Mamalis, P. published the artcileAmino?xy derivatives. II. Some derivatives of N-hydroxybiguanide, Category: catalysis-chemistry, the publication is Journal of the Chemical Society (1960), 229-38, database is CAplus.
The preparation of some amino?xyalkanes and their corresponding biguanides, together with certain arylmethyl analogs, was described. A summary of bacteriostatic activities was included. Benzohydroxamates (I) were prepared by reaction of Na benzohydroxamate with an alkyl or arylmethyl halide. The following new I were obtained (substituent and m.p. or b.p. given): hexyl, 138-40¡ã/0.3 mm.; 4-methylbenzyl, 107-8¡ã; 4-chlorobenzyl, 162¡ã; 4-bromobenzyl, 176¡ã; 2-nitrobenzyl, 121¡ã; 3,4-dichlorobenzyl, 134¡ã; cinnamyl, 118-20¡ã; 1-naphthylmethyl, 140¡ã; 2-naphthylmethyl, 131¡ã; 2-methyl-1-naphthylmethyl, 150¡ã; 1-bromo-2-naphthylmethyl, 144¡ã; 8-quinolylmethyl, 133-4¡ã; 6-chloro-8-(1,3-benzodioxanylmethyl), 131-2¡ã. The required arylmethyl bromides were prepared by side chain bromination of toluenes and methylnaphthalenes with N-bromosuccinimide (II) in CCl4 in the presence of Bz2O2. 4-BrC6H4CH2Br, 1-(bromomethyl)naphthalene, and 1-bromo-(2-bromomethyl)naphthalene did not appear to have been prepared by this method. Bromination of 2-methylnaphthalene with II afforded 2-(bromomethyl)naphthalene, m. 48¡ã; in one run a substance, m. 128¡ã, was also obtained in low yield and shown to be 1-(dibromomethyl)naphthalene, since with refluxing H2O it yielded 2-naphthaldehyde, leaflets, m. 57-8¡ã; semicarbazone m. 245¡ã (Me2CO). The following I were prepared with properties in agreement with those in the literature: Me, Et, allyl, Bu, PhCH2, and 4-nitrobenzyl. Cinnamyl benzohydroxamate (1 g.) in 15 ml. alc. and 15 ml. EtOAc shaken 3 min. with H and 10% Pd-C gave 0.88 g. crude product and distillation at 120-40¡ã 33 ¡Á 10-5 mm. gave 3-phenylpropyl benzohydroxamate, m. 45-6¡ã. Benzohydroxamic acid (6.9 g.) and 2 g. NaOH in 50 ml. alc. refluxed 4 hrs. with 9-(chloromethyl)phenanthrene yielded 2.1 g. N-benzoyl-O,N-bis(9-phenanthrylmethyl)hydroxylamine, m. 209-10¡ã (aqueous HCONMe2). Addition of H2O to the original mother liquors precipitated 8.6 g. 9-phenanthrylmethyl benzohydroxamate, m. 160-1¡ã (EtOAc). K salt of hydroxyurethan and the alkyl bromides yielded alkyloxyurethans (III), colorless oils or low melting solids, purified by distillation or crystallization: (alkyl group and b.p./mm. or m.p. given): allyl, 123¡ã/28; isobutyl, 55¡ã/0.2; pentyl, 76¡ã/0.08; hexyl, 86¡ã/0.35; heptyl, 93¡ã/0.3; octyl, 98¡ã/0.04; nonyl, 103-4¡ã/0.3; decyl, 112¡ã/0.05; undecyl, 130¡ã/0.3; 2-methyldecyl, 128¡ã/0.2; tetradecyl, 39-40¡ã; hexadecyl, 40.5-1.5¡ã; octadecyl, 45-6¡ã. N-Decyl-N-decyloxyurethan was isolated as a by-product from the reaction of hydroxyurethan with decyl bromide, b0.1 154¡ã, nD18 1.4490. A mixture of 5.6 g. NH2OH.HCl, 12.5 g. anhydrous Na2CO3, and 37 ml. H2O added dropwise at 15-20¡ã to 13.4 g. benzyl chloroformate, the mixture stirred 4 hrs., acidified, and the liberated oil extracted with Et2O yielded 10.2 g. N-benzyloxycarbonylhydroxylamine (IV), m. 68-9¡ã (Et2O-ligroine). NaOH (0.96 g.) in 25 ml. alc. treated with 4 g. IV, the Na salt separated, after addition of 3.4 g. MeI the mixture refluxed 4 hrs., H2O added, the oily product isolated with Et2O, and the solvent removed gave 3.3 g. oil. The oil left overnight at room temperature with 10 ml. 20% solution HBr in AcOH, evaporated, and the residual solid crystallized from alc.-Et2O gave 1.5 g. amino?xymethane-HBr, plates, m. 102¡ã. Me benzohydroxamate (3 g.), 15 ml. concentrated HCl, and 15 ml. H2O refluxed 2 hrs., 2.1 g. BzOH collected, and the filtrate evaporated gave 1.4 g. amino?xy methane-HCl, plates, m. 148-9¡ã (EtOAc-alc.). Aminooxyethane-HCl obtained from III (allyl) crystallized as plates, m. 172-4¡ã. The above HCl salt (5.0 g.) in 50 ml. alc. shaken with H and 10% Pd-C gave 4.8 g. 1-amino?xypropane-HCl (V), m. 150-1¡ã (EtOAc). III (Pr) (11.5 g.) and 60 ml. 6% alc.-HCl refluxed 1 hr. gave 6.4 g. V. III (Pr) (11.1 g.) and 100 ml. 17% HCl refluxed 2 hrs. (black oil separated), cooled, extracted with Et2O, the aqueous layer evaporated, and the residual solid triturated with EtOAc-alc. gave 2.35 g. NH4Cl; the Et2O layer extracted with aqueous NaHCO3 gave 4.8 g. BzOH. Evaporation of the Et2O layer gave 2.95 g. material which on hydrolysis gave 2 g. BzOH and a little low boiling oil. III (Bu) (17 g.) and 80 ml. 6% alc.-HCl refluxed 2 hrs. gave 7.8 g. 1-amino?xybutane-HCl, plates, m. 155-6¡ã (EtOAc-alc.). 1-Amino?xypentane-HCl was similarly prepared as plates, m. 148¡ã. Amino?xyisobutane-HCl was prepared by alk. hydrolysis of the urethan as leaflets, m. 134-5¡ã (EtOAc). Amino?xyhexane-HCl similarly prepared, m. 151¡ã. 1-Amino?xyheptane-HCl separated as leaflets, m. 151-2¡ã (EtOAc-alc.). 1-Amino?xyoctane-HCl formed as plates, m. 147-9¡ã. 1-Amino?xynonane-HCl failed to crystallize and the crude material was used for the preparation of the biguanide. 1-Amino?xydecane-HCl crystallized as plates, m. 145.5-6.5¡ã (EtOAc-alc.), the HBr salt as plates, m. 135-6¡ã; the hydrochloride (2.1 g.) 1.25 g. salicylaldehyde, 0.4 g. NaOH in 2 ml. H2O, and 15 ml. alc. refluxed 1 hr. gave 1.9 g. 1-salicylideneamino?xydecane, lemon-yellow oil, b0.3 132¡ã. 1-Furfurylideneamino?xydecane was similarly prepared as a yellow oil, b0.08 114¡ã. 1-Aminooxyundecane-HCl crystallized similarly, m. 145-6¡ã. 1-Aminooxytetradecane-HCl separated as leaflets, m. 137-8¡ã. The base crystallized as leaflets, m. 68-70¡ã (EtOAc-ligroine). 1-Amino?xyhexadecane-HCl was obtained as leaflets, m. 133-4¡ã; free base, leaflets, m. 45-7¡ã (ligroine). 1-Aminooxyoctadecane crystallized as needles, m. 50-2¡ã. I (PhCH2) (4.3 g.) and 30 ml. 6% alc.-HCl refluxed 20 min. gave 2.7 g. amino?xymethylbenzene-HCl, m. 230-2¡ã. Similar preparations gave 88% p-amino?xymethyltoluene-HCl, leaflets, m. 233¡ã (alc.-H2O);-chlorobenzene-HCl, leaflets, m. 243¡ã; -bromobenzene-HCl, plates, m. 246-7¡ã (alc.-Et20); and -nitrobenzene-HCl, leaflets, m. 216¡ã; o-amino?xymethylnitrobenzene-HCl, needles, m. 165-6¡ã; 4-amino?xymethyl-1,2-dichlorobenzene-HCl, leaflets, m. 197¡ã (EtOAc-alc.); 3-amino?xypropylbenzene-HCl, plates, m. 168-9¡ã (alc.-Et2O); 1-amino?xymethylnaphthalene-HCl, needles, m. 198¡ã (EtOAc); 2-amino?xymethyl isomer, leaflets, m. 247¡ã (aqueous alc.) (N-benzyloxycarbonyl derivative, leaflets, m. 93-4¡ã); 1-amino?xymethyl-2-methylnaphthalene-HCl.H2O, needles, m. 192-3¡ã (alc.-Et2O); 2-amino?xymethyl-1-bromonaphthalene-HCl, needles, m. 199¡ã (alc.-H20); 9-amino?xymethylphenanthrene-HCl, needles, m. 216-17¡ã (alc.); and the 1-isomer, needles, m. 184-6¡ã. Chloromethylation of Tetralin gave a mixture, b15 142-8¡ã, of some 5- with 6-chloromethyl derivative of Tetralin. The mixture with Na benzhydroxamate gave mixed benzamido?xymethyl derivatives of Tetralin as a thick yellow oil. This (18 g.) refluxed 3 hrs. with 150 ml. 6% alc. HCl gave 6.8 g. 6-amino?xymethyl derivative -HCl of Tetralin, m. 190-1¡ã (alc.). 8-Amino?xymethyl-6-chloro-1,3-benzodioxan-HCl was prepared by alcoholysis of the benzohydroxamate as needles, m. 204-5¡ã (alc.-Et2O). Benzohydroxamate (3.2 g.) with alc. HCl gave 2.3 g. 8-amino?xymethylquinoline-2HCl, m. 193¡ã. The amino?xy HCl salt (0.1 mole), 0.1 mole dicyandiamide, and 70 ml. alc. refluxed 2-4 hrs., filtered, the mixture evaporated, and treated with alc.-HCl and Et2O gave the RONHC(:NH)(NHC(:NH)NH2 (VI).2HCl, which usually crystallized and was collected and recrystallized VI.2HCl were often deliquescent and this precluded anal. results. These compounds were characterized by their picrates. The following results were thus obtained (substituent and derivative of VI, and m.p. given): Me, 2HCl, 183-4¡ã; Et, 2HCl, 180-1¡ã; Et, picrate, 235-6¡ã; Pr, 2HCl, 142-7¡ã; Pr, picrate, 219-20¡ã; Bu, 2HCl, 135-6¡ã; iso-Bu, 2HCl, 142-4¡ã; iso-Bu, picrate, 225¡ã; pentyl, 2HCl, 129-33¡ã;pentyl, 95-6¡ã; pentyl, picrate, 204-5¡ã; hexyl, 2HCl, 138-41¡ã; hexyl, picrate, 204-5¡ã; hexyl, -, 102-3¡ã; heptyl, 2HCl, 135-7¡ã; heptyl, picrate, 210¡ã; octyl, -, 99-100¡ã; octyl, picrate, 209¡ã; nonyl, 2HCl, 148-52¡ã; decyl, 2HCl, 123-30¡ã; decyl, -, 100-1¡ã; decyl, picrate, 204-5¡ã; undecyl, 2HCl, 145-8¡ã 2-methyldecyl, 2HCl, 108-11¡ã; dodecyl, 2HCl, 162-4¡ã; dodecyl, picrate, 207-8¡ã; tetradecyl, HCl, 140¡ã; tetradecyl, picrate, 210-12¡ã; hexadecyl, -, 101-3¡ã. Benzyloxybiguanide-2HCl (VII) crystallized as needles, m. 150-1¡ã (alc.-EtOAc); the base-formed as plates, m. 111¡ã (H2O) [picrate, leaflets, m. 226-7¡ã (alc.-Me2CO)]. VII (1.4 g.) in 15 ml. alc. shaken 15 min. with H and 10% Pd-C, the filtered solution evaporated, the gum triturated with Et2O, and the product crystallized gave hydroxybiguanide-2HCl (VIII), m. 139-40¡ã (alc.-Et2O). In a 2nd experiment the filtered hydrogenation solution seeded yielded the pure material directly. The aqueous solution of VIII with aqueous Li picrate gave the picrate, yellow prisms, m. above 300¡ã, which appeared to be guanylurea picrate. On prolonged storage VIII decomposed to guanylurea-HCl, m. 173-4¡ã. p-Amino?xymethyltoluene-HCl (8.5 g.), 4.1 g. dicyandiamide (IX), and 50 ml. alc. refluxed 2 hrs.. evaporated, treated with alc.-HCl, Et2O, the 8 g. di-HCl salt dissolved in the min. amount of hot H2O, and basified gave the base as leaflets, m. 177¡ã (EtOAc-alc.). Isonicotinonoylhydrazine (X) (1.35 g.), 0.84 g. IX, and 15 ml. MeOH refluxed 24 hrs. gave 1.92 g. prisms, m. 138-42¡ã. This substance with picric acid gave isonicotinoylhydrazine dipicrate-H2O, m. 204-5¡ã. X (1.35 g.), 0.84 g. IX, 15 ml. MeOH, and 1 ml. concentrated HCl refluxed 1 hr. gave 1.86 g. isonicotinamidobiguanide-2HCl, m. 200¡ã (H2O). The following RONHC(:NH)NHC(:NH)NH2 were prepared (substituent, and derivative and m.p. given): p-ClC6H4CH2, -; 175¡ã; o-BrC6H4CH2, -, 188¡ã; p-O2NC6H4CH2, HCl, 216¡ã; o-O2NC6H4CH2. HCl, 179¡ã; 3,4-Cl2C6H3CH2, 2HCl, 171¡ã; 3-phenylpropyl, 2HCl.EtOH, 153-5¡ã; 1-naphthylmethyl, -, 145¡ã; 2-naphthylmethyl, -, 213¡ã; 1-methyl-2-naphthylmethyl, -, 1658¡ã; 1-bromo-2-naphthylmethyl, -, 158-60¡ã; 9-phenanthrylmethyl, H2O, 107-8¡ã; 9-phenanthrylmethyl, -, 95-8¡ã; 1-phenanthrylmethyl, H2O, 190¡ã; 6-tetrahydronaphthylmethyl, 2HCl, 138-41¡ã; 6-tetrahydronaphthylmethyl, -, 157-8¡ã; 6-chloro-8-(1,3-benzodioxanyl)methyl, -, 191-2¡ã. Benzohydrazide (20 g.), 12.5 g. IX, and 100 ml. alc. containing 5.1 g. dry HCl refluxed 3 hrs. gave 26.9 g. benzamidobiguanide-2HCl, m. 169-70¡ã (alc.-H2O). 1-Amino?xydecane (XI) (1.32 g.), 0.64 g. IX, and 10 ml. alc. refluxed 20 hrs. gave 0.60 g. unchanged IX and 1.2 g. XI. 8-Amino?xymethyl-6-chloro-1,3-benzodioxan (1.24 g.), 0.48 g. IX, and 10 ml. MeOH refluxed 20 hrs. gave only unchanged materials. IX was recovered when refluxed 24 hrs. in MeOH. ¦Á-Amino?xyheptanoic acid-HCl (2 g.) refluxed 1 hr. with 20 ml. 5% MeOH-HCl and evaporated gave a gum, which refluxed 2 hrs. with 0.84 g. IX and 20 ml. alc., then 2 hrs. with 25 ml. N NaOH, the solvent removed, the product taken up in H2O, brought to pH 6, and the solid collected gave 1.5 g. monohydrate, m. 127-8¡ã. Distillation with xylene gave 1-carboxyhexyloxybiguanide, m. 194¡ã. ¦Á-Amino?xyoctanoic acid (1 g.) in 20 ml. MeOH saturated with HCl refluxed 2 hrs., evaporated, the gum refluxed 2 hrs. with 0.48 g. IX, and 10 ml. alc., and hydrolyzed gave 0.5 g. 1-carboxyheptyloxybiguanide-H2O, m. 129-31¡ã (aqueous alc.). ¦Á-Amino?xynonanoic acid (0.8 g.) treated as above gave 0.3. g. 1-carboxyoctyloxybiguanide-H2O, m. 128-9¡ã. ¦Á-Amino?xydecanoic acid (1 g.) similarly gave 1.1 g. 1-carboxynonyloxybiguanide. H2O, m. 122-5¡ã (aqueous alc.), and thence by use of xylene 1-carboxynonyloxy-biguanide, m. 187-8¡ã.
Journal of the Chemical Society published new progress about 6084-58-8. 6084-58-8 belongs to catalysis-chemistry, auxiliary class Salt,Amine,Aliphatic hydrocarbon chain, name is O-Isobutylhydroxylamine hydrochloride, and the molecular formula is C4H12ClNO, Category: catalysis-chemistry.
Referemce:
https://courses.lumenlearning.com/boundless-chemistry/chapter/catalysis/,
Catalysis – Wikipedia