Organic Syntheses, CV 8, 498
Submitted by Tamotsu Fujisawa and Toshio Sato
1.
Checked by Cynthia Smith and Andrew S. Kende.
1. Procedure
Caution!
Oxalyl chloride is toxic. This preparation should be carried out in a
well-ventilated hood.
A.
N,N-Dimethylchloromethylenammonium chloride. A
500-mL, three-necked, round-bottomed flask is equipped with a
magnetic stirring bar, a
thermometer (Note
1), and a
three-way stopcock fitted with a
drying tube containing anhydrous calcium chloride and a
rubber septum. The flask is charged with
50 mL of dichloromethane (Note
2) and
3.07 (0.042 mol) of N,N-dimethylformamide (Note
3) added through the septum from a syringe, and cooled in an
ice bath. To the cooled mixture is slowly added
5.23 mL (0.06 mol) of oxalyl chloride (Note
4) by means of a syringe. The addition is accompanied by gas evolution and formation of a white precipitate. The reaction mixture is stirred for an additional hour at 0°C. Excess
oxalyl chloride and solvent are removed under reduced pressure by first using a
water aspirator and then a
rotary pump at room temperature through the drying tube. The white solid remaining in the flask is
N,N-dimethylchloromethylenammonium chloride, which is used directly in Part B.
B.
6-Oxodecanal. The drying tube is removed and the flask is flushed with
nitrogen. A
nitrogen atmosphere is maintained throughout the subsequent reaction. A
dropping funnel is attached and charged with
7.45 g (0.04 mol) of 6-oxodecanoic acid (Note
5),
3.32 g of pyridine (Note
6), and
80 mL of tetrahydrofuran (Note
7), which are mixed well by shaking. The flask is charged with
45 mL of acetonitrile (Note
8) and
80 mL of tetrahydrofuran and cooled (
methanol–liquid
nitrogen) to −30°C. The contents of the funnel are added to the flask at −30°C over 30 min. The reaction mixture is stirred at −30°C for an additional hour and at −20°C for 30 min. After the mixture is cooled to −90°C (Note
9),
34 mL (0.046 mol) of a 1.35 M solution of lithium tri(tert-butoxy)aluminum hydride in tetrahydrofuran (Note
10) is injected through the septum by means of a syringe over 30 min, while the internal temperature is kept below −85°C. Stirring is continued for an additional 30 min at −90°C. To the flask is added
50 mL of 2 M hydrochloric acid solution, and the cooling bath is immediately removed. The organic layer is separated and the aqueous layer is extracted with three
50-mL portions of ether. The combined organic extracts are washed with two
50-mL portions of saturated sodium hydrogen carbonate solution and
50 mL of brine, dried over anhydrous
sodium sulfate, and filtered. The solvent is removed with a
rotary evaporator and the residual liquid is distilled under reduced pressure to yield
5.78–6.35 g (
85–93%) of
6-oxodecanal as a fragrant liquid, bp
85–90°C (1.4 mm) (Note
11).
2. Notes
1. The thermometer must be able to measure temperatures as low as −90°C.
3.
N,N-Dimethylformamide was distilled under reduced pressure, bp
45–47°C (20 mm), and stored over Linde 4A molecular sieves.
4.
Oxalyl chloride purchased from Wako Chemicals was used without purification. The checkers found that
oxalyl chloride, purchased from Aldrich Chemical Company, Inc., gives better yields if freshly distilled.
7.
Tetrahydrofuran was freshly distilled from the
sodium ketyl of benzophenone.
9. The checkers used a 1 : 1 methanol : ethanol/liquid nitrogen bath.
11. GLC analysis of the product using a 3-mm × 1-m stainless-steel column, 15% SE-30 on Chromosorb W (AW), 60–80 mesh, 150°C, 50 mL of
nitrogen per minute showed a purity of 99.2% (the retention times is 4.0 min). The spectral properties of the product are as follows: IR (liquid film) cm
−1: 2950, 2930, 2870, 2720, 1710, 1455, 1410, 1370;
1H NMR (60 MHz, CCl
4) δ: 0.87 (t, 3 H,
J = 7, CH
3), 1.1–1.9 (m. 8 H, CH
2), 2.1–2.6 (m, 6 H, CH
2C=O), 9.73 (t, 1 H,
J. = 1.4, H-C=O).
3. Discussion
Various reagents have been suggested for the conversion of carboxylic acids into aldehydes, such as modified aluminum hydride reagents,
4 Grignard reagents catalyzed by
dichlorobis(π-cyclopentadienyl)titanium,
5 lithium in methylamine,
6 and
boron hydride reagents.
7 However, these reagents have some drawbacks in availability, lack of chemoselectivity due to the high reactivity of the reagents, and isolation of products.
The present procedure, a modified one reported earlier by the submitters, illustrates a general method of aldehyde synthesis from carboxylic acids in a one-pot operation using the readily available,
N,N-dimethylchloromethylenammonium chloride.
8 Strong activation of carboxylic acids by the iminium salt via the carboxymethylenammonium salt
9 and a weak reducing reagent,
lithium tri(tert-butoxy)aluminum hydride, achieve the chemoselective reduction of carboxylic acids to aldehydes. The present procedure has several advantages: (a) easy availability of the reagents; (b) use of a slight excess of the hydride reagent; (c) high yields of both aliphatic and aromatic aldehydes; (d) high chemoselectivity, which tolerates nitrile, ester, halide, olefin, and even ketone; and (e) easy isolation of the product.
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