Organic Syntheses, CV 7, 105
Submitted by Attilio Citterio
Checked by Robert Haessig, Leo Widler, and Dieter Seebach.
1. Procedure
Caution! Like all vinyl monomers, 3-buten-2-one is toxic and the preparation should be carried out in a well-ventilated hood.
A
500-mL, four-necked, round-bottomed flask equipped with a
magnetic stirring bar, a
thermometer, a
gas inlet, an
externally cooled, pressure-equalizing dropping funnel (Note
1), and a
gas bubbler is charged with
15% aqueous titanium trichloride (92 mL, 0.109 mol) (Note
2).
N,N-Dimethylformamide (Note 3) (70 mL) is added during 45 min with stirring and cooling (ice-bath; 0–5°C) while
nitrogen is bubbled through the solution. Freshly distilled
3-buten-2-one (5.7 mL, 0.066 mol) is added at 0–5°C by syringe. The
nitrogen flow is stopped, and
4-chlorobenzenediazonium chloride solution (0.044 mol) (Note
4) is added dropwise at 0–5°C from the dropping funnel. After 2–3 min,
nitrogen evolution commences, and the rate of addition is adjusted so that 1–2 bubbles per second are vented through the bubbler.
Nitrogen evolution continues for 20 min after the addition is complete (1.5 hr). The
ice bath is removed and the solution stirred for 1 hr at room temperature.
Ether, 50 mL, is added with stirring, and the organic phase is separated. The aqueous phase is extracted with
ether (3 × 50 mL) and the combined organic extracts are washed with
3% aqueous Na2CO3 (2 × 30 mL) and water, dried over
magnesium sulfate, and concentrated under reduced pressure. The residue is distilled to give
5.2–6.0 g (
65–75% yield) of
4-(4-chlorophenyl)butan-2-one as a pale-yellow liquid, bp
90–91°C (0.5 mm) (Note
5).
2. Notes
1. The checkers used a dropping funnel with temperature-control jacket [Normag N 8055, Otto Fritz GmbH, Normschliff-Aufbaugeräte (Normag), D-6238 Hofheim am Taunus].
5. The physical properties of the product are as follows:
nD25 1.5251; IR (liquid film) cm
−1: 1715;
1H NMR (CDCl
3) δ: 2.0 (s, 3 H), 2.6–2.8 (m, 4 H), 6.8–7.3 (m, 4 H); mass spectrum
m/e: 182 (M);
semicarbazone, mp
165°C (164–165.5°C
2). GLC analysis (
glass capillary column, 20 m, pluronic L-64, program: 120–200°C at 5°C/min): >99% pure.
3. Discussion
This synthesis is only one example of a wide range of reactions that involve aryl (or alkyl) radical addition to electron-deficient double bonds resulting in reduction.
3,4,5 The corresponding oxidative reaction using aryl radicals is the well-known Meerwein reaction,
6 which uses copper(II) salts.
General arylation reactions are summarized by the following equations and some specific examples are presented in Table I.
Homolytic cleavage of diazonium salts to produce aryl radicals is induced by titanium(III) salt, which is also effective in reducing the α-carbonylalkyl radical adduct to olefins, telomerization of
methyl vinyl ketone, and dimerization of the adduct radicals. The reaction can be used with other electron-deficient olefins, but telomerization or dimerization are important side reactions.
Other limitations of the reaction are related to the regioselectivity of the aryl radical addition to double bond, which is determined mainly by steric and radical delocalization effects.
7 Thus,
methyl vinyl ketone gives the best results, and lower yields are observed when bulky substituents are present in the β-position of the alkene. However, the method represents complete positional selectivity because only the β-adduct radicals give reductive arylation products whereas the α-adduct radicals add to diazonium salts, because of the different nucleophilic character of the alkyl radical adduct.
7,8
TABLE I
REDUCTIVE ARYLATION OF ELECTRON-DEFICIENT OLEFINS BY ARENEDIAZONIUM SALTS INDUCED BY TITANIUM(III) SALTS
|
|
|
|
X |
R |
R' |
Y |
Yield (%)a |
|
4-OCH3 |
H |
H |
COCH3 |
65 |
H |
H |
H |
COCH3 |
75 |
4-Br |
H |
H |
COCH3 |
68 |
4-COCH3 |
H |
H |
COCH3 |
72 |
4-Cl |
H |
H |
CHO |
63 |
4-Cl |
CH3 |
H |
COCH3 |
44 |
4-Cl |
CH(CH3)2 |
H |
COCH3 |
28 |
4-Cl |
C(CH3)3 |
H |
COCH3 |
14 |
4-Cl |
CH3 |
CH3 |
COCH3 |
12 |
4-Cl |
Ph |
H |
COCH3 |
18 |
4-Cl |
H |
H |
CN |
25b |
4-Cl |
H |
H |
COOH |
33b |
4-Cl |
H |
H |
COOEt |
32b |
|
a From the diazonium salt.
|
b Telomers are formed; the reactions are carried out with twice the amount of titanium(III) salt.
|
13
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