtrate was evaporated under vacuum and the residue was
recrystallized in ethanol/water yielding a white solid (35.6 mg,
1
1
85%) with mp 242-245 C (partial decomposition). H NMR
ethanol/water yielding a white solid with mp 290 °C dec. H
(400 MHz, DMSO-d6): δ 10.95 (s, 1H), 10.73 (s, 1H), 5.34 (s,
1H), 3.72 (s, 2H), 1.13 (s, 9H). 13C NMR (400 MHz, DMSO-d6):
δ 210.0, 164.5, 152.0, 151.2, 101.2, 44.3, 27.1, 26.2. ESI/APCI-
HRMS Anal. Calcd for C10H15N2O3 (M þ Hþ) 211.1077, found
211.1081.
NMR (400 MHz, DMSO-d6): δ 10.96 (s, 1H), 10.71 (s, 1H), 5.34
(s, 1H), 3.58 (s, 2H), 2.15 (s, 3H). 13C NMR (400 MHz, DMSO-
d6): δ 203.0, 164.5, 151.9, 150.3, 101.3, 46.5, 30.3. ESI/APCI-
HRMS Anal. Calcd for C7H9N2O3 (M þ Hþ) 169.0608, found
169.0649.
6-(2-Oxo-2-(1-adamantyl)ethyl)uracil (20). 1-(1-Adamantyl)-
2-(2,6-dimethoxypyrimidin-4-yl)-ethanone (8) (57.0 mg, 0.18
6-(Diphenylphosphoryl)uracil (25). After distillation of ammo-
nia (50 mL) Ph2P-Naþ (0.26 mmol) as described above. The
5276 J. Org. Chem. Vol. 75, No. 15, 2010

Bardagı and Rossi
JOCArticle
irradiation was started and then1 (43.6 mg, 0.25 mmol) was added
to the solution dissolved in 1 mL of dried ethyl ether. The reaction
mixture was irradiated for 10 min. Ammonium nitrate was added
(42 mg, 0.5 mmol) and the ammonia was allowed to evaporate.
Hydrogen peroxide 20 vol (2 mL) and HCl 0.2 M were added
(15 mL) and the coldfinger condenser was changed for a con-
denser. The mixture was heated at reflux for 48 h. The reaction was
allowed to cool to rt, the solution was neutralized with NaOH
(1 M), and the solvent was evaporated under vacuum. Acetone
was added to the residue and the solution was filtered to eliminate
the inorganicsalts. The solvent was allowed to evaporate slowlyto
improve crystallization and the residue was washed with diethyl
ether yielding a yellow solid(42.8mg, 55%, 95% purity). The solid
was recrystallized from acetone yielding a white solid with mp
performed as described above for this compound. 1 (43.6 mg,
0.25 mmol) and AsPh3 (80.2 mg, 0.26 mmol) were used. The
solid was washed with diethyl ether yielding a yellow solid
(58.5 mg, 69%, 97% purity).
Typical Procedure for “One-Pot” Reactions (Hydrolysis with
MW Irradiation). The first reaction was performed as described
above for each compound. The second reaction was performed
as described in the typical procedure for MW hydrolysis. The
final concentration of HCl was 0.1 M in all cases.
6-(3,3-Dimethyl-2-oxobutyl)uracil (19). 1 (43.2 mg, 0.247
mmol), potassium tert-butoxide (118.0 mg, 1.05 mmol), and
pinacolone (125 μL, 1.00 mmol) were used. The irradiation time
was 10 min yielding a yellow solid (43.3 mg, 82%, 97% purity).
6-(2-Oxo-2-(1-adamantyl)ethyl)uracil (20). Methanol (20%)
was used as cosolvent in the hydrolysis reaction. 1 (43.60 mg,
0.25 mmol), potassium tert-butoxide (117.5 mg, 1.05 mmol),
and 1-adamantyl methyl ketone (177.6 mg, 1.0 mmol) were used.
The irradiation time was 20 min. The solid was washed with
diethyl ether yielding a yellow solid (30.5 mg, 42%, 96% purity).
6-(Diphenylarsanyl)uracil (21). Methanol (20%) was used as
cosolvent in the hydrolysis reaction. 1 (42.5 mg, 0.24 mmol) and
AsPh3 (77.1 mg, 0.25 mmol) were used. The irradiation time was
20 min. The solid was washed with diethyl ether yielding a yellow
solid (46.0 mg, 56%, 98% purity).
1
243 °C dec. H NMR (400 MHz, DMSO-d6): δ 11.37 (s, 1H),
11.31 (d, H-PJ = 5.0 Hz, 1H), 7.78-7.71 (m, 6H), 7.64-7.60
(m, 4H), 5.53 (d, H-PJ = 11.4 Hz, 1H). 31P NMR (162 MHz,
DMSO-d6): δ 22.12. 13C NMR (400 MHz, DMSO-d6): δ 163.1 (d,
P-CJ = 15.6 Hz), 151.8 (d, P-CJ = 11 Hz), 149.4, 148.5, 133.7,
133.6, 132.4, 132.3, 129.7, 129.6, 129.5, 128.6, 108.9 (P-CJ = 10.5
Hz). ESI/APCI-HRMS Anal. Calcd for C16H14N2O3P (M þ Hþ)
313.0737, found 313.0740.
6-(3,3-Dimethyl-2-oxobutyl)uracil (19). The reaction was trea-
ted as described for compound 24. 1 (43.7 mg, 0.25 mmol),
potassium tert-butoxide (117.0 mg, 1.04 mmol), and pinacolone
(125 μL, 1.00 mmol) were used yielding a yellow solid (44.2 mg,
84%, 96% purity).
6-(Diphenylphosphoryl)uracil (25). 1 (44.6 mg, 0.255 mmol)
and PPh3 (69.4 mg, 0.26 mmol) were used with an irradiation time
was 20 min, yielding a yellow solid (35.3 mg, 44%, 98% purity).
6-(2-Oxo-2-(1-adamantyl)ethyl)uracil (20). Anion 7 was pre-
pared and the reaction was performed as described in the synth-
esis of compound 8. After evaporation of ammonia, methanol
(5 mL) and HCl (0.2 M) were added (15 mL) and the hydrolysis
was performed as described for this compound above. 1 (43.7 mg,
0.25 mmol), potassium tert-butoxide (117.0 mg, 1.04 mmol),
and 1-adamantylmethyl ketone (177.8 mg, 1.0 mmol) were used.
The solid was washed with diethyl ether yielding a yellow solid
(32.5 mg, 45%, 98% purity).
Acknowledgment. This work was supported in part by the
ꢀ
Agencia Cordoba Ciencia (ACC), Consejo Nacional de
Investigaciones Cientıficas y Tecnicas (CONICET), SE-
ꢀ
ꢀ
CYT, Universidad Nacional de Cordoba, and FONCYT,
Argentina. J.I.B. gratefully acknowledges receipt of a fellow-
ship from CONICET.
6-(Diphenylarsanyl)uracil (21). Anion 15 was prepared and
the first reaction was performed as described in the synthesis of
compound 18. After evaporation of ammonia, methanol (5 mL)
and HCl (0.2 M, 15 mL) were added and the hydrolysis was
Supporting Information Available: Additional conditions,
tables and graphical, 1H NMR, 13C NMR, and 2D experiment.
This material is available free of charge via the Internet at http://
pubs.acs.org.
J. Org. Chem. Vol. 75, No. 15, 2010 5277