Synthesis of dill-apiole & tetraMeO-allylbenzene
(Rated as: excellent)
The following is taken from J. Chem. Soc. 2, 1934, p. 1681-1684 :
A convenient method for the preparation of 1,2-dihydroxy-3,4-dimethoxybenzene (I) in quantity has now been found in the oxidation of the accessible gallacetophenone 3,4-dimethyl ether with H2O2 in alkaline solution, and it has been used in the synthesis of dill-apiole in the following manner. Treatment with allyl bromide in acetone in presence of K2CO3 yielded a monallyl ether, which underwent molecular rearrangement on heating with production of 1,2-dihydroxy-3,4-dimethoxyallylbenzene (II) (uncharacterised) as the chief product. Since migration of an allyl group under these conditions always yields an o- or a p-hydroxyallylbenzene, the production of (II) probably means that the monoallyl ether is chiefly the 2-O-allyl ether. Methylenation of (II) with CH2I2 and anhydrous K2CO3 in acetone yielded directly almost pure dill-apiole (III), characterised by the formation of monobromodill-apiole dibromide, which was directly compared (mixed mp.) with a specimen prepared from natural dill-apiole. The allyl groups in these compounds cannot occupy position 6, since the final product would then be an isomeride of dill-apiole and not dill-apiole itself, the constitution of which was definitely established by the researches of Ciamician and Silber (Ber.,1896, 29, 1799) and Thoms (Arch. Pharm., 1904, 242, 328). Dill-apiole has been isolated from dill oil (Ciamician and Silber, loc. cit.), from matico oil from the leaves of Piper augustifolium (Thoms, loc. cit.), from sea-fennel oil (Delépine, Compt. Rend., 1909, 149, 215), and from Crithmum maritimum (Francesconi and Sernagotti, Atti R. Acad. Lincei, 1913, 22, 231, 312).
Methylation of (II) with methyl sulphate and alkali readily gave 1,2,3,4-tetramethoxy-5-allylbenzene, which is apparently identical with a product isolated by Thoms (Ber., 1908, 41, 2753) from parsley oil and to which this consitution was assigned. Direct comparision of the synthetic and the natural product was not possible in this case.
As possible intermediates in the synthesis of parsley apiole the following compounds have been prepared : pyrogallol methylene ether (2,3-methylenedioxyphenol) (IV), by the direct methylenation of pyrogallol with CH2Br2 and K2CO3 in acetone; gallacetophenone-4-methyl ether, by the nuclear acylation of pyrogallol 1-monomethyl ether (Baker, Montgomery, and Smith, J. Chem. Soc., 1932, 1282); 7-methoxy-8-acetyl-2-methylchromone - this compound could not be hydrolysed to the monomethyl ether of 2,4-diacetylresorcinol. Hydrolysis of 7-methoxy-8-acetyl-2-methylchromone
Gallacetophenone 3,4-dimethyl ether
To a boiling mixture of gallacetophenone (16.8 gr; 1 mol), benzene (400 cc) and anhydrous K2CO3 (55 gr) was added methyl sulphate (26.5 gr, 2.05 mols) in one portion, and the whole refluxed for 6 hours with occasional shaking. After the addition of water (750 cc) and shaking, the benzene layer was separated and shaken several times with NaOH solution, and the alkaline extracts solidified. The precipitated gallacetophenone 3,4-dimethyl ether after crystallisation from MeOH had mp. 75-77° (yield, 10 gr) (for previous methods of preparation from gallacetophenone, see Perkin, J., 1895, 67, 997 ; Perkin and Wilson, J., 1903, 83,132 ; David and von Kostanecki, Ber., 1903, 36, 127).
Gallacetophenone 3,4-dimethyl ether (9.8 gr) in 10% NaOH solution (40 cc) was oxidised by the addition of a 3% solution of hydrogen peroxide (75 cc) in an atmosphere of coal gas. Considerable rise of temp occurred and the mixture darkened. After about 30 min. the solution was acidified, and extracted with ether, the extracts dried and distilled, and 1,2-dihydroxy-3,4-dimethoxybenzene obtained as a pale yellow oil (5 gr), bp.160-170/20mm.
To 1,2-dihydroxy-3,4-dimethoxybenzene (12 gr) and allyl bromide (8.5 gr) in acetone (25 cc) was added anhydrous K2CO3 (12 gr), and the mixture refluxed for 18 hours with frequent shaking. After evaporation of the acetone, the mixture was acidified with dilute H 2SO4 and extracted with ether, the extracts were shaken with an excess of dil. aq. NaOH, and the phenolic products precipitated from the alkaline layer by acid and again extracted with ether. After removal of the solvent the monoallyl ether was heated in an oil bath to about 165°; its temp then suddenly rose to 190°, and ,after being kept at 200° for a few minutes, it was distilled at diminished pressure. The thick oily product (4 gr), bp. 160-173°/14mm, which partly solidified was directly used in the following experiments.
Pyrogallol methylene ether (IV)
Pyrogallol (50 gr), acetone (400 cc), Me2Br2 (110 gr) and anhydrous K2CO3 were refluxed for 30 hours, then diluted, acidified, and extracted with a large volume of ether. The ethereal extract was shaken several times with water, filtered, and shaken with aq. NaOH. The alkaline layer was acidified, extracted several times with warm light petroleum (bp. 40-60°), and yielded a semi-solid product which, after being presses on porous porcelain and recrystallised from light petroleum had an mp. 65°
"There are many things under the sun."
Synthesis of Gallacetophenone
(Rated as: excellent)
Synthesis of Gallacetophenone (2,3,4-trihydroxyacetophenone)
In a 250mL RB flask, fitted with a reflux condenser to which is attached a calcium chloride tube, 28g (0.21 mole) of freshly fused and finely powdered zinc chloride (Note 1) is dissolved in 38mL of glacial acetic acid by heating in an oil bath at 135–140°C. Forty grams (0.37 mole) of 95% acetic anhydride is then added to the clear, pale brown liquid, followed by the addition in one lot of 50g (0.4 mole) of distilled pyrogallol (Note 2). The mixture is heated at 140–145°C (Note 3) for 45 minutes with frequent and vigorous shaking. The unused acetic anhydride and acetic acid are removed by distilling under reduced pressure. The red-brown cake is broken up by the addition of 300mL of water with mechanical stirring for a few minutes. The mixture is cooled in ice water, filtered with suction, and washed with cold water. The crude material, 45–50g, is crystallized from 500mL of boiling water saturated with sulfur dioxide. The yield of straw-colored needles melting at 171–172°C is 36–38g (54–57% of the theoretical amount). On saturating the mother liquor with salt and cooling to 10°C, 4–5g of crude material is obtained, which on recrystallization yields 3–4g of pure material (Note 4).
1.) A good quality of zinc chloride must be used, and it is an advantage to fuse it immediately before use.
2.) Variations in the proportions of acetic acid, acetic anhydride, and zinc chloride did not result in increased yields.
3.) The temperature must be carefully regulated and must not exceed 150°C. In this preparation, as well as in the preparation of other ketones by the Nencki reaction, higher temperatures lead to the formation of a highly colored and resinous product which probably contains a little diketone.
4.) This method has been used for the preparation of other phenolic ketones such as resacetophenone, 2-acetyl-1-naphthol, 2-phenylacetyl-1-naphthol, and 2-phenylpropionyl-1-naphthol.
Reference: Organic Syntheses, CV 2, 304 (http://www.orgsyn.org/orgsyn/orgsyn/pre
I'm dreaming of the white crystals.
Synthesis of all Apiole Positional Isomers
(Rated as: excellent)
Methylenedioxybenzene Derivates. 27.
The Synthesis of Dimethoxy-Methylenedioxy-Allylbenzenes
Chem. Ber. 102, 2663-2676 (1969) (../rhodium/pdf /apioles.dall
The synthesis of 2,3-Dimethoxy-4,5-Methylenedioxy- (Dillapiole), 2,5-Dimethoxy-3,4-Methylenedioxy- (Parsley Apiole), 4,6-Dimethoxy-2,3-Methylenedioxy-, 2,6-Dimethoxy-3,4-Methylenedioxy-, 5,6-Dimethoxy-2,3-Methylenedioxy- and 4,5-Dimethoxy-2,3-Methylenedioxy-allylbe
The Hive - Clandestine Chemists Without Borders