Petrow, V.’s team published research in Journal of Pharmacy and Pharmacology in 10 | CAS: 18437-58-6

Petrow, V. published the artcileAnalgesics. II. Aryloxyalkyl oxaalkylamines, Recommanded Product: 4-Amino-2-picoline, the publication is Journal of Pharmacy and Pharmacology (1958), 86-95, database is CAplus and MEDLINE.

cf. C.A. 51, 8723b. Compounds formally related to aryloxypropanolamine in which the aryl and amine residues are joined by combinations derived from glycerol and ethylene glycol are synthesized. Adding 108 g. ο-cresol to 40 g. NaOH in 450 ml. EtOH and 40 ml. H₂O followed by 143 g. (ClCH₂CH₂)₂O and refluxing 5 hrs. formed an oil with fractons b_0.3 36-95° (52.4 g.), 100-20° (111.9 g.), and 160° (26.9 g.). The 2nd fraction yielded 5-ο-tolyloxy-3-oxapentyl chloride (I), b_0.3 92°, and the 3rd fraction yielded 1,5-bis-ο-tolyloxy-3-oxapentane, b_0.3 156°. I was heated with piperidine to form N-(5-ο-tolyloxy-3-oxapentyl)piperidine, b_0.3 130° (picrate, yellow nodules from EtOAc-ligroine, m. 77- 8°). N-(5-ο-Tolyloxy-3-oxapentyl)pyrrolidine, oil, b_0.3 122°; Δ³-piperideine analog, b_0.3 138° (picrate, yellow needles from EtOAc-ligroine, m. 92-4°). 3-Phenoxy-1,2-epoxy- propane and N-(2-hydroxyethyl)piperidine in C₆H₆ were refluxed 20 hrs. to form N-(5-hydroxy-6-phenoxy-3-oxahexyl)-piperidine, b_0.1. 150°; the 6-ο-methoxyphenoxy-3-oxahexyl analog b_0.1 160°. 2-ο-Tolyloxyethanol and 2,3-epoxypropyl chloride with polyphosphoric acid were heated at 100° for 20 hrs. to form 2-hydroxy-6-ο-tolyloxy-4-oxahexyl chloride, b_0.5 136°. 2-ο-Tolyloxyethanol was refluxed with NaOMe in MeOH for several min., the residual product was suspended in dry C₆H₆, 1-chloro-2,3-epoxypropane added, and the mixture refluxed 8 hrs. to yield from the main distillation fraction 1,2-epoxy-6-ο-tolyloxy-4-oxahexane (II) (oil, b_0.05 100°) and from the top fraction a viscous oil, b_0.07 210°. Treatment of the foregoing chlorohydrin with an equivalent of KOH in MeOH at 0° followed by dilution and extraction with CHCl₃ yielded II. II in C₆H₆ with Δ³-piperideine formed N-(2-hydroxy-6-ο-tolyloxy-4-oxahexyl)-Δ³-piperideine, b_0.3 162° [HCl salt, hygroscopic, m. 50-60°; picrate, m. 81-3° (EtOAc-Et₂O)]. 3-ο-Tolyloxy-1,2-epoxypropane and allyl alc. treated carefully with H₂SO₄ and heated at 100° for 2 hrs. yielded from the residual fraction b_0.25 120° 6-hydroxy-7-ο-tolyloxy-4-oxa-1-heptene (III), b_1.2 130-2°; the fraction b_0.25-1 124-44° contained a high proportion of 3-ο-tolyloxypropane-1,2-diol. 2-Hydroxy-3-ο-tolyloxypropyl chloride (100 g.) and 232 g. allyl alc. with 33.6 g. powd. KOH added in portions then heated at 100° for 8 hrs., diluted, and extracted with CHCl₃ yielded 97.8 g. III, b_0.1 113°. Adding 63 g. III to a cold solution of 39.15 g. perbenzoic acid in 995 ml. C₆H₆, keeping at 0° for 2 days and then room temperature for 2 days, and refractionating the fraction (37.7 g.), b_0.3 118-50°, yielded 1,2-epoxy-6-hydroxy-7-ο-tolyloxy-4-oxaheptane, b_0.4 144°, which condensed with Et₂NH in C₆H₆ to form N-(2,6-dihydroxy-7-ο-tolyloxy-4-oxaheptyl)diethylamine, b_0.3 174° (piperidine analog, b_0.4 194°). 6-Hydroxy-7-phenoxy-4-oxa-1-heptene b_0.05 110°. 1,2-Epoxy-6-hydroxy-7-phenoxy-4-oxaheptane b_0.4 140°. N-(2,6-Dihydroxy-4-oxahexyl)-p-anisidine, m. 65-7° (EtOAc-ligroine), refluxed 5 hrs. in MeOH with MeI and Na₂CO₃ formed N-methyl-N-(2,6-dihydroxy-4-oxahexyl)-p-anisidine, b_0.1 180°; the N-Et analog, b_0.1 185°. N-(2,6-Dihydroxy-4-oxahexyl)-p-phenetidine (by alk. condensation in MeOH), light yellow prisms, m. 70-2° (EtOAc-ligroine) [picrate, m. 127-8° (EtOH)]; N-Et derivative, _0.3 180°. N (2,6-Dihydroxy-4-oxahexyl)-p-propoxyaniline (61% yield) b_0.1 192-8°, light yellow needles, m. 71-3° (EtOAc-ligroine); p-butoxyaniline analog, b_0.4 195-200°, yellow needles, m. 69-71° (EtOAc-ligroine); ο-phenetidine analog, b_0.4 182-6°, pale yellow needles, m. 57-8° (EtOAc-ligroine); morpholine analog, b_0.5 144°; Δ³-piperideine analog, b_0.3, 140°; pyrrolidine analog, b_0.1 118°. N-(2,9-Dihydroxy-4,7-dioxanonyl)-p-phenetidine b_0.5 220°; picrate, bright yellow needles, m. 120-1° (EtOAc). N-(2,6-Dihydroxy-4-oxaheptyl)-p-phenetidine on fractionation (b_0.04-0.05 200-5°) gave a white solid (A), m. 102-4° (EtOAc-ligroine), soluble in hot H₂O; picrate, yellow fluffy needles, m. 130-2° (EtOAc). The concentrated mother liquors from A yielded a main fraction B, b_0.8 210°, m. 54-6° (Et₂O-ligroine), more soluble in cold H₂O than A. Tentative structures were for A, p-EtC₆H₄NHCH₂CH(OH)CH₂OCH₂CH(OH)Me, for B, p-EtC₆H₄NHCH₂CH(OH)CH₂OCHMeCH₂OH. The p-anisidine analog fractionated by b_0.5 200-20° yielded 2 isomers; the less soluble crystallized from H₂O [picrate, m. 134-6° (EtOAc-ligroine)]; the more soluble m. 64-6° (Et₂O-ligroine) [picrate, m. 12 6° (EtOAc-ligroine)]. Tentative structures were analogous to those of A and B. N-p-Ethoxyphenylmorpholine b_0.5 120°, m. 75-6° (EtOH-H₂O); HCl salt, m. 170-1° (EtOH-Et₂O). 3-(3,4,5-Trimethoxyphenyl)aminopropane-1,2-diol b_0.2 210°; HCl salt, white needles with blue-green tinge, m. 148-50° (EtOH-Et₂O). 4-ο-Tolyloxybut-2-yn-1-yl chloride b_0.3 110°. 1-Diethylamino-4-phenoxybut-2-yne, from 4-phenoxybut-2-yn-1-yl chloride and Et₂NH as the base, b_0.2 110-15°; HCl salt, m. 138-9° (EtOH-Et₂O). 1-Diethylamino-4-ο-tolyloxybut-2-yne b_0.6 126-8°; HCl salt, m. 116-17° (EtOH-Et₂O). 1-Δ³-Piperideino-4-ο-tolyloxybut-2-yne b_0.5 130°; HCl salt, m. 126-7° (iso-PrOH-Et₂O).

Journal of Pharmacy and Pharmacology published new progress about 18437-58-6. 18437-58-6 belongs to pyridine-derivatives, auxiliary class Pyridine,Amine, name is 4-Amino-2-picoline, and the molecular formula is C6H8N2, Recommanded Product: 4-Amino-2-picoline.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem