Alkylaminomethylhydroquinones and related compounds.

Abstract

cf. CA 56, 15504d. Condensation of PhCH2NH2 (I) and (PhCH2)2NH (II) with CH2O (III) in the presence of p-benzyloxyphenol (IV) and hydroquinone (V) was studied. To 30.6 ml. 40% III in PrOH and 50 ml. dioxane was added with stirring during 3-4 min. at 10-15° 22 ml. I, followed by 40 g. IV and 25 ml. dioxane. After being stirred until homogeneous, refluxed 2 hrs., allowed to stand 22 hrs. at 25°, and evapd., the mixt. gave a solid which was dissolved in 300 ml. Et2O and 150 ml. H2O contg. 11 g. NaOH. The Et2O layer gave 57 g. crude 3,4-dihydro-3-benzyl-6-benzyloxy-2H1,3-benzoxazine (VI), m. 86-7° (2:5 MeOH-EtOH). Similarly, 2-benzylaminomethyl-4-hydroxyphenol (VII) was converted in 91.5% yield to 3,4-dihydro-3-benzyl-6-hydroxy-2H-1,3-benzoxazine, m. 105-6° (CCl4). A soln. of 3.6 g. VI and 3 ml. concd. HCl in 25 ml. EtOH was distd. until 15 ml. EtOH (and III) was removed, and the residue was cooled and treated with 20 ml. acetone to give 3.4 g. 2-benzylaminomethyl-4-benzyloxyphenolHCl (VIII), m. 170-1° (EtOH). A stirred mixt. of 4.95 g. VIII and 1.5 ml. HOCH2CH2NH2 in 150 ml. H2O was extd. with Et2O to give 4.16 g. 2-benzylaminomethyl-4-benzyloxyphenol (IX), m. 90-1° (MeOH). To a soln. of 6.39 g. IX in 100 ml. MeOH was added to 0° 1.5 ml. 37% aq. III, and the mixt. refluxed 2 hrs. to give 5.3 g. VI. Refluxing 30 min. a mixt. of 8.8 g. IX and 15 ml. concd. HCl gave 5.1 g. 2-benzylaminomethylhydroquinoneHCl (X), m. 177-8° (iso-PrOH). IV was similarly cleaved to V. An aq. soln. of X was satd. with KHCO3 and extd. with Et2O to give VII, m. 120-20.5° (C6H6). Attempted condensations of II, III, and either IV or V under a variety of conditions led to 96100% tetrabenzyldiaminomethane (XI). XI did not react further with III and IV. Neither I nor I.HCl would react with III and V. [on SciFinder(R)]