Kinetics of the enolisation reactions of 3-acetyl-2,5-dimethylfuran and of 2-acetylselenophene

Article abstract of DOI:10.1002/(SICI)1099-0690(199809)1998:9<1867::AID-EJOC1867>3.0.CO;2-M

Rate constants for the enolisation reactions of title compounds have been measured by their rates of halogenation at 25 °C in water, in several buffers, in dilute hydrochloric acid, in dilute sodium hydroxide, and in the presence of some metal ion salts. The results have been compared with those previously obtained from the corresponding reactions of acetophenone and a number of other acetyl heterocycles. Electronegativity of the heteroatoms and the "π-excessive" nature of the heterocyclic rings appear to be the main factors determining the relative reactivities in the acid-catalysed reactions. Bronsted β values and isotope effects, k_H/k_D, point to a more symmetrical transition state for the investigated acetyl heterocycles than that for acetophenone in the general base-catalysed reaction. Metal-activating factors (MAF), i.e. the catalytic constant for metal-ion (Cu²⁺, Zn²⁺, and Ni²⁺) catalysis, k_M, relative to that for proton catalysis, k_H, are discussed as an empirical measure of the "hard or soft" character of the carbonyl groups in acyl heterocycles.

Full text of DOI:10.1002/(SICI)1099-0690(199809)1998:9<1867::AID-EJOC1867>3.0.CO;2-M

FULL PAPER
Kinetics of the Enolisation Reactions of 3-Acetyl-2,5-dimethylfuran and of
2-Acetylselenophene
Paolo De Maria*a, Antonella Fontanaa, Gabriella Siania, and Domenico Spinellib
a
`
Istituto di Scienza del Farmaco, Universita “G. D’Annunzio” ,
Via dei Vestini 29, I-66013 Chieti, Italy
Fax: (internat.) ϩ39(0)871/3556778
E-mail: demaria@phobos.unich.it
b
´
Dipartimento di Chimica Organica “A. Mangini”, Universita di Bologna ,
Via S. Donato 15, I-40127 Bologna, Italy
Received March 5, 1998
Keywords: Catalysis / Metal ion catalysis / Kinetics / 3-Acetyl-2,5-dimethylfuran /2-Acetylselenophene / Enolisation
reaction
Rate constants for the enolisation reactions of title
compounds have been measured by their rates of
halogenation at 25 °C in water, in several buffers, in dilute
hydrochloric acid, in dilute sodium hydroxide, and in the
presence of some metal ion salts. The results have been
compared with those previously obtained from the
corresponding reactions of acetophenone and a number of
reactivities in the acid-catalysed reactions. Brønsted β values
and isotope effects, kH/kD, point to a more symmetrical
transition state for the investigated acetyl heterocycles than
that for acetophenone in the general base-catalysed reaction.
Metal-activating factors (MAF), i.e. the catalytic constant for
metal-ion (Cu2+, Zn2+, and Ni2+) catalysis, kM, relative to that
for proton catalysis, kH, are discussed as an empirical
other acetyl heterocycles. Electronegativity of the measure of the “hard or soft” character of the carbonyl
heteroatoms and the “π-excessive” nature of the heterocyclic
groups in acyl heterocycles.
rings appear to be the main factors determining the relative
The occurrence of metal-ion (e.g. Cu2ϩ, Zn2ϩ, Ni2ϩ) ca- information on the effect of the heterocyclic moiety on the
talysis in the enolisation reaction of particular carbonyl structure of the reaction transition states.
compounds in aqueous solutions is firmly estab-
lished[1][2][3]. The Brønsted and/or Lewis[4] basicity of a ke-
tone is an important factor in determining the relative effec-
tiveness of acid- and metal-ion catalysis. Thus, for example,
the less basic β-diketones display metal-ion catalysis be-
cause the additional carbonyl group acts as a second coor-
dination site, but acid catalysis is either very weak or not
observed at all[1b][5]. The opposite situation applies to ace-
tophenone and a number of five-membered acetyl heterocy-
cles[3a][3b]. However, high metal-activating factors (MAF),
i.e. the catalytic constant for metal-ion catalysis, kM, relative
to that for proton catalysis, kH, have been found for acetyl-
pyrroles[3b][3c] as well as for 2- and 4-acetylthiazoles[3c]. The
formation of a chelate complex preceding the enolisation
step was detected for 2-acetylpyridine[2] and 2-acetylimida-
zole[3d] and this complex enolises much faster than the un-
complexed substrate. Within this framework we have stud-
ied the enolisation reaction of the title compounds in water,
in dilute hydrochloric acid, in dilute sodium hydroxide, in
Results
The rates of enolisation of 2-acetylselenophene (2AS)
and 3-acetyl-2,5-dimethylfuran (3AF) were measured in
water, in dilute aqueous hydrochloric acid and sodium hy-
droxide, in different buffers (chloroacetate, acetate, mandel-
ate, hydrogen phosphate, and borate) and in the presence of
Zn2ϩ, Ni2ϩ, and Cu2ϩ salts at 25.0 ± 0.1°C by trapping the
enol with halogen (iodine or bromine). All reactions are
strictly zero order with respect to halogen concentration,
with the rate-determining step being the formation of the
enol or enolate ion. There was no evidence of reversibility
of the iodination reaction under the adopted experimental
conditions. The iodination reactions were monitored under
pseudo-zero-order conditions[3a][3b][3c] and the rate law had
the form shown in Eq. (1), where S refers to the substrate
and [I2]tot refers to the total concentration of iodine {[I2] ϩ
[I3Ϫ]}.
Ϫd[I2]tot/dt ϭ ke[S]
(1)
several buffer solutions, and in the presence of Zn2ϩ, Ni2ϩ
and Cu2ϩ solutions at 25.0 ± 0.1°C. The obtained results
,
The rate constants for the OHϪ-catalysed enolisation re-
allow a comparison of the relative importance of the differ- action of the title substrates and some [D3]acetyl hetero-
ent factors governing the acidϪbase and metal-ion cata- cycles (2-[D3]acetylthiophene, 3-[D3]acetylthiophene, 2-
lysed enolisation reactions of the present and the previously [D3]acetylselenophene, and [D3]acetophenone) were meas-
studied[3a][3b][3c] acetyl heterocycles. Primary kinetic isotope ured by their bromination reactions under pseudo-first-or-
effects (kH/kD) and Brønsted β values provide additional der conditions[3a]
.
Eur. J. Org. Chem. 1998, 1867Ϫ1872
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1998
1434Ϫ193X/98/0909Ϫ1867 $ 17.50ϩ.50/0
1867

P. De Maria, A. Fontana, G. Siani, D. Spinelli
FULL PAPER
Enolisation of 2AS and 3AF in Dilute Hydrochloric Acid
basic component of the buffer and k represents the second-
order rate constant of the general acidϪbase-catalysed reac-
tion. The results are collected in Tables 2Ϫ4.
Reaction rates were measured with concentration of the
ketone in the range 5·10Ϫ3 to 8·10Ϫ3 mol dmϪ3 and with
HCl concentration in the range 0.25Ϫ60·10Ϫ2 mol dmϪ3 ke ϭ ko ϩ k[B]
(3)
and [IϪ] ϭ 2·10Ϫ3 mol dmϪ3. The observed rate law was
Several sets of ke values were measured for the two ke-
tones at different buffer ratios, r ϭ [B]/[A] (where A is the
acidic component of the buffer), each set at five or more
different concentrations of base in a range of ca. a factor
of ten. The values of k determined in chloroacetate buffer
for 2AS and 3AF and in mandelate and acetate buffers for
3AF showed evidence of general acid catalysis by the acidic
component of the buffer as they were dependent of r. The
separate contributions of buffer base, kB, and buffer acid,
kA, to ke (Eq. 4) were obtained by plotting the values of k,
measured at the different r values, against 1/r and evaluat-
ing kB as the intercept and kA as the slope, according to
Eq. (5).
given by Eq. (2) with ke being of the form shown in Eq. (1).
ke ϭ ko ϩ kH [Hϩ]
(2)
To obtain ke values for 2AS a gentle stream of nitrogen
was bubbled in the cuvette in order to avoid oxidation of
the substrate at the highest concentrations of acid. The fol-
lowing results were obtained:
2AS ko ϭ 16.6 (±9.5)·10Ϫ9 sϪ1
kH ϭ 2.99 (±0.08)·10Ϫ6 dm3 molϪ1 sϪ1
3AF ko ϭ 48.2 (±9.4)·10Ϫ9 sϪ1
kH ϭ 14.8 (±0.3)·10Ϫ6 dm3 molϪ1 sϪ1
As the above intercepts, ko, obtained from ke versus [Hϩ]
plots are subject to a large uncertainty, the “spontaneous”
(water-catalysed) rate constants were preferably measured
ke ϭ ko ϩ kB[B] ϩ kA[A]
k ϭ kB ϩ kA/r
(4)
(5)
directly in water and are reported in Table 1 as kH O
.
2
Enolisation of 2AS and 3AF in Hydrogen Phosphate and Borate
Buffers
Enolisation of 2AS and 3AF in Chloroacetate, Mandelate, and
Acetate Buffers
Ketone concentrations were varied over the range
Ketone concentrations were varied over the range
2Ϫ8·10Ϫ3 mol dmϪ3 and the observed rate constants, ke 2Ϫ8·10Ϫ3 mol dmϪ3 and the observed rate constants, ke
[Eq. (1)], were of the form shown in Eq. (3), where B is the [Eq. (1)], were of the form shown in Eq. (3) where k is
Table 1. Catalytic constants (k/dm3 molϪ1 sϪ1) for the enolisation reaction of acetophenone and some 2-and 3-acetyl heterocycles at 25°C
and ionic strength 0.3 mol dmϪ3
[a]
[b]
[c]
Values measured directly in water. Units are sϪ1. Ϫ
Ionic strenght 0.5 mol dmϪ3 at [NaOH] ϭ 0.4 and 0.49 mol dmϪ3. Ϫ See
ref.[3a]. Ϫ See ref.[3b]. Ϫ See ref.[3c]
.
[d]
[e]
1868
Eur. J. Org. Chem. 1998, 1867Ϫ1872

Kinetics of the Enolisation Reactions of 3-Acetyl-2,5-dimethylfuran
FULL PAPER
Table 2. Slopes k and intercepts ko from the plot of the experimental pseudo-first-order rate constants (ke/sϪ1) of enolisation of 3AF
against concentration of buffer base in aqueous solution at 25°C and ionic strength 0.3 mol dmϪ3, buffer ratios and range of buffer
concentration
Buffer base
r
pH
ko/10Ϫ8 sϪ1
k/10Ϫ6 dm3 molϪ1 sϪ1
[B]/mol dmϪ3
ClCH2COOϪ[a]
0.6
2
2.51
3.03
3.20
3.42
2.91
3.21
3.68
3.90
4.01
4.30
4.61
5.08
5.30
7.05
7.54 (±1.14)
3.68 (±0.31)
4.25 (±0.25)
4.49 (±0.28)
3.59 (±0.70)
1.85 (±0.21)
2.71 (±0.02)
5.35 (±0.79)
5.28 (±0.17)
7.44 (±0.54)
3.33 (±0.18)
5.18 (±0.13)
4.44 (±0.31)
13.2 (±0.6)
2.52 (±0.10)
0.80 (±0.03)
0.55 (±0.02)
0.32 (±0.02)
3.04 (±0.08)
1.74 (±0.02)
0.54 (±0.01)
0.44 (±0.06)
0.76 (±0.03)
0.62 (±0.06)
0.52 (±0.02)
0.47 (±0.01)
0.44 (±0.02)
21.5 (±0.46)
0.012Ϫ0.203
0.021Ϫ0.199
0.026Ϫ0.251
0.025Ϫ0.250
0.020Ϫ0.150
0.020Ϫ0.198
0.015Ϫ0.100
0.025Ϫ0.250
0.008Ϫ0.100
0.010Ϫ0.150
0.020Ϫ0.198
0.025Ϫ0.250
0.025Ϫ0.250
0.003Ϫ0.025
3
5
C6H5CH(OH)COOϪ[a]
CH3COOϪ
0.5
1
3
5
0.25
0.5
1
3
5
2Ϫ
HPO4
1
[a]
Corrected for the dissociation of the buffer acid.
Table 3 Slopes k and intercepts ko from the plot of the experimental pseudo-first-order rate constants (ke/sϪ1) of enolisation of 2AS
against concentration of buffer base in aqueous solution at 25°C and ionic strength 0.3 mol dmϪ3, buffer ratios and range of buffer
concentration
Buffer base
r
pH
ko/10Ϫ9 sϪ1
k/10Ϫ7 dm3 molϪ1 sϪ1
[B]/mol dmϪ3
ClCH2COOϪ[a]
0.172
1.96
2.42
2.73
3.20
3.42
2.73
3.21
3.68
3.90
4.30
4.61
5.08
5.30
7.05
9.08
29.8 (±4.4)
23.4 (±4.7)
21.1 (±1.9)
12.0 (±2.5)
11.5 (±0.7)
13.5 (±1.2)
13.3 (±0.8)
9.26 (±0.93)
9.22 (±1.20)
7.58 (±1.15)
2.28 (±3.89)
21.3 (±4.6)
7.11 (±1.37)
41.2 (±4.0)
6690 (±910)
19.8 (±0.5)
8.14 (±0.30)
4.48 (±0.13)
2.01 (±0.14)
1.58 (±0.05)
10.4 (±0.2)
4.07 (±0.06)
2.19 (±0.09)
1.67 (±0.08)
7.22 (±0.15)
6.64 (±0.32)
6.61 (±0.27)
6.50 (±0.09)
302 (±5)
0.018Ϫ0.135
0.028Ϫ0.254
0.027Ϫ0.252
0.031Ϫ0.296
0.015Ϫ0.250
0.013Ϫ0.126
0.020Ϫ0.200
0.015Ϫ0.180
0.025Ϫ0.250
0.013Ϫ0.125
0.020Ϫ0.198
0.030Ϫ0.300
0.025Ϫ0.250
0.001Ϫ0.015
0.013Ϫ0.150
0.5
1
3
5
C6H5CH(OH)COOϪ[a]
CH3COOϪ
0.333
1
3
5
0.5
1
3
5
2Ϫ
HPO4
1
Ϫ
H2BO3
1
1010 (±110)
[a]
Corrected for the dissociation of the buffer acid.
Table 4. Rate constants (dm3 molϪ1
s
Ϫ1) for general base or acid catalysis, kB or kA, of enolisation of 2AS and 3AF, calculated from data
reported in Tables 2 and 3
3AF
2AS
Buffer base
kB/10Ϫ7
kA/10Ϫ7
kB/10Ϫ7
kA/10Ϫ7
ClCH2COOϪ[a]
C6H5CH(OH)COOϪ[a]
CH3COOϪ
0.254 (±0.111)
1.34 (±0.95)
4.38 (±0.08)
21.5 (±0.5)
15.0 (±0.14)
14.8 (±0.8)
0.81 (±0.04)
1.15 (±0.22)
1.06 (±0.07)
6.41 (±0.10)
302 (±5)
3.23 (±0.08)
3.11 (±0.04)
0.37 (±0.09)
2Ϫ
HPO4
Ϫ
H2BO3
1010 (±110)
[a]
Corrected for the dissociation of the buffer acid.
coincident with kB as the two buffer acids are too weak to 5, correlation coefficient ϭ 0.998), for 2AS and 3AF respec-
allow a general acid catalysis contribution to be detected. tively.
The values of ke were measured at one buffer ratio, r ϭ 1,
and at five different concentrations of base in a range of
ca. a factor of ten (See Tables 2 and 3). The kB values for
Enolisation of 2AS, 3AF and the [D3]Acetyl Heterocyles in Dilute
Sodium Hydroxide
carboxylate, hydrogen phosphate and borate buffers fitted
Ionisation rates in dilute aqueous hydroxide were too fast
well a Brønsted plot with slopes β ϭ 0.52 (±0.03) (n ϭ 6, to measure using zero-order iodination conditions as above.
correlation coefficient ϭ 0.995) and β ϭ 0.55 (±0.02) (n ϭ The rates were measured instead under pseudo-first-order
Eur. J. Org. Chem. 1998, 1867Ϫ1872
1869

P. De Maria, A. Fontana, G. Siani, D. Spinelli
FULL PAPER
conditions[3a][3b][3c] as rates of bromination and the rate law Table 5. Metal-ion catalysed enolisation of some acetyl heterocycles
and acetophenone
was given by Eq. (6) where S refers to the substrate (2AS,
3AF, 2-[D3]acetylthiophene, 3-[D3]acetylthiophene, 2-[D3]a-
cetylselenophene, and [D3]acetophenone).
Ϫd[OBrϪ]/dt ϭ ke[S]
(6)
The second-order rate constants, kOH, obtained from Eq.
(7) are reported in Table 1.
ke ϭ ko ϩ kOH[OHϪ]
(7)
Experimental ke values were obtained in a range of hy-
droxide concentration 5Ϫ25·10Ϫ2 mol dmϪ3 for 2AS,
2-[D3]acetylthiophene
and
3-[D3]acetylthiophene,
2.5Ϫ25·10Ϫ2 mol dmϪ3 for 3AF, 2.5Ϫ49·10Ϫ2 mol dmϪ3 for
2-[D3]acetylselenophene and 5Ϫ20·10Ϫ2 mol dmϪ3 for
[D3]acetophenone. In the case of 2-[D3]acetylselenophene
the ionic strenght at [NaOH] ϭ 0.40 and 0.49 was 0.50 mol
dmϪ3. Experimental ke values agree with ke values calcu-
lated from Eq. (7) to within 5%.
Metal Ion Catalysed Enolisation of 2AS and 3AF
The effect of Zn2ϩ, Ni2ϩ, and Cu2ϩ on the rates of enoli-
sation of the two ketones was studied in unbuffered solu-
tions (pH in the range 4Ϫ6). Substrate concentrations were
ca. 10Ϫ2 mol dmϪ3 and the concentrations of I2 and IϪ were
the same[3a][3b][3c] as those for reactions carried out in the
absence of metal ions. Ionic strength was 0.3 mol dmϪ3 for
all reactions (KCl). Rates were measured at several metal
ion concentrations in the range 2.5Ϫ75·10Ϫ3 mol dmϪ3. In
the case of Cu2ϩ the concentration range 0.25Ϫ7.5·10Ϫ3
mol dmϪ3 was chosen instead, in order to avoid precipi-
tation of CuI2. Values of ke showed a linear increase with
increasing metal ion concentration according to Eq. (8),
[a]
[b]
[c]
See ref.[3b]. Ϫ See ref.[3a]. Ϫ See ref.[3c]
.
where [M2ϩ] represents the molar concentration of Zn2ϩ
,
ported values vary from Ϫ0.51 to ϩ0.20 over the substitu-
ent range examined, probably due to the different possibi-
lity of H-bonding interaction in the neutral or the anionic
Ni2ϩ, or Cu2ϩ
.
ke ϭ ko ϩ kM[M2ϩ
]
(8)
form of substituted pyrrole-2-carboxylic acids[7]
.
There was no evidence of saturation even at the highest
used metal ion concentration, at variance with the behav-
For 3-acetylheterocycles this electronegativity effect on
kH is apparently more than offset by the fact that five-mem-
bered acetyl heterocycles possess π-excessive rings; thus,
they are more reactive than acetophenone in the H3Oϩ-cat-
alysed reaction. As an average kH values for 3-acetyl hetero-
cycles are about a factor of four higher than those for the
iour previously observed with more basic substrates[2][3d]
The results are collected in Table 5.
.
Discussion
Kinetic results for the “spontaneous” and acidϪbase-cat- corresponding 2-acetyl heterocycles.
alysed enolisation reactions of some 2- and 3-acetyl-substi-
On the other hand the results for the “spontaneous” and
tuted five-membered heterocycles and acetophenone are the base-catalysed reactions can hardly be explained simply
summarized in Table 1 (where acetate ion is taken as a typi- in terms of either effect, as previously pointed out[3c]
cal general base useful for comparison).
.
Brønsted β values and isotope effects for the OHϪ-cata-
It can be seen that in the H3Oϩ-catalysed reaction (kH) lysed reaction of 2- and 3-acetylthiophene, 2-acetylseleno-
2-acetyl heterocycles are less reactive than acetophenone phene, 3-acetyl-2,5-dimethylfuran, and acetophenone are
and this can probably be simply accounted for in terms of reported in Table 6. In spite of the similar reactivity of ace-
the electronegativity of the heteroatoms, as the accepted en- tophenone and acetyl heterocycles (Table 1 and 4) it ap-
olisation mechanism[6] involves, in its first step, a fast pro- pears that the structures of the corresponding transition
tonation of the carbonyl oxygen atom with subsequent rate- states in base-catalysed reactions are quite different. Both
determining CϪH ionisation being assisted by water or the β values and isotope effects point to a considerably more
conjugate base of the acid catalyst. In fact positive σ values symmetrical[6] transition state for the investigated acetyl
are reported for the 2-furyl (σ ϭ 1.10[7]), 2-thienyl (σ ϭ heterocycles than that for acetophenone. The different ρ
0.66[7]), and 2-selenyl (σ ϭ 0.60[7]) groups. A reliable σ values[8] for the OHϪ-catalysed reaction of 4- and 5-substi-
value for the 2-pyrrolyl group cannot be taken, as the re- tuted 2-acetylthiophenes (ρ ϭ 1.61) and of m- and p-substi-
1870
Eur. J. Org. Chem. 1998, 1867Ϫ1872

Kinetics of the Enolisation Reactions of 3-Acetyl-2,5-dimethylfuran
FULL PAPER
kZn (2AT) ϭ 2.09·10Ϫ7 kZn (2AS) ϭ 14.7·10Ϫ7 dm3 molϪ1 sϪ1
tuted acetophenones (ρ ϭ 1.03), was attributed to a su-
perior capability of the former to transmit the substituent
effects.
However, MAF values are probably a better indication
than kM of the “hard and soft” character of the carbonyl
groups of the substrates under discussion and the related
effectiveness of metal-ion catalysis, as mentioned in the In-
troduction. From the present and the previously obtained
results acetophenone and the so far investigated acetyl het-
erocycles can be ranked in the group shown in Scheme 1,
according to their MAF values (See Table 7).
Table 6. Brønsted β coefficients and deuterium isotope effects in
the base-catalysed reaction of some acetyl heterocycles and aceto-
phenone
Scheme 1
Table 7. MAF values for some acetyl heterocycles and acetophe-
none
2AF 3AT
A
2AT 2AS 3AF 2APH 3AP
Cu2ϩ 0.0
0.012 0.028 0.059 0.32 0.54 20
740
[a]
M. Aurelly, G. Lamaty, Bull. Soc. Chim. Fr. 1980, 385Ϫ388.
Zn2ϩ
Ref.
0.011 0.016 0.032 0.053 0.49 0.19 1.3
3.0
[a]
[b]
[b]
[b]
[c]
[a]
this this
work work
The efficiency of metal-ion catalysis in the enolisation re-
action can probably be rationalised in terms of “hard and
soft”[9] carbonyl groups. Hardness and softness are not as
precisely defined as the strenghts of acids and bases and
there is no convenient measurement in common use ana-
logous to pKa. However, the development of frontier orbital
theory has allowed hardness and softness to be described
more satisfactorily. Soft bases have high-energy HOMOs
and soft acids have low-energy LUMOs and this explains
why soft acids and soft bases have an affinity with each
other. On the other hand what is important in the interac-
tion of a hard base with a hard acid is the electrostatic
attraction between the two species. MAF values can be
taken as an empirical probe of hard-soft interactions in the
reaction under examination. The investigated ketones can
therefore be distinguished[3d] depending upon their exper-
imental MAFs. Accordingly, the carbonyl groups of ketones
with MAF values << 1 can be defined “hard” while those
with MAF values Ն 1 can be defined “soft” with respect to
[a]
[b]
[c]
See ref.[3b]. Ϫ See ref.[3a]. Ϫ See ref.[3c]
.
It can be concluded that the acetyl groups of 2AS and
3AF behave quite similarly towards metal-ion catalysis, due
to a similar “borderline” character of their carbonyl groups.
We wish to thank CNR and MURST (Rome) for financial sup-
port.
Experimental Section
General: UV/Vis: Varian Cary 1E, Kontron Uvikon 860 spectro-
photometer equipped with a Hi-tech rapid kinetic accessory for the
faster reactions. Ϫ NMR: Varian Gemini 300 MHz. TMS was used
as internal standard, CD3CN and CDCl3 as solvents.
Materials: All inorganic salts [KCl, NaClO4, KI, NaBr, ZnCl2,
CdCl2, NiCl2, Cu(NO3)2] and halogens (I2 and Br2) were samples
of AnalaR grade (Aldrich, Merck, or Carlo Erba) and were used
without further purification.
some specified “borderline” (Cu2ϩ, Ni2ϩ, Zn2ϩ [10]
acids.
)
Lewis
3-Acetyl-2,5-dimethylfuran (3AF): This was a commercial sample
(Aldrich), purified by distillation under reduced pressure.
As far as the presently investigated acetyl heterocycles,
2AS and 3AF, are concerned it is interesting to note that
they both display substantial catalysis by the above-men-
tioned metal ions. An examination of kM values (Table 5)
shows that, for example, the enolisation of 3AF is much
more effectively promoted by Cu2ϩ and Zn2ϩ than that of
2-Acetylselenophene (2AS): This compound was prepared by es-
sentially the same procedure described in ref.[11a] for the synthesis
of 2-acetylthiophene. The procedure was slightly modified in order
to use a smaller quantity of the expensive selenophene (Aldrich).
Selenophene (5 g, 0.038 mol) and acetic anhydride (4.36 g, 0.043
mol) were stirred toghether and heated to 50°C. Orthophosphoric
acid (0.18 g, 0.0018 mol) was added in one portion and the mixture
warmed at 80Ϫ90°C for 2 h. The mixture was then cooled to room
temperature and washed three times with water and then with
aqueous Na2CO3 (10%, w/w). Diethyl ether (few milliliters) was
added to the water-insoluble organic material. The ethereal layer
was dried with sodium sulphate and the recovered oil distilled un-
der reduced pressure. Ϫ 1H NMR (CD3CN): δ ϭ 8.52 (1 H, dd,
J3,5 ϭ 1.07 Hz, J4,5 ϭ 5.47 Hz, 5-H), 8.05 (1 H, dd, J3,5 ϭ 1.07,
the structurally related 2AF[3b]
.
kCu (2AF) no catalysis observed kCu (3AF) ϭ 7.92·10Ϫ6 dm3
molϪ1 sϪ1
kZn (2AF) ϭ 3.56·10Ϫ8
kZn (3AF) ϭ 2.81·10Ϫ6 dm3 molϪ1 sϪ1
Metal-ion catalysis is somewhat more effective on 2AS
than on its sulfur analogue 2AT.
kCu (2AT) ϭ 2.35·10Ϫ7 kCu (2AS) ϭ 9.46·10Ϫ7 dm3 molϪ1 sϪ1
J3,4 ϭ 4.00, 3-H), 7.49 (1 H, dd, J3,4 ϭ 3.93, J4,5 ϭ 5.47, 4-H), 2.59
Eur. J. Org. Chem. 1998, 1867Ϫ1872
1871

P. De Maria, A. Fontana, G. Siani, D. Spinelli
FULL PAPER
[1] [1a]
[1b]
1
K. J. Pedersen, Acta Chem. Scand. 1948, 2, 252Ϫ263. Ϫ
(3 H, s, CH3). Ϫ H NMR (CDCl3): δ ϭ 8.38 (1 H, dd, J3,5 1.06,
K. J. Pedersen, Acta Chem. Scand. 1948, 2, 385Ϫ399.
B. G. Cox, J. Am. Chem. Soc. 1974, 96, 6823Ϫ6828.
J4,5 5.60, 5-H), 7.91 (1 H, dd, J3,5 1.06, J3,4 3.97, 3-H), 7.40 (1 H,
dd, J3,4 4.03, J4,5 5.49, 4-H), 2.59 (3 H, s, CH3). Ϫ 13C NMR
(CD3CN): δ ϭ 191.89 (CϭO), 151.28 (C-2), 140.08 (C-5), 135.58
(C-3), 131.07 (C-4), 25.33 (CH3). Ϫ The identity of the product
was confirmed by the fact that the recorded 1H- and 13C-NMR
spectra are essentially coincident with those reported[11b] in [D6]-
acetone.
[2]
[3] [3a]
P. De Maria, A. Fontana, D. Spinelli, J. Chem. Soc., Perkin
[3b]
Trans. 2 1991, 1067Ϫ1070. Ϫ
P. De Maria, A. Fontana, S.
Frascari, F. Ferroni, D. Spinelli, J. Chem. Soc., Perkin Trans. 2
[3c]
1992, 825Ϫ828. Ϫ
P. De Maria, A. Fontana M. Arlotta,
S. Chimichi, D. Spinelli, J. Chem. Soc., Perkin Trans. 2 1994,
415Ϫ419. Ϫ [3d] P. De Maria, A. Fontana, D. Spinelli, G. Maca-
luso, Gazz. Chim. Ital. 1996, 126, 1996, 45Ϫ51.
[4]
S. Shambayati, S. L. Schreiber, in Comprehensive Organic Syn-
thesis (Eds.: B. Trost, J. Fleming), Pergamon Press, Cambridge,
1991, part 1, vol. 1, pp. 283Ϫ324.
Deuteration Procedure: 2-Acetylselenophene (2AS) (1 g, 0.0058
mol), 2-acetylthiophene (2AT) (2 g, 0.0159 mol), 3-acetylthiophene
(3AT) (2 g, 0.0159 mol), and acetophenone (A) (2 g, 0.0167 mol)
were separately dissolved in a small volume (ca. 2 ml) of dioxane,
a pellet of NaOH was added to each ketone followed by deuterium
oxide (5 ml), and each mixture was kept in a sealed tube for up to
24 h at room temperature. Extraction with diethyl ether gave the
deuterated products that were purified by distillation under reduced
[5]
[6]
M. J. Hynes, C. A. Blanco, M. T. Mooney, J. Chem. Soc., Perkin
Trans. 2 1991, 2055Ϫ2059 and refs. cited herein.
R. P. Bell, The Proton in Chemistry, 2nd ed., Chapman and
Hall, London, 1973.
P. Tomasik, C. D. Johnson, Adv. Heterocycl. Chem. 1976, 20,
1Ϫ64 and refs. cited herein.
[7]
[8]
J. R. Jones, G. Pearson, D. Spinelli, G. Consiglio, C. Arnone, J.
Chem. Soc., Perkin Trans. 2 1985, 557Ϫ558.
1
pressure. H-NMR spectra of the deuterated compounds were re-
[9]
G. Pearson, Hard and Soft Acids and Bases Principle in Organic
Chemistry, Academic Press, New York, 1977.
corded and the acetyl group turned out to be more than 98% deu-
terated in all cases.
[10]
A. Jacobs, Understanding Organic Reaction Mechanisms, Cam-
bridge University Press, Cambridge, 1997, chapter 2, p. 39.
Kinetic Measurements: The enolisation reactions were monitored
by measuring spectrophotometrically the rate of halogenation of
the substrates as previously described[3a][3b][3c]. All kinetic measure-
ments were made at 25.0 ± 0.1°C and with an ionic strenght of 0.3
mol dmϪ3 (KCl or NaClO4) unless otherwise stated.
[11] [11a]
H. D. Hartough, A. I. Kosak, J. Amer. Chem. Soc. 1947,
[11b]
69, 3093Ϫ3096. Ϫ
F. Fringuelli, S. Gronowitz, A.-B.
Hornfeldt, I. Johnson, A. Taticchi, Acta Chem. Scand., Ser. B
1974, 28, 175Ϫ184.
[98107]
1872
Eur. J. Org. Chem. 1998, 1867Ϫ1872