Preparation of the Sweetening Agent P4000
A. J. de Koning University of Botswana, Lesotho and Swaziland Roma, Lesotho. Africa
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A student project
It appears t h a t t h e sweetest compound known t o us is 1n-propoxy-2-amino-4-nitrobenzene, a substance which is 4000 timessweeter than sugar. Its preparation and properties were described by Verkade and collaborators 30 years ago.'.2 T h e history of its discovery-as told by Verkade in his valedictory lecture a t the Technical University of Delft in 196l3-is little known and is well worth recording. During t h e German occupation of Holland in the second world war, Verkade was asked to prepare a sweetening agent which was soluble in petrol. At first nobody knew why this strange request was made until it was found t h a t it was based on a misunderstanding. T h e term "sweetening of gasoline," which of course means the removal of certain sulfur-containing compounds from petrol, had been taken literally! The most incredible part of the story, however, is t h a t Verkade succeeded in synthesizing a powerful sweetening agent, which was soluble in petrol. I have D . r e ~ a r e dthe c o m ~ o u n dwith mv final year students for many years and, since its preparation is notfound in any organic chemistry laboratory manual, I wish t o report it here. It can be prepared with simple lahoratory equipment in about seven laboratorv Deriods of three-hours duration. Its synthesis consists of threesteps &
tated NaCl is filtered with suction and the filtrate is concentrated in vacuo in a rotary evaporator. The residual oil is taken up in 400 ml of ether and washed with 100 ml of 1%aqueous NaOH and water. The ethereal solution is dried over anhydrous NazS01, filtered, and evaporated in small portions in a weighed 500-ml conical flask on the water bath in the fumehood. Forty-three grams of oily l-n-propoxy2,4-dinitrohenzeneis so obtained. In order to crystallize the oil a small portion of it is removed on a watch glass, treated with some petroleum ether (40-6O0C), and scratched. The material soon crystallizes, showinga mp of about 30% Recrystallization of the material can he done by dissolvingit in 100 ml of hot n-propanol, cwling it in ice, and seeding it with a crystal. The material is filtered, washed with same petroleum ether (4M0°C), and dried with suction at the pump. The yield is about 35 g of pure 1-n-propoxy-2,4-dinitrohenzene of mp 31-32%. Calculate the % yield of the reaction. Why is the ethereal solution washed with 1%NaOH? Preparation of the Isomer Mixture l-n-Propoxy-2-Amino-4Nitrobenzene and l-n-Propoxy-2-Nitro-4-Aminobenzene This preparation exemplifies a partial reduction of a dinitro compound with Na&. It clearly shows t h a t each of t h e nitro croups mav he reduced and consequently a mixture of isomers
The preparation of l-n-propoxy-2,4-dinit10henzenefrom 1chloro-2,4-dinitrohenzene and propaay ion: a nucleophilic suhstitution. The partial reduction of ln-propoxy-2,4-dinitrohenzeneto a mixture of the isomers l-n-propoxy-2-amino-4-nitrobenzene and l-n-propoxy-2-nitro-4-minobenzene.
The separation of the mixture into the two components. The nature of the compound, in particular its sweetness, but also its beautiful orange color, makes its preparation a very rewarding and interesting student project. Preparation of l-n-Propoxy-2,4-Dinitrobenme This svnthesis is a good e x a m ~ l of e an aromatic nucleophilic substitution; the ch6rine atom is activated by t h e two nitro ~ r o u a sand substitution hv the n-propoxy ion takes place readily.
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NHt Experimental Into a 500-ml three-necked flask, fitted with a condenser, a mechanical stirrer, and a dropping funnel, 22.6 g of 1-n-propoxy-2,4dinitrobenzene and 100 ml of water are placed. The water is heated to boiling and a solution of 3l.2gaf NazS.9H20and 4.2 g ofsulfur in 100 ml of water is added dropwise in 2 hr while stirring vigorously. After the addition is complete the mixture is heated for 1hr longer. The mixture is cooled and the oil" ~ r o d u cextracted t with 300 ml of portions in a weighed 500-ml conical flask on the water bath in the fumehood. A yield of about 18 g of the mixture of isomers is ohtained. Calculate the % yield of the reaction.
Experimental The experimentalprocedures outlined in this report are essentially those of Verkade and collaborators (1,2). Into a 1-1 three-necked flask, equipped with a condenser, a mechanical stirrer, and a dropping funnel, a solution of 40.5 g of 1chloro-2.4-dinitrobenzene(this substance is harmful to the skin and any material spilt on it should he washed off immediately) in 400 ml of n-propanol is placed. The solution is kept at 70°C in a water bath and stirred vigorously while 200 ml of a 1M solution of NaOH in n-propanol (prepare this solution a week before the start of the experiment, since NaOH dissolves very slowly in n-propanol) is added dropwise in the course of 2 hr. The solution is stirred for a further 30 min while being kept at 70'C. After cooling, the precipi-
Separation of the Mixture Into the Two Components The separation is based on the difference in basicity of the two amines. In 1.5 M HCI a t room temperature l - n propoxy-2-nitro-4-aminobenzene forms a n insoluble hydrodoes chloride while l-n-propoxy-2-amino-4-nitrohenzene not.
Because of unknown toxicity, students should not taste the prodll"t.~
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Verkade, P. E., van Dijk, C. P., and Meerhurg, W., Rec. Trau. Chim., 65,346 (1946). Verkade, P. E., and Meerburg, W., Ree. Trou. Chim., 65, 768 (1946). Werkade, P. E., Chemisch Weekblad, 57,353 (1961) Volume 53.Number 8. August 1976 / 521
Experimental Eighteen grams of the mixture of isomers is boiled with 200 ml of 1.5 M HCI in a 500-ml conical flask. The hot solution is filtered over glasswool to remove traces of insoluble debris, and left to cwl to room temperature. The precipitated hydrochloride salt of l-n-propoxy2-nitra-4-aminabenzene is filtered with suction and washed with a .;mall quantity u f 1 3 .\f H('1 The filtmce and wash liquid contain PJul0. and in order to Itherate i t , the wlutwn li c d e d in ice toabout ., ( and carefully neutralized w r h a 20% NaOH solutiun \I'hen -0
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522 / Journal of Chemical Education
neutral, the precipitated P4W0 is filtered off with suction, washed with water, and dried in a vacuum desiccator. The yield obtained is about 11g of mp 46-47% Recrystallization from a mixture of petroleum ether (60-80PC): n-propanol (21) gives beautiful orangebrown crystals of mp 47-Ei°C. The crude hydrochloride of l-n~roooxv-2-nitro-4-aminobenzene is recrvstallized from 1.5 M HCI. - ~ . . Tgofmp220-2.W dried i n a n w ~ n , a n dw~~ghrd.'l'neyieldi.rnhoor Idru Calculate the 4,yirld d buth isomerr ohtoined in the reamon. IVhirh of the two lsomrrs do you belieye is the stronger haw? ~~
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