Development of reactions of 6- and 5-substituted 1,3-dimethyluracils with dimethylsulfoxonium methylide

Article abstract of DOI:10.1021/jo981906e

6-Chloro-1,3-dimethyluracil (1) reacts with dimethylsulfoxonium methylide (3, 2 equiv) to give sulfoxonium ylide 8 (51%). The structure of 8 is established spectroscopically and by its reactions with various electrophiles and electron-deficient olefins. Thus, 8 is converted by HCl to sulfoxonium chloride 7, which then yields the 6-(chloromethyl)uracil 17 by heating in acetonitrile. Ylide 8 undergoes deuterium exchange at the 5- position, at its methine carbon, and into its methyl groups attached to sulfur. Reaction of 8 with benzoyl chloride gives the highly substituted ylide 19 or the nucleophilic substitution products 17 and 18 depending on reaction conditions. Treatment of 8 with electron-deficient olefins yields 6- cyclopropyluracils 20-31. Many of the cyclopropyluracils have been converted to trans-1-(1,3-dimethyluracilyl)-2-vinylcyclopropanes and cycloheptenyluracils. Reactions of 5-substituted uracils 2 (Z = SOPh and SeOPh) with ylide 3 have been developed. 5-(Phenylsulfinyl)uracil 48 yields cyclothymine derivative 49; 5-phenylseleninyluracil 52 gives methylide 8 as the major product.

Full text of DOI:10.1021/jo981906e

7290
J . Org. Chem. 1999, 64, 7290-7298
Develop m en t of Rea ction s of 6- a n d 5-Su bstitu ted
1,3-Dim eth ylu r a cils w ith Dim eth ylsu lfoxon iu m Meth ylid e
Peter Norris1 and Harold Shechter*
Department of Chemistry, The Ohio State University, 100 West 18th Avenue, Columbus, Ohio 43210
Received September 21, 1998
6-Chloro-1,3-dimethyluracil (1) reacts with dimethylsulfoxonium methylide (3, 2 equiv) to give
sulfoxonium ylide 8 (51%). The structure of 8 is established spectroscopically and by its reactions
with various electrophiles and electron-deficient olefins. Thus, 8 is converted by HCl to sulfoxonium
chloride 7, which then yields the 6-(chloromethyl)uracil 17 by heating in acetonitrile. Ylide 8
undergoes deuterium exchange at the 5-position, at its methine carbon, and into its methyl groups
attached to sulfur. Reaction of 8 with benzoyl chloride gives the highly substituted ylide 19 or the
nucleophilic substitution products 17 and 18 depending on reaction conditions. Treatment of 8
with electron-deficient olefins yields 6-cyclopropyluracils 20-31. Many of the cyclopropyluracils
have been converted to trans-1-(1,3-dimethyluracilyl)-2-vinylcyclopropanes and cycloheptenyluracils.
Reactions of 5-substituted uracils 2 (Z ) SOPh and SeOPh) with ylide 3 have been developed.
5-(Phenylsulfinyl)uracil 48 yields cyclothymine derivative 49; 5-phenylseleninyluracil 52 gives
methylide 8 as the major product.
Sch em e 1
In tr od u ction
6-Chloro-1,3-dimethyluracil (1) undergoes many reac-
tions with nucleophiles and is a useful intermediate for
synthesis of 6-substituted derivatives via nucleophilic
displacement.2 Investigation has now been made of the
behavior of 1 and 5-substituted 1,3-dimethyluracils (2)
with dimethylsulfoxonium methylide (3) and determina-
tion of the products thereof. Further objectives of this
study are synthesis of 6-cyclopropyluracils (4), their
transformations, and various 5,6-uracilocyclopropenes
(5).
its elemental analysis, its mass, 1H and 13C NMR spectra,
and its chemical behavior as will be described. A likely
mechanism for formation of 8 involves attack of 3 at C-6
of 1, loss of chloride ion from 6, and then deprotonation
of sulfoxonium chloride 7 by the second equivalent of 3
(Scheme 1).
The 1H NMR of 8 raises questions as to the exact
1
structure of the ylide. The H NMR signal for the proton
attached at the methanide carbon of 8 is a sharp singlet
at 4.25 ppm. Dimethylsulfoxonium 3-methylides 9 and
10, however, exhibit broad signals for their methine
protons on carbon adjacent to sulfur.5 The broad singlets
in 9 and 10 signal the possibility of exocyclic cis-trans
geometrical isomerism at C-3 and interconversions as
illustrated for 9 by 11 and 12 (eq 1). The proton NMR of
8 suggests that the ylide is a single geometric isomer,
presumably 13. A second geometric isomer, 14, is less
favorable because of steric interactions between the
Resu lts a n d Discu ssion
Reaction of 1 with 3 (2.2 equiv, prepared from trimeth-
ylsulfoxonium chloride and sodium hydride3) in THF at
20-25 °C gives crystalline dimethylsulfoxonium (1,3-
dimethyl-6-uracilyl)methylide (8, Scheme 1) in 51%
yield.4 Ylide 8 is a stable solid (mp 193-195 °C) that is
storable for months and whose structure is assigned from
(4) Similar methodology for functionalization of various hetero-
cycles with diphenylsulfonium methylide and 32 has been employed
by: (a) Taylor, E. C.; Martin, S. F. J . Am. Chem. Soc. 1972, 94, 2874.
(b) Taylor, E. C.; Martin, S. F. J . Am. Chem. Soc. 1972, 94, 6218. (c)
Taylor, E. C.; Martin, S. F. Heterocycles 1973, 1, 59.
(5) Tamura, Y.; Miyamoto, T.; Nishamura, T.; Eiho, J .; Kita, Y. J .
Chem. Soc., Perkin Trans. 1 1974, 102.
(1) Present address: Department of Chemistry, Youngstown State
University, 1 University Plaza, Youngstown, OH 44555-3663.
(2) (a) Pfleiderer, W.; Schu¨ndehu¨tte, K.-H. Liebigs Ann. Chem. 1958,
158. (b) Strauss, G. Liebigs Ann. Chem. 1960, 205. (c) Pfleiderer, W.;
Ram, V. J .; Knappe, W. R. Liebigs Ann. Chem. 1982, 762.
(3) Corey, E. J .; Chaykovsky, M. J . Am. Chem. Soc. 1965, 87, 1353.
10.1021/jo981906e CCC: $18.00 © 1999 American Chemical Society
Published on Web 08/31/1999

Reactions of 6- and 5-Substituted 1,3-Dimethyluracils
J . Org. Chem., Vol. 64, No. 20, 1999 7291
sulfoxonium moiety and the methyl group attached to N-1
of the uracil ring.
displacement of the dimethylsulfoxonium group by chlo-
ride ion to give 6-(chloromethyl)uracil 17 (72%) and
dimethyl sulfoxide occurs upon heating 8 in acetonitrile.
Of value in synthesis is that benzoyl ylide 19 (72%) is
obtained from 8 and benzoyl chloride in acetonitrile in
the presence of triethylamine. In the absence of triethyl-
amine, benzoyl chloride and 8 in refluxing acetonitrile
yield 6-(R-chlorophenacyl)uracil 18 (34%) along with 17
(42%). In the latter experiment, 18 is presumably formed
by benzoylation of 8 and displacement of dimethyl
sulfoxide by chloride ion. As previously described, 17 is
readily formed by reaction of chloride ion with 7 as now
generated in situ.
Sulfoxonium ylide 8 reacts with olefinic Michael ac-
ceptors with extrusion of dimethyl sulfoxide to give (6-
uracilyl)cyclopropanes. Thus, 8 and N-phenylmaleimide
(1.5 equiv) in refluxing acetonitrile yield trans-3-(6-
uracilyl)-1,2-cyclopropanedicarboximide 20 (91%). The
structural assignment of 20 is based on its elemental
1
analysis, H and 13C NMR, and MS and on precedent.7
1
The H NMR triplet at δ 2.73 with J ) 2.9 Hz and the
doublet at δ 2.93 with J ) 3.3 Hz support the assignment
that the dimethyluracilyl and the phenylmaleimido
groups are trans. Trans coupling constants in cyclopro-
panes generally fall within the range 3-5 Hz, whereas
those for cis coupling usually lie in the 6-10 Hz range.8
Ylide 8 undergoes many reactions (Scheme 2) that are
consistent with its assigned structure. Hydrogen chloride
in acetone or aqueous hydrochloric acid in acetonitrile
at 0 °C converts 8 to sulfoxonium chloride 7 (72%), a
readily handled solid. Sodium methoxide in methanol at
room temperature effects deprotonation of 7 to 8. Re-
fluxing 8 in THF containing deuterium oxide resulted in
15 (Scheme 2) with ∼85% deuterium at C-5 of the uracil
ring, ∼20% at the methanide carbon, and ∼40% into the
methyl groups attached to sulfur. As expected, deuterium
was not exchanged into the N-1 or the N-3 methyl groups
of 8.
Further, 1,4-naphthoquinone undergoes addition of 8
in acetonitrile at ∼82 °C followed by expulsion of di-
methyl sulfoxide to yield trans-cyclopropane 21 (61%).
The cyclopropyl hydrogens in the cycloadduct have
coupling constants of ∼5 Hz that are consistent with the
assignment of 21 as trans. As in formation of 20,
avoidance of severe steric repulsion around the cyclopro-
pyl ring explains exclusive formation of 21.
Sch em e 2
Ylide 8 also effects efficient cyclopropanations of
electron-deficient, acyclic disubstituted olefins. For ex-
ample, 8 reacts with trans-dibenzoylethylene in acetoni-
trile to give, after chromatography, isomers 22 and 23
in an 8:1 ratio and 71% overall yield. The first product
to elute is 22, the cyclopropane having one benzoyl group
cis and the second trans to its dimethyluracil group.
1
Stereochemical assignment of 22 is made from its H and
13C NMR spectra. Cycloadduct 22 exhibits distinct ab-
sorbances for three different cyclopropyl hydrogens and
three different cyclopropyl carbons. The coupling con-
stants for the hydrogen on the cyclopropyl carbon to
which the uracil group is attached are 6.2 and 9.2 Hz
and thus indicate that this proton is trans to a second
proton and cis to a neighbor substituent. The second
1
cycloadduct has a much simpler H NMR spectrum than
1
does 22. H NMR absorptions for all of its cyclopropyl
protons occur between δ 3.4 and 3.5, and, since the 13C
NMR spectrum reveals resonances for only two types of
(6) Egg, H.; Volgger, I. Synthesis 1982, 12, 1071.
(7) Trost, B. M.; Melvin, L. S. In Sulfur Ylides; Academic Press: New
York, 1975; and references therein.
(8) Morris, D. G. In The Chemistry of the Cyclopropyl Group;
Rappoport, Z., Ed.; J ohn Wiley and Sons: New York, 1987; p 116.
Raney nickel in ethanol-water at 20-25 °C effects
reductive elimination of the dimethylsulfoxonium moiety
in 8 to yield 1,3,6-trimethyluracil6 (16, 92%). Further,

7292 J . Org. Chem., Vol. 64, No. 20, 1999
Norris and Shechter
cyclopropyl carbons, this isomer is assigned as 23. There
is no evidence for formation of the relatively highly
strained all cis isomer in these experiments.
trans- and cis-cyclopropanes are also obtained in reac-
tions of 8 with acrolein and with methyl vinyl ketone.
Acrolein and 8 give 28 and 29 in a 4.25:1 ratio (94%
yield), and methyl vinyl ketone and 8 form 30 and 31 in
6:1 ratio (91% yield). As in the previous examples, the
stereochemistry of a present cycloadduct is assigned from
1
the H NMR coupling constants of its cyclopropyl hydro-
gens, its chromatographic properties, and the melting
points of the members of the isomeric cyclopropane
product pair. Thus, the NMR signal of the cyclopropyl
hydrogen adjacent to the dimethyluracil group in 28
reveals coupling to two trans protons (J ) 5.6, 4.8 Hz)
and one cis proton (J ) 10.1 Hz). In 29, coupling
constants of 6, 8, and 8 Hz for the methylene proton trans
to the uracil ring and the aldehyde group indicate that
the proton is cis to two vicinal neighbors. Coupling
constants in 30 for the proton on carbon to which the
acetyl group is attached are 5.1, 4.5, and 8.6 Hz, and thus,
this proton is trans to two hydrogen neighbors and cis to
another. The corresponding proton in isomer 31 is cis to
two adjacent protons as evidenced by coupling constants
of 8.1 and 14 Hz. In support of the stereochemical
assignments of 28-31, cis isomers 29 and 31 are eluted
more slowly on silica gel and melt higher than their
respective trans isomers 28 and 30. Further, the trans/
cis ratios of the cyclopropanes from reactions of 8 with
acrylonitrile, acrolein, and methyl vinyl ketone show that
as the alkene substituent becomes bulkier, the proportion
of trans cycloadduct formed increases. Such effects are
expected since substituents cis rather than trans to the
dimethyluracil groups in the cyclopropanes result in
steric repulsion.
trans-Benzylideneacetophenone reacts readily with 8
to yield two separable cyclopropanes, 24 and 25, in a 1:1
ratio in 63% total yield. Each product exhibits coupling
constants of ∼5.3 and 8.4 Hz for its cyclopropyl hydrogen
adjacent to its uracil ring. A conclusion is that the
hydrogen is cis to one hydrogen and trans to a second
hydrogen in the cyclopropyl ring of each product. Choice
as to which products are 24 and 25 cannot be made,
however, on the basis of present NMR data. As will be
indicated later, in all cases uracilylcyclopropanes con-
taining cis highly polar substituents on C-2 (â positions)
of their cyclopropyl rings elute more slowly on column
chromatography and melt higher than do their corre-
sponding trans isomers. On such bases the structures of
the products of cyclopropanations of trans-benzylidene-
acetophenone with 8 are assigned provisionally as 24 and
25, respectively.
Monoactivated Michael acceptors are also effectively
cyclopropanated by 8. For example, acrylonitrile and 8
at 40 °C in acetonitrile give trans- and cis-cyclopropanes
26 and 27 in ∼2:1 ratio in 67% yield. Isomers 26 and 27
are separable by chromatography on silica gel and
crystallization from CHCl3/Et2O. Cyclopropane 26 is
assigned as having its cyano and dimethyluracil groups
Reactions of carbonylcyclopropanes 28-31 with the
Wittig ylide methylenetriphenylphosphorane (32)9 were
then investigated in order to prepare uracil derivatives.
trans-Uracilylcyclopropanecarboxaldehyde 28 reacts with
32 at -78 to +25 °C to give trans-uracilyl(vinyl)cyclo-
propane 33 (91%). Assignment of 33 is made from DEPT
13C multiplicities and from the 1H NMR coupling con-
stants of its terminal vinyl group. The 13C NMR of 33
shows signals at 98.7 ppm for C-5 in the uracil ring (one
proton attached), 115.5 ppm for the terminal vinyl carbon
(two protons attached), and 137.7 ppm for the internal
1
trans on the basis of the H NMR coupling constants for
its cyclopropyl hydrogens. Values of 4.0 and 8.4 Hz from
26 for the proton on carbon attached to a cyano group
indicate that this hydrogen is cis to only one other proton.
The corresponding coupling constants for the hydrogen
atom on the cyclopropyl carbon adjacent to the uracil
group in 27 are 7.6 and 11.5 Hz, thus indicating that the
proton is cis to two cyclopropyl hydrogen neighbors. In
further support of the stereochemical assignments, the
product designated as the cis isomer 27 is eluted on silica
more slowly and has a higher melting point than does
the trans product 26.
1
vinyl carbon (one proton attached). Further, the H NMR
of 33 reveals couplings of 1.3 Hz between the geminal
protons and of 14 and 11 Hz between the trans- and the
cis-vicinal protons of the vinyl group. Couplings of 5.5,
4.1, and 6.9 Hz for the methine ring proton (Hi in 33)
confirm that this hydrogen is cis to one neighbor. The
corresponding proton in a cis-divinylcyclopropane will
have two cis neighbors and therefore two large coupling
constants.
(9) March, J . In Advanced Organic Chemistry, 4th ed.; J ohn Wiley
and Sons: New York, 1992; p 956 and references therein.

Reactions of 6- and 5-Substituted 1,3-Dimethyluracils
J . Org. Chem., Vol. 64, No. 20, 1999 7293
trans-2-Acetylcyclopropyluracil 30, a methyl ketone
homologue of 28, is converted by phosphorane 32 at -70-
25 °C to trans-divinylcyclopropane derivative 39 (91%).
The behavior of 30 is therefore similar to that of 29 with
32. Uracilylcyclopropane 39 is assigned from its analyses
1
and its H NMR signals at 4.8 ppm for its terminal olefin
protons and at 5.5 ppm for its C-5 uracilyl proton as
follows. The latter signal is a finely split doublet (J )
0.8 Hz) because of allylic coupling with the hydrogen on
the cyclopropyl carbon attached to the uracilyl group.
This cyclopropyl hydrogen is coupled to two trans neigh-
bors (J ) 6, 6.8 Hz) and one cis neighbor (J ) 12.8 Hz),
and thus, the stereochemistry of 39 as a trans-cyclopro-
pane is established.
cis-Uracilylcyclopropanecarboxaldehydes 29 and 32
react while warming from -78 to +25 °C to yield
cycloheptenouracil 35 (Scheme 3, 63%) as a crystalline
Sch em e 3
Reaction of cis-2-acetylcyclopropyluracil 31 with 32
(Scheme 3) occurs on warming above -70 °C to give
cycloheptenyluracil 42 (75%) presumably upon formation
and spontaneous rearrangement of cis-divinylcyclopro-
pane 40 followed by tautomeric isomerization via 41.
Production of 42 so readily from 31 and 32 illustrates
again vividly the importance of precise stereochemistry
in divinylcyclopropane rearrangements. As to be ex-
pected, pyrolysis of trans-divinylcyclopropane 39 (Scheme
4) at 320 °C also produces 42 (70%). Of particular
Sch em e 4
solid. Formation of cis-divinylcyclopropane 34, the ex-
pected Wittig product, is likely the first step in the
transformation to 35. Intermediate 34 has its vinyl and
uracilyl groups properly aligned for rapid [3,3] sigmat-
ropic rearrangement10 to 35. Isomerization of 35, possibly
through its enol, then yields the more highly conjugated
derivative 36 (Scheme 3). Conversion of 34 to 35 is
similar to the spontaneous rearrangement of cis-vinyl-
cyclopropylcyclohexenone 37 to cycloheptadienocyclohex-
ane 38 (eq 2).11 Further, heating 33 (Scheme 3) for 30 h
1
significance to the structural assignment of 42 is the H
NMR absorption for only one vinyl hydrogen at 5.3 ppm,
which is coupled to the allylic methyl group (J ) 1.4 Hz)
and adjacent aliphatic protons (J ) 4 Hz). As with 36,
there is no signal for a proton at C-5 in the uracil ring of
42.
Investigation was then initiated of reactions of 3 with
5-substituted uracils 2 to form 5-substituted 5,6-meth-
anouracils 43 (cyclothymines), which might eliminate to
uracilocyclopropenes 44 and (or) 45 (Scheme 4). Uracils
such as 44 and 45 are unknown and are of biochemical
and medical interest as thymine mimics and for the great
reactivities expected for their cyclopropene double bonds.
Reaction of 1,3-dimethyluracil (2, Z ) H) with 3 has been
previously reported to give cyclothymine 46a ,12 1,3-
at 320 °C in o-dichlorobenzene yields 36 efficiently.
Although rearrangement of 33 is not nearly as facile as
for 34, reorganization of the stereochemistry after break-
ing the three-membered ring in 33 allows proper orbital
interaction for the thermal conversion to 35, which then
converts to 36.
(10) Hudlicky, T.; Fan, R.; Reed, J . W.; Gadamasetti, K. G. Org.
React. 1992, 41, 1.
(11) For example, see: (a) Marino, J . P.; Kanecko, T. J . Org. Chem.
1974, 39, 3175. (b) Bradbury, R. H.; Gilchrist, T. L.; Rees, C. W. J .
Chem. Soc., Perkin Trans. 1 1981, 3225.
(12) (a) Kunieda, T.; Witkop, B. J . Am. Chem. Soc. 1969, 91, 7751.
(b) Kunieda, T.; Witkop, B. J . Am. Chem. Soc. 1971, 93, 3478. (c)
Torrence, P. F.; Witkop, B. Biochemistry 1972, 11, 1731.

7294 J . Org. Chem., Vol. 64, No. 20, 1999
Norris and Shechter
dibenzyluracil, and phenylmercuric bromodichloromethane
yield cyclothymine 46b,13 and (E)- and (Z)-cyclothymines
46c are obtained by addition-displacements of 5-bromo-
1,3-dimethyluracil by sodium ethyl phenylacetate.14
elimination than its precursor and does not serve as a
preparative source of 44 or 45.
Study was then directed to syntheses of 5-(phenylse-
lenyl)uracil 51, 1,3-dimethyl-5-phenylseleninyluracil 52,
and 5,6-methano-5-(phenylseleninyl)uracil 53 as in Scheme
6. Seleninylcyclothymine 53 is expected to eliminate at
lower temperatures than does 49. Selenyluracil 51 is
readily prepared (80%, Scheme 6) by phenylselenation
of 2 (Z ) H) with diphenyl diselenide (1 equiv) and
ammonium peroxydisulfate (2 equiv) in refluxing ethanol.
Uracil 51 is assigned from its elemental, NMR, IR, and
MS analyses. It has been previously established17 that
(C6H5)2Se2/(NH4)2S2O8 functions as an electrophilic phen-
ylselenylating (C6H5Se+) agent, and uracils undergo
substitutions at their C-5 positions upon reactions with
various electron-deficient reagents.18 The assignment of
51 as the 5-isomer follows from the signal at 7.46 ppm
in its proton NMR spectrum, which is typical for H-6 in
1,3-dimethyluracils. Synthesis of 51 has since been
reported by a similar method in which [bis(trifluoro-
acetoxy)iodo]benzene was used to oxidize diphenyl di-
selenide in the presence of 1,3-dimethyluracil.19 Oxidation
of 51 with MMPP in ethanol/water then gives 52 (88%,
Scheme 6).
In present efforts to prepare 5-bromo-5,6-methano-
uracil 43 (Z ) Br) for possible synthesis of 44 and/or 45,
reactions of 2 (Z ) Br) with 3 (Scheme 4) or with 32 in
THF at 0-25 °C are found to give inseparable polar
products. However, 5-(phenylsulfinyl)uracil 48, as ob-
tained by oxidation of 5-(phenylsulfenyl)uracil 4715 with
magnesium monoperoxyphthalate (MMPP, 59% yield) in
ethanol/water or meta-chloroperoxybenzoic acid (m-
CPBA, 80% yield) in methylene chloride, and 3 yield
(phenylsulfinyl)cyclothymine 49 (68%, Scheme 5). Cy-
Sch em e 5
Reaction of 52 with excess 3 (4 equiv) in THF at 20-
25 °C followed by column chromatography using methanol/
chloroform as eluents is of particular interest in that the
principal product is 8 (34%, Scheme 6). Formation of 8
apparently arises from Michael-like addition of 3 to 52,
proton transfer in 54, and elimination of PhSeOH in 55
(Scheme 6). Seleninyluracil 52 is as yet not usable for
preparing 44 or 45.
Study is now being made of the behavior of 52 with
other methylene-transfer reagents and of syntheses of
cyclothymines with appropriate leaving groups at C-6
and C-7 for use in preparing 44 and 45.
clothymine 49 is assigned from its analysis, its detailed
NMR and MS properties, and its reduction by Raney
nickel in water/ethanol to 1,3-dimethylcyclothymine (46a ,
16%) and 1,3,6-trimethyluracil (16, 42%).
Since sulfoxides having cis â-hydrogens eliminate
thermally to olefins and sulfenic acids (RSOH),16 cy-
clothymine 49 was heated in various solvents for possible
preparation of 44 and/or 45. In refluxing THF for 12 h
or in toluene in sealed tubes at 180 °C, 49 is stable.
Pyrolyses of 49 in sealed tubes in xylenes at 270 °C,
toluene at 240 °C, and acetonitrile at 200 and 280 °C give
complex mixtures containing at least four compounds
that could not be separated preparatively. Decomposition
of 49 in the presence of anthracene at 275 °C in xylenes
in efforts to trap 44 and/or 45 by Diels-Alder reactions
gives a product mixture identical with that obtained in
the absence of the trapping agent. 5-(Phenylsulfonyl)-
uracil 50, prepared by oxidation (88% yield) of 49 with
MMPP in ethanol/water is more resistant to pyrolytic
Exp er im en ta l Section
Gen er a l P r oced u r es. Melting points are uncorrected.
Mass spectra were obtained in EI mode at 70 eV. 1H NMR
were recorded at either 200, 250, or 300 MHz; 13C NMR were
determined at 75 MHz. All NMR spectra were obtained for
solutions in CDCl3 or (CD3)3SO as noted. Flash chromatogra-
phy20 was performed on silica gel 60 (230-400 mesh, E. Merck)
and thin-layer chromatography (TLC) on aluminum-backed
plates of silica gel 60 F254 (E. Merck). Elemental analyses
were performed by Atlantic Microlabs, Norcross, GA.
(4,6-Dia za -4,6-d im et h yl-3,5-d ioxocycloh ex-1-en yl)d i-
m eth yloxosu lfon iu m Meth a n id e (8). Sodium hydride (2.52
g, 63.0 mmol as a 60% dispersion in mineral oil) was syringe-
washed with Et2O. The system was evacuated and purged with
argon, and trimethylsulfoxonium chloride (8.09 g, 63.0 mmol)
was added followed by anhydrous THF (200 mL). The resulting
(13) (a) Thellier, H. P. M.; Kooman, G. J .; Pandit, U.K. Tetrahedron
1977, 33, 1493. (b) Thellier, H. P. M.; Kooman, G. J .; Pandit, U.K.
Heterocycles 1974, 2, 467.
(14) Hirota, K.; Sajiki, H.; Maki, Y.; Inoue, H.; Ueda, T. J . Chem.
Soc., Perkin Trans. 1 1989, 1659.
(15) Senda, S.; Hirota, K.; Takahashi, M. J . Chem. Soc., Perkin
Trans. 1 1975, 503.
(16) March, J . In Advanced Organic Chemistry, 4th ed.; J ohn Wiley
and Sons: New York, 1992; p 1021 and references therein.
(17) Tiecco, M.; Testaferri, M.; Tingoli, D.; Chianella, D.; Bartoli,
D. J . Org. Chem. 1991, 56, 4529.
(18) Bradshaw, T. K.; Hutchinson, D. W. Chem. Soc. Rev. 1977, 6,
50.
(19) Kyoung, R. K.; Chang, H. K.; Kim, Y. H. Heterocycles 1998, 3,
437.
(20) Still, W. C.; Kahn, M.; Mitra, A. J . Org. Chem. 1978, 43, 2923.

Reactions of 6- and 5-Substituted 1,3-Dimethyluracils
J . Org. Chem., Vol. 64, No. 20, 1999 7295
Sch em e 6
suspension was stirred and vigorously refluxed for 3 h, after
which time evolution of hydrogen ceased. The milky white
mixture was cooled to 0 °C, and 6-chloro-1,3-dimethyluracil
(1, 5.0 g, 28.6 mmol) in anhydrous THF (100 mL) was added
over 30 min. The mixture was stirred at room temperature
for 18 h, cooled to 0 °C, and filtered. The solid was washed
with anhydrous THF and then extracted with boiling acetone.
Removal of the acetone in vacuo gave a colorless solid (3.45 g)
that was recrystallized from acetone to yield 8 (3.3 g, 51%) as
5.59 (s, 1H); 13C NMR (CDCl3) 20.1, 27.9, 31.6, 101.2, 151.3,
152.5, 162.4; found M+ 154.0740, C7H10N2O2 requires m/z
154.0740. The physical properties of 16 agree with those of
an authentic sample.6
6-(Ch lor om eth yl)-1,3-d im eth ylu r a cil (17). Sulfoxonium
salt 7 (50.0 mg, 0.19 mmol) was suspended in dry acetonitrile
(5 mL), and the solution was refluxed for 2 h. Evaporation of
the solvent in vacuo left a colorless oil that, on chromatography
on silica gel (5 g) using petroleum ether-EtOAc (2:1) as eluent,
yielded colorless crystals of chloromethyl derivative 17: mp
86-88 °C; νmax (CHCl3) 1705, 1667 cm-1; 1H NMR (CDCl3) 3.31
(s, 3H), 3.49 (s, 3H), 4.29 (s, 2H), 5.82 (s, 1H); 13C NMR (CDCl3)
28.1, 31.4, 41.3, 103.0, 148.7, 152.3, 162.1; found M+ 188.0367,
C7H9N2O2Cl requires m/z 188.0353. Anal. Calcd for C7H9N2O2-
Cl: C, 44.67; H, 4.82. Found: C, 44.62; H, 4.80.
colorless crystals: mp 193-195 °C; νmax (KBr) 1690, 1630 cm-1
;
1H NMR (DMSO-d6) 3.07 (s, 3H), 3.17 (s, 3H), 3.51 (s, 6H),
4.25 (s, 1H), 5.06 (s, 1H); 13C NMR (DMSO-d6) 27.7, 38.8, 39.7,
40.0, 40.3, 57.7, 81.6, 153.3, 154.8, 163.4; found M+ 230.0763,
C9H14N2O3S requires m/z 230.0735. Anal. Calcd for C9H14N2-
O3S: C, 46.94; H, 6.13. Found: C, 47.03; H, 6.12.
(4,6-Dia za -4,6-d im et h yl-3,5-d ioxocycloh ex-1-en yl)d i-
m eth yloxosu lfon iu m Ch lor id e (7). Ylide 8 (230 mg, 1.0
mmol) was dissolved in refluxing acetone (100 mL). Hydrogen
chloride was bubbled through the solution for 10 min, during
which time a solid precipitated. The solution was cooled to 0
°C and filtered. Recrystallization of the solid from methanol-
benzene yielded colorless crystals of sulfoxonium salt 7 (170
mg, 0.72 mmol, 72% yield): mp 133-135 °C; νmax (KBr) 1690,
1670 cm-1; 1H NMR (DMSO-d6) 2.53 (s, 6H), 3.14 (s, 3H), 3.35
(s, 3H), 4.75 (s, 2H), 5.96 (s, 1H); 13C NMR (DMSO-d6) 27.6,
31.1, 40.4, 41.4, 101.6, 126.9, 161.5; found M+ 231.0735,
6-(Ben zoyld im et h ylsu lfoxon iu m )-1,3-d im et h ylu r a cil
Meth ylid e (19). Benzoyl chloride (0.15 g, 1.1 mmol) was added
to a solution of methylide 8 (0.23 g, 1.0 mmol) and triethyl-
amine (0.11 g, 1.0 mmol) in dry acetonitrile (50 mL), and the
mixture was stirred at room temperature for 2 h. After removal
of the solvent in vacuo, the residue was adsorbed onto silica
gel and chromatographed using CHCl3-methanol (20:1) as
eluent. The residue obtained was triturated with Et2O to give
colorless crystals of methylide 19 (0.24 g, 0.72 mmol, 72%
1
yield): mp 88-90 °C; νmax (CHCl3) 1698, 1652 1605 cm-1; H
NMR (CDCl3) 3.30 (s, 3H), 3.41 (s, 3H), 3.60 (s, 3H), 3.71 (s,
3H), 5.69 (s, 1H), 7.29 (m, 5H); 13C NMR (CDCl3) 27.9, 33.6,
42.1, 42.7, 45.6, 78.7, 110.0, 127.0, 128.3, 130.9, 138.5, 146.1,
152.5, 162.0, 183.2; found M+ 334.0989, C16H18N2O4S requires
m/z 334.0987. Anal. Calcd for C16H18N2O4S: C, 54.47; H, 5.43.
Found: C, 54.21; H, 5.52.
6-(r-Ch lor op h en a cyl)-1,3-d im et h ylu r a cil (18) a n d 6-
(Ch lor om eth yl)-1,3-d im eth ylu r a cil (17). A solution of ylide
8 (0.23 g, 1.0 mmol) and benzoyl chloride (0.15 g, 1.1 mmol)
in acetonitrile (50 mL) was refluxed for 1 h. The solvent was
evaporated and the residue applied to a column of silica gel.
Elution with petroleum ether-EtOAc (1:1) afforded two color-
less solids. The first product eluted was identified as 18 (0.10
g, 0.34 mmol, 34%): mp 162-164 °C; νmax (CHCl3) 1707, 1662,
1597 cm-1; 1H NMR (CDCl3) 3.32 (s, 3H), 3.43 (s, 3H), 5.97 (s,
1H), 6.09 (s, 1H), 7.48-7.97 (m, 5H); 13C NMR (CDCl3) 28.2,
32.1, 57.0, 104.0, 129.0, 129.3, 133.0, 135.0, 148.1, 152.2, 161.7,
188.0; found M+ 292.0579, C14H13N2O3Cl requires m/z 292.0615.
The second product eluted was identical with 17 produced
above (0.08 g, 0.42 mmol, 42%): mp 86-88 °C.
tr a n s-6-(4,6-Dia za -4,6-d im et h yl-3,5-d ioxocycloh ex-1-
en yl)-3-p h en yl-3-a za bicyclo[3.1.0] h exa n e-2,4-d ion e (20).
A solution of uracil methanide 8 (230 mg, 1.0 mmol), N-
phenylmaleimide (260 mg, 1.5 mmol), and dry acetonitrile (25
mL) was refluxed for 5 h. After removal of the acetonitrile in
vacuo, the residue was taken up in water and extracted with
CHCl3. The combined organic extracts were washed with
saturated brine, dried (MgSO4), filtered, and concentrated in
vacuo. The residue was chromatographed on silica gel using
petroleum ether-ethyl acetate (1:1) as eluent to give cyclo-
C9H15N2O3SCl requires m/z 231.0803. Anal. Calcd for C9H15
-
N2O3SCl: C, 40.59; H, 5.68. Found: C, 40.34; H 5.69.
Alternatively, methanide 8 (100 mg, 0.43 mmol) was stirred
with concentrated hydrochloric acid (0.5 mL) in dry acetonitrile
(5 mL) at 0 °C for 30 min. The resulting solid was filtered and
washed with dry acetone to leave colorless crystals of 7, mp
1
134-135 °C. The H and 13C NMR of the product are identical
with that of 7 prepared above.
Regen er a tion of Ylid e 8. Sodium methoxide (17.0 mg, 0.3
mmol) was added to a solution of sulfoxonium salt 7 (50.0 mg,
0.2 mmol) in dry methanol (10 mL). After the mixture was
stirred at room temperature for 2 h, the solvent was evapo-
rated in vacuo to leave a colorless residue to which ethanol
(15 mL) was added. The solution was filtered and evaporated
to ∼3 mL, and Et2O was then added until the solution became
cloudy. Filtration yielded colorless crystals of methanide 8
(35.0 mg, 73%), mp 190-193 °C. The 1H NMR (DMSO-d6) of
the product agreed with that of 8 previously prepared.
1,3,6-Tr im eth ylu r a cil (16). Ylide 8 (50 mg, 0.217 mmol)
was dissolved in a 1:1 mixture of water and ethanol (10 mL),
and Raney nickel (∼100 mg, 50% slurry in water) was added.
The mixture was stirred at room temperature for 30 min and
filtered. The solvents were removed in vacuo, and the residue
was dissolved in CHCl3 and then washed with water. The
organic layer was dried (MgSO4), filtered, and evaporated to
a colorless oil. Chromatography (silica gel, 2 g) using petroleum
ether-EtOAc (1:3) as eluent afforded 16 as a colorless solid
(34 mg, 0.2 mmol, 92%): mp 104-106 °C; νmax (CHCl3) 1702,
1664 cm-1; 1H NMR (CDCl3) 2.22 (s, 3H), 3.30, 3.38 (2 s, 6H),

7296 J . Org. Chem., Vol. 64, No. 20, 1999
Norris and Shechter
propane 20 as a colorless solid (295 mg, 91%, recrystallized
from ethanol): mp 258-261 °C; νmax (CHCl3) 1785, 1724, 1666
3.60 (s, 3H), 5.50 (s, 1H); 13C NMR (CDCl3) 5.5, 13.5, 21.8, 27.8,
31.7, 99.8, 118.7, 150.4, 151.9, 161.9; found M+ 205.0850,
C10H11N3O2 requires m/z 205.0851.
1
cm-1; H NMR (CDCl3) 2.73 (t, 1H, J ) 3.0 Hz), 2.93 (d, 2H,
J ) 3.0 Hz), 3.34 (s, 3H), 3.59 (s, 3H), 5.64 (s, 1H), 7.23 (m,
5H); 13C NMR (CDCl3) 26.5, 28.1, 31.9, 32.0, 100.8, 126.2,
128.9, 128.3, 130.9, 147.6, 151.9, 161.8, 170.8; found M+
325.1074, C17H15N3O4 requires m/z 325.1062. Anal. Calcd for
The second compound eluted was collected as a colorless
solid that was recrystallized from CHCl3-Et2O and identified
as cis isomer 27 (110 mg, 23%): mp 190-192 °C; 1H NMR
(CDCl3) 1.60 (m, 2H), 2.10 (m, 1H), 2.25 (m, 1H), 3.35 (s, 3H),
3.58 (s, 3H), 5.70 (s, 1H); 13C NMR (CDCl3) 6.0, 12.4, 20.7, 28.0,
31.6, 102.3, 117.2, 148.9, 152.1, 162.1; found M+ 205.0852,
C
17H15N3O4: C, 62.76; H, 4.65. Found: C, 62.86; H, 4.72.
tr a n s-1-(4,6-Dia za -4,6-d im et h yl-3,5-d ioxocycloh ex-1-
en yl)-1a ,7a -d ih yd r o-1H -cyclop r op a [b ]n a p h t h a len e-2,7-
d ion e (21). Ylide 8 (0.23 g, 1.0 mmol) and 1,4-naphthoquinone
(0.24 g, 1.5 mmol) were refluxed in acetonitrile (10 mL) for 24
h. After the solvent had been evaporated under reduced
pressure, the residue was dissolved in CHCl3 and the solution
washed with water. Drying (MgSO4) and evaporation afforded
C
10H11N3O2 requires m/z 205.0851. For the mixture: νmax
(CHCl3) 3019, 2400, 2246, 1704, 1666, 1625 cm-1
.
tr a n s- a n d cis-2-(4,6-Dia za -4,6-d im eth yl-3,5-d ioxocy-
cloh ex-1-en yl)-cyclop r op a n e ca r ba ld eh yd es (28 a n d 29).
A solution of methanide 8 (500 mg, 2.15 mmol), dry acetonitrile
(50 mL), and freshly distilled acrolein (0.43 mL, 6.45 mmol)
was heated at 50 °C for 3 h. The volatiles were removed in
vacuo, and the residue was dissolved in CHCl3 and washed
with water. The aqueous layers were washed with CHCl3, and
the combined organic extracts were dried (MgSO4), filtered,
and adsorbed onto silica gel. Chromatography (petroleum
ether-EtOAc 1:2 as eluent) afforded trans-cyclopropane 28
(recrystallized from CHCl3-Et2O, mp 86-88 °C) followed by
cis isomer 29 (recrystallized from CHCl3-Et2O, mp 116-120
°C). Overall, 430 mg of product was collected (94%). Integration
of the 1H NMR spectrum of the crude reaction product
indicated the ratio of 28:29 to be 4.5:1.
a
yellow oil that was then chromatographed (silica gel,
petroleum ether-EtOAc 1:1) to afford 21 as an unstable yellow
solid (0.19 g, 61%): mp >300 °C; νmax (CHCl3) 1710, 1690, 1665
1
cm-1; H NMR (CDCl3) 2.75 (t, 1H, J ) 3.3 Hz), 2.97 (d, 2H,
J ) 3.5 Hz), 3.33 (s, 3H), 3.45 (s, 3H), 5.77 (s, 1H), 7.80-8.11
(m, 4H); 13C NMR (CDCl3) 26.9, 31.9, 32.4, 33.6, 100.6, 127.9,
130.7, 149.1, 151.9, 162.1, 165.9, 189.6; found M+ 310.0973,
C
17H14N2O4 requires m/z 310.0953.
1-(4,6-Dia za -4,6-d im et h yl-3,5-d ioxocycloh ex-1-en yl)-
2,3-d iben zoylcyclop r op a n es (22 a n d 23). A solution of 8
(230 mg, 1.0 mmol) and 1,2-trans-dibenzoylethylene (354 mg,
1.5 mmol) in dry acetonitrile (15 mL) was refluxed for 8 h.
The solvent was removed, and the residue was chromato-
graphed on silica gel (petroleum ether-EtOAc 1:1 as eluent)
to give two isomeric cyclopropanes. The first product eluted
was recrystallized from ethanol to yield colorless crystals of
22 (244 mg, 63%): mp 210-212 °C; 1H NMR (CDCl3) 3.11 (m,
1H), 3.32 (s, 3H), 3.34 (s, 3H), 3.80 (m, 1H), 3.99 (m, 1H), 5.86
(s, 1H), 7.50 (m, 6H); 13C NMR (CDCl3) 27.9, 30.7, 31.9, 32.7,
33.9, 103.2, 128.4, 128.5, 129.0, 134.2, 134.3, 136.0, 136.2,
148.2, 152.2, 162.1, 192.2, 195.0. The second product eluted
was a colorless oil (31 mg, 8%) identified as 23: 1H NMR
(CDCl3) 3.36 (s, 3H), 3.40 (m, 3H), 3.60 (s, 3H), 5.74 (s, 1H),
7.41 (m, 10H). For a mixture of the two isomers: νmax (CHCl3)
3019, 1702, 1662, 1621, 1597 cm-1; found M+ 388.1423,
For 28: νmax (CHCl3) 2956, 1701, 1662 cm-1; 1H NMR (CDCl3)
1.49 (m, 1H), 1.60 (m, 1H), 2.20 (m, 1H), 2.40 (m, 1H), 3.30 (s,
3H), 3.50 (s, 3H), 5.55 (s, 1H), 9.60 (d, 1H); 13C NMR (CDCl3)
14.5, 14.7, 22.1, 27.3, 29.5, 31.1, 98.9, 151.7, 151.9, 161.9, 198.0;
found M+ 208.0851, C10H12N2O3 requires m/z 208.0848. Anal.
Calcd for C10H12N2O3: C, 57.67; H, 5.81. Found: C, 57.65; H,
5.83.
For 29: νmax (CHCl3) 2950, 1700, 1659 cm-1; 1H NMR (CDCl3)
1.65 (m, 1H), 1.80 (m, 1H), 2.25 (m, 2H), 3.30 (s, 3H), 3.45 (s,
3H), 5.75 (s, 1H), 8.90 (d, 1H); 13C NMR (CDCl3) 11.9, 23.0,
27.8, 28.9, 31.5, 101.9, 146.6, 152.0, 162.0, 197.6; found M+
208.0850, C10H12N2O3 requires m/z 208.0857. Anal. Calcd for
C
10H12N2O3: C, 57.67; H, 5.81. Found: C, 57.66; H, 5.85.
tr a n s- a n d cis-1-Acetyl-2-(4,6-d ia za -4,6-d im eth yl-3,5-
C
23H20N2O4 requires m/z 388.1457. Anal. Calcd for C23H20N2-
d ioxocycloh ex-1-en yl)cyclop r op a n es (30 a n d 31). A solu-
tion of ylide 8 (500 mg, 2.17 mmol) and freshly distilled methyl
vinyl ketone (2 mL) in dry acetonitrile (50 mL) was heated at
45 °C for 18 h and then concentrated in vacuo. Water was
added, and the solution was extracted with CHCl3. The
combined organic layers were washed with water, dried
(MgSO4), filtered, and evaporated to a colorless oil. Chroma-
tography (silica gel, petroleum ether-EtOAc 1:1 as eluent)
gave trans-cyclopropane 30 (380 mg, 79%), mp 79-81 °C
(recrystallized from CHCl3-Et2O) and cis isomer 31 (60 mg,
12%), mp 116-118 °C (recrystallized from CHCl3-Et2O).
For 30: νmax (CHCl3) 1701, 1662, 1621 cm-1; 1H NMR (CDCl3)
1.25 (m, 1H), 1.46 (m, 1H), 2.20 (m, 1H), 2.25 (m, 1H), 2.28 (s,
3H), 3.19 (s, 3H), 3.37 (s, 3H), 5.41 (s, 1H); 13C NMR (CDCl3)
16.8, 23.8, 27.6, 28.9, 30.7, 31.4, 98.9, 152.1, 152.7, 162.2, 204.7;
found M+ 222.1001, C11H14N2O3 requires m/z 222.1004. Anal.
Calcd for C11H14N2O3: C, 59.43; H, 6.35. Found: C, 59.53; H,
6.36.
O4: C, 70.20; H, 5.36. Found: C, 69.72; H, 5.18.
1-(4,6-Dia za -4,6-d im eth yl-3,5-d ioxocycloh ex-1-en yl)-2-
ben zoyl-3-p h en ylcyclop r op a n es (24 a n d 25). A solution of
ylide 8 (100 mg, 0.42 mmol) and trans-benzylideneacetophe-
none (265 mg, 1.30 mmol) in dry acetonitrile (15 mL) was
refluxed for 36 h. After solvent removal, the residue was
chromatographed (silica gel, petroleum ether-EtOAc, 2:1 as
eluent) to yield two isomeric cyclopropanes 24 and 25. The first
product eluted was 24, a colorless oil that crystallized from
CHCl3-Et2O (50 mg, 32%): mp 145-147 °C; νmax (CHCl3)
3019, 1701, 1660, 1618, 1449 cm-1; 1H NMR (CDCl3) 3.10 (m,
2H), 3.28 (s, 3H), 3.34 (s, 3H), 3.66 (m, 1H), 5.86 (s, 1H), 7.20
(m, 5H), 7.50 (m, 5H); 13C NMR (CDCl3) 27.9, 29.9, 31.9, 32.5,
35.3, 102.3, 127.0, 127.9, 128.2, 128.9, 133.6, 133.9, 136.6,
149.6, 152.1, 162.3, 196.1; found M+ 360.1522, C23H20N2O4
requires m/z 360.1570.
The second product eluted was 25, an oil that upon tritu-
ration with Et2O gave a colorless solid (48 mg, 31%) that was
recrystallized from CHCl3-Et2O: mp 160-161 °C; νmax (CHCl3)
3020, 1699, 1660, 1620, 1440 cm-1; 1H NMR (CDCl3) 2.70 (m,
1H), 3.30 (s, 3H), 3.32 (m, 1H), 3.41 (s, 3H), 3.50 (m, 1H), 5.92
(s, 1H), 7.20 (m, 8H), 7.93 (m, 2H); 13C NMR (CDCl3) 27.9,
31.9, 32.6, 33.0, 33.7, 103.3, 126.6, 127.7, 128.2, 128.9, 129.0,
133.8, 136.9, 137.2, 149.9, 152.4, 162.4, 193.9; found M+
360.1505, C23H20N2O4 requires m/z 360.1570.
For 31: νmax (CHCl3) 1705, 1660, 1615 cm-1; 1H NMR (CDCl3)
1.45 (m, 1H), 1.59 (m, 1H), 2.18 (m, 1H), 2.22 (s, 3H), 2.50 (m,
1H), 3.24 (s, 3H), 3.35 (s, 3H), 5.65 (s, 1H); 13C NMR (CDCl3)
13.9, 24.9, 27.7, 27.8, 31.5, 31.6, 103.0, 149.9, 152.2, 162.3,
202.9; found M+ 222.1022, C11H14N2O3 requires m/z 222.1004.
Anal. Calcd for C11H14N2O3: C, 59.43; H, 6.35. Found: C,
59.40; H, 6.31.
tr a n s-6-(2-Eth en ylcyclopr opyl)-1,3-dim eth ylu r acil (33).
A solution of n-BuLi (1.37 mL, 2.19 M, 3.0 mmol) was added
dropwise to a cold (-70 °C) suspension of methyltriphenyl-
phosponium bromide (1.03 g, 2.9 mmol) in dry THF (30 mL).
The mixture was stirred at -78 °C for 30 min. A solution of
trans-cyclopropylcarboxaldehyde 28 (500 mg, 2.4 mmol) in
THF (15 mL) was then added dropwise. After being allowed
to warm to room temperature, the mixture was stirred for 18
h. The solvent was removed and the residue was chromato-
graphed (silica gel, petroleum ether-EtOAc 1:2 as eluent) to
tr a n s- a n d cis-2-(4,6-Dia za -4,6-d im eth yl-3,5-d ioxocy-
cloh ex-1-en yl)cyclop r op a n e-1-ca r bon itr iles (26 a n d 27).
Ylide 8 (500 mg, 2.17 mmol) and freshly distilled acrylonitrile
(2 mL) were refluxed in acetonitrile (50 mL) for 24 h. The
solvent was removed and the residue chromatographed (silica
gel, petroleum ether-EtOAc 1:2 as eluent) to give first trans
isomer 26 as a colorless solid (210 mg, 44%) which was
1
recrystallized from CHCl3-Et2O: mp 141-143 °C; H NMR
(CDCl3) 1.50 (m, 1H), 1.70 (m, 2H), 2.35 (m, 1H), 3.35 (s, 3H),

Reactions of 6- and 5-Substituted 1,3-Dimethyluracils
J . Org. Chem., Vol. 64, No. 20, 1999 7297
give alkene 33 as a colorless oil (450 mg, 91%): 1H NMR
(CDCl3) 1.00 (m, 2H), 1.55 (m, 2H), 3.35 (s, 3H), 3.45 (s, 3H),
4.95 (dd, 1H), 5.10 (dd, 1H), 5.30 (m, 1H), 5.45 (s, 1H); 13C
NMR (CDCl3) 13.8, 22.2, 25.2, 27.8, 31.8, 98.7, 115.5, 137.7,
152.4, 154.6, 162.8; found M+ 206.1021, C11H14N2O2 requires
m/z 206.1055.
5-Ben zen esu lfin yl-1,3-d im eth ylu r a cil (48). Sulfide 47
(2.48 g, 10.0 mmol)16 was dissolved in dry CH2Cl2 (75 mL),
and the solution was cooled to 0 °C. m-CPBA (2.16 g, 10.0
mmol, ∼80% assay) was added portionwise with stirring in
30 min. After being stirred for 3 h at room temperature, the
mixture was washed with saturated Na2CO3 solution and
water, dried (MgSO4), filtered, and evaporated in vacuo to a
colorless solid that was then recrystallized from benzene to
yield colorless crystals of 48 (2.11 g, 8.0 mmol, 80% yield): mp
2,4-Dia za -2,4-d im eth yl-1,3-d ioxobicyclo[5.4.0]u n d ec-7-
en e (36). A solution of methylenetriphenylphosphorane (32)
was prepared as in the previous experiment from n-BuLi (0.59
mL, 2.19 M, 1.3 mmol) and methyltriphenylphosphonium
bromide (445 mg, 1.25 mmol) in THF (10 mL). A solution of
cis-carboxaldehyde 29 (216 mg, 1.04 mmol) in THF (7 mL) was
added dropwise. After the mixture was warmed to room
temperature and stirred for 18 h, the solvent was removed
and the residue chromatographed (silica gel using petroleum
ether-EtOAc 1:1 as eluent) to afford cycloheptadiene 36 as a
pale yellow oil (135 mg, 63%): νmax (neat) 2906, 1693, 1481,
180-182 °C; νmax (CHCl3) 1713, 1665, 1478, 1445 cm-1 1H
;
NMR (CDCl3) 3.28 (s, 3H), 3.52 (s, 3H), 7.46 (m, 3H), 7.78 (s,
1H), 7.80 (m, 2H); 13C NMR (CDCl3) 27.8, 37.7, 117.3, 125.0,
129.1, 131.6, 141.6, 143.4, 151.1, 159.1; found M+ 264.0549,
C
12H12N2O3S requires m/z 264.0569. Anal. Calcd for C12H12
-
N2O3S: C, 54.53; H, 4.58. Found: C, 54.43; H, 4.55.
2,4-Dia za -5-ben zen esu lfin yl-2,4-d im eth yl-3,5-d ioxobi-
cyclo[4.1.0]h ep ta n e (49). Sodium hydride (0.17 g, 4.2 mmol,
60% suspension in mineral oil) was syringe-washed with
anhydrous Et2O. The system was evacuated and purged with
argon, and trimethylsulfoxonium chloride (0.53 g, 4.2 mmol)
was added followed by anhydrous THF (30 mL). The mixture
was refluxed for 3 h and cooled to 0 °C, and 48 (1.0 g, 3.8 mmol)
was added dropwise in dry THF (30 mL). After being at room
temperature for 1 h, the mixture was filtered and the filtrate
was evaporated in vacuo to a colorless oil that solidified upon
trituration with Et2O to 39 (0.71 g, 2.55 mmol, 67%): mp 134-
137 °C (recrystallized from CHCl3-Et2O); νmax (CHCl3) 3442,
1
1431 cm-1; H NMR (CDCl3) 2.28 (m, 2H), 2.98 (m, 2H), 3.25
(m, 2H), 3.33 (s, 3H), 3.48 (s, 3H), 5.48 (m, 1H), 5.63 (m, 1H);
13C NMR (CDCl3) 22.1, 24.6, 27.3, 28.5, 31.8, 112.5, 127.0,
128.0, 151.6, 162.0; found M+ 206.1039, C11H14N2O2 requires
m/z 206.1055.
Alternatively, trans-divinylcyclopropane 33 was pyrolyzed
at 320 °C in o-dichlorobenzene in a sealed tube for 30 h.
Removal of solvent by vacuum distillation left a brown residue
that was chromatographed (silica gel using petroleum ether-
EtOAc 1:1 as eluent) to give cycloheptene 36, identical in all
respects to the sample prepared in the previous experiment.
1703, 1665, 1479 cm-1 1H NMR (CDCl3) 1.26 (dd, 1H, J )
;
5.1, 6.2 Hz), 1.98 (dd, 1H, J ) 6.3, 7.2 Hz), 3.06 (s, 3H), 3.10
(s, 3H), 3.31 (dd, 1H, J ) 5.0, 7.8 Hz), 7.44 (m, 3H), 7.62 (m,
2H); 13C NMR (CDCl3) 16.9, 27.7, 32.4, 35.4, 43.9, 124.7, 128.9,
132.1, 141.5, 150.3, 165.7; found M+ - SOPh 153.0710,
C7H9N2O2 (M - SOPh) requires m/z 153.0664.
tr a n s-6-[2-(2-P r op en yl)cyclop r op yl]-1,3-d im eth ylu r a -
cil (39). To a suspension of methyltriphenylphosphonium
bromide (536 mg, 1.5 mmol) in dry THF (15 mL) at -70 °C
under argon was added n-BuLi (1 M in hexane, 1.5 mL, 1.5
mmol) dropwise, and the resultant yellow solution was stirred
at -70 °C for 30 min. trans-Cyclopropyl ketone 30 (222 mg,
1.0 mmol) was added dropwise in dry THF (10 mL) and the
mixture then warmed to room temperature. After the mixture
was stirred for 12 h, the solvent was removed in vacuo and
the residue was dissolved in CHCl3, washed with water, dried
(MgSO4), and evaporated to a colorless oil. Chromatography
(silica gel using petroleum ether-EtOAc 1:1 as eluent) afforded
divinylcyclopropane 39 (200 mg, 91%): mp 80-82 °C (recrys-
tallized from CHCl3-Et2O); νmax (CHCl3) 1665, 1618, 1442,
Red u ction of Cyclop r op a n e 49; P r ep a r a tion of 46a
a n d 16. Cyclopropane 49 (278 mg, 1.0 mmol) was stirred at
room temperature with Raney nickel (∼500 mg as an aqueous
slurry) in ethanol (25 mL) for 1 h. The mixture was filtered,
and the solvent was then removed. Chromatography of the
residue (silica gel using petroleum ether-EtOAc 1:1 as eluent)
afforded, first, 1,3-dimethylcyclothymine (46a ) as a colorless
oil (25 mg, 16%). The TLC mobility and 1H and 13C NMR
spectra of 46a matched that of an authentic sample.12 The
second product, collected as a colorless oil (65 mg, 42%), was
1
1377 cm-1; H NMR (CDCl3) 1.08 (m, 2H), 1.61 (m, 1H), 1.66
1
identified as 16 by comparison of its H and 13C NMR spectra
(s, 3H), 1.72 (m, 1H), 3.26 (s, 3H), 3.44 (s, 3H), 4.78 (m, 2H),
5.47 (s, 1H); 13C NMR (CDCl3) 12.5, 19.7, 20.4, 27.7, 27.9, 31.6,
98.6, 111.1, 142.2, 152.3, 155.1, 162.7; found M+ 220.1206,
with an authentic sample.6
2,4-Dia za -5-ben zen esu lfon yl-2,4-d im eth yl-3,5-d ioxobi-
cyclo[4.1.0]h ep ta n e (50). m-CPBA (450 mg, ∼2.1 mmol,
∼85% assay) was added portionwise to a solution of cyclopro-
pane 49 (500 mg, 1.80 mmol) in CH2Cl2 (25 mL) at 0 °C. The
mixture was stirred at room temperature for 4 h and washed
with water and saturated NaHCO3. The organic layer was
dried (MgSO4) and filtered, and the solvent was evaporated
to afford a colorless oil that was chromatographed (silica gel
using petroleum ether-EtOAc 1:1 as eluent) to give sulfone
50 as a colorless solid (360 mg, 68%): mp 196-198 °C; νmax
(CHCl3) 1703, 1666, 1583, 1479, 1444 cm-1; 1H NMR (CDCl3)
1.32 (dd, 1H, J ) 5.4, 6.3 Hz), 2.07 (dd, 1H, J ) 6.5, 7.4 Hz),
3.10 (s, 3H), 3.20 (s, 3H), 3.92 (dd, 1H, J ) 5.3, 7.5 Hz), 7.51
(m, 3H), 8.01 (m, 2H); 13C NMR (CDCl3) 19.3, 28.1, 35.5, 38.5,
44.2, 128.8, 129.7, 134.3, 138.3, 150.1, 162.8; found M+ - SO2-
Ph 153.0644, C7H9N2O2 (M - SO2Ph) requires m/z 153.0664.
Anal. Calcd for C13H14N2O4S: C, 53.05; H, 4.80. Found: C,
52.96; H, 4.79.
1,3-Dim eth yl-5-selen op h en ylu r a cil (51). A mixture of
diphenyl diselenide (6.24 g, 20.0 mmol), ammonium persulfate
(9.12 g, 40.0 mmol), and 1,3-dimethyluracil (2.8 g, 20.0 mmol)
in absolute ethanol (300 mL) was refluxed 12 h and cooled,
and the solvent was removed in vacuo to leave a yellow solid.
Water was added, and the mixture was extracted with CHCl3.
The combined organic extracts were washed with water, dried
(MgSO4), filtered, and evaporated to a pale yellow solid.
Trituration with Et2O afforded selenide 51 (4.7 g, 16.0 mmol,
80%): mp 116-118 °C; νmax (CHCl3) 1706, 1652, 1617, 1578
cm-1; 1H NMR (CDCl3) 3.35 (s, 3H), 3.37 (s, 3H), 7.23 (m, 3H),
7.46 (s, 1H), 7.47 (m, 2H); 13C NMR (CDCl3) 28.6, 37.0, 102.9,
C
12H16N2O2 requires m/z 220.1212.
2,4-Dia za -2,4,8-tr im eth yl-1,3-d ioxobicyclo[5.4.0]u n d ec-
7-en e (42). To a solution of methylenetriphenylphosphorane
(32), prepared by adding n-BuLi (2.19 M, 0.14 mL, 0.30 mmol)
to a suspension of methyltriphenylphosphonium bromide (96.4
mg, 0.27 mmol) in dry THF (5 mL) at -70 °C, was added cis-
cyclopropyl ketone 31 (50 mg, 0.225 mmol). The solution was
warmed to room temperature and stirred for 12 h. Removal
of solvent in vacuo left a yellow residue that was dissolved in
CHCl3, washed with water, dried (MgSO4), filtered, and
evaporated to a colorless oil. Chromatography (silica gel using
petroleum ether-EtOAc 1:1 as eluent) yielded a colorless oil
that crystallized upon trituration with Et2O (37 mg, 0.169
mmol, 75%): mp 101-103 °C; νmax (CHCl3) 1693, 1645, 1480,
1
1431 cm-1; H NMR (CDCl3) 1.70 (s, 3H), 2.25 (m, 2H), 2.89
(m, 2H), 3.27 (m, 2H), 3.36 (s, 3H), 3.46 (s, 3H), 5.28 (m, 1H);
13C NMR (CDCl3) 24.5, 26.8, 27.0, 27.4, 28.5, 31.7, 98.0, 111.3,
121.7, 135.7, 151.3, 162.2; found M+ 220.1216, C12H16N2O2
requires m/z 220.1212.
Alternatively, trans-divinylcyclopropane 39 (200 mg, 0.91
mmol) was pyrolyzed at 320 °C in o-dichlorobenzene in a sealed
tube for 48 h. Removal of solvent by vacuum distillation left a
brown residue that was chromatographed (silica gel, 10 g)
using petroleum ether-EtOAc (1:1) as eluent to give cyclo-
heptene 42 as a colorless solid (140 mg, 0.64 mmol, 70%), mp
1
100-103 °C. The H, 13C, and mass spectral properties of this
product were identical to those of cycloheptene 42 prepared
in the previous experiment.

7298 J . Org. Chem., Vol. 64, No. 20, 1999
Norris and Shechter
127.6, 129.3, 129.4, 132.4, 146.4, 151.5, 161.8; found M+
296.0040, C12H12N2O2Se requires m/z 296.0063. Anal. Calcd
for C12H12N2O2Se: C, 48.65; H, 4.09. Found: C, 48.47; H, 4.07.
1,3-Dim et h yl-5-p h en ylselen in ylu r a cil (52). 5-Seleno-
phenyluracil 51 (2.95 g, 10.0 mmol) and MMPP (magnesium
monoperoxyphthalate) (3.71 g, 6.0 mmol, 80% assay) were
dissolved in a 1:1 mixture of ethanol and water (50 mL). The
mixture was kept at 50 °C for 1 h, and the ethanol was
removed in vacuo. The aqueous mixture was extracted with
CHCl3, and the combined organic extracts were washed with
water, dried (MgSO4), filtered, and evaporated to a pale yellow
solid. Trituration with Et2O afforded selenoxide 52 (2.74 g, 8.8
mmol, 88% yield): mp 182-185 °C (recrystallized from ben-
mixture was refluxed for 3 h and cooled to 0 °C, and 5-phen-
ylseleninyluracil 52 (0.311 g, 1.0 mmol) was added dropwise
in dry THF (15 mL) The mixture was stirred at room
temperature for 12 h. Removal of solvent in vacuo produced a
yellow oil that on chromatography (silica gel using methanol-
CHCl3 1:2 as eluent) yielded sulfoxonium ylide 8 as a pale
yellow solid (78 mg, 0.34 mmol, 34%), mp 192-195 °C. The
spectral properties are identical to those given for 8 above.
Ack n ow led gm en t. We thank the National Insti-
tutes of Health for financial support. We also thank Dr.
Kurt Loening and Mr. Carl Engleman of the Depart-
ment of Chemistry at The Ohio State University for
assistance with nomenclature and for help obtaining
NMR spectra, respectively, and Mr. Dick Weisenberger
of the OSU SAIL facility for mass spectral analyses.
zene); νmax (CHCl3) 1710, 1657, 1520, 1478 cm-1 1H NMR
;
(CDCl3) 3.27 (s, 3H, NCH3), 3.48 (s, 3H, NCH3), 7.47 (m, 3H,
aromatic), 7.81 (m, 2H, aromatic), 7.95 (s, 1H, H-6); 13C NMR
(CDCl3) 27.9, 37.6, 113.8, 126.0, 129.5, 131.4, 141.4, 142.9,
151.2, 160.5; found M+ 312.0018, C12H12N2O3Se requires m/z
312.0013. Anal. Calcd for C12H12N2O3Se: C, 46.30; H, 3.88.
Found: C, 46.70; H, 4.03.
Rea ction of 52 a n d 3. Sodium hydride (0.312 g, 3.3 mmol)
was syringe-washed with anhydrous Et2O. The flask was
purged with argon, and trimethylsulfoxonium chloride (0.416
g, 3.3 mmol) was added followed by dry THF (15 mL). The
Su p p or tin g In for m a tion Ava ila ble: Copies of the 1H and
13C NMR spectra for compounds 18, 21, 24-27, 33, 36, 39,
42, and 49. This material is available free of charge via the
Internet at http://pubs.acs.org.
J O981906E