A catalyst-free synthesis of asymmetric diaryl ketones from aryltins

Article abstract of DOI:10.1016/j.jorganchem.2005.12.027

A series of diaryl ketones have been synthesized in good yields (40-78%) through the catalyst-free reaction of trimethylarylstannanes with aroyl chlorides in chlorobenzene as solvent. In addition, an attractive feature is that these reactions are completely regioselective making possible the synthesis of diarylketones which are not usually available under the influence of the directing forces of the substituents present in the aromatic ring. Also, the reaction conditions are mild enough to be applied to acid sensitive molecules.

Full text of DOI:10.1016/j.jorganchem.2005.12.027

Journal of Organometallic Chemistry 691 (2006) 1520–1524
www.elsevier.com/locate/jorganchem
Note
A catalyst-free synthesis of asymmetric diaryl ketones from aryltins
,1
*
*
´
Gustavo F. Silbestri, Romina Bogel Masson, Marıa T. Lockhart , Alicia B. Chopa
INIQO, Departamento de Quı´mica, Universidad Nacional del Sur, Avda. Alem 1253, 8000 Bahı´a Blanca, Argentina
Received 8 December 2005; accepted 8 December 2005
Available online 19 January 2006
Abstract
A series of diaryl ketones have been synthesized in good yields (40–78%) through the catalyst-free reaction of trimethylarylstannanes
with aroyl chlorides in chlorobenzene as solvent. In addition, an attractive feature is that these reactions are completely regioselective
making possible the synthesis of diarylketones which are not usually available under the influence of the directing forces of the substit-
uents present in the aromatic ring. Also, the reaction conditions are mild enough to be applied to acid sensitive molecules.
Ó 2005 Elsevier B.V. All rights reserved.
Keywords: Aryltin; Diarylketones; Aromatic acylation
1. Introduction
based on the exceptional leaving group ability of the trim-
ethylstannyl group in electrophilic aromatic substitutions.
The acylation of aromatic systems is an important reac-
tion in organic synthesis. Thus, a large number of related
literature references have appeared since the first Friedel–
Crafts reaction [1].
2. Results and discussion
We synthesized a series of electronically diverse starting
aryltrimethylstannanes (1–8, 60–100%) by reaction of
either the corresponding trimethylarylammonium salts
[6a] or diethyl aryl phosphates [6b] with trimethyltin anion
in liquid ammonia. These routes of synthesis have two
advantages: they allow the presence of sensitive substitu-
ents on the aromatic ring and the arylstannanes were
obtained in very good global yields starting from economic
and commercially available phenols or anilines, as is shown
in Scheme 1.
Organometallics are interesting starting materials for the
synthesis of aromatic ketones and numerous efficient meth-
ods have been described in the last years [2]. Among them,
the reaction of organotin compounds with acid chlorides
have been widely used either in reactions catalyzed by
Lewis acids [3] or in Pd-catalyzed cross-coupling reactions
[4]. Although these reactions are efficient methods to form
ketones in good yields, there are some disadvantages
related with them. Thus, whereas in the first case the cata-
lyst used cannot be easily recovered and a large amount of
toxic waste is generated, in the latter case, although Pd cat-
alysts could be recovered, it is usually necessary to find the
appropriate catalytic protocol for each pair of reactants.
Continuing with our studies related with the application
of arylstannanes as intermediates in organic synthesis [5],
we wish now to report a catalyst-free route to diarylketones
The reaction of these arylstannanes with aroyl chlorides
were carried out in chlorobenzene as solvent, at 130 °C.
The general scheme of Eq. (1) applies for all the reactions
studied:
ArCOCl
Ar0SnMe3 ! ArCOAr0 þ Me3SnCl
ð1Þ
C6H5Cl
130 ꢀC
The results obtained are summarized in Table 1. All the
yields given are of isolated products by column chromatog-
raphy (Silica gel).
*
Corresponding authors. Fax: +54 291 4595187.
E-mail address: abchopa@uns.edu.ar (A.B. Chopa).
Member of CIC.
1
0022-328X/$ - see front matter Ó 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2005.12.027

G.F. Silbestri et al. / Journal of Organometallic Chemistry 691 (2006) 1520–1524
1521
As seen from Table 1, arylstannane 1 reacted with
benzoyl- and naphtoyl chloride in 60 h rendering the
diarylketones 10 [7] and 11 in good yields (65% and
60%, respectively) (entries 1 and 2). Similar reactions car-
ried out with arylstannanes 2–4 proceeded efficiently
giving diarylketones 12 (78%), 13 (68%), 14 (65%) and
15 (70%) [7] (entries 3–6). It should be mentioned that
the reaction conditions are mild enough to be applied
to acid sensitive molecules such as 5, leading to the cor-
responding ketone 16 (40%, 20 h), the protecting group
remaining unchanged (entry 7) [8]. However, longer reac-
tion times (40 h) led to 16 together with considerable
amounts of secondary products that make difficult its
purification.
ArNH
ArOH
2
a
(75-98%)
b
(70-89%)
+
-
ArN Me , X
3
ArDEP
c
c
ArSnMe
3
(60-100%)
(a) MeI (or Me2SO4) 2,6-Lutidine, DMF, r.t.; (b)
HP(O)(OEt)2, NEt3, CCl4, r.t.; (c) Me3Sn-Na+, NH3 (l),
hν.
Scheme 1.
Table 1
Reaction of trimethylaryltin compounds with aroyl chloridesa
Entry
1
ArSnMe3
Aroyl chlorides
Product
Time (h)
60
Yield (%)b
65
SnMe
O
O
3
Cl
1
10
2
3
60
40
60
78
SnMe
O
O
3
Cl
11
O
O
O
O
SnMe
Cl
3
2
12
4
5
6
7
65
90
60
20
68
65
70
O
O
O
SnMe
3
O
Cl
3
13
O
O
O
SnMe
SnMe
3
O
Cl
14
O
O
3
Cl
O
4
O
15
40
SnMe
O
O
3
Cl
THPO
5
THPO
16
(continued on next page)

1522
G.F. Silbestri et al. / Journal of Organometallic Chemistry 691 (2006) 1520–1524
Table 1 (continued)
Entry
8
ArSnMe3
Aroyl chlorides
Product
Time (h)
49
Yield (%)b
71
O
O
SnMe
3
Cl
6
17
O
9
50
90
64
30
O
SnMe
3
Cl
18
10
O
SnMe
I
O
3
I
Cl
7
19
11
90
90
90
52
58
64
SnMe
O
O
20
O
3
Cl
NC
NC
8
NC
NC
12
SnMe
O
3
Cl
21
13c
O
O
SnMe
3
Cl
Cl
O
O
22
a
b
c
Substrate:ArCOCl = 1:1.2.
Yields reported are based on isolated products.
Substrate:ArCOCl = 1:0.6.
The more sterically hindered arylstannane 6 also reacted
It should be mentioned that in all the experiments that
we have carried out, it has been detected the presence of
small amounts (not quantified) of ipso-protodestannylation
products, probably this being due to the presence of small
amounts of HCl that could not be eliminated from the
aroyl chloride. These protodestannylation products are
irrelevant compared with the yields of the diarylketones
obtained.
It is important to note that all the reactions studied were
regioselective and that they went, exclusively, through an
ipso-aroyldestannylation independently whether the direct-
ing influences of the aryl substituents and the trimethyl-
stannyl group are either matched (compounds 2, 4 and 5)
or mismatched (compounds 1, 3, 7 and 8). Even the known
high directing force of MeO group could be completely
overcompensated (compound 3).
in effect with aroyl chlorides giving ketones 17 and 18 in
good yields (71% and 64%, respectively) [9]. The results
obtained with both compounds 2 and 6 (higher yields
and lower reaction times) show that the electrophilic attack
of arylstannanes is accelerated by the existence of neigh-
boring groups on the arene system.
Arylstannanes 7 and 8 reacted with aroyl chlorides lead-
ing to the expected ketones in lower yields after longer
reaction times. Thus, ketones 19, 20 and 21 were obtained
in 30% (90 h), 52% (90 h) and 58% (90 h), respectively. The
decreased reactivity of these substrates is presumably due
to the presence of electron-withdrawing groups such as
iodine and nitrile, attached to the arene ring.
In addition, the reaction of arylstannane 6 with tereph-
thaloyl chloride led to diketone 22 in 64% yield. This result
enables us to say that this method could be also applied to
the synthesis of triaryl diketones.
The high ipso-directing force shown by the trimethyl-
stannyl group is probably due to the b-effect of the tin atom

G.F. Silbestri et al. / Journal of Organometallic Chemistry 691 (2006) 1520–1524
1523
which makes easier the cleavage of an aryl group from the
4. Experimental
tin via an electrophilic ipso-substitution [10].
The method proposed is a straightforward and conve-
nient route for the synthesis of unsymmetrical diaryl
ketones. Nevertheless, one disadvantage is the generation
of trimethyltin chloride (Eq. (1)) soluble in the aqueous
phase during the workup of the reaction. Because of the
environmental problems caused by the well known toxicity
of triorganotin residues, we considered really important to
trap the Me3SnCl generated. With this aim, the organotin
chloride is removed in ca. 80%, by filtration as the insoluble
trimethyltin fluoride (see Section 4).
The reactions were carried out under dry nitrogen using
standard Schlenk techniques and syringes. All acid chlo-
rides were commercially available and used as received
except benzoyl chloride which was fractionally distilled
under nitrogen before use. The aryltins were prepared
according to the literature methods [5,6]. Chlorobenzene
was dried by standard methods, distilled under dry nitro-
gen and stored over molecular sieves. The NMR spectra
1
were recorded on a Bruker ARX 300 (300.1 MHz for H,
75.5 MHz for 13C) using CDCl3 as solvent and SiMe4 as
internal reference. Mass spectra were obtained by use of
a GC/MS HP 6890.
3. Conclusions
4.1. Representative procedure for aroyldestannylation:
preparation of 3-methoxybenzophenone (13; Table 1, entry
4)
This paper reports a simple and direct route for the
selective synthesis of asymmetric diaryl ketones. The dom-
inant leaving characteristic of the trimethylstannyl group
overcompensate the directing forces of groups such as
Me, OMe, I, CN, making possible the aroylation of aro-
matic rings in otherwise not available positions under the
influence of these groups. The method proposed has the
advantage of enabling a high regioselective formation of
diaryl ketones without employing a catalyst. Moreover,
the reaction conditions are mild enough to be applied to
acid sensitive molecules.
Taking into account that the starting arylstannanes have
been synthesized in two steps from the corresponding phe-
nols or anilines, i.e., generation of the corresponding
diethyl aryl phosphates or trimethyl aryl ammonium salts,
respectively, and trimethylstannylation, the method pro-
posed allows the regioselective substitution of a hydroxy
or an amino group on an aromatic ring, rendering specific
diaryl ketones and triaryl diketones in good global yields.
Two examples are sketched in the following equations:
The reaction was carried out in a 25-mL one-necked
round-bottomed flask equipped with a Teflon valve. To a
stirred solution of 3-methoxyphenyl(trimethyl)stannane
(3, 0.271 g, 1.00 mmol) in chlorobenzene (0.5 mL) was
added benzoyl chloride (140 lL, 0.169 g, 1.20 mmol) dis-
solved in chlorobenzene (0.5 mL), dropwise. The reaction
solution was heated at 130 °C (oil bath) for 65 h (monitor-
ing the disappearance of the stannane by TLC). A few
drops of DMSO (100 lL) were added [11], the mixture
was diluted with dichloromethane (5 mL), stirred at r.t.
for a few minutes and washed successively with a saturated
solution of sodium carbonate, brine, and water, dried over
sodium sulphate and concentrated in vacuo. Column chro-
matography on silica gel (230–400 mesh) of the crude mix-
ture gave 0.144 g (68%) of 3-methoxyacetophenone (13)
(using a mixture of 5% ethyl acetate in hexane). Spectro-
scopic data see Ref. [12].
O
OH
MeO
DEP
MeO
SnMe
3
MeO
MeO
Ph
4.2. Disposal method for trimethyltin chloride
89%
90%
55%
68%
The aqueous solution (ꢁ15 mL for 1.0 mmol scale
reaction) was adjusted to ca. pH 1.0 with acid chloride
and then saturated with potassium fluoride. Diethyl ether
(10 mL) was added and the mixture was vigorously sha-
ken. The precipitated trimethyltin fluoride [13] (0.145 g,
79%) was removed by filtration at reduced pressure.
The amorphous solid obtained was stored for future
applications.
ð2Þ
O
NMe
NMe ,X
SnMe
3
2
3
Ph
98%
100%
52%
NC
NC
NC
NC
51%
ð3Þ
It is important to note that although we were able to re-
move organotin residues from final products we could
only trap 80% of the Me3SnCl generated during the reac-
tions. In order to decrease the level of pollution, we have
started the study of an alternative route to obtain diaryl
ketones using polymer-supported organotin reagents as
key intermediates. This strategy should combine the
advantages of the method described in this paper with
those expected from polymer-supported tin reagents. This
work is in progress.
Acknowledgements
This work was partially supported by the Consejo Nac-
ional de Investigaciones Cientıficas y Tecnicas (CONI-
CET), the Comision de Investigaciones Cientıficas de la
Provincia de Buenos Aires (CIC), the Fundacion Antor-
chas and the Universidad Nacional del Sur, Bahıa Blanca,
Argentina. CONICET is thanked for a research fellowship
to G.F.S.
´
´
´
´
´
´

1524
G.F. Silbestri et al. / Journal of Organometallic Chemistry 691 (2006) 1520–1524
(Caryl), 131.3 (Caryl), 130.8 (CHaryl), 128.4 (CHaryl), 128.5 (CHaryl), 127.3
References
(CHaryl), 127.2 (CHaryl), 126.8 (CHaryl), 125.8 (CHaryl), 124.7 (CHaryl),
121.8 (CHaryl), 117.8 (CHaryl), 113.4 (CHaryl), 54.5 (CH3); MS (m/z,
relative intensity): 262 (75, M+), 231 (14), 155 (100), 127 (75), 92 (11), 77
(21);
(g) Compound 16: 1H NMR: d 7.79–6.76 (m, 9H), 5.46 (m, 1H), 3.81 (m,
1H), 3.48 (m, 1H), 1.88–1.32 (m, 6H). 13C NMR: d 196.5 (Ccarbonyl),
170.0 (Caryl), 138.9 (Caryl), 138.7 (Caryl), 133.3 (CHaryl), 132.4 (CHaryl),
130.1 (CHaryl), 128.6 (CHaryl), 115.7 (CHaryl), 95.2 (CH), 63.4 (CH2),
31.1 (CH2), 25.8 (CH2), 20.1 (CH2);
[1] J. March, Advanced Organic Chemistry, third ed., Wiley, 1985.
[2] K. Dieter, Tetrahedron 55 (1999) 4177.
[3] W.P. Neumann, H. Hillga¨rtner, K.M. Baines, R. Dicke, K. Vorspohl,
U. Kowe, U. Nussbeutel, Tetrahedron 45 (1989) 951.
[4] J.W. Labadie, J.K. Stille, J. Am. Chem. Soc. 105 (1983) 6129.
[5] A.B. Chopa, G.F. Silbestri, M.T. Lockhart, J. Organomet. Chem.
690 (2005) 3865.
[6] (a) A.B. Chopa, M.T. Lockhart, G.F. Silbestri, Organometallics 20
(2001) 3358;
(b) A.B. Chopa, M.T. Lockhart, V.B. Dorn, Organometallics 21
(2002) 1425.
[7] Identified by comparison of spectroscopic data with those of the
commercial reagent.
[8] GLC analysis of 16 resulted in cleavage of the protecting group.
[9] In conventional electrophilic aromatic substitution reactions it is
difficult to effect substitution at a position between two methyl
substituents meta to each other.
[10] (a) C. Dallaire, M.A. Brook, Organometallics 12 (1993) 2332;
(b) C. Eaborn, K.C. Pande, J. Chem. Soc. (1960) 1566.
[11] The coordinating ability of DMSO competes with the ketone
improving the water solubility of trimethyltin chloride.
[12] Data for aryl ketones. For compound 11, see: (a) R. Kakino, S. Yasumi,
I. Shimizu, A. Yamamoto, Bull. Chem. Soc. Jpn. 75 (2002) 137;
(b) For compounds 12 and 13, see: L.A. Liebeskind, J. Srogl, J. Am.
Chem. Soc. 122 (2000) 11260;
(h) Compound 17: 1H NMR: d 7.71 (m, 2H), 7.45 (m, 1H), 7.32 (m, 2H),
7.11 (m, 1H), 6.95 (m, 2H), 2.00 (s, 6H). 13C NMR: d 200.7 (Ccarbonyl),
140.1 (Caryl), 137.5 (Caryl), 134.5 (Caryl), 134.0 (CHaryl), 129.8 (CHaryl),
129.3 (CHaryl), 129.1 (CHaryl), 128.0 (CHaryl), 19.7 (CH3). MS (m/z,
relative intensity): 210 (85, M+), 209 (100), 192 (38), 165 (16), 133 (50),
105 (64), 77 (88);
(i) Compound 18: 1H NMR: d 8.06 (m, 1H), 7.91 (m, 1H), 7.80–7.71 (m,
3H), 7.48–7.35 (m, 2H), 7.16 (m, 1H), 6.99 (m, 2H), 2.04 (s, 6H).13
C
NMR: d 200.7 (Ccarbonyl), 140.3 (Caryl), 136.4 (Caryl), 135.0 (Caryl), 134.8
(Caryl), 133.2 (Caryl), 132.4 (CHaryl), 130.2 (CHaryl), 129.3 (CHaryl),
129.22 (CHaryl), 129.20 (CHaryl), 128.3 (CHaryl), 128.1 (CHaryl), 127.21
(CHaryl), 124.6 (CHaryl), 19.8 (CH3); MS (m/z, relative intensity): 260
(100, M+), 259 (75), 242 (46), 228 (12), 215 (19), 155 (28), 127 (76), 105
(29), 77 (40);
1
(j) Compound 22: H NMR: d 7.78 (s, 4H), 7.18 (m, 2H), 6.99 (d, 4H,
3J(H,H) 7.4 Hz), 2.04 (s, 12H). 13C NMR: d 200.2 (Ccarbonyl), 140.9 (Caryl),
139.5 (Caryl), 134.6 (Caryl), 130.1 (CHaryl), 129.5 (CHaryl), 128.1 (CHaryl),
19.8 (CH3). MS (m/z, relative intensity): 342 (95, M+), 327 (12), 209
(100), 194 (27), 165 (18), 132 (90), 105 (59), 77 (30).
(c) For compound 19, see: G.A. Olah, Q. Wang, G. Sandford, G.K.
Surya Prakash, J. Org. Chem. 58 (1993) 3194;
[13] Organotin fluorides are relatively benign compounds. They are
high melting, nonvolatile, insoluble (in both organic solvents and
in water) and not easily absorbed through the skin, therefore the
risks of organotin fluorides are less than those of other
organotins: J.E. Leibner, J. Jacobus, J. Org. Chem. 44 (1979)
449.
(d) For compound 20, see: I. Kazmierski, M. Bastienne, C. Cosmini, J.-
´
M. Paris, J. Perichon, J. Org. Chem. 69 (2004) 936;
(e) For compound 21, see: J.H.P. Utley, G.G. Rozenberg, Tetrahedron
58 (2002) 5251;
(f) Compound 14: 1H NMR: d 8.24–7.01 (m, 11H); 3.78 (s, 3H). 13C
NMR: d 195.4 (Ccarbonyl), 158.7 (Caryl), 138.3 (Caryl), 134.3 (Caryl), 133.9