Organic Syntheses, CV 7, 470
Submitted by Adolf Thalmann, Konrad Oertle, and Hans Gerlach
1.
Checked by James R. Pribish and Edwin Vedejs.
1. Procedure
A.
Ricinelaidic acid.
Ricinoleic acid (Note 1) (39.75 g, 0.106 mol) and
586 mg (2 mol %) of diphenyl disulfide dissolved in
1000 mL of hexane are placed in a
photochemical reactor (Note
2) and irradiated for 3 hr with a
Philips HP(L) 250-W medium-pressure mercury lamp. After irradiation the solvent is removed under reduced pressure and the semisolid residue is recrystallized from
185 mL of hexane to yield
11.3 g of crude
ricinelaidic acid, mp
39–43°C. The irradiation is repeated with the mother liquor under the same conditions to yield, after removal of the solvent and recrystallization of the residue from
135 mL of hexane, an additional
7.2 g, mp
38–42°C; total yield of crude
ricinelaidic acid is
18.5 g (
58%). The product after recrystallization from
220 mL of hexane weighs
15.6 g (
49%), mp
43–45°C, and is suitable for the following step. Repeated recrystallization from
hexane yields
ricinelaidic acid with mp
51.0–51.5°C (Note
3) and (Note
4).
C.
Ricinelaidic acid lactone. Dry
acetonitrile (100 mL),
3.5 mL of 1 M silver perchlorate in
toluene (Note
7) and (Note
8), and a magnetic stirring bar are placed in a
500-mL flask equipped with a reflux condenser that carries a Hershberg dropping funnel. The solution is heated in an
oil bath so that the boiling
acetonitrile returns from the condenser at the rate of 5–10 drops per second (Note
9). Then the
acetonitrile solution of the
ricinelaidic acid S-(2-pyridyl)carbothioate is added dropwise during 1 hr through the condenser to the magnetically stirred refluxing
silver perchlorate solution (Note
9). The slightly turbid mixture is boiled for an additional 15 min and the solvent is removed under reduced pressure in a
rotary evaporator. The residue is diluted with
30 mL of 0.5 M potassium cyanide solution and the mixture containing suspended solids is extracted with three
50-mL portions of benzene. The
benzene extracts are washed with 30 mL of water, dried with anhydrous
magnesium sulfate, and filtered, and the solvent is removed under reduced pressure. Crude product is obtained as an oil (
710 mg). It can be purified by chromatography on 40 g of
silica gel (Note
10) with
benzene as eluant. Fractions of 10 mL are collected at 30-min intervals. Fractions 7–19 contain
283–296 mg (
84–88%) of
ricinelaidic acid lactone (Note
11).
2. Notes
1.
Technical-grade (80%) ricinoleic acid was obtained from Fluka AG Buchs, Switzerland or from Tridom Chemicals, Inc. Saponification of
methyl ricinoleate2 also gives suitable material.
3. The purity of the products has been checked by capillary gas liquid chromatography of the corresponding methyl ester obtained with ethereal
diazomethane solution (Carlo Erba Fractovap 20-m glass capillary coated with UCON HB at 160°C).
Ricinelaidic acid, mp
49–50°C, contains 4%, that with mp
51.0–51.5°C, less than
1% of ricinoleic acid. Submitters obtained higher yields (
58%, mp
49–50°C), perhaps due to better quality starting material.
5.
2,2'-Dipyridyl disulfide obtained from Fluka AG, Buchs, Switzerland, was recrystallized from
hexane (30 mL/g) to yield a suitable product, mp
58–59°C.
7.
Silver perchlorate monohydrate (9 g) (obtained from Fluka AG) is suspended in
110 mL of toluene together with a
Teflon-coated magnetic stirring bar. The solution is magnetically stirred and heated in an oil bath until
70 mL of toluene has distilled.
9. This reflux rate is crucial for predilution of the carbothioate in the condenser. Lower reflux rates require an accordingly slower addition of the
S-(2-pyridyl)carbothioate during 2–4 hr.
10. Silica gel 60 Merck in a 2.5-cm-diameter column was used.
11. The product distills at 110°C (0.01 mm) in a
Kugelrohr distillation apparatus and has an optical rotation of
[α]D +42° (CHCl
3,
c 1).
3. Discussion
The silver ion-promoted lactonization of hydroxy-
S-(2-pyridyl)carbothioates was introduced by the submitters
3 as a mild method for the synthesis of naturally occurring macrolides as, for example, nonactin
4 and recifeiolide
5 from the corresponding hydroxy acids. If the method of Mukaiyama et al.
6 is used for the formation of the
S-(2-pyridyl)carbothioate, no protection of the hydroxyl group is needed in this step. The cited examples show that silver ion-promoted lactonization can be used to effect ring closure of base-sensitive and unsaturated acid-sensitive hydroxy acids in good yield.
Similar methods to effect lactonization have been proposed by Corey et al.
7 and Masamune et al.
8 The first consists of prolonged heating of hydroxy-
S-(2-pyridyl)carbothioates in boiling
xylene; the second is the mercury trifluoroacetate-promoted cyclization of a
hydroxy-S-tert-butyl carbothioate.
Ricinelaidic acid was selected for the submitted procedure because it has a moderately complex structure and can be prepared easily from commercially available
technical grade ricinoleic acid. This conversion represents an example of the facile cis–trans interconversion of olefins
9 caused by photochemically generated phenylthiyl radicals leading to the thermodynamic equilibrium.
This preparation is referenced from:
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