Rhodium (Chief Bee) 09-12-03 10:47 No 458693 |
Structure and Synthesis of Croweacin (Rated as: excellent) |
|||||||
The Structure and Synthesis of Croweacin W. Baker, A. R. Penfold, J. L. Simonsen J. Chem. Soc. 439-443 (1939) (../rhodium /crowea The naturally occurring substance croweacin has been proved to be 2-methoxy-3,4-methylenedioxyallylbenzene Croweacin, isolated from Eriostemon crowei (Crowei saligna) by Penfold and Morrison (J. Proc. Roy. Soc. N.S.W., 1922, 56, 227), has recently been shown by Penfold, Ramage, and Simonsen (J. Chem. Soc, 1938, 756) to be either 2-methoxy-3,4-methylenedioxyallylbenzene During the course of entirely independent work on the synthesis of parsley apiole and derivatives (Baker and Savage, J., 1938, 1602) 2-hydroxy-3,4-methylenedioxybenzoic acid (I) and 2-hydroxy-3,4-methylenedioxyallylbenzene Further proof that croweacin is correctly represented by the formula (IV) was obtained by ozonolysis of natural croweacin in methyl acetate solution. The products isolated were formaldehyde (as its 2,4-dinitrophenylhydrazone), 2-methoxy-3,4-methylenedioxyphenylacetal A difference in behaviour of synthetic and natural croweacin towards alcoholic potash established the fact that the former was not a homogeneous substance, and this may well account for the fact, previously mentioned, that their physical constants are not exactly the same. When natural croweacin was heated with alcoholic potash, it was converted into the liquid propenyl isomer isocroweacin (V), which was separated from a trace of sesquiterpene via the characteristic picrate, and which when oxidised with potassium permanganate yielded croweacic acid. When, however, the synthetic croweacin was submitted to the same treatment, it gave not only isocroweacin, but also a solid isomer, mp 64°C, in about 20% yield. This substance gave a dibromo-dibromide when treated with bromine in acetic acid, and when oxidised it gave, not croweacic acid, but 4-methoxy-2,3-methylenedioxybenzoic acid, thus proving it to be 4-methoxy-2,3-methylenedioxypropenylbenz It was evident that in the preparation of (III) by rearrangement of the allyl ether of pyrogallol methylene ether, the usual o-migration of the allyl group had been accompanied by a p-migration, and hence the derived croweacin contained the position isomer corresponding to (VI). With the small amount of material at our disposal it has not been possible to prepare a homogeneous specimen of synthetic croweacin, as the accompanying isomer appears to possess a boiling point extremely close to that of croweacin itself. The non-homogeneity of (III) does not invalidate the synthesis of parsley apiole already recorded. The unusually large amount of p-migration of the allyl group which occurs in the molecular rearrangement of the allyl ether of pyrogallol methylene ether is noteworthy; it is probably due to the influence of the five-membered methylenedioxy ring. Isocroweacin behaves in an unexpected manner towards bromine in acetic acid at room temperature, with which it yields 1,2,3-tribromo-4-methoxy-5,6-methylenedi |
||||||||
Rhodium (Chief Bee) 09-12-03 10:54 No 458696 |
Structure and Synthesis of Croweacin (Part II) (Rated as: excellent) |
|||||||
Experimental Oxidation of Natural Croweacin (IV) (a) With ozone A solution of the oil (3 mL) in methyl acetate (20 mL) at 0°C was ozonized until ozone was present in the issuing gases, which, during the oxidation, had been passed through water (A). The solvent was removed under diminished pressure and the residual gum was mixed with water (10 mL) and heated on the water-bath for 1 hour and then on the sand-bath for 15 minutes under conditions permitting the escape of any readily volatile ketone (or aldehyde), the vapour being passed through a dilute acetic acid solution of p-nitrophenylhydrazine (B). The cooled reaction mixture, which contained a heavy brown oil, was extracted with ether, and the extract washed with aqueous sodium carbonate (C) and then with aqueous sodium hydroxide (2.5%) (D). The last solution was deep brown and there was obvious aerial oxidation. The ethereal extract, after washing with water, was dried; evaporation of the solvent left a mobile yellow oil (1.7 g). The oil was mixed with an excess of semicarbazide acetate; the semicarbazone, dec. 190-195°C, which formed very rapidly, was collected and washed with ether to remove a trace of resinous impurity. 2-Methoxy-3,4-methylenedioxyphenylacetal (b) With potassium permanganate Croweacin (10 mL.) was oxidised with potassium permanganate under the conditions used by Penfold and Morrison (loc. cit., p. 230). The crude glycol (4.7 g) was crystallised (twice) from ligroin (bp 100-120°C) and finally from ether, from which it separated in nodules or rosettes of needles, mp 90-91°C after softening at 87°C. This mp was unchanged by sublimation in a low vacuum or by crystallisation from either cyclohexane or dilute methyl alcohol. The original mother-liquor was distilled in steam to remove the solvent; the residual oil (isolated by extraction with chloroform) gave a further quantity of the glycol on trituration with ether. The oil, which was soluble in ether, reacted with Brady's reagent to yield a 2,4-dinitrophenylhydrazone crystallising from ethyl acetate in red needles, mp 252-253°C, both alone and in admixture with 2-methoxy-3,4-methylenedioxybenzaldehyde Oxidation of Croweacin Glycol (a) With potassium permanganate The finely powdered glycol (0.25 g, mp 90-91°C, prepared from natural croweacin) was suspended in water (25 mL) containing some sodium hydroxide and shaken with powdered potassium permanganate at room temperature until a permanent pink colour was obtained. The filtered solution was concentrated and acidified; the acid which separated, mp 145-150°C, after crystallisation from hot water had mp 153°C, both alone and in admixture with croweacic acid. (b) With lead tetra-acetate The glycol (0.41 g) in acetic acid (20 mL, distilled over lead tetraacetate) was treated with lead tetra-acetate (0.9 g, 1.1 mol) with occasional shaking. After 24 hours, water (40 mL) and a solution of 2,4-dinitrophenylhydrazine (1 g) in dilute sulphuric acid were added; the orange precipitate (containing lead sulphate) was collected, washed, and extracted with boiling alcohol-ethyl acetate. The extracts yielded 2-methoxy-3,4-methylenedioxyphenylacetal Isocroweacin (V) Natural croweacin (4 g, bp 129-131°C/10 mmHg, was refluxed for 68 hours with potassium hydroxide (16 g) in alcohol (60 mL.), and the mixture diluted and submitted to steam-distillation. The colourless oil extracted from the distillate was twice distilled, head and tail fractions being neglected, and then had bp 145-147°C/12 mmHg. It was now treated with an equivalent of picric acid in hot alcoholic solution, and the picrate which separated was twice crystallised from alcohol; it formed garnet-red prismatic needles, mp 75-76°C. The isocroweacin regenerated from the picrate was unaltered in bp, but had nD20° 1.5675. It possesses a very weak odour of the croweacin type. It may be noted that croweacin yields no picrate. 1,2,3-Tribromo-4-methoxy-5,6-methylenedi Iso-Croweacin was treated with an excess of bromine in acetic acid solution (slight warming) and after 2 hours water was added, the solid was collected, washed with water and alkali, and crystallised twice from alcohol. The 1,2,3-tribromo-4-methoxy-5,6-methylenedi 2-Methoxy-3,4-methylenedioxybenzoic Acid (Croweacic Acid) (II) 2-Hydroxy-3,4-methylenedioxybenzoic acid (I) (Baker and Savage, loc. cit.), dissolved in a solution of potassium hydroxide (2 g) in water (5 mL) and acetone (5 mL), was warmed and shaken during the alternate addition of methyl sulphate (6 mL) and a solution of potassium hydroxide (2 g) in water (5 mL). After heating on the water-bath, the crude croweacic acid which was precipitated on the addition of hydrochloric acid was collected, washed, and crystallized from hot water (needles, mp 147-149°C, giving a very weak ferric chloride reaction). This acid was remethylated as before, and then separated from water in fine needles which gave no ferric chloride reaction, mp 152-153°C, undepressed on admixture with a specimen of croweacic acid prepared from natural croweacin. Synthetic Croweacin (IV), containing 4-Methoxy-2, 3-methylenedioxyallylbenzene 2-Hydroxy-3,4-methylenedioxyallylbenzene Dibromocroweacin Dibromide The synthetic croweacin was brominated in acetic acid as described by Penfold, Ramage, and Simonsen. After precipitation with water the oily product was seeded with a trace of crystalline dibromocroweacin dibromide from natural croweacin, and after 12 hours the almost completely solid material was rubbed with a little light petroleum (bp 80-100°C), and crystallized from light petroleum (bp 40-60°C). It separated in prismatic needles, mp 102-104°C The mixed mp with a specimen of dibromocroweacin dibromide (mp 106-107°C) prepared from natural croweacin was 103-105°C, and the mixture completely solidified on cooling. Action of Alcoholic Potash on Synthetic Croweacin: Preparation of isoCroweacin (V) and 4-Methoxy-2,3-methylenedioxypropenylbenz A mixture of synthetic croweacin (2 g), potassium. hydroxide (8 g), and alcohol (30 mL) was heated on the water-bath for 48 hours (the same result was achieved when heating was continued for a further 48 hours), diluted, and steam-distilled. A colourless oil and then a solid came over, and after several hours the solid was collected, thoroughly drained and dried. The filtrate (a) and solid (b) were separately examined. The filtrate (a), which consisted of a milky suspension, yielded to ether isocroweacin as a colourless oil (1.2 g), which was twice distilled under diminished pressure; it had bp 150-151°C/15 mmHg., higher-boiling residue in the flask deposited on standing a trace of the solid isomer (b). The isocroweacin was identified by the characteristic picrate, mp 72-73°C, mixed mp with the picrate previously described, 73-75°C, and by conversion into 1,2,3-tribromo-4-methoxy-5,6-methylenedi The solid (b) was crystallised twice from light petroleum (bp 40-60°C), in which it was easily soluble on warming. 4-Methoxy-2,3-methylenedioxypropenylbenz 5,6,alpha,beta-Tetrabromo-4-methoxy-2,3- Compound (VI) (0.1 g.) in acetic acid (2 ml) was treated with excess of bromine, and after 12 hours the crystalline tetrabromo-derivative (0.12 g.) was collected, washed with acetic acid, and crystallised twice from alcohol, in which it was rather sparingly soluble. It separated in thin blunt-ended prisms, mp 115°C. Oxidation of Synthetical isocroweacin (V) and 4-Methoxy-2,3-methylenedioxypropenylbenz Oxidation was carried out by shaking the propenyl compounds, dissolved in a little light petroleum, with excess of potassium permanganate at room temperature for 20 minutes. After passage of sulfur dioxide and removal of petroleum by boiling, the acids separated from the cooled solutions and were purified by crystallisation from water. The isocroweacin yielded croweacic acid (in the crude state accompanied by a little 4-methoxy-2,3-methylenedioxybenzoic acid), mp and mixed mp 153°C. The 4-methoxy-2,3-methylenedioxypropenylbenz Myristicin Glycol (2,3-Dihydroxy-3-methoxy-4,5-methylenedi To a mixture of myristicin (7.5 ml), water (500 ml), and crushed ice (500 g), were added potassium hydroxide (1.5 g) and then powdered potassium permanganate (11 g) in small portions with continual shaking. After completion of the reaction (10 minutes) the liquid was filtered, filtrate and residue extracted with chloroform, and the extracts dried and distilled, leaving an oil which solidified on standing (1.5 g). The glycol was crystallised twice from benzene and obtained in spherulitic bunches of fine needles, mp 90-91°C. The substance gave a large depression of the mp when mixed with croweacin glycol, mp 91°C. Myristicinaldehyde 2,4-dinitrophenylhydrazone Myristicinaldehyde was warmed with a dilute alcoholic solution of 2,4-dinitrophenylhydrazine sulphate. The bright red precipitate crystallised. from alcohol-ethyl acetate in dark brownish-red needles, mp 232°C after previous sintering. |
||||||||