Novel method of synthesis of 2-(beta-aminopropyl)-1,4-dimetoxybenzene
Y.M. Yutylov, V.F. Malutina, L.I. Shcherbina, K.M. Krylova
Institute of phisical and organic chemistry and carbonchemistry, NAS of Ukraine, Donetsk.
Requsted by Chimimanie.
Experimental part.
The chromatographing of 2-(beta-oxypropyl)-1,4-dimetoxibenzene and 2-(beta-aminopropyl)-1,4-dimetoxibenzene
was executed on a gas chromatograph L.CH.M.-8M. The length of the column 1.5 m, the diameter 3mm;
The bearer - Chromaton N-AW (0.16 - 0.20 mm ), containing 5% of XE-60 phase; Temperature of the thermostat 200 C,
temperature of the evaporator - 250; gas-bearer - helium.
2-(beta-oxypropyl)-1,4-dimetoxibenzene (V).
A) Into 0.25 L flask , equipped with a low-temperature thermometer, stirrer, drop funnel, backflow condenser,tube for the introduction of dry nitrogen (the speed of one was controled by a sweet counter, connected to the backflowcondenser exit), 10 ml of the absolute ether were placed. When the flask was flushed by nitrogen, 1.4 g. of well cuted lithium were added, with constant flow of nitrogen. Lithium had a form of a plate with a square 1 sm^2, and thickness 1-2mm. The temperature was reduced to -15 C. During constant stirring, 10.3 ml (9.16 g., 0,2 mol) of a dry n.-butylchloride were added from the drop funnel at temperature (-15)-(-10) C. The reaction mass was holded at 0 C during 2 hr., and then temperature was rised to 20 C (it rises by itself) and a solution of 10.35 g. (0.075 mol) 1,4-dimetoxibenzene [13] in 40 ml of absolute ether was added in one portion. The mixture was stirred during 1 hr., and left for a night. 10 ml (8.59 g, 0.15 mol) of a dry alpha-propyleneoxide at 0 C were added dropwise to the reaction mixture at 0 C the next day during 1 hr., and the mixture was stirred
during 3 hr., and left for a nihgt. The content of the flask was poured out into 150 ml of cooled water. The layer of ether was separated and water solution was extracted with 2x20 ml ether, united, dried over waterless Na2SO4, then the solvent was topped. The residue was distiled in vacuum and a fraction 159-161 C at 8 mmHg was gathered. 12.8 g. (87%) of 2-(beta-oxypropyl)-1,4-dimetoxibenzene of a high purity were obtained.
B) Butyllithium, which was received as described in the section A from 30g (4.28 mol) of lithium, 244 ml (217 g) of chlorous n.-butylchloride in 110ml of dry ether, was added, during intensive stirring at 0 C to a solution of 220(1.6 mol) g of dimethyl ether hydroquinone in 350 ml of dry m-xylol. (Volume of the flask = 2L) Reaction mass was holded during 1hr. with constant growth of temperature from 0 to 10 C, then temperature was raised to 20 C and the mass was holded during 16 hr. Then temperature was decreased to 0 C and 223 ml (191g, 3.3 mol) of dry propylenoxide were added by drops at intansive stirring. The mixture was heated to room temperature and holded for 16 hr. then it was poured out into water, water layer was separated and washed thrice by portions of 15s ml of m-xylol. The xylolic solutions were united with the main mass of xylol solution and dried over waterless Na2SO4 for 2-3 hr., then m-xylol and diethyl ether hydroquinone were distiled (130-132 C 8 mmHg.). The residue was distiled in vacuum 159-161 C at 8 Hgmm. Yield of spirit - 281.5g (90%).
C) 500 ml of dry m-xylol were added to 70g (10 mol) of fine cutted lithium in argon atmosphere in a 5 L three-neck-flask equiped with a stirrer, backflow condenser, drop funnel, a thermometer and a tube for a introduction of a gas. 570 ml (507.3 g 5.48 mol) of n-butylchloride were added by drops at an intensive stirring and temperature (-15 C) -(-10 C). After 2 hr. of stirring solution of 515g (3.73 mol) of dimethyl ether hydroquinone in 1000 ml of dry m-xylol was added to the mixture at 0 C, then stirring during 1 hr.
and then holding at room temperature 15-17 hr. Then the mixture was cooled to 0 C and 520 ml (446.68 g 7.7 mol) of dried over molecular sieves of 3A type propylenoxide (15g of sieve per 0.5 L) was added during 1.5-3.0 hr. After 3 hr. of stirring the mixture was holded at room temperature during 15-17hr. Then unreacted lithium was separated, reaction mass was washed by water, dried over 100 g. of waterless sodium sulfate, then m-xylol was topped and the product of the reaction was distiled in vacuum. boiling point 159-161 C at 8 mmHg .
Yield of spirit 475 g. (~65%).
D) 51.5g (0.37 mol) of dimethyl ether hydroquinone and 7 g. (1 mol) of fine cutted lithium were added to a solution of 100 ml of dry m-xylol in argon environment. (The mixture is in a 0.5 L round-bottom flask equipped with a low-temperature thermometer, stirrer, drop funnel, backflow condenser, tube for the introduction of a gas). The temperature reduced to -10 C. Then at constant stirring 10.3 ml (0.1 mol)of n-butylchloride was added by drops at temperature -10 C. Then the mixture was holded at the temperature during 2 hr., then temperature was enabled to raise spontaneously to room temp. and the mixture was holded during 15-17 hr. Then the reaction mass was cooled to 0 C, and 52 ml (0.75 mol) of dried over molecular sieves propylenoxide was added by drops during 1-1.5 hr. After 2 hr. of stirring the mixture was left at room temperature for 15-17 hr. Then unreacted lithium was separated, the reaction mass was washed by water, dried over 10 g. of waterless sodium sulfate, then m-xylol was topped and then unreacted 1,4-dimetoxybenzene and the product of the reaction was distilled in vacuum. Boiling point 159-161 C 8 mmHg . The yielfd of spirit 46 g. (63%).
2-(beta tosyloxipropyl)-1,4dimetoxybenzene (V|||).
982 g.(5 mol)of 2-(beta-oxypropyl)-1,4-dimetoxybenzene and 2.0 L.(24.7mol) of pyridine, dried over solid alkali were loaded in a 5 L. flask . The content of the flask cooled to 0 C and at intensive stirring 953 g. (5 mol )
of a fines n-toluenesulfochloride were added. Rise of temperature to 55 C was observed. The flask was closed up by a cork and putted to a refrigerator (+5 C) for 15 -20hr.
A residue of muriatic pyridine and a weak yellow color appeared. The reaction mixture was poured out into 10 L of water with ice. The reaction product was filtered, washed by water, by 5% solution of hydrochloric acid, again by water and by 0.1 L of methanol. Received 2-(beta tosyloxipropyl)-1,4-dimetoxybenzene was dried on air.
The yield of tosylat is 1647-1699 g. (94-97%). The boiling point 73.5-74.0 C.
The filtrate was acidified by a concentrated HCl (1 L), evaporated, the recidue was hardly alkalified by a Concentrated solution of NaOH, pyridine was separated, dried and distilled.
2-(beta-benzenesulfonyloxipropyl)-1,4 dimetoxibenzene (|X).
into 250 mL flask there were placed 39 g. (0.2 mol) 2-(beta-oxipropyl)-1,4dimetoxibenzene and 20 ml (0.24 mol)dried pyridine. The mixture was cooled to 0 C and to a stirred mixture 26 g. (0.2 mol) of benzenesulfochloride was added. The rxn was left standing for 20 hr. at 0-5 C. Then the rxn was poured into 300 ml of 10% solution of hydrochloric acid. The upper organic layer was separated and dried on air during 5 hr.
Yield – 65 g. (97.2%) Boiling point 44.5-46.0 C.
2-(beta-n-Nitrobenzenesulfonyloxypropyl)-1,4-dimetoxybenzene (X||)
The experiment was made similar to the receiving of tosylat (V|||) from 1.96 g. (0.01 mol) 2-(beta-oxypropyl)-1,4-dimetoxybenzene in 40 ml of pyridine and 4.4 g. (0.02 mol) n-nitrobenzenesulfochloride.
Yield of nitrobenzenesulfonate – 3.3 g. (87%). Purification – recrystallization from a spirit. Boiling point 97-98 C.
2-(beta-aminopropyl)-1,4- dimetoxybenzene (|)
A. Into 2.7L autoclave, (for work at 50 atm.) there were placed 350.5 g. (1 mol) of 2-(beta-tosyloxpropyl)-1,4-dimetoxybenzene (V|||) and 1700-1800 Ml of liquid ammonia, then the mixture was warmed during 8 hr at 50-60 C. After the ending of the rxn the valve of the autoclave was opened and with light warming (40-45C) ammonia was slowly distilled into a small steel vacuum balloon (3.5 L) cooled to 5-10 C. After cooling to room temperature into opened autoclave 300 ml of benzene were poured and stirred until lime appeared. The residue of the ammonium salt of n-toluenesulfacid was filtered out in Buchner funnel and washed by 3 portions of benzene (3 x 50ml). The bezene solution of amine was washed in a separating funnel in two
Portions (2x250 ml) of weak hydrochloric acid (1:3). Amine was separated by adding to water-acid extract 20% solution of KOH until pH 9-10 wasn’t received. The oily layer, containing amine was separated and dissolve in benzene (200ml). The solution was dried for 5 hr. by solid alkali and after the distillation of the dissolvent, 2-(beta-aminopropyl)-1,4dimetoxibezene at 144-148 C 8 mmHg was distilled
Yield of amine 168-176 g. (86-90 %)
B) Ammonolysis of 2-(beta-n-nitrobenzenesulfonyloxipropyl)-1,4-dimetoybenzene (X||) was made similarly to Ammonolysis of tosylate (V|||). From 38.1 g. (0.1 mol) nitrobenzenesulfonate (X||) in 150ml of liquid ammonia 14.4 g. (65%) of amine(|) were received.
C) Ammonolysis 2-(beta-benzenesulfonyloxipropyl)-1,4dimetoxybenzene (|X) was made similarly to Ammonolysis of tosylate (V|||). From 33.6 g. (0.1 mol) of benzenesulfonate (|X) in 150 ml of liquid ammonia 13.7 g. (70%) of 2-(beta-aminopropyl)-1,4-dimetoxybenzene (|) were received.
