4 -Chlormethyl- -Hydrochlorid

Die leichte Spaltbarkeit von 1,3-Oxazol-Derivaten macht diese zu geeigneten Ausgangs-materialien fur die Synthese von 2-Amino-a kanolen, wie die Herstellung von 3-Amino-4-benzyloxy-l, 2-butandiol-Hydrochlorid bus 4-(Benzyloxy-methyl)-5-hydroxymelhyl-2-tri-chlormethyl-4,5-dihydro-l,3-oxazol zeigt2 ... 

A solution 35.6 g of 4-chlormethyl-6,7-dihydroxycoumarin and 27.3 g of morpholine in 4.5 L methyl ethyl ketone was refluxed for 9 hours. On cooling the morpholine hydrochloride was deleted. Methyl ethyl ketone was evaporated in vacuum. The solid product was mixed with 500 ml of water and dried in vacuum with P205. Yield of crude 6,7-dihydroxy-4-(morpholinomethyl)coumarin is 41.5 g. After recrystallization from ethanol was obtained 6,7-dihydroxy-4-(morpholinomethyl)coumarin with M.P. 232°C. 

Hydrochlorid E2, 130 [(Benzyl-carboxymethyl-amino)-methyl]-tri-chlormethyl- E2, 129 Benzyl-ethyl- -ethylester XII/1, 257 [ -(l-benzylidenamino-ethylamino)-benzylJ-methyl-E2, 131... 

Chlormethyl-5-methoxy-4H-pyron ergibt mit Thioharnstoff nicht das erwartete Isothiuro-nium-chlorid, sondern 2-Amino-5-hydroxy-6-meihoxy-l,3-henzothiazol-Hydrochlorid (63% Schmp. 2S2-284")287 ... 

Dichlorobenzaldehyde is activated for the phase transfer step as the cyano-diethylamino-adduct. 3-Chloromethylpyridine is prepared from 3-hydroxymethyl pyridine by treatment with thionylchloride. The hydrochloride salt of the product is taken up in water and the solution is tised directly in the phase transfer step. Strict temperature control, proper speed of addition of the 3-chlormethyl -pyridine solution and the use of a cosolvent like e.g. hexane ensure a reliable yield of enamine greater than 95%. The enamine reacts at room temperature quantitatively with the hydrochloride salt of 0-methylhydroxylamine to give the corresponding oxime ether as an E/Z-mixture of 3 7. Addition of sulfuric acid to this oximation reaction and an increase of reaction temperature to about 50 C yields pyrifenox rapidly in the desired E/Z-equilibrium ratio of about 1 1. No special purification processes are required in the whole synthesis. 

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