A new synthesis and application of 1-aryl-2,4-diones

Article abstract of DOI:10.1055/s-1998-2057

Methyl ketones or ethyl acetate react with aromatic α-bromo ketones in the presence of two equivalents of tert-butoxy or diethylaminomagnesium bromide in benzene (toluene) under reflux to produce 1-aryl-2,4-diones. The conversion, apparently, occurs via aldol condensation and subsequent [1,2]- sigmatropic rearrangement of the intermediate 3-bromo-2-hydroxy ketones. A number of fused aromatic and heteroaromatic phenols have been prepared by cyclodehydration of 1-aryl-2,4-diones.

Full text of DOI:10.1055/s-1998-2057

May 1998
SYNTHESIS
729
A New Synthesis and Application of 1-Aryl-2,4-diones
Alexander V. Kel’in,* Yurii Yu. Kozyrkov
Department of Chemistry, Belarussian State University, Fr. Skorina Av. 4, 220080 Minsk, Belarus
Fax +70(172)208821; E-mail: organic@chem.bsu.unibel.by
Received 30 July 1997; revised 13 October 1997
diones 5a–u. The formation of 1-aryl-2,4-diones under
the action of the magnesium enolate of acetylmesitylene
on a-bromo ketones was reported by Kohler and Tishler
as long ago as 1935.15 However, the authors did not pro-
pose any mechanism nor preparative variant of the trans-
Abstract: Methyl ketones or ethyl acetate react with aromatic a-
bromo ketones in the presence of two equivalents of tert-butoxy-
or diethylaminomagnesium bromide in benzene (toluene) under
reflux to produce 1-aryl-2,4-diones. The conversion, apparently,
occurs via aldol condensation and subsequent [1,2]-sigmatropic
rearrangement of the intermediate 3-bromo-2-hydroxy ketones. A
number of fused aromatic and heteroaromatic phenols have been formation. Later, the rearrangement of halomagnesium
prepared by cyclodehydration of 1-aryl-2,4-diones.
derivatives of b-halohydrins to ketones with heating in
benzene was found.16 That reaction occurs through migra-
Key words: a-bromo ketones, magnesium bases, aldol condensa-
tion, [1,2]-sigmatropic rearrangement, 1-aryl-2,4-diones, cyclode-
hydration, fused phenols
tion of an aryl or alkyl group and was ap-plied to the prep-
aration of several cycloalkanones.16,17 The concerted
“withdrawal” (pinacol-like), or “oxide” mechanism of
this transformation was discussed.16
1,3-Dicarbonyl compounds are widely used as intermedi-
In our case, we assume that the mechanism of the rear-
ates in organic synthesis for the construction of C–C
rangement of 3-bromo-2-hydroxy ketones 3a–u, or their
bonds by alkylation,1 condensation (Knoevenagel-type),1
bromomagnesium derivatives generated as intermedi-
and 1,4-conjugate addition (Michael-type)2 reactions, and
ates, to 1-aryl-2,4-diones 5a–u may be concerted,16 but
also for the preparation of a great variety of five- and six-
with a high probability of the formation of carbenium
membered heterocyclic systems.3, 4
ions 4a–u in the transition state (at least in intimate ion
The main approach to the synthesis of 1,3-dicarbonyl pairs with the bromide anion) (see Scheme 1). Subse-
compounds is the condensation of ketones,5 or their deriv- quent [1,2]-sigmatropic migration of the aryl group in
atives such as enamines6 and silyl ethers,7 with esters,5 the carbocation 4a–u gives the corresponding 1,3-di-
acyl chlorides6, 8 or anhydrides.5 At the same time this ap- ketones 5a–u, which produce stable magnesium
proach is hardly applicable to the synthesis of 1-aryl-2,4- chelates8 by deprotonation with an additional equivalent
diones, mainly because of the low yields, regioselectivity, of magnesium base. The fact that the reaction proceeds
and availability of starting compounds. A few compara- more smoothly (partly even at room temperature14)
tively new methods for 1,3-diketone synthesis, such as the when stabilized secondary 4j–l, n–q, s or, especially,
arylation of disodium salts of 1,3-diketones by diaryliodo- tertiary 4m and benzylic 4r carbocation-like transition
nium chlorides,9 oxidation of the corresponding aldols,4 states occur confirms the proposed mechanism.
condensation of diazo ketones10 or their lithium enolates11
This mechanism is also in agreement with the fact that
with aldehydes, condensation of lithium enolates with
analogous transformation with 1-bromo-2-hydroxy ke-
ketenes,12 as well as rearrangement of 3-methoxy-4-
tone 6 (see Scheme 2) under the same conditions does not
phenylthio ketones,13 give better results in the synthesis of
occur. In this case, a carbocation-like transition state
1-aryl-2,4-diones. However, these methods are usually
ought to be destabilized by the carbonyl group. A pro-
multistep procedures and preparatively complicated.
longed refluxing of erythro-2-bromo-3-hydroxy-1,3-
In our present research we propose a simple and efficient diphenylpropan-1-one (6) with excess tert-butoxymagne-
one-step synthesis of 1-aryl-2,4-diones based on readily sium bromide–diethyl ether complex in benzene gave
available methyl ketones and aromatic a-bromo ketones. only traces of 1,3-dicarbonyl compounds (see experimen-
Earlier, the method of cross aldol condensation of methyl tal part), a small quantity of dehydration (crotonization-
ketones with a-bromo ketones in the presence of tert- type) product,18 and unreacted starting compound. The
butoxy- or diethylaminomagnesium bromide at room configuration of bromohydrin 6 has been established by
temperature with formation of 3-bromo-2-hydroxy ke- its transformation to the known trans-epoxy ketone 719 by
tones has been described.14 The latter compounds were treatment with triethylamine. The fact that epoxy ketone 7
transformed to the corresponding 1,4-diketones by treat- and the product of its rearrangement, the corresponding
ment with triethylamine. The rearrangement, probably, 1,2-diketone,20 do not appear in the reaction of bromohy-
occurs through intermediate hydroxycyclopropyl ketone drin 6 with tert-butoxymagnesium bromide, in our opin-
formation.
ion, excludes the formation of 1-aryl-2,4-diones 5a–u via
the epoxides (“oxide” mechanism16).
Now we report that application of an additional equivalent
of magnesium base and higher temperature for the con- The condensation of alkyl methyl ketones 1b,c with a-
densation of methyl ketones 1a–g or ethyl acetate with a- bromo ketones 2a–l in the presence of tert-butoxymagne-
bromo ketones 2a–l leads to the corresponding 1-aryl-2,4- sium bromide occurs strictly regioselectively at the meth-

730
Papers
SYNTHESIS
yl group. In all cases isomeric products of the reaction at
the methylene group of ethyl methyl ketone (1b) have not
been found. The reaction is sensitive to steric hindrance.
Thus, refluxing acetophenone with 1-bromo-2-methyl-
propyl phenyl ketone (2g) and excess tert-butoxymagne-
sium bromide in toluene for ten hours produced the
corresponding 1,3-diketone 5l in low yield (40%). An at-
tempt to involve 2-bromo-1-tetralone in this reaction in
order to cause ring contraction failed fully. Primary alkyl
groups and hydride ion do not migrate under these condi-
tions. The reaction of 2-bromopentan-3-one and 2-bro-
mobutanal with acetophenone in the presence of excess
tert-butoxymagnesium bromide gave complicated mix-
tures of products and only traces of 1,3-dicarbonyl com-
pounds. Ester groups (i.e. 5i,s) and activated double bonds
(i.e. 5g,q) remained unchanged under the reaction condi-
tions, but in the latter case the yield of 1,3-diketone 5g was
lower. The (chloromethyl)aryl group in 1g is completely
converted to the (bromomethyl)aryl group in 5o, appar-
ently due to an exchange reaction with magnesium bro-
mide.
We have elaborated three variants of the condensation
procedure. In the first (Method A), all components were
mixed at once and refluxed; this was applied to a-bromo
ketones 2f–l containing secondary or tertiary a-carbon
atoms. Formation of the least stabilized primary carbo-
cations 4a–i in the transition state is hampered, and in this
case the competitive process is the rearrangement of the
intermediate 3-bromo-2-hydroxy ketones 3a–i into the
corresponding 1,4-diketones.14 In addition, a substantial
quantity of byproducts, a result of the self-condensation14
of primary a-bromo ketones 2a–e, is formed. To prevent
the self-condensation of bromo ketones 2a–e, we utilized
their dropwise addition to a refluxing mixture of methyl
ketones 1a–e and tert-butoxymagnesium bromide in ben-
zene or toluene (Method B). The yields of 1-aryl-2,4-di-
ones 5a–i increase with increasing nucleophilicity of the
migrating aryl group. This becomes apparent especially
when passing from the phenyl (5a) to the 4-methyl- (5b,c)
and 4-methoxyphenyl (5d–f) group and may be explained
in terms of transition state stabilization by the electron-do-
nating migrating ring. Ethyl acetate did not react with a-
bromo ketones in the presence of tert-butoxymagnesium
bromide. At the same time, 3-oxo esters 5t,u were ob-
tained from ethyl acetate when diethylaminomagnesium
bromide was used as the condensation agent (Method C).
Unfortunately, only a-bromo ketones 2c,i containing aro-
matic rings activated by an electron-donating substituent
gave acceptable yields of the corresponding 3-oxo esters
5t,u.
Scheme 1
Three methods for the isolation of 1-aryl-2,4-diones were
used. The yields of products in the reaction of methyl ke-
tones 1a–g with a-bromo ketones 2f–l containing a sec-
ondary or tertiary a-carbon atom were close to
quantitative (except 51). The reaction product, after de-
composition of the magnesium complex, was purified by
flash chromatography on a short column of silica gel
(Method A), or by distillation (Method B). A convenient
Scheme 2

May 1998
SYNTHESIS
731
netic stirrer and reflux condenser. After the reaction had started, a so-
lution of EtBr (1.76 mL, 24 mmol) in benzene (toluene, see Table 1)
(10 mL) was added dropwise through the reflux condenser at such a
rate that the mixture was not hot (35–40°C). When the reaction was
complete, subsequent procedure was carried out by one of the follow-
ing methods:
method for the isolation of pure 1-aryl-2,4-diones 5a–i, in
cases where moderate yields are obtained, is treatment of
the reaction mixture with an aqueous solution of cop-
per(II) acetate, followed by filtration and decomposition
of the copper(II) complex5 (Method C).
In this paper we also propose the synthetic application of Method A: The resulting solution of EtMgBr·Et2O in benzene (tolu-
ene) was cooled to 0°C, and a solution of t-BuOH (2.30 mL,
24 mmol) in benzene (toluene) (1 mL) was added slowly, dropwise
1-aryl-2,4-diones for the preparation of fused aromatic
ring systems (see Scheme 3). Cyclodehydration of poly-
through the reflux condenser. The cooling bath was removed, and
ketides21 or products of self-condensation of 1,3-
methyl ketone 1a–g (13 mmol), and a-bromo ketone 2a,f–l (10
diketones22 under acidic, basic or fluoride catalysis with
mmol) were added successively. The mixture was stirred under reflux
formation of aromatic compounds has been described. It
is also thought that the biosynthesis of aromatic rings pro-
ceeds in a similar manner.21 We have found that the cyclo-
dehydration of 1-phenyl-2,4-diones 5a,k may be achieved
by heating with polyphosphoric acid. The analogous
transformation of 1-(2-thienyl)-2,4-diones 5p,r,s occurs
under much milder conditions and was accomplished by
refluxing with phosphoryl chloride in carbon tetrachlo-
ride. To prevent the oxidation of the 6-hydroxyben-
zo[b]thiophenes 8p,r,s obtained, they were converted to
the corresponding acetates.
for the time given in Table 1, cooled, quenched with cold 5% aq
H2SO4 (15 mL), washed 5% aq NaCl (2´10 mL), and dried
(Na2SO4). 1,3-Diketones 5a,j–s were isolated by one of the methods
(see Table 1) given below.
Method B: A solution of the a-bromo ketone 2b–e (10 mmol) in ben-
zene (toluene) (5–7 mL) was added dropwise through the reflux con-
denser over 40–60 min to a refluxing and stirred mixture of t-
BuOMgBr·Et2O in benzene (toluene), prepared as above (Method
A), and methyl ketone 1a–e (13 mmol). The mixture was stirred under
reflux for 30–40 min, cooled, and quenched as above (Method A).
1,3-Diketones were isolated by Method C given below.
Method C: Et2NH (2.48 mL, 24 mmol) was added to the solution of
EtMgBr·Et2O in benzene, prepared as described above, and the mix-
ture was stirred for 15 min and cooled to 0°C. A solution of EtOAc
(3.00 mL, 30 mmol) and a-bromo ketone 2c,i (10 mmol) in benzene
(5 mL) was added dropwise over 20–30 min to the resulting solution
of Et2NMgBr·Et2O under stirring and cooling (0°C). The cooling
bath was removed, the mixture was heated under reflux for 0.5 h,
cooled, and treated as described above. For the isolation of 3-oxo es-
ters 5t,u, see Table 1.
Isolation:
Scheme 3
Method A: The solvent was evaporated under vacuum, and the residue
was mixed with benzene (7 mL), and chromatographed over a short
column of silica gel (approximately 6 g) with benzene as eluent.
In conclusion, the method described gives very good re-
sults in the synthesis of 1-aryl-2,4-diones containing elec-
tron-donating substituents or without substituents in the
aromatic ring. At the same time, the method is not appli-
cable for the preparation of 1-aryl-2,4-diones with elec-
tron-poor aromatic rings. 1-Aryl-2,4-diones appear to be
promising substrates for the synthesis of fused aromatic
and heteroaromatic systems.
Method B: The product was purified by distillation of the residue un-
der vacuum (1 Torr): bp 102–104°C (5j); 165–170°C (5k); 97–99°C
(5m).
Method C: To the mixture, after the evaporation of approximately two-
thirds of the solvent volume, hexane (5 mL) and sat. aq Cu(OAc)2
(30 mL) were added. The mixture was stirred vigorously for 1–2 h, al-
lowed to stand ovemight at 0–5°C, and filtered. The copper(II) com-
plex was washed thoroughly with cold benzene/hexane (1:2) (for
compounds 5a,i,q 1:4) (10 mL), placed in a separating funnel and de-
composed by shaking with 10% aq HCl (10 mL) and benzene (7 mL).
The organic layer was separated, washed with 5% aq NaCl (2 ´) and
chromatographed over a short column with a layer of silica gel (ap-
1H NMR spectra were recorded on a “Tesla-BS 467A” (60 MHz)
spectrometer. Samples were examined in CCl4 containing 5% by vol-
ume of HMDS. IR spectra of products as 0.01 M solns in CCl4 were
obtained on a Specord IR-75 spectrophotometer. MS were recorded proximately 3 g) below, and anhyd Na2SO4 above, using benzene as
on a “Class-5000” chromato-mass spectrometer at 70 eV. Methyl ke-
tones 1a–f, and a-bromo ketones 2a–c,f,h were commercially avail-
able. 2-Acetyl-4-(chloromethyl)thiophene (1g) was obtained by
chloromethylation of 2-acetylthiophene.23 a-Bromo ketones were
synthesized by bromination of the corresponding ketones with diox-
ane dibromide.24 All ketones were commercially available, except
ethyl 5-acetyl-2,4-dimethylfuran-3-carboxylate (obtained by conden-
sation of acetoacetic ester with tribromopropane, followed by
acylation25) and the 2-thienyl ketones (synthesized by acylation of
thiophene with the corresponding acyl chlorides26). The solvents, t-
BuOH and Et2NH were dried by distillation from Na before use.
eluent to afford 1,3-diketones 5a–i,o–q of high purity.
erythro-2-Bromo-3-hydroxy-1,3-diphenylpropan-1-one (6):
To a solution of t-BuOMgBr·Et2O in benzene, prepared as described
above from Mg (0.29 g, 12 mmol), EtBr (1.05 mL, 14 mmol), Et2O
(1.80 mL), benzene (20 mL), and t-BuOH (1.20 mL, 12 mmol), a-
bromoacetophenone (1.99 g, 10 mmol) and PhCHO (1.02 mL,
10 mmol) were added. The mixture was stirred for 5 h, allowed to
stand overnight, treated with 5% aq H2SO4 (15 mL), washed with 5%
aq NaCl (2 ´ 10 mL), and dried (Na2SO4). Chromatography of the
mixture over a short column of silica gel (6 g) with benzene as eluent
gave bromohydrin 6 as a slightly yellow, viscous oil (3.00 g, 95%).
IR: n = 3573, 3060, 3027, 1680, 1453, 1280, 680 cm–1.
1-Aryl-2,4-diones 5a–u; General Procedure:
Preparation:
Mg (0.58 g, 24 mmol), Et2O (3.10 mL), and EtBr (0.20 mL) were 1H NMR: d = 3.47 (s, 1H), 4.87 (d, 1H, J = 9 Hz), 5.07 (d, 1H, J =
placed in a one-neck, round-bottom, 25-mL flask fitted with a mag- 9 Hz), 7.0–7.5 (m, 8H), 7.7–8.0 (m, 2H).

732
Papers
SYNTHESIS
Table 1. 1-Aryl-2,4-diones 5a–u Prepared
Prod-
ucta
R
R1
R2
Ar
Prepa- Timeb Isolation
Yieldc
(%)
nD20 or
mp (°C) (Solvent)
ration
(h)
5a
5b
5c
5d
5e
5f
n-Pr
Me
Et
Me
Et
H
H
H
H
H
H
H
H
H
H
H
H
Ph
A
Be
Be
B
B
B
2
Cd
C
C
C
C
C
36
50
65
77
78
81
1.5346
1.5515
1.5364
1.5525
1.5440
55–56
4-MeC6H4
4-MeC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
1.5
1.5
1.5
1.5
1.5
Ph
(pentane/Et2O 2:1)
78–79
5g
PhCH=CH H
H
4-MeOC6H4
B
1.5
C
41
(hexane/CCl4 1:1)
1.5540
1.5097
5h
5i
Et
n-Pr
H
H
H
H
2-thienyl
4-ethoxycarbonyl-
Be
B
1.5
1.5
C
C
58
67
3,5-dimethyl-
2-furyl
Ph
Ph
5j
5k
5l
Et
Ph
Ph
H
H
H
Me
Me
i-Pr
A
2
1.5
10
B
B
–
84
86
41
1.5343
1.6157
91–92
A
f
Ph
Ae
(pentane/Et2O 35:1)
1.5302
1.5463
5m
5n
5o
Et
Me
4-(bromo-
methyl)-
2-thienylg
Ph
Me
H
H
Me
Me
Me
Ph
A
A
A
3
1
1
B
A
C
83
98
81
4-MeOC6H4
4-MeOC6H4
1.6409
5p
H
Me
2-thienyl
A
1
C
82
34–35
(pentane/Et2O 3:1)
1.5902
1.6113
1.5162
1.5234
5q
5r
5s
5t
Me2C=CH
Me
Me
EtO
EtO
H
H
H
H
H
Me
Ph
2-thienyl
2-thienyl
2-thienyl
4-MeOC6H4
4-MeOC6H4
A
A
A
C
C
1.5
1
2
0.5
0.5
C
A
A
–
A
80
96
90
34
80
(CH2)7CO2Et
H
Me
h
5u
34–35 (pentane/Et2O 2:1)
a
For all compounds satisfactory microanalyses were obtained: C ± 0.38, H ± 0.35.
b
c
d
e
f
Reaction time included the time of a-bromo ketone 2b–e addition, when Method B was applied.
Yield of isolated product based on 2.
Mp of copper(II) complex of 5a 148–150°C (lit.9 mp 149–151°C); bp of 5a 116–118°C/1 Torr (lit.9 bp 145–l48°C/7 Torr).
The condensation was carried out in toluene.
The product 5l was isolated by crystallization.
g
The starting compound was 2-acetyl-4-(chloromethyl)thiophene (1g). The fact of chloro–bromine exchange was established by elemental
analysis and the mass spectrum of the product 5o. MS: m/z (%) = 382 (M+, 1.40), 380 (M+, 1.35), 301 (M+-Br, 5.10), 135 (4-
MeOC6H4C+HCH3, 100).
h
The product 5t was isolated by column chromatography (silica gel, benzene).
Table 2. Fused Phenols 8 Prepared
Producta
R
R1
X
Reagent Time Yieldb mp (°C)
(h)
(%)
40
73
74
83
55
(Solvent)
8a
8k
8p
8r
8s
4-propyl-2-naphthol
n-Pr
Ph
H
CH=CH PPA
CH=CH PPA
2
33–34
(pentane)
104–l05
1-methyl-4-phenyl-2-naphthol
Me
Me
Ph
4
(hexane)
6-hydroxy-7-methyl-4-phenylbenzo[b]thiophene
6-hydroxy-4-methyl-7-phenylbenzo[b]thiophene
Ph
S
S
POCl3
3
72–73c
(pentane/ Et2O 1:1)
Me
POCl3
POCl3
1
94–95c
(pentane/Et2O 1:2)
oil
7-(7-ethoxycarbonylheptyl)-6-hydroxy-4-methyl- Me
(CH2)7CO2Et S
3
benzo[b]thiophene
a For all compounds satisfactory microanalyses were obtained: C ± 0.33, H ± 0.30.
b Yield of isolated phenols 8a–s.
c Mp of the corresponding acetate.

May 1998
SYNTHESIS
733
Table 3. 1H NMR Spectra of 1-Aryl-2,4-diones 5a–u
Prod- 1H NMR (Major Form)b
d (3-H) of
Ratiod
ucta d, J (Hz)
Minor Formc Enol/Ketone
5a
5b
5c
5d
5e
0.77 (t, 3H, J = 7), 1.45 (sextet, 2H, J = 7), 2.04 (t, 2H, J = 7), 3.43 (s, 2H), 5.21 (s, 1H), 7.13 (s, 5H)
1.80 (s, 3H), 2.20 (s, 3H), 3.30 (s, 2H), 5.17 (s, 1H), 6.93 (s, 4H)
1.00 (t, 3H, J = 7), 2.13 (q, 2H, J = 7), 2.27 (s, 3H), 3.37 (s, 2H), 5.20 (s, 1H), 6.97 (s, 4H)
1.73 (s, 3H), 3.20 (s, 2H), 3.53 (s, 3H), 5.07 (s, 1H), 6.53 (d, 2H, J = 8), 6.87 (d, 2H, J = 8)
0.90 (t, 3H, J = 7), 2.03 (q, 2H, J = 7), 3.07 (s, 2H), 3.37 (s, 3H), 5.07 (s, 1H), 6.53 (d, 2H, J = 8), 6.87 3.40
(d, 2H, J = 8)
3.61
3.47
3.53
3.37
95:5
94:6
94:6
85:15
85:15
5f
3.42 (s, 2H), 3.60 (s, 3H), 5.87 (s, 1H), 6.63 (d, 2H, J = 8), 7.00 (d, 2H, J = 8), 7.1–7.3 (m, 3H),
7.5–7.7 (m, 2H)
–
> 97:3
5g
5h
5i
3.38 (s, 2H), 3.60 (s, 3H), 5.30 (s, 1H), 6.17 (d, 1H, J = 16), 6.63 (d, 2H, J = 8), 6.6–7.5 (m, 8H)
0.75 (t, 3H, J = 7), 2.10 (q, 2H, J = 7), 3.57 (s, 2H), 5.27 (s, 1H), 6.6–6.9 (m, 2H), 6.9–7.2 (m, 1H)
0.80 (t, 3H, J = 7), 1.20 (t, 3H, J = 7), 1.2–1.8 (m, 2H), 1.93 (s, 3H), 1.9–2.3 (m, 2H), 2.33 (s, 3H),
3.27 (s, 2H), 4.03 (q, 2H, J = 7), 5.07 (s, 1H)
–
3.73
3.22
> 97:3
85:15
75:25
5j
5k
5l
0.87 (t, 3H, J = 7), 1.27 (d, 3H, J = 7), 2.00 (q, 2H, J = 7), 3.40 (q, 1H, J = 7), 5.20 (s, 1H), 7.17 (s, 5H) 3.17
87:13
97:3c
> 97:3
1.50 (d, 3H, J = 7), 3.70 (q, 1H, J = 7), 6.03 (s, 1H), 7.0–7.4 (m, 8H), 7.5–7.8 (m, 2H)
0.63 (d, 3H, J = 7), 0.93 (d, 3H, J = 7), 2.1–2.7 (m, 1H), 2.97 (d, 1H, J = 11), 6.03 (s, 1H), 7.0–7.8
(m, 8H), 7.6–7.9 (m, 2H)
3.83
–
5m
5n
0.88 (t, 3H, J = 7), 1.33 (s, 6H), 2.03 (q, 2H, J = 7), 5.13 (s, 1H), 7.30 (s, 5H)
1.23 (d, 3H, J = 7), 1.73 (s, 3H), 3.38 (q, 1H, J = 7), 3.63 (s, 3H), 5.23 (s, 1H), 6.73 (d, 2H, J = 8), 7.30 3.20
(d, 2H, J = 8)
3.10
91:9
80:20
5o
5p
5q
1.38 (d, 3H, J = 7), 3.48 (q, 1H, J = 7), 3.62 (s, 3H), 4.20 (s, 2H), 5.75 (s, 1H), 6.67 (d, 2H, J = 8),
6.9–7.5 (m, 4H)
1.48 (d, 3H, J = 7), 3.83 (q, 1H, J = 7), 5.97 (s, 1H), 6.76 (d, 2H, J = 3), 7.00 (t, 1H, J = 3), 7.1–7.4
(m, 3H), 7.5–7.8 (m, 2H)
1.43 (d, 3H, J = 7), 1.77 (s, 3H), 2.05 (s, 3H), 3.73 (q, 1H, J = 7), 5.20 (s, 1H), 5.47 (s, 1H), 6.77 (d,
2H, J = 4), 6.9–7.1 (m, 1H)
–
> 97:3
> 97:3
97:3
–
3.33
5r
5s
1.80 (s, 3H), 4.90 (s, 1H), 5.37 (s, 1H), 6.7–6.9 (m, 2H), 7.0–7.1 (m, 1H), 7.17 (s, 5H)
1.0–1.7 (m, 15H), 1.88 (s, 3H), 1.9–2.3 (m, 2H), 3.53 (t, 1H, J = 7), 3.95 (q, 2H, J = 7), 5.33 (s, 1H),
6.7–6.9 (m, 2H), 6.9–7.1 (m, 1H)
3.33
3.33
93:7
90:10
5t
1.17 (t, 3H, J = 7), 3.20 (s, 2H), 3.57 (s, 2H), 3.67 (s, 3H), 4.03 (q, 2H, J = 7), 6.67 (d, 2H, J = 8),
7.00 (d, 2H, J = 8)
1.10 (t, 3H, J = 7), 1.23 (d, 3H, J = 7), 3.10 (d, 2H, J = 2), 3.63 (s, 3H), 3.70 (q, 1H, J = 7), 3.93 (q,
2H, J = 7), 6.67 (d, 2H, J = 8), 6.97 (d, 2H, J = 8)
4.70
4.73
25:75
10:90
5u
a
IR spectra of all 1,3-dicarbonyls 5a–u contained broad absorption peaks in the fields of n = 3280–2370 cm–1 (associated OH), and n = 1760–
l500 cm–1 (C=O + C=C).
Enolic form of 1,3-diones 5a–s, keto form of 3-oxo esters 5t,u. Signal of OH proton of enolic form of 1,3-diones 5a–s was not fixed.
(3-CH2) of keto form of 1,3-diones 5a–s, (3-CH) of enolic form of 3-oxo esters 5t,u.
Approximate ratio for 10% solns in CCl4, established by 1H NMR spectroscopy.
Lit.12 d (3-CH2) î 3.5, enol/ketone = 90:10.
b
c
d
e
Table 4. 1H NMR and IR Spectra of Fused Phenols 8
Product 1H NMR, d, J (Hz)
IR n (cm–1)
8a
8k
8p
0.83 (t, 3H, J = 7), 1.55 (sextet, 2H, J = 7), 2.77 (t, 2H, J = 7), 6.77 (s, 2H), 7.0–7.5 (m, 4H),
7.7–7.9 (m, 1H)
3600, 3413, 3067, 2920,
2867, 1627, 1600, 1173, 840
2.33 (s, 3H), 5.17 (s broad, 1H), 6.63 (s, 1H), 6.8–7.8 (m, 9H)
3600, 3440, 3080, 3027,
2920, 1600, 1373, 1347, 693
2.27 (s, 3H), 5.17 (s broad, 1H), 6.50 (s, 1H), 6.93 (d, 1H, J = 5), 7.0–7.2 (m, 6H)
acetate: 2.10 (s, 3H), 2.23 (s, 3H), 6.83 (s, 1H), 7.0–7.4 (m, 7H)
3513, 3060, 3027, 2920,
1360, 1153, 693
3060, 3027, 2913, 1760,
1360, 1147, 693
8r
8s
2.40 (s, 3H), 4.83 (s, 1H), 6.67 (s, 1H), 6.93 (d, 1H, J = 6), 7.10 (d, 1H, J = 6), 7.33 (s, 5H)
acetate: 1.77 (s, 3H), 2.43 (s, 3H), 6.72 (s, 1H), 7.0–7.2 (m, 2H), 7.23 (s, 5H)
3507, 3060, 3027, 2920,
1367, 693
3060, 3027, 2920, 1760,
1360, 1187, 693
0.8–1.8 (m, 13H), 1.9–2.3 (m, 2H), 2.33 (s, 3H), 2.5–2.8 (m, 2H), 3.97 (q, 2H, J = 7), 6.03 (s, 1H),
6.47 (s, 1H), 6.97 (d, 1H, J = 5), 7.07 (d, 1H, J = 5)
3507, 2920, 2850, 1733,
1373, 677
acetate: 0.9–1.7 (m, 13H), 1.9–2.2 (m, 2H), 2.17 (s, 3H), 2.43 (s, 3H), 2.5–2.8 (m, 2H),
3.93 (q, 2H, J = 7), 6.67 (s, 1H), 7.53 (s, 2H)
2920, 2853, 1760, 1733,
1467, 1373, 680

734
Papers
SYNTHESIS
Anal. calcd for C15H13BrO2: C, 59.02; H, 4.26. Found C, 58.87; H,
4.18.
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Condensation of a-bromoacetophenone with PhCHO in the presence
of t-BuOMgBr (2 equiv) at r.t. for 20 h and reflux for 6 h gave mainly
the same product (according to 1H NMR spectra), with traces of
dibenzoylmethane, 2,3-diphenyl-3-oxopropanal, and 2-bromo-1,3-
diphenylprop-2-en-1-one [according to TLC analysis (Kavalier silu-
fol UV 254, benzene)].
trans-2,3-Epoxy-1,3-diphenylpropan-1-one (7):
Et3N (0.17 mL, 1.20 mmol) was added to a solution of bromohydrin
6 (0.30 g, 1 mmol) in MeOH (3 mL) under stirring and cooling (0°C).
The mixture was stirred at 0 °C for 1 h, and allowed to stand overnight
at 0–5°C. Epoxy ketone 7 was filtered, washed with cold aq MeOH
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Substituted 2-Naphthols (8a,k); General Procedure:
A mixture of PPA (3 mL) (prepared by dehydration of concd H3PO4
at 150°C/15 Torr for 6 h) and the 1-phenyl-2,4-dione 5a,k (1 mmol)
was stirred at 135–140°C for the time given in Table 2, cooled, dilut-
ed with water (10 mL), and extracted with benzene (5 mL). The or-
ganic layer was separated, dried (Na2SO4) and chromatographed over
a column of silica gel with benzene as eluent to afford naphthols 8a,k
(Tables 2, 4).
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Substituted 6-Hydroxybenzo[b]thiophenes (8p,r,s); General Pro-
cedure:
To a solution of the 1-(2-thienyl)-2,4-dione 5p,r,s (1.5 mmol) in CCl4
(4 mL) was added POCl3 (0.30 mL, 3.2 mmol), and in cases 5p,s one
drop of concd H3PO4 (to start the reaction). The mixture was refluxed
for the time given in Table 2, cooled, poured into water, and extracted
with benzene/hexane (1:1) (12 mL). The organic layer was separated,
washed with 20% aq NaOAc and chromatographed over a short col-
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Na2SO4 above, (benzene/hexane 1:1) to afford the pure ben-
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to the corresponding acetates by successive treatment of the cold (0°C)
solution in benzene (2 mL) with pyridine (0.21 mL, 2.6 mmol), and
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We thank the Foundation of Fundamental Research of the Republic
of Belarus for financial support for this work (grant M96-062).
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