A selective and benign synthesis of functionalized benzalacetones via Mizoroki-Heck reaction using aryldiazonium salts

Article abstract of DOI:10.1002/adsc.200900868

Palladium-catalyzed Mizoroki-Heck reactions were carried out in the presence of calcium carbonate in alcoholic solvents. Under these conditions an efficient preparation of functionalized benzalacetones was developed. The reactions were carried out at room temperature and aerobic conditions, giving the products within several minutes in up to 95% isolated yields. Furthermore, some kinetic investigations, mechanistic insights and considerations are presented.

Full text of DOI:10.1002/adsc.200900868

FULL PAPERS
DOI: 10.1002/adsc.200900868
A Selective and Benign Synthesis of Functionalized
Benzalacetones via Mizoroki–Heck Reaction Using
Aryldiazonium Salts
Therese Stern,a Sven Rꢀckbrod,a Constantin Czekelius,b Constanze Donner,a
and Heiko Brunnera,*
a
Atotech Deutschland GmbH, Erasmusstrasse 20, 10553 Berlin, Germany
Fax : (+49)-030-34985-727; phone: (+49)-030-34985-589; e-mail: heiko.brunner@atotech.com
Institut fꢀr Chemie und Biochemie, Freie Universitꢁt Berlin, Takustrasse 3, 14195 Berlin, Germany
b
Received: December 16, 2009; Revised: June 30, 2010; Published online: August 16, 2010
Abstract: Palladium-catalyzed Mizoroki–Heck reac- isolated yields. Furthermore, some kinetic investiga-
tions were carried out in the presence of calcium car- tions, mechanistic insights and considerations are
bonate in alcoholic solvents. Under these conditions presented.
an efficient preparation of functionalized benzalace-
tones was developed. The reactions were carried out Keywords: aryldiazonium tetrafluoroborate salts;
at room temperature and aerobic conditions, giving benzalacetones; calcium carbonate; charcoal; Mizo-
the products within several minutes in up to 95%
ACHTUNGTRENNrUNG oki–Heck reaction; palladium acetate
Introduction
of sophisticated phosphines[9] and/or bases like proton
sponge[8]
[1,8-bis-(dimethylamino)-naphthalene]
Benzalacetones represent useful synthetic intermedi- proved mandatory.
ates and building blocks[1] as well as biologically
Another drawback in the Heck reaction is the need
for expensive aromatic iodides or bromides as electro-
active compounds.[2]
Despite the importance of these products the syn- philes. An interesting alternative to aryl halides for
thetic access is frequently limited to classical aldol cross-couplings has been the use of aryldiazonium
condensations[3] that often suffers from moderate salts due to the economic advantage of anilines com-
yields due to polymerizations as side reactions. Al- pared to aryl bromides and iodides.[10] Other advan-
though the palladium-catalyzed Heck reaction has tages are the short reaction times, the mild and green
emerged as a powerful synthetic tool for the prepara- reaction conditions and the superior reactivity of the
tion of vinylic aromatics[4] the utilization of this diazonium nucleofuge over the halides. In particular
method for the synthesis of benzalacetones compared for the arylation of acrylates, cinnamates, acryloni-
to other vinylic compounds is very limited.
triles, acrylamides and for the preparation of stil-
Next to the classical aldol condensations employing benes, several protocols and catalytic systems were
aromatic aldehydes and acetone only aryl iodides[1j,5,6] developed.[13]
and bromides[7] were used for the preparation of ben-
Although the use of aryldiazonium salts has re-
zalacetones in the Pd-catalyzed Mizoroki–Heck reac- ceived a major stimulus in cross-coupling reactions
tion.[5–9] Most of the results were obtained using elec- during the last three decades[10] and the fact that the
tron-neutral or electron-rich aryl bromides or iodides. Mizoroki–Heck reaction is probably the best explored
Therefore, one of the major drawbacks of the Heck- one,[11–13] the application of these electrophiles for the
reaction frequently represents the formation of minor preparation of functionalized benzalacetones was not
amounts of hydroarylation-products (arylbutanones) described to date and is still pending. Noteworthy, ac-
hampering the isolation of the pure benzalace- cording to previous results[10–12] even the preparation
tones.[5,8]
of halogenated benzalacetones bearing iodine and
To by-pass this problem Cacchi et al.[8] and Santelli bromine atoms should be possible.
and co-workers[9] have developed two efficient proto-
Based on our precedent results[11,12] concerning the
cols recently. Although excellent results were ob- development and utilization of CaCO3 in Mizoroki–
tained with respect to yield and purity, the utilization Heck reactions together with aryldiazonium salts we
Adv. Synth. Catal. 2010, 352, 1983 – 1992
ꢂ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1983

Therese Stern et al.
FULL PAPERS
were stimulated to apply this synthetic approach for equivalents of butenone and 0.5 to 1 equivalent
the preparation of functionalized benzalacetones. CaCO3 were satisfying results were obtained at ambi-
We would like to report now the first synthetic ent temperature (Table 1, entry 7). A significant de-
method of a Mizoroki–Heck reaction using aryldiazo- crease in yield was observed presumably due to acid-
nium salts for a facile and benign synthesis of func- mediated side reactions and polymerizations (Table 1,
tionalized benzalacetones in the presence of entry 8 and Table 2, entry 2). Noteworthy, decomposi-
Pd
G
tion in absence of CaCO3 is even more pronounced in
the case of diazonium salts bearing electron-with-
drawing groups (Table 2, entry 4).
Results and Discussion
We have found that the reaction is stereoselective
giving the E-isomers exclusively. Furthermore, no ar-
At the beginning of our investigations we examined ylbutanones (via hydroarylation) were obtained which
the conversion of 4-methoxybenzenediazonium tetra- are frequently observed and described in the case of
fluoroborate with butenone using a combination of aryl iodides and aryl bromides.[5,6,8]
Pd
(OAc)2 as catalyst and CaCO3 as base under differ-
All reactions could be carried out under ambient
conditions using commercial and non-degassed sol-
ent reaction conditions (Table 1).
Gas evolution indicated the consumption of the vents like methanol, ethanol and isopropyl alcohol in
starting material as well as the progress of reaction. accordance to previous results.[11–13,20] The reaction
Regarding the results in Table 1 it is shown that spe- conditions were explored with various arenediazoni-
cific reaction conditions like the amount of catalyst, um tetrafluoroborates (Table 3).
CaCO3, and butenone are needed for a successful
Starting materials with different substitution pat-
preparation of the corresponding benzalacetones. terns gave the corresponding products in useful yields.
Only by means of at least 2 mol% PdACTHNURTGNENG(U OAc)2, two This synthetic protocol exhibits outstanding compati-
Table 1. Optimization of reaction conditions.
Entry
Catalyst loading [mol%]
Equiv. 2
Equiv. CaCO3
Reaction time [min]
Yield[a] [%]
1
2
3
4
5
6
7
8
0.5
0.5
0.5
1.0
2.0
2.0
2.0
2.0
1.0
1.0
1.2
1.0
1.0
1.5
2.0
2.0
0.5
0.5
0.5
0.5
0.5
0.5
0.5
–
30
39
34
35
34
39
56
74
58
720
300
65
45
10
10
10
[a]
Isolated yields.
Table 2. Impact of the base.
Entry
Functional group FG
Equiv. 2
Equiv. CaCO3
Yield[a] [%]
1
2
3
4
4-OMe
4-OMe
4-NO2
4-NO2
2.0
2.0
2.0
2.0
0.5
–
0.5
–
74
58
84
52
[a]
Isolated yields.
1984
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ꢂ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 1983 – 1992

A Selective and Benign Synthesis of Functionalized Benzalacetones via Mizoroki–Heck Reaction
Table 3. Scope of reaction.
Entry
1
Product
Yield[a] [%]
74
Entry
8
Product
Yield[a] [%]
74
2
3
62
85
9
95
87
10
4
56
11
72
5
6
69
59
51
12
13
14
80
84
7
29,[c] 48[b,c}
[a]
Isolated yields.
[b]
[c]
4 mol% Pd
ACHTUNGTRENNUNG(OAc)2 were employed.
The product could not be isolated in pure form.
bility with a wide range of functional groups. In con- be obtained which are not accessible in good yields
sistence with previous results[10–13,20] an excellent che- via aldol reactions without special precautions.
moselectivity towards halide functionalties was stated.
A different situation is found in the case of cyano
Thus, halogenated benzalacetones bearing iodine, substituents. Using 4-cyanobenzenediazonium tetra-
bromine, or chlorine atoms, respectively, could be fluoroborate a significant decrease in reactivity and
easily obtained in good yields. Hence, brominated isolated yield was observed. A suitable explanation
and iodinated benzalacetones are accessible for the for this observation might be complexation of the cat-
first time via the Mizoroki–Heck reaction in higher alytically active palladium species by the cyano group
yields compared to the classical synthetic access using and is supported by mechanistic studies of the Mizo-
aldol condensations.[15]
ACHTUNGTRENrNGNU oki–Heck reaction involving aryldiazonium salts in
Beside the nitro group, other functional groups like acetonitrile by Eberlin, Correia and co-workers.[16]
esters or ketones are also tolerated and functionalized These investigations using electrospray ionization
benzalacetones bearing carbonyl groups could easily mass spectrometry (ESI-MS and ESI-MS/MS) clearly
Adv. Synth. Catal. 2010, 352, 1983 – 1992
ꢂ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1985

Therese Stern et al.
FULL PAPERS
indicate the formation of several cationic Pd inter-
mediates with acetonitrile in the coordination sphere
and their impact on the insertion of the olefin as the
rate-determining step in the catalytic cycle. Thus, the
presence of the cyano group might influence the in-
sertion of the butenone in the occuring cationic inter-
mediates of the oxidative addition step and therefore
the synthetic outcome of the reaction.
Furthermore, it is known that benzonitriles can act
as ligands for palladium(II) salts.[17] This assumption is
further supported by the fact that a doubling of the
catalyst loading to 4 mol% significantly increased the
yield of the product. A similar decrease in catalytic
activity using this experimental set-up was also ob-
served in the case of reactions with acrylates in con-
trol reactions. Despite the fact that high yields of iso-
lated cinnamic esters bearing cyano groups could be
obtained these conversions showed significantely pro-
longed reaction times compared to other aryldiazoni-
um salts. However, in the case of the reaction with
butenone significant amounts of polymerization by-
products were formed, making it difficult to isolate
the pure 4-cyanobenzalacetone.
In order to broaden the applicability of the method
modified conditions for substrates which merely have
given moderate yields were investigated. Further-
more, we have noticed that shorter reaction times fre-
Figure 1. Reaction kinetics.
This assumption is supported by control experi-
(OAc)2 was reduced by formic acid
purity of the products. Therefore, we have studied the or by pre-reduction of Pd(OAc)2 by methanol to
quently led to better results with respect to yields and ments, in which Pd
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
kinetics of the reaction to gain more mechanistic in- Pd(0). In all cases a significant decrease of the above-
sight paving the road towards a better and more effi- mentioned initial period could be observed. Specifi-
cient catalytic system. cally, pre-reduction shortened the initial period to 22–
As mentioned before, the progress of the reaction 23 seconds.
can easily be monitored by the gas evolution that
It has to be stated that no Heck reaction has taken
clearly indicates the consumption of the diazonium place in the absence of alcoholic solvents. Thus, the
salt. Based on the recorded gas quantity it is possible reaction completely failed when it was carried out in
to get detailed information about the kinetic course THF or butenone as solvent. Hence, the butenone
of this cross-coupling reaction and the active catalyst can be excluded as a reducing agent for PdACHTUNGTRENNUNG(OAc)2
present. Therefore, the progress of the reaction was and the utilization of alcoholic solvents is mandatory
monitored by measurement of the gas evolution over for this synthetic protocol.
time. Based on these results the rates of consumption
of several diazonium salts were investigated and are than the electron-rich methoxy derivative.
shown in Figure 1. To improve the catalytic activity even further and
Generally, electron-poor substrates reacted faster
In all cases an initial phase of approximately 54 sec- to avoid potential agglomerizations that might dimin-
onds was observed that was similar for diazonium ish the catalytic activity we were seeking for a suita-
salts bearing electron-donating and electron-with- ble immobilization of our generated Pd(0) species.[19]
drawing groups, respectively. This indicates that at the Felpin and co-workers have recently reported the uti-
beginning of the reaction the formation of catalytical- lization of charcoal as suitable material for the immo-
ly more active Pd species is taking place. Thus, the bilization of Pd(0) species in cross-coupling reactions
Pd
this reaction. During the reaction we have observed
the formation of black Pd species. It is well known plied Pd
that Pd(OAc)2 is reduced to Pd(0) by alcoholic sol- protocol. For obtaining a very reactive Pd(0)/charcoal
vents.[18] Therefore, the reduction of Pd
(OAc)2 to catalyst Pd(OAc)2 was pre-reduced by the solvent
ACHTUNGTRENNUNG
(OAc)2 employed only represents a pre-catalyst for using aryldiazonium tetrafluoroborates.[20]
Stimulated by this elegant approach we have ap-
(OAc)2/charcoal mixtures in our synthetic
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
Pd(0) species by the solvent methanol is considered methanol in the presence of charcoal for 15 min
the initial step of this reaction and is also taken into before starting the Mizoroki–Heck reaction. Thereby,
account by other authors.[13e,20d]
the formation of Pd(0) clusters could be verified and
1986
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Adv. Synth. Catal. 2010, 352, 1983 – 1992

A Selective and Benign Synthesis of Functionalized Benzalacetones via Mizoroki–Heck Reaction
ꢀ1
tion rates are higher (2.43ꢃ10ꢀ2 mmols
10ꢀ2 mmols)ꢀ1 using the catalyst Pd
(OAc)2/charcoal
compared to Pd(OAc)2 during the formation of 4-me-
thoxybenzalacetone (3). The higher catalytic activity
of the Pd(OAc)2/charcoal system is also reflected in a
higher turn-over frequency [875 hꢀ1 compared to
745 hꢀ1 using Pd
(OAc)2].
vs. 2.07ꢃ
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
By using charcoal as supporting material the ag-
glomerization of the Pd clusters can be avoided and
on the site of reaction becomes clearly defined by the
reduced dimensionality of the surface by loading the
catalytically active Pd(0) species onto charcoal-sur-
face.[26]
Hence, a shorter initial period, a decrease of the re-
action time and superior isolated yields were ob-
tained. These results are consonant with observations
using the PdACTHUNRGTNEUNG(OAc)2 system, in which shorter reaction
Figure 2. SEM image of the immobilized catalyst.
times frequently led to better results with respect to
yields and purity of the products. In the absence of
characterized by scanning electron microscopy (SEM) charcoal the agglomerization of the Pd(0) species is
and EDX analysis (Figure 2). even more pronounced which causes lower catalytic
In all cases shorter reaction times and better isolat- activity and worse synthetic results. This becomes ap-
ed yields were obtained using this optimized catalytic parent by a prolongation of the pre-reduction period.
system compared to Pd
G
Thus, an extension of the reduction period up to 24 h
Thus, on one hand the initial reaction time was re- led to lower yields and a significant decrease of the
markably diminished and on the other hand the reac- reaction rate. Thereby, the tendency for agglomeriza-
Figure 3. The reaction kinetics of the Pd-catalyzed Mizoroki–Heck reaction.
Adv. Synth. Catal. 2010, 352, 1983 – 1992
ꢂ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1987

Therese Stern et al.
FULL PAPERS
tion appeared through the formation of a metallic
mirror onto the reaction flask surface.
The modified catalyst was explored with several ar-
yldiazonium tetrafluoroborates that gave only moder-
ate yields using PdACHTNUTRGENNG(U OAc)2 alone (Table 4).
Regarding this heterogeneous catalyst, it has to be
pointed out that the isolated yield of 4-acetylbenzal-
ACHTUNGTRENNUNGacetone 9 (Table 4, entry 5) obtained by this approach
is significantly higher compared to that from the reac-
tion conditions reported by Molnar et al. using the
corresponding 4-bromoacetophenone and a Pd cata-
lyst deposited onto an organic-inorganic hybrid sup-
port. In this case the desired product was only ob-
tained in a very low 6% yield.[21]
Figure 4. Preparation of 4-cyanobenzalacetone using Pd/C.
Despite the higher efficiency of the Pd
ACHTUNGRTENUN(NG OAc)2/char-
coal system compared to Pd(OAc)2 only by using
AHCTUNGTRENNUNG
6 mol% catalyst pure 4-cyanobenzalacetone could be
obtained in a reasonable yield of 68% (Figure 4).
The need for a higher amount of catalyst can be ex-
plained by a complexation of the Pd(0) species by the
cyano functionality. Thus, the adsorption of nitriles on
Pd surfaces has been stated by X-ray photoelectron Figure 5. Conversion of heterocyclic diazonium salts.
spectroscopy.[25] Furthermore, an interaction of the
cyano group in the catalytic cycle has to be taken into
account as mentioned before.[16]
Table 4. The Pd
ACHTUNGTRENNUNG
Besides aryldiazonium tetrafluoroborates, heterocy-
clic diazonium salts could also be applied in the
above-mentioned procedures. Thus, the thiophene de-
rivative 17 was easily converted with butenone to the
corresponding
boxylic acid methyl ester (18) by using Pd
Pd(OAc)2/charcoal as catalytic system in identical
yields (Figure 5). Therefore, no significant poisoning
of the catalyst by the thiophene moiety was observed.
3-(3-oxo-but-1-enyl)thiophene-2-car-
AHCTUNGTRENNUNG
Entry
1
Product
Yield[a] [%]
82
AHCTUNGTRENNUNG
Conclusions
We have presented a new method for the synthesis of
functionalized benzalacetones via the Mizoroki–Heck
reaction using aryldiazonium salts as electrophiles.
This method provides a selective and benign access to
the products when using palladium(II) acetate in the
presence of CaCO3 in methanol. Due to the fact that
this catalytic reaction is complete within several mi-
nutes, this method is one of the fastest and easiest
compared to traditional aldol condensations or Mizor-
oki–Heck reactions using aryl bromides or iodides.
First kinetic investigations indicate that a palladi-
um(0) species is involved in the catalytic cycle. Based
on these results an improved catalytic system and pro-
cedure was developed and applied by using a combi-
2
3
65
65
4
5
73
65
nation of PdACTHNUTRGNE(UNG OAc)2, charcoal, and CaCO3. This proto-
col represents a more convenient and more efficient
method compared to the protocol using only
PdACTHNGUETR(UNNG OAc)2 and CaCO3. Further investigations concern-
[a]
Isolated yields.
1988
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Adv. Synth. Catal. 2010, 352, 1983 – 1992

A Selective and Benign Synthesis of Functionalized Benzalacetones via Mizoroki–Heck Reaction
The crude material was purified by flash chromatography to
give the corresponding benzalacetones.
ing kinetics, catalysts, characterization of catalysts,
and applications towards target-oriented synthesis are
currently underway in our laboratory and will be re-
ported in due course.
(E)-4-Methoxy-benzalacetone (3): This compound was
prepared according to the general procedures A and B. Pu-
rification by flash chromatography (hexane: ethyl acetate
9:1!8:2) gave a yellow solid: mp 698C [Lit.[22]: 70–728C].
IR (neat): n=1680, 1586, 1245, 988, 817 cmꢀ1 1H NMR
;
Experimental Section
(CDCl3, 250 MHz): d=2.36 (s, 3H), 3.84 (s; 3H), 6.60 (d,
3JH,H =17.5 Hz, 1H), 6.91 (d, 3JH,H =7.5 Hz, 2H), 7.48 (d,
3
3JH,H =17.5 Hz, 1H), 7.49 (d, JH,H =7.5 Hz, 2H), 13C NMR
General Remarks
(CDCl3, 100 MHz): d=27.3, 55.3, 114.4, 124.9, 126.9, 129.9,
143.2, 161.5, 198.3; MS (EI): m/z (rel. intens.)=177.2 [M+
H]+ (100).
NMR spectra were recorded on Bruker AC 250 and JOEL
ECX 400 spectrometers. Chemical shifts in proton and
carbon NMR spectra are reported in ppm relative to the
TMS peak at 0.00 ppm or relative to CDCl3 peak at
77.0 ppm, coupling constants (J) in Hz. Infrared (IR) spectra
were recorded as neat samples in ATR mode using a Spec-
trum One (Perkin–Elmer) spectrometer. Mass spectra were
recorded on Bruker micrOTOF-QII and Waters-micromass
Quatro micro spectrometers. Yields refer to isolated materi-
al determined to be pure by NMR spectroscopy, mass spec-
trometry, and thin layer chromatography (TLC), unless
specified otherwise in the text. Flash chromatography (FC):
Merck silica gel 60 (240–400 mesh) and Merck aluminium
oxide 90 active neutral (70–230 mesh). Melting points were
recorded using a Bꢀchi Melting point apparatus M-560. The
scanning electron microscopy (SEM) image has been ob-
tained with a Zeiss Gemini 1550 microscope. The catalyst
was dispersed onto a carbon adhesive tape. Elemental analy-
sis was carried out at the Fraunhofer Institute for Applied
Polymer Research in Potsdam-Golm. Diazonium salts used
in this study were all known and prepared as described in
the literature, see Ref.[14] Solvents and chemicals were pur-
chased from VWR or Aldrich and used as received. Activat-
ed charcoal (particle size ꢁ150 mm, 90%) was purchased
from Merck.
(E)-3-Methoxy-benzalacetone (4): This compound was
prepared according to the general procedures A and B. Pu-
rification by flash chromatography (hexane:ethyl acetate
9:1!8:2) gave an orange oil. IR (neat): n=1666, 1246, 974,
1
685 cmꢀ1; H NMR (CDCl3, 250 MHz): d=2.38 (s, 3H), 3.83
3
(s; 3H), 6.66 (d, 3JH,H =15.0 Hz, 1H), 6.91 (dd, JH,H
=
4
4
10.0 Hz, JH,H =2.5 Hz 1H), 7.03 (t, JH,H =2.5 Hz, 1H), 7.09
3
3
(d, JH,H =7.5 Hz, 1H), 7.28 (t, JH,H =7.5 Hz, 1H), 7.44 (d,
3JH,H =17.5 Hz, 1H); 13C NMR (CDCl3, 100 MHz): d=27.4,
55.2, 114.4, 112.9; 116.3; 120.9, 127.3, 129.8, 143.2, 159.8,
198.3; MS (EI): m/z (rel. intens.)=177.2 [M+H]+ (100).
(E)-Benzalacetone (5): This compound was prepared ac-
cording to the general procedure. Purification by flash chro-
matography (hexane:ethyl acetate 9:1!8:2) gave a white
solid; mp 348C [Lit.[22]: 36–398C]. IR (neat): n=1668, 1607,
1
1255, 975, 747, 690 cmꢀ1; H NMR (CDCl3, 250 MHz): d=
3
2.38 (s, 3H), 6.72 (d, JH,H =15.0 Hz, 1H), 7.40 (m, 2H), 7.51
(d, 3JH,H =17.5 Hz, 1H), 7.55 (m, 3H); 13C NMR (CDCl3,
100 MHz): d=27.3, 126.9, 128.0, 128.8, 130.3, 134.2, 143.2,
198.3; MS (EI): m/z (rel. intens.)=147.12 [M+H]+ (100).
(E)-Trimethoxybenzalacetone (6): This compound was
prepared according to the general procedures A and B. Pu-
rification by flash chromatography (hexane:ethyl acetate
9:1!8:2) gave a white solid; mp 868C [Lit.[23]: 87–898C]. IR
General Procedure A for the Preparation of
Functionalized Benzalacetones using PdACTHUNRGTNEUNG(OAc)2
1
(neat): n=1667, 1578, 1418, 1243, 1122, 979 cmꢀ1; H NMR
(CDCl3, 250 MHz): d=2.39 (s, 3H), 3.90 (s; 9H), 6.63 (d,
3JH,H =17.5 Hz; 1H), 6.78 (s; 2H, J=15.4 Hz, 1H), 7.44 (d,
3JH,H =17.5 Hz, 1H); 13C NMR (CDCl3, 100 MHz): d=27.2,
56.0, 60.8, 105.3, 126.3, 129.7, 130.3, 140.2, 143.2, 153.3,
198.0; MS (EI): m/z (rel. intens.)=237.18 [M+H]+ (100).
(E)-4-Methoxycarbonylbenzalacetone (7): This compound
was prepared according to the general procedure A. Purifi-
cation by flash chromatography (hexane:ethyl acetate 9:1!
8:2) gave a greenish solid; mp. 1028C. IR (neat): n=1718,
To a suspension of diazonium salt (5 mmol) in 25 mL metha-
nol were added 10 mmol butenone, 2.5 mmol CaCO3, and
2 mol% PdACHTUNGTRENNUNG(OAc)2 at 258C. The resulting mixture was
stirred. After the gas evolution had ceased the reaction mix-
ture was poured into ice-cooled water. The aqueous phase
was extracted 3 times with diethyl ether (25 mL). The com-
bined organic phases were dried over MgSO4 and then con-
centrated under reduced pressure. The crude material was
purified by flash chromatography to give the corresponding
benzalacetones.
1
1661, 1279, 1104, 761 cmꢀ1; H NMR (CDCl3, 250 MHz): d=
3
2.41 (s, 3H), 3.94 (s; 3H), 6.79 (d, JH,H =15.0 Hz, 1H), 7.53
(d, 3JH,H =15.0 Hz, 1H), 7.63 (d, 3JH,H =10.0 Hz, 2H), 7.98
(d, 3JH,H =7.5 Hz, 2H); 13C NMR (CDCl3, 100 MHz): d=
27.7, 52.2, 128.0, 128.9, 140.0, 131.4, 138.6, 141.7, 166.3,
197.9; MS (EI): m/z (rel. intens.)=205.18 [M+H]+ (100).
(E)-2-Methoxycarbonylbenzalacetone (8): This compound
was prepared according to the general procedures A and B.
Purification by flash chromatography (hexane:ethyl acetate
9:1!8:2) gave a yellow solid; mp 30–318C. IR (neat): n=
General Procedure B for the Preparation of
Functionalized Benzalacetones using Pd/C (5 wt%)
0.1 mmol PdACHTUNGTRENNUNG(OAc)2, 7.5 mmol charcoal, and 2.5 mmol
CaCO3 were suspended in 25 mL methanol and stirred for
15 min at 258C. Afterwards, 10 mmol butanone and 5 mmol
diazonium salt were added. The resulting mixture was
stirred. After the gas evolution had ceased the reaction mix-
ture was filtered and the resulting filtrate poured into ice-
water. The aqueous phase was extracted 3 times with diethyl
ether (25 mL). The combined organic phases were dried
over MgSO4 and then concentrated under reduced pressure.
1716, 1670, 1245, 1077, 748 cmꢀ1
;
1H NMR (CDCl3,
3
250 MHz): d=2.43 (s, 3H), 3.94 (s; 3H), 6.53 (d, JH,H
=
3
15.0 Hz, 1H), 7.47 (d, JH,H =7.5 Hz, 1H), 7.59 (m, 2H); 8.01
(d, 3JH,H =7.5 Hz, 2H), 8.40 (d, 3JH,H =17.5 Hz, 1H);
13C NMR (CDCl3, 100 MHz): d=26.7, 52.2, 127.7, 129.4,
Adv. Synth. Catal. 2010, 352, 1983 – 1992
ꢂ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1989

Therese Stern et al.
FULL PAPERS
3
130.2, 130.8, 132.4, 136.5, 142.8, 167.0, 198.8; MS(EI): m/z
(rel. intens.)=205.18 [M+H]+ (30), 173.05 [MꢀOCH3]
(100), 131.05 (100); HR-MS (ESI): m/z=205.0859, calcd. for
C12H12O3: 205.0854; anal. calcd. for C12H12O3: C 70.58, H
5.92; found: C 70.62, H 6,32.
7.5 Hz, 2H), 7.43 (d, 3JH,H =17.5 Hz, 1H), 7.74 (d. JH,H
=
7.5 Hz, 2H); 13C NMR (CDCl3, 100 MHz): d=27.6, 96.7,
127.5, 129.6, 133.8, 138.1, 142.0, 198.0; MS (EI): m/z (rel.
intens.)=273.09 [M+H]+ (100).
(E)-4-Nitrobenzalacetone (15): This compound was pre-
pared according to the general procedure. Purification by
flash chromatography (hexane:ethyl acetate 9:1!8:2) gave
a yellow solid; mp 1058C [Lit.[24]: 106–1078C]. IR (neat): n=
(E)-4-Acetylbenzalacetone (9): This compound was pre-
pared according to the general procedures A and B. Purifi-
cation by flash chromatography (hexane:ethyl acetate 9:1!
8:2) gave a white solid; mp 1078C [Lit.[22]: 105–1068C]. IR
1665, 1513, 1342, 975, 827, 742 cmꢀ1 1H NMR (CDCl3,
;
250 MHz): d=2.43 (s, 3H), 6.83 (d, 3JH,H =15.0 Hz, 1H),
7.55 (d, 3JH,H =15.0 Hz, 1H), 7.72 (d, 3JH,H =10.0 Hz, 2H),
1
(neat): n=1674, 1355, 1253, 977, 813 cmꢀ1; H NMR (CDCl3,
3
250 MHz): d=2.41 (s, 3H), 2.62 (s, 3H), 6.79 (d, JH,H
=
=
8.65 (d, JH,H =10.0 Hz, 2H); 13C NMR (CDCl3, 100 MHz):
3
3
3
15.0 Hz, 1H), 7.53 (d, JH,H =15.0 Hz, 1H), 7.63 (d, JH,H
10.0 Hz, 2H), 7.98 (d, 3JH,H =10.0 Hz, 2H); 13C NMR
(CDCl3, 100 MHz): d=27.6, 27.7, 128.3, 128.8, 129.0, 138.0,
138.8, 141.6, 197.3, 198.0; MS (EI): m/z (rel. intens.)=189.16
[M+H]+ (100).
d=27.9, 124.1, 128.7, 130.3, 140.0, 140.6, 148.5, 197.4; MS
(EI): m/z (rel. intens.)=192.16 [M+H]+ (60).
(E)-4-Cyanobenzalacetone (16): This compound was pre-
pared according to the general procedure B using 6 mol%
catalyst. Purification by flash chromatography (hexane:ethyl
(E)-4-Methylbenzalacetone (10): This compound was pre-
pared according to the general procedure A. Purification by
flash chromatography (hexane:ethyl acetate 9:1!8:2) gave
a green solid; mp 318C [Lit.[22]: 33–348C8C]. IR (neat): n=
acetate 9:1!8:2) gave a white solid; mp 102–1038C [Lit.[22]
:
105–1068C]. IR (neat): n=2224, 1665, 1364, 1253, 1208, 970,
957, 812 cmꢀ1; H NMR (CDCl3, 250 MHz): d=2.42 (s, 3H),
1
6.80 (d, 3JH,H =17.5 Hz, 1H), 7.50 (d, 3JH,H =17.5 Hz, 1H),
7.65 (d, 3JH,H =10.0 Hz, 2H), 7.71 (d, 3JH,H =10.0 Hz, 2H);
13C NMR (CDCl3, 100 MHz): d=27.9, 113.4, 118.2, 128.5,
129.6, 129.7, 132.6, 138.7, 140.5, 140.6, 197.6; MS (EI): m/z
(rel. intens.)=172.1 [M+H]+ (100).
1
1663, 1609, 1254, 799 cmꢀ1; H NMR (CDCl3, 250 MHz): d=
3
2.37 (s, 6H), 6,68 (d, 3JH,H =15.0 Hz, 1H), 7.20 (d, JH,H
=
=
3
7.5 Hz, 2H), 7.44 (d, 3JH,H =7.5 Hz, 2H), 7.49 (d, JH,H
15.0 Hz, 1H); 13C NMR (CDCl3, 100 MHz): d=21.4, 27.3,
126.1, 128.2, 129.6, 131.6, 140.9, 143.4, 198.0; MS (EI): m/z
(rel. intens.)=161.14 [M+H]+ (100).
(E)-3-(3-Oxobut-1-enyl)-thiophene-2-carboxylic
acid
methyl ester (19): This compound was prepared according
to the general procedure A and B. Purification by flash
chromatography (hexane:ethyl acetate 9:1!8:2) gave a red
solid; mp 79–808C. IR (neat): n=1709, 1664, 1417, 1254,
(E)-4-Fluorobenzalacetone (11): This compound was pre-
pared according to the general procedure A. Purification by
flash chromatography (hexane:ethyl acetate 9:1!8:2) gave
a greenish oil; IR (neat): n=1667, 1597, 1507, 1227, 1159,
1210, 975, 771 cmꢀ1; H NMR (CDCl3, 250 MHz): d=2.43 (s,
1
1
975, 815 cmꢀ1; H NMR (CDCl3, 250 MHz): d=2.38 (s, 3H),
3H), 3.93 (s, 3H), 6.58 (d, 3JH,H =17.0 Hz, 1H), 7.38 (d,
3JH,H =6.2 Hz, 1H), 7.50 (d, 3JH,H =6.2 Hz, 1H), 8.45 (d,
3JH,H =17.0 Hz, 1H); 13C NMR (CDCl3, 100 MHz): d=26.4,
52.2, 126.4, 130.9, 135.7, 142.3, 162.2, 199.2; MS (EI): m/z
(rel. intens.)=211.11 [M+H]+ (70), 179.06 [MꢀOCH3]
(100); HR-MS (ESI): m/z=211.0444, calcd. for C10H10O3S:
211.0423; anal. calcd. for C10H10O3S: C 57.13, H 4,79, S
15,25; found: C 57,32, H 4,86, S 15,28.
3
3
6,65 (d, JH,H =15.0 Hz, 1H), 7.09 (t, JH,H =7.5 Hz, 2H), 7.48
(d, 3JH,H =15.0 Hz, 1H), 7.55 (m, 2H); 13C NMR (CDCl3,
100 MHz): d=27.5, 116.1 (d, JC,F =21.75 Hz), 126.7, 130.1,
2
1
130.6, 141.9, 163.9 (d, JC,F =250,3 Hz, CF), 198.0; MS (EI):
m/z (rel. intens.)=165.12 [M+H]+ (100).
(E)-4-Chlorobenzalacetone (12): This compound was pre-
pared according to the general procedure A. Purification by
flash chromatography (hexane:ethyl acetate 9:1!8:2) gave
a green solid; mp 528C [Lit.[8a]: 54–558C]. IR (neat): n=
1656, 1587, 1250, 1088, 976, 813 cmꢀ1 1H NMR (CDCl3,
;
250 MHz): d=2.37 (s, 3H), 6.67 (d, 3JH,H =17.5 Hz, 1H),
7.35 (d, 3JH,H =10.0 Hz, 2H), 7.41 (d, 3JH,H =15.0 Hz, 1H),
7.46 (d, 3JH,H =7.5 Hz, 2H); 13C NMR (CDCl3, 100 MHz):
d=27.6, 127.4, 129.2, 129.3, 132.8, 136.3, 141.7, 197.9; MS
(EI): m/z (rel. intens.)=181.10 [M+H]+ (100).
Acknowledgements
Mr. Christian Doll and Mr. Markus Friedel are gratefully ac-
knowledged for recording the mass spectra. Mrs. Kußmann is
gratefully acknowledged for SEM investigations.
(E)-4-Bromobenzalacetone (13): This compound was pre-
pared according to the general procedure A. Purification by
flash chromatography (hexane:ethyl acetate 9:1!8:2) gave
a greenish solid; mp 75–768C [Lit.[22]: 76–788C]. IR (neat):
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