Vicarious nucleophilic substitution of hydrogen (VNS) in 1,4-naphthoquinone derivatives - Competition between VNS and vinylic nucleophilic substitution (SNV)

Article abstract of DOI:10.1016/S0040-4020(01)00962-0

Carbanions of dimethyl chloromalonate, ethyl 2-chloroacetoacetate and dimethyl malonate react with naphthoquinone derivatives mainly via vicarious nucleophilic substitution or oxidative nucleophilic substitution of hydrogen processes. These reactions in 2

Full text of DOI:10.1016/S0040-4020(01)00962-0

TETRAHEDRON
Pergamon
Tetrahedron 57 ꢀ2001) 9615±9621
Vicarious nucleophilic substitution of hydrogen ꢀVNS) in
,4-naphthoquinone derivativesÐcompetition between VNS
and vinylic nucleophilic substitution ꢀS V)
1
N
p
Mieczysøaw M aÎ kosza and Shamil Nizamov
Institute of Organic Chemistry, Polish Academy of Sciences, Warsaw 42, P.O. Box 58, Kasprzaka 44/52, 01-224 Warsaw, Poland
Received 21 June 2001; revised 22 August 2001; accepted 13 September 2001
AbstractÐCarbanions of dimethyl chloromalonate, ethyl 2-chloroacetoacetate and dimethyl malonate react with naphthoquinone
derivatives mainly via vicarious nucleophilic substitution or oxidative nucleophilic substitution of hydrogen processes. These reactions in
2
N
-halo substituted naphthoquinones are generally faster processes than vinylic nucleophilic substitution of halogen ꢀS V). Introduction of
one Cl substituent into position 2- of 1,4-naphthoquinone increases substantially its electrophilic activity resulting in much faster addition of
the carbanion in the position occupied by hydrogen. On the other hand addition of the carbanions to 2,3-dichloro-1,4-naphthoquinone
proceeds slower than to 1,4-naphthoquinone. q 2001 Published by Elsevier Science Ltd.
Vicarious nucleophilic substitution ꢀVNS) of hydrogen is a
general reaction between electrophilic arenes and nucleo-
philes containing leaving groups at the nucleophilic centre.
A variety of carbon as well as amino and hydroxy sub-
stituents can be directly introduced into aromatic rings via
quinones were notavailable. 1,4-Naph ht oquinone ꢀ 1a) was
selected as the model quinone for these studies, because it is
reasonably stable and readily available.
Our ®rst attempts to execute the VNS reaction of 1a with
a-halocarbanions typically used for this process, such as
chloromethyl p-tolyl sulfone or ethyl chloroacetate, carried
outin th e presence of t-BuOK in THF, even at 2708C, gave
negative results. Apparently eventual VNS products were
totally decomposed under the strongly basic reaction
conditions.
1
±4
this reaction. A similar reaction may occur with electro-
philic alkenes or aldimines.
5
±10
Due to their strong electro-
philic character quinones appear to be active potential
reactants in this reaction. In the literature one example of
VNS type reaction of quinones was reported, however
1
1
mechanistic features of this process were not recognized.
We have already reported reactions of halomethyl aryl
sulfone carbanions with anthraquinone derivatives, some
of them proceeding along the VNS pathway when the
On the other hand, less active carbanions, formed from more
acidic precursors such as dimethyl chloromalonate ꢀ2a) or
ethyl 2-chloroacetoacetate ꢀ2b) in the presence of DBU, a
much milder base than t-BuOK, reacted smoothly with 1a
giving the expected VNS products 3a or 3b in good yields
1
2
aromatic ring was activated by the quinone moiety. An
intramolecular variant of such process had been reported
earlier.
1
3,14
ꢀScheme 1).
In the course of exploring the scope and limitations of the
VNS reaction it was of substantial interest to clarify a
possibility of execution of this process in the quinone
rings. Another interesting question was the relation between
rates of nucleophilic addition at the carbon atom bonded
with hydrogen and halogen of the quinone ring. It was
already well recognized, that, as a rule, in the electrophilic
aromatic systems carbanionic nucleophiles add faster at
positions occupied by hydrogen, than at, equally activated,
The reaction of 2a or 2b with 2-chloro-1,4-naphthoquinone
ꢀ1b) proceeded under similar conditions exclusively along
the VNS pathway giving 3c and 3d. Nucleophilic replace-
mentof ht e halogen, S NV was notobserved under such
conditions ꢀScheme 1). These results indicate that the
addition of the carbanions of 2a and 2b to 2-chloro-1,4-
naphthoquinone proceeds much faster in the position
occupied by hydrogen than in that occupied by Cl.
1
5±18
positions occupied by halogens,
however such data for
The VNS reactions in nitroarenes proceed via addition of
nucleophiles bearing a leaving group X, in positions
connected with the hydrogen of the ring, giving anionic
Keywords: quinones; carbanions; vicarious nucleophilic substitution;
vinylic nucleophilic substitution.
Corresponding author. Tel.: 148-22-631-87-88; fax: 148-22-632-66-8;
e-mail: icho-s@icho.edu.pl
H
p
s -adducts, followed by base induced b-elimination of
HX. This mechanism has been experimentally veri®ed,
1
±4
0040±4020/01/$ - see front matter q 2001 Published by Elsevier Science Ltd.
PII: S0040-4020ꢀ01)00962-0

9616
M. M aÎ kosza, S. Nizamov / Tetrahedron 57 ꢀ2001) 9615±9621
Scheme 1.
in particular it was shown that the reaction rate strongly
depends on the strength and concentration of base. These
conclusions were based on results of competitive experi-
ments in which the ratio of competing nucleophilic substi-
Further proton shift and elimination of the chloride anion
in 5b could give 4, whereas base induced b-elimination
leads to the VNS product 3c. The reaction with
higher concentration of base led to the VNS product only
ꢀ63%).
tution of halogen ꢀS Ar) and VNS was found to be a
N
1
5±18
function of base concentration.
In order to elucidate
H
the mechanism of VNS in quinones the same approach
was attemptedÐnamely studies of competition between
Itseems however mostlikely ht at 4 was produced from s
adduct 5b upon chromatographic puri®cation. Indeed, when
the reaction mixtures were separated using silicagel
pretreated with AcOH/hexane before use, compound 4
was notobserved and ht e yield of 3c became lower.
1
9±23
vinylic nucleophilic substitution of Cl ꢀS V)
and VNS
in 1b as a function of base concentration. It is well known
N
that some carbanions replace readily the halogens in 2,3-
dichloro-1,4-naphthoquinone,
2
4±28
a similar replacementof
2
9
the halogen proceeds with enamines, however notmuch is
known aboutreplacementof ht e halogen in 2-chloro-1,4-
naphthoquinone ꢀ1b) with carbanions. Reactions of other
Control of competing reactions of nucleophilic substitution
of hydrogen and halogen by base concentration is possible
provided that the formation of the s adducts is truly a
H
2
2
nucleophiles: F , MeO and dialkyl amines with 1b
reversible process. One can therefore expect that this control
can be more pronounced ata higher etmper aut re when
dissociation of the s adducts is accelerated. However,
2
2
indicate that hard nucleophiles ꢀF , MeO ) add preferably
to the carbon atom connected to Cl whereas dialkylamines
add to that connected to hydrogen.
H
3
0
when the reaction of 1b with 2a in the presence of a base
in low concentration was carried out at higher temperature,
When the reaction of 1b with 2a was carried outat 2708C
with low base concentration, the only observed change was
a decrease of yield of the VNS product 3c ꢀ60%) whereas
the S V product 4 was notob at ined.
N
H
Preferable formation of the s adductand accelera it on of
productS V ꢀ4) was formed in a negligible amountꢀ2%)
N
the equilibration process at higher temperature was
observed in the reaction of 1b with dimethyl malonate
ꢀ2c) which is unable to enter VNS. When the reaction was
carried outat 21008C, only the product of the oxidative
nucleophilic substitution of hydrogen ꢀONSH) 3c was
ꢀ
the ipso substitution via intermediate 5a and cine sub-
Scheme 2). This productcould be formed in wt o waysÐ
2
stitution proceeding via addition of the carbanion in position
3
2
- occupied by hydrogen to give an intermediate 5b .
Scheme 2.

M. M aÎ kosza, S. Nizamov / Tetrahedron 57 ꢀ2001) 9615±9621
9617
Scheme 3.
formed. Higher temperature of the reaction favoured
formation of the S V product 3a ꢀScheme 3).
yield 31%. In a separate experiment it was shown that
compound 3e does not react with the carbanion of 2a
under the reaction conditions. Moreover, when 1c was
treated with an equimolar amount of the carbanion of 2a,
and the reaction mixture was quenched after 5 min at 2708C
N
In halonitroarenes nucleophilic replacement of F occurs
much faster than Cl when the halogens are located in
3
1
1
13
equally activated positions. In our studies we have
observed that a-halocarboanions reacted with chloronitro-
arenes only via the VNS pathway, whereas the reaction with
intermediate 7 was observed by H, C and MS spectra. In
this experiment product 3e was obtained in low yield ꢀ6%),
whereas two products of the S V reaction {617} were
N
1
analogous ¯uoronitrobenzenes gave S Ar and VNS
N
observed in combined yield about30% ꢀaccording ot
H
products in a ratio depending on strength and concentration
NMR spectra). Compound 7 was transformed into
compound 6 during an attempt of puri®cation by column
chromatography and could not be separated from 6 by
recrystallisation.
1
±4,15±18
of the base.
VNS and S V should be a function of base concentration in
We could, therefore, expect that ratio of
N
the reaction of 2a with 2-¯uoro-1,4-naphthoquinone ꢀ1c).
When this quinone was subjected to the reaction with 2a
in the presence of an excess of DBU at 2708C, two products
were formed: the expected VNS product 3e ꢀ33%) and
compound 6 ꢀ8%) ꢀScheme 4).
2
These results indicate that rates of addition of 2a to 1c in
H
the positions occupied by hydrogen and ¯uorine giving s
and s adducts are similar, the former adduct produces the
F
2
F
VNS product 3e whereas departure of F from the s adduct
gives 4 which reacts further producing 6. In order to gain
insight into how halogen substituents affect activity of
naphthoquinone in reactions with carbanions, rates of the
reactions of 1a, 1b and 2,3-dichloro-1,4-naphthoquinone
ꢀ1d) with 2a and 2c were directly compared in competitive
experiments. When a mixture of 1a ꢀ1.5 mmol), 1b
Formation of 6 can be rationalised by a speculative mechan-
istic pathway in which the initial step is S V process giving
4
N
2
which reacts further with 2a as shown in Scheme 4.
Indeed, when DBU was added slowly to a mixture of 1c
1 mmol) and 2a ꢀ2 mmol), compound 6 was obtained in
much higher yield ꢀ30%) and product 3e was formed in
ꢀ
Scheme 4.

9618
M. M aÎ kosza, S. Nizamov / Tetrahedron 57 ꢀ2001) 9615±9621
Scheme 5.
ꢀ
1.5 mmol) and 2a ꢀ1 mmol) was added to an excess of DBU
carbanion to 1a proceeds faster than to 1d in spite of the
presence of two Cl substituents in 1d.
at 2708C the only process was VNS in 1b giving 3c ꢀ76%
yield based on 2a) ꢀScheme 5). Unreacted 1a ꢀ1.31 mmol)
and 1b ꢀ0.23 mmol) were recovered from the reaction
mixture. Thus Cl substituent activates 1b for the addition
of carbanions in position 3- occupied by hydrogen, so it
reacts much faster than 1,4-naphthoquinone ꢀ1a). On the
other hand in the reaction of 1a ꢀ1.5 mmol) and 1d
Results of these competitive experiments show a peculiar
effect of Cl substituents on the electrophilic reactivity of
naphthoquinones. The presence of one Cl increases substan-
tially the electrophilic activity of 1b, resulting in much
faster addition of the carbanion to 1b ꢀthan to 1a) in t he
position occupied by hydrogen. There is no reason to
suppose that the second Cl substituent would exert the
opposite effect, however, in spite of the expected higher
general electrophilicity of the molecule of 1d, Cl sub-
stituents occupying the addition sites protect them against
nucleophilic addition, thus it proceeds much slower than to
1b and 1a. Similarly, in nitroarenes the Cl substituents
increase the general electrophilic activity of the ring and
simultaneously protect positions they occupy against
nucleophilic attack.
ꢀ
1.5 mmol) with 2a ꢀ1 mmol) in the presence of an excess
of DBU at 2708C, the carbanion of 2a reacted only with 1a
giving the VNS product 3a ꢀ66%) and product 8 ꢀ17%)
ꢀ
Scheme 5).
Compound 8 was apparently formed via a reaction of the
carbanion of 3a with 1d proceeding as S V process
ꢀ
between {1a11d} and 2a was ®nished athigher
temperature ꢀ08C) VNS product 3a was obtained in
low yield ꢀ5%), whereas product 8 was obtained in yield
N
VNS1S V) ꢀScheme 5). Indeed, when the reaction
N
69%. In addition to that, when a 1:1 mixture of 3a and 1d
was treated with DBU product 8 was obtained in 75%
Since ONSH usually proceeds slower than VNS, we
expected that the competition between S V in 1d and
N
yield.
ONSH in 1a could give additional information concerning
the relation of the electrophilic activities of 1a and 1d.
When a mixture of 1a, 1d and dimethyl malonate ꢀ2c) in
THF was added to a solution of DBU in THF at 2708C, the
main process was ONSH in 1a giving 3a ꢀ16%) and 8
Reaction S V in 1d is a relatively slow process. For
N
example, treatment of 1d with 2a in the presence of DBU
at 2708C for 30 min gave the S V product 9 in 10% yield
N
only, and about 75% of both educts were recovered. When
this reaction was carried out at 1208C and quenched after
ꢀ28%), butS V process in 1d also took place in this case
N
giving 3c in low 5% yield ꢀScheme 7).
6
ꢀ
0 min product 9 was obtained in a higher yield ꢀ45%)
Scheme 6). These results indicate that the addition of the
In this connection it was of interest to compare the effects of
Scheme 6.

M. M aÎ kosza, S. Nizamov / Tetrahedron 57 ꢀ2001) 9615±9621
9619
Scheme 7.
Cl and F substituents in 2-halo substituted naphthoquinones
on the competition between S V and ONSH, in the reaction
keto form), 6.84 ꢀs, 1H, enolic form), 5.18 ꢀd, 1H,
Jˆ0.9 Hz, keto form), 4.27 ꢀq, 2H, Jˆ7.1 Hz, enolic
form), 4.19 ꢀq, 2H, Jˆ7.1 Hz, keto form), 2.41 ꢀs, 3H,
keto form), 2.00 ꢀs, 3H, enolic form), 1.31 ꢀt, 3H,
Jˆ7.1 Hz, keto form), 1.17 ꢀt, 3H, Jˆ7.1 Hz, enolic
N
2
with 2c . The reaction of dimethyl malonate ꢀ2c) with
2
-¯uoro-1,4-naphthoquinone ꢀ1c) gave mostly S V product
N
3a ꢀ50%) ꢀScheme 7) whereas the product of ONSH ꢀ3e)
was formed in low amountꢀ1%).
form). IR ꢀ®lm) n : 2984, 1743, 1724, 1667, 1596,
max
1301, 1254, 1196. Anal. calcd for C H O : C 67.13, H
4.93; found: C 67.10, H 4.83.
16 14 5
Although these results are purely qualitative one can
conclude that similarly as in nitroarenes Cl activates the
ring for nucleophilic addition, but protects the position it
occupies, whereas similar effects of F are much weaker.
1.1.3. 2-[Diꢀmethoxycarbonyl)]methyl-3-chloro-1,4-
naphthoquinone ꢀ3c). Yield 235 mg ꢀ73%), yellow
3
crystals, mp 152±1538C ꢀethanol), lit. : mp 153.58C
5
1
ꢀ
methanol). H NMR: 8.25±8.10 ꢀm, 2H), 7.85±7.75 ꢀm,
2H), 5.16 ꢀs, 1H), 3.81 ꢀs, 6H). IR nmax: 1750, 1733, 1674,
273, 1252, 1035, 753. Anal. calcd for C H ClO : C
1
. Experimental
1
1
5
11
6
Melting points are uncorrected. IR spectra were recorded in
KBr on Beckmann IR-4240 spectrometer. H- and C NMR
spectra were taken in CDCl3 on Varian Gemini 200
55.83, H 3.44, Cl 10.99; found: C 55. 89, H 3.30, Cl 11.18.
1
13
1.1.4. 2-[ꢀAcetyl-ꢀethoxycarbonyl)]methyl-3-chloro-1,4-
naphthoquinone ꢀ3d). Yield 242 mg ꢀ75%), yellow
ꢀ
200 MHz) spectrometer, chemical shifts are given in
2
crystals, mp 105±1068C ꢀhexane/ether), lit. : mp 106±
6
d ppm referred to TMS as internal standard. Mass spectra
were recorded on AMD 604 spectrometer. Column chroma-
tography was performed using silica gel 230±400 mesh ꢀE.
Merck). All reactions were performed under Ar. The follow-
ing compounds were prepared by known methods: 2-chloro-
1
1078C ꢀethanol). H NMR ꢀexists only in enolic form):
13.20 ꢀs, 1H), 8.27±8.09 ꢀm, 2H), 7.86±7.75 ꢀm, 2H),
4.18 ꢀq, 2H, Jˆ7.1 Hz), 1.91 ꢀs, 3H), 1.16 ꢀt, 3H,
Jˆ7.1 Hz), lit.: IR nmax: 1684, 1665, 1646, 1596, 1395,
1340, 1284, 1242, 710. Anal. calcd for C16H13ClO : C
5
3
2
1
1c),
,4-naphthoquinone ꢀ1b),
2-¯uoro-1,4-naphthoquinone
Other
3
3
34
ꢀ 2,3-dichloro-1,4-naphthoquinone ꢀ1d).
reagents are commercially available.
59.92, H 4.08, Cl 11.06; found: C 60.01, H 3.97, Cl 11.16.
1
.1.5. 2-[Diꢀmethoxycarbonyl)]chloromethyl-1,4-naphtho-
quinone ꢀ4). To a stirred solution of dimethyl chloro-
malonate ꢀ333 mg, 2 mmol) and 2-chloro-1,4-
1.1. General procedure for VNS reaction in naphtho-
quinones 1a±d
naphthoquinone ꢀ385 mg, 2 mmol) in THF ꢀ15 mL) a solu-
tion of DBU ꢀ304 mg, 2 mmol) in THF ꢀ5 mL) was added
dropwise at 2708C. The reaction mixture was kept at this
temperature for 20 min and then poured into cold 3% HCl
solution and extracted with CH Cl . The combined extracts
To a stirred solution of DBU ꢀ380 mg, 2.5 mmol) in THF
8 mL) a solution of the carbanion precursor ꢀ1 mmol) and
the quinone ꢀ1 mmol) in THF ꢀ2 mL) was added dropwise at
58C. The mixture was stirred for 5 min at 158C, the cool-
ꢀ
2
2
1
were dried with MgSO . The solvents were evaporated in
4
ing bath was removed and the reaction mixture was allowed
to warm up to 1208C, and kept at this temperature for
vacuo at room temperature and the products 3c and 4 were
isolated from the half of the residue by column chromato-
graphy ꢀhexane/CH Cl /ether eluent) in yields 195 mg
1
3
0 min. The reaction mixture was then poured into cold
% HCl solution and extracted with CH Cl . The combined
2
2
2
2
ꢀ60%) and 8 mg ꢀ2%) respectively. The second half of the
residue was puri®ed by column chromatography using
extracts were dried with MgSO . The solvents were evapo-
4
rated in vacuo and the products were isolated from the
residue by column chromatography ꢀhexane/CH Cl
eluent).
silicagel pretreated with AcOH/hexane to give 3c only
ꢀ
2
2
1
179 mg, 56%). 4, brown oil: H NMR: 8.16±8.06 ꢀm,
1
3
2H), 7.85±7.74 ꢀm, 2H), 7.29 ꢀs, 1H), 3.89 ꢀs, 6H).
C
NMR: 184.2, 182.4, 165.2, 144.9, 136.3, 135.0, 134.5,
31.7 ꢀ2C), 127.2, 126.4, 72.4, 54.5. MS ꢀCI): 662 ꢀ20)
[2M 1NH ], 340 ꢀ100) [M 1NH ].
4 4
1
quinone ꢀ3a). Yield 237 mg ꢀ82%), yellow crystals, mp
.1.1.
2-[Diꢀmethoxycarbonyl)]methyl-1,4-naphtho-
1
1
1
3
10±1118C ꢀhexane/AcOEt), lit. : mp 1358C ꢀmethanol).
5
1
1
H NMR: 8.18±8.04 ꢀm, 2H), 7.82±7.72 ꢀm, 2H), 7.06 ꢀd,
H, Jˆ0.9 Hz), 5.08 ꢀd, 1H, Jˆ0.9 Hz), 3.82 ꢀs, 6H). IR
1
1.2. The reaction of dimethyl malonate ꢀ2c) with 2-
chloro-1,4-naphthoquinone ꢀ1b) at various temperatures
ꢀcompetition between ONSH and S V) ꢀScheme 3)
N
n
calcd for C H O : C 62.50, H 4.20; found: C 62.46, H
: 1750, 1730, 1664, 1317, 1302, 1237, 752. Anal.
max
1
5
12
6
4
.05.
To a stirred solution of dimethyl malonate ꢀ132 mg,
1 mmol) and 2-chloro-1,4-naphthoquinone ꢀ193 mg,
1 mmol) in THF ꢀ8 mL) a solution of DBU ꢀ152 mg,
1 mmol) in THF ꢀ2 mL) was added dropwise at temperature
indicated in Scheme 3. After 30 min the reaction mixture
1
.1.2. 2-[Acetyl-ꢀethoxycarbonyl)]methyl-1,4-naphtho-
1
quinone ꢀ3b). Yield 221 mg ꢀ77%), oil. H NMR: 13.21
s, 1H, enolic form), 8.18±8.04 ꢀm, 2H, both forms),
.83±7.71 ꢀm, 2H, both forms), 7.08 ꢀd, 1H, Jˆ0.9 Hz,
ꢀ
7

9620
M. M aÎ kosza, S. Nizamov / Tetrahedron 57 ꢀ2001) 9615±9621
was poured into cold 3% HCl solution and extracted with
CH Cl . The combined extracts were dried with MgSO .
Thus spectral data for 7 were obtained after subtracting
the spectra of 6 from the spectra of mixture 617.
2
2
4
The solvents were evaporated in vacuo and after ¯ash
column chromatography ꢀhexane/CH Cl /ether) educt and
a mixture of products 3a and 3c were obtained. The ratio
1.4.1.
2-[Diꢀmethoxycarbonyl)]chloromethyl-3-[di-
ꢀ7).
Pale pink powder, H NMR: 8.15±8.02 ꢀm, 2H), 7.84±
.75 ꢀm, 2H), 6.15 ꢀs, 1H), 3.89 ꢀs, 3H), 3.88 ꢀs, 3H), 3.86
2
2
ꢀmethoxycarbonyl)]methyl-1,4-naphthoquinone
1
1
3
a/3c was determined on the basis of H NMR spectra.
7
1
3
1.3. Reaction of 2-¯uoro-1,4-naphthoquinone ꢀ1c) with
dimethyl chloromalonate ꢀ2a)
ꢀs, 3H), 3.83 ꢀs, 3H). C NMR: 189.6, 185.7, 165.1, 165.0,
164.9, 162.9, 141.5, 135.5, 135.3, 134.9, 134.8, 134.7,
127.4, 126.8, 71.7, 55.2, 54.4, 54.2, 53.18, and 53.1. MS
ꢀLSIMS HR): calcd for C20
found: 453.0605.
1
To a stirred solution of DBU ꢀ380 mg, 2.5 mmol) in THF
H18ClO10 ꢀ[M1H] ): 453.0589;
ꢀ8 mL) a solution of 2a ꢀ167 mg, 1 mmol) and 2-¯uoro-1,4-
naphthoquinone ꢀ176 mg, 1 mmol) in THF ꢀ2 mL) was
added dropwise at 2708C. The mixture was stirred for
1.5. Competitive reaction of 1,4-naphthoquinone ꢀ1a)
3
and extracted with CH Cl . The combined extracts were
0 min at 2708C, then poured into cold 3% HCl solution
and 2-chloro-1,4-naphtoquinone ꢀ1b) with dimethyl
chloromalonate ꢀ2a)
2
2
dried with MgSO . The solvents were evaporated in vacuo
4
and the residue separated by column chromatography
ꢀ
To a stirred solution of DBU ꢀ380 mg, 2.5 mmol) in THF
hexane/CH Cl /ether eluent, silicagel was washed with
2 2
ꢀ
1
8 mL) a solution of 1a ꢀ237 mg, 1.5 mmol), 1b ꢀ289 mg,
.5 mmol) and 2a ꢀ167 mg, 1 mmol) in THF ꢀ7 mL) was
added slowly at 2708C. The mixture was stirred for
0 min at this temperature, then poured into cold 3% HCl
solution and extracted with CH Cl . The combined extracts
AcOH/hexane before use) to give 3e ꢀ101 mg, 33%) and 6
33 mg, 16%).
ꢀ
3
When DBU ꢀ2 mmol) was added to a mixture of 2a
2 mmol) and 1c ꢀ1 mmol), product 3e was obtained in
yield 95 mg ꢀ31%) and 6 was isolated in yield 124 mg
30%).
2
2
ꢀ
were dried with MgSO . The solvents were evaporated in
4
vacuo and the residue was separated by column chromato-
graphy ꢀhexane/CH Cl /ether eluent) to give 3c ꢀ247 mg,
ꢀ
2
2
7
1
6% yield), 1b ꢀ44 mg, 0.23 mmol) and 1a ꢀ207 mg,
.31 mmol).
1
.3.1.
naphthoquinone ꢀ3e). Yellow crystals, mp 130±1318C
2-[Diꢀmethoxycarbonyl)]methyl-3-¯uoro-1,4-
1
ꢀ
ꢀ
hexane/CH Cl ). H NMR: 8.24±8.12 ꢀm, 2H), 7.90±7.78
2 2
1
m, 2H), 5.03 ꢀs, 1H), 3.84 ꢀs, 6H). C NMR: 182.8
3
1.6. Competitive reaction of 1,4-naphthoquinone ꢀ1a)
and 2,3-dichloro-1,4-naphthoquinone ꢀ1d) with dimethyl
chloromalonate ꢀ2a)
ꢀ
JC±Fˆ11 Hz), 177.1 ꢀJ ˆ23 Hz), 166.0 ꢀJ ˆ2 Hz),
C±F
C±F
1
4
4
59.2 ꢀJ ˆ292 Hz), 134.9, 134.4, 131.2, 130.2 ꢀJ
ˆ
C±F
C±F
Hz), 127.2, 126.6 ꢀJ ˆ3 Hz), 123.3 ꢀJ ˆ4 Hz), 53.4,
C±F
C±F
6.7. IR nmax: 1747, 1683, 1652, 1284, 1259, 1197, 747.
To a stirred solution of DBU ꢀ380 mg, 2.5 mmol) in THF
ꢀ8 mL) a solution of 1a ꢀ237 mg, 1.5 mmol), 1d ꢀ341 mg,
1.5 mmol) and 2a ꢀ167 mg, 1 mmol) in THF ꢀ7 mL) was
added slowly at 2708C. After stirring for 30 min at
2708C the reaction mixture was poured into cold 3% HCl
solution and extracted with CH Cl . The combined extracts
Anal. calcd for C H FO : C 58.83, H 3.62, F 6.20;
1
found: C 58.83, H 3.47, F 6.22.
5
11
6
1
.3.2.
2,3-bis-[Diꢀmethoxycarbonyl)]methylene-1,4-
naphthoquinone ꢀ6). White powder, mp 148±1508C
2
2
1
dec.) ꢀhexane/CH Cl ). H NMR: 8.22±8.12 ꢀm, 2H),
ꢀ
were dried with MgSO and evaporated in vacuo. The
4
2
2
1
3
7
1
5
1
.90±7.80 ꢀm, 2H), 3.91 ꢀs, 6H), 3.83 ꢀs, 6H). C NMR:
83.8, 164.3, 162.0, 139.8, 135.6, 134.3, 133.1, 127.7,
3.33, 53.26. IR nmax: 1732, 1721, 1701, 1691, 1310,
246, 1116. MS ꢀLSIMS HR): calcd for C H O
17 10
residue was separated by column chromatography ꢀhexane/
CH Cl /ether eluent) to give educts 1d ꢀ237 mg, 1.04 mmol)
and 1a ꢀ90 mg, 0.57 mmol), and products 3a ꢀ190 mg, 66%
yield) and 8 ꢀ82 mg, 17% yield).
2
2
2
0
1
ꢀ[M1H] ): 417.0821; found: 417.0805. Anal. calcd for
C H O : C 57.69, H 3.87; found: C 56.92, H 3.90.
2
0
16 10
When this reaction was carried out for additional 30 min at
08C products 3a and 8 were obtained in yield 15 mg ꢀ6%)
and 331 mg ꢀ69%), respectively.
1
.4. Reaction 1c with 2a and equimolar amount of DBU
To a stirred solution of 2-¯uoro-1,4-naphthoquinone 1c
In reaction 3a ꢀ1 mmol) with 1d ꢀ1 mmol) was carried outat
270 to 1208C for 30 min and the product 8 was obtained in
yield 358 mg ꢀ75%).
ꢀ176 mg, 1 mmol) in THF ꢀ8 mL) a solution of 2a
ꢀ167 mg, 1 mmol) and DBU ꢀ152 mg, 1 mmol) in THF
ꢀ2 mL) was added dropwise at 2708C. The mixture was
stirred for 5 min at 2708C, then poured into cold 3% HCl
solution and extracted with CH Cl . The combined extracts
were dried with MgSO . The solvents were evaporated in
4
1.6.1. bis-1,4-Naphthoquinone derivate ꢀ8). Yellow
powder, mp 222±2238C ꢀdec.) ꢀhexane/CH Cl /AcOEt).
H NMR: 8.32±8.09 ꢀm, 4H), 7.93±7.78 ꢀm, 4H), 4.33 ꢀs,
2
2
2
2
1
1
3
vacuo and the products 3e ꢀ18 mg, 6%) and a mixture of
6
1H), 3.78 ꢀs, 3H), 3.77 ꢀs, 3H). C NMR: 182.5, 181.8,
180.7, 177.1, 166.4, 166.2, 146.0, 142.1, 141.9, 140.5,
135.4, 135.2, 135.1, 134.9, 132.2, 132.0, 131.9, 131.7,
128.3, 128.0, 127.8, 127.5, 53.8 ꢀ2C), 52.9. MS ꢀEI), m/z
1
17 ꢀ1:3 from H NMR spectra) ꢀ65 mg, ca. 30%) were
isolated from the residue by column chromatography
hexane/CH Cl /ether eluent, silicagel was washed with
ꢀ
2
2
1
AcOH/hexane before use). This mixture could not be sepa-
rated neither by recrystallisation nor by chromatography.
ꢀ%): 478 ꢀ8) [M ], 444 ꢀ11), 353 ꢀ100), 213 ꢀ14). IR nmax:
1750, 1733, 1673, 1656, 1321, 1277, 1244. Anal. calcd for

M. M aÎ kosza, S. Nizamov / Tetrahedron 57 ꢀ2001) 9615±9621
9621
C H ClO : C 62.71, H 3.16, Cl 7.40; found: C 62.35, H
2
2. M aÎ kosza, M. Synthesis 1991, 103.
3. M aÎ kosza, M.; Wojciechowski, K. Liebigs Ann/Receuil. 1997,
805.
5
15
8
2
.92, Cl 7.27.
1
1
1
.6.2. 2-[Diꢀmethoxycarbonyl)]chloromethyl-3-chloro-
,4-naphthoquinone ꢀ9). To a stirred solution of dimethyl
4. M aÎ kosza, M.; Kwast, A. J. Phys. Org. Chem. 1998, 11, 341.
5. M aÎ kosza, M.; Kwast, A. Chem. Commun. 1984, 1195.
6. M aÎ kosza, M.; Kwast, A. Tetrahedron 1991, 47, 5001.
7. Jo n czyk, A.; Owczarczyk, Z.; M aΠkosza, M.; Winiarski, J.
Bull. Soc. Chim. Belg. 1987, 96, 303.
chloromalonate ꢀ167 mg, 1 mmol) and 2,3-dichloro-1,4-
naphtoquinone ꢀ227 mg, 1 mmol) in THF ꢀ15 mL) a solu-
tion of DBU ꢀ152 mg, 1 mmol) in THF ꢀ2 mL) was added
drop wise at0 8C. The cooling bath was removed and the
reaction mixture was allowed to warm up to 1208C, and
kept at this temperature for 1 h. The reaction mixture was
poured into cold 3% HCl solution and extracted with
CH Cl . The combined extracts were dried with MgSO .
8. Ballini, R.; Bosica, G. Tetrahedron 1995, 51, 4213.
9. M aÎ kosza, M.; Nizamov, S.; Kwast, A. Mendeleev Commun.
1996, 185.
10. M aÎ kosza, M.; Nizamov, S.; Kwast, A. In preparation.
11. Aldersley, M. F.; Dean, F. M.; Nayyir-Mazhir, R. J. Chem.
Soc., Perkin Trans. 1 1983, 1753.
12. M aΠkosza, M.; Nizamov, S.; Urba n czyk-Lipkowska, Z.
Tetrahedron 1998, 54, 6147.
13. Murphy, Jr., R. A.; Cava, M. P. Tetrahedron Lett. 1984, 25,
2
2
4
The solvents were evaporated in vacuo and the product 9
159 mg, 45%) was isolated from the residue by column
chromatography ꢀhexane/CH Cl /ether eluent, silicagel
ꢀ
2
2
was washed with AcOH/hexane before use).
8
03.
1
Yellow crystals, mp 193±1948C ꢀhexane/CH Cl ).
H
NMR: 8.24±8.05 ꢀm, 2H), 7.89±7.76 ꢀm, 2H), 3.91 ꢀs,
14. Cava, M. P.; Ahmed, Z.; Benfaremo, N.; Murphy, Jr., R. A.;
O'Mally, G. J. Tetrahedron 1984, 40, 4767.
2
2
1
3
6
1
1
H). C NMR: 179.7, 176.7, 164.6, 146.4, 144.1, 135.0,
34.7, 131.4, 131.0, 127.6, 127.5, 69.2, 54.9. IR nmax
766, 1737, 1683, 1664, 1285, 1209, 707. Anal. calcd for
15. M aÎ kosza, M.; Glinka, T. J. Org. Chem. 1983, 48, 3860.
16. M aÎ kosza, M.; Sienkiewicz, K. J. Org. Chem. 1998, 63, 4199.
17. M aÎ kosza, M.; Biaøecki, M. J. Org. Chem. 1998, 63, 4878.
18. M aÎ kosza, M.; Lemek, T.; Kwast, A. Tetrahedron Lett. 1999,
40, 7541.
:
C H Cl O : C 50.44, H 2.82, Cl 19.85; found: C 50.30, H
2
1
5
10
6
2
.80, Cl 19.95.
1
9. Patai, S.; Rappoport, Z. In The Chemistry of Alkenes, Patai, S.,
Ed.; Wiley: London, 1964; p. 469.
1.7. The competition between S V in 1d and ONSH in 1a
N
with dimethyl malonate ꢀ2c)
20. Rappoport, Z. Adv. Phys. Org. Chem. 1969, 7, 1.
1. Rappoport, Z. Recl. Trav. Chim. Pays-Bas 1985, 104, 309.
2
To a stirred solution of 1a ꢀ237 mg, 1.5 mmol), 1d ꢀ341 mg,
1
22. Rappoport, Z. Acc. Chem. Res. 1992, 25, 474.
23. Shainyan, B. A. Usp. Khim. 1986, 55, 942.
24. Finley, K. T. In The Chemistry of the Quinonid Compounds,
Patai, S., Ed.; Wiley: London, 1974; p. 877.
25. Kutyrev, A. Tetrahedron 1991, 38, 8043.
26. Michel, F. Chem. Ber. 1900, 33, 2406.
27. Reynolds, G. A.; VanAllan, J. A.; Adel, R. E. J. Org. Chem.
1956, 30, 3819.
.5 mmol) and 2c ꢀ132 mg, 1 mmol) in THF ꢀ15 mL) a solu-
tion of DBU ꢀ152 mg, 1 mmol) in THF ꢀ2 mL) was added
slowly at 2708C. After stirring for 30 min at 2708C t he
reaction mixture was poured into cold 3% HCl solution
and extracted with CH Cl . The combined extracts were
2
2
dried with MgSO and evaporated in vacuo. The residue
4
was separated by column chromatography ꢀhexane/
CH Cl /ether eluent) to give educts 1a ꢀ126 mg,
28. Hudson, A. T.; Pether, M. J. J. Chem. Soc., Perkin Trans. 1
1983, 35.
29. Albahari, M.; Bittner, S. Synthesis 2000, 8, 1087.
2
2
0
ꢀ
.80 mmol) and 1d ꢀ204 mg, 0.9 mmol), and products 3a
45 mg, 16%), 3c ꢀ15 mg, 5%) and 8 ꢀ135 mg, 28%).
3
0. Cameron, D. W.; Chalmers, P. J.; Feutrill, G. I. Tetrahedron
Lett. 1984, 52, 6031.
1.8. The competition between S V and ONSH in 1c with
N
dimethyl malonate
31. Terrier, F. Nucleophilic Aromatic Displacement; Verlag
Chemie: Weinheim, 1991.
The reaction 1c ꢀ176 mg, 1 mmol) with 2c ꢀ132 mg,
1
for 1b and 2c at 2708C, and the products 3a ꢀ143 mg, 50%)
and 3e ꢀ3 mg, 1%) were separated by column chromato-
graphy.
32. Thapliyal, P. C. Synth. Commun. 1998, 28, 1123.
33. Cameron, D. W.; Feutrill, G. I.; Grif®ts, P. G.; Richards, K. R.
Aust. J. Chem. 1982, 35, 1509.
mmol) was carried outanalogously to described procedure
34. Shi, S.; Katz, T. J.; Yang, B. W.; Liu, L. J. Org. Chem. 1995,
60, 1285.
3
5. Akatsuka, K. Yakugaki Zasshi 1970, 160 Chem. Abstr. 1970,
2, 100347.
7
References
1
. M aÎ kosza, M.; Winiarski, J. Acc. Chem. Res. 1987, 20, 282.