2-(aziridin-1-yl)-1-phenylethanol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To the stirred solution of thiocyanic acid is added a solution of the crude dl-α-phenyl-1-aziridineethanol in 250 ml. of ethanol at a rate sufficient to keep the reaction temperature at 30°-35° C. After the aziridine addition is complete, 72 g. of a methanolic solution of hydrogen chloride (0.35 mole) is added and the solution stirred for 1.5 hours at room temperature. An additional 0.05 mole of hydrogen chloride in 10 g. of ethanol is added, and the reaction heated at 35°-40° C. for 0.5 hour. It is then allowed to proceed at room temperature for 2.5 days. The mixture is concentrated under reduced pressure to about 100 ml., filtered, washed with ethanol and dried to give 27.1 g. of white crystals, melting point 198°-200° C. The yield is 42% (based on styrene oxide) or 71% (based on dl-α-phenyl-1-aziridineethanol). at 30°-35° C the reaction heated at 35°-40° C. for 0.5 hour to proceed at room temperature for 2.5 days The mixture is concentrated under reduced pressure to about 100 ml , filtered washed with ethanol dried to give 27.1 g

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To the stirred solution of thiocyanic acid is added a solution of the crude dl-α-phenyl-1-aziridineethanol in 250 ml. of ethanol at a rate sufficient to keep the reaction temperature at 30°-35° C. After the aziridine addition is complete, 72 g. of a methanolic solution of hydrogen chloride (0.35 mole) is added and the solution stirred for 1.5 hours at room temperature. An additional 0.05 mole of hydrogen chloride in 10 g. of ethanol is added, and the reaction heated at 35°-40° C. for 0.5 hour. It is then allowed to proceed at room temperature for 2.5 days. The mixture is concentrated under reduced pressure to about 100 ml., filtered, washed with ethanol and dried to give 27.1 g. of white crystals, melting point 198°-200° C. The yield is 42% (based on styrene oxide) or 71% (based on dl-α-phenyl-1-aziridineethanol). at 30°-35° C the reaction heated at 35°-40° C. for 0.5 hour to proceed at room temperature for 2.5 days The mixture is concentrated under reduced pressure to about 100 ml , filtered washed with ethanol dried to give 27.1 g

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 43.0 g. (1.0 mole) of ethyleneimine and 60.0 g. (0.5 mole) of styrene oxide is added 3 drops of water and 0.2 g. of potassium hydroxide. The mixture is heated at reflux for 11/2 hours. Distillation of the excess ethyleneimine from the crude product gives 55.6 g. (68%) of the crystalline product. Recrystallization gives pure dl-α-phenyl-1-aziridineethanol with melting point 74°-76° C. The mixture is heated at reflux for 11/2 hours Distillation of the excess ethyleneimine from the crude product gives 55.6 g Recrystallization

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 1-hydroxy-1-phenyl-2-ethyleniminoethane (16.3 g) in dioxan (35 ml) was added dropwise and with stirring at 0° C to an aqueous solution of thiocyanic acid (200 ml of 1N solution). After the addition the mixture was stirred in the cold for 1 hour. It was then heated under reflux for 1 hour and the solution cooled. The desired compound crystallised in 96% yield, m.p. 160° C. After the addition the mixture It was then heated under reflux for 1 hour the solution cooled The desired compound crystallised in 96% yield, m.p. 160° C.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The simplest compound according to formula I, 1-(2'-hydroxy-2'-phenylethyl)aziridine is known and may be made according to A. Funke and G. Benoit, Bulletin de la Societe Chimique de France, 1953, 1021. These authors, using ethylenimine and styrene oxide in equimolar ratios obtained yield of no more than 48%. We have repeated these experiments and have found that the material so produced is far from pure and, unless subjected to a separate purification process, is unsuitable as a starting material for Reaction 1. Impurities, particularly gums, are formed in Funke's process, presumably oligomers or polymers of either styrene or ethylenimine or of both which are difficult to remove and which contaminate the ultimate reaction products when Funke's compound is used in further reactions and render the isolation of the ultimate products difficult or inefficient. The conditions under which undesired side reactions of the two reactants, epoxides and aziridines, particularly polymerisation, can be prevented, unfortunately are in conflict; strongly alkaline conditions favour stability of the aziridines, but lead to spontaneous polymerisation of epoxides and acids polymerise or ring-open the aziridines. In addition we consider that under Funke's conditions the undesired isomer ##STR18## is formed which is particularly difficult to separate and to analyse. The presence of these impurities leads to further undesired by-products in subsequent reactions which cannot be readily removed or analysed and which prevent the crystallisation of the desired products. This is a serious difficulty. As far as we are aware, the synthesis of compounds of the formula V from basic chemicals currently made on technical scale has hitherto been suggested as a multistep process only. Even according to the simpler process of the present invention a 3 to 4 step synthesis is required; if in the first reaction of our combination process, the reaction between an epoxide and an aziridine, gums and impurities are formed, the crude reaction product cannot be used efficiently. It, and subsequent intermediates, must either be purified or, alternatively, yields in subsequent steps fall off rapidly. Thus, in a combination process involving 3 to 4 steps and starting from an impure first reaction product, the ultimate yield is drastically diminished, either because a sequence of purification processes involves losses, or because of low yields and difficulties with isolation. obtained yield of no more than 48% so produced unless subjected to a separate purification process is unsuitable as a starting material for Reaction 1