von Walther, R. F.; Zipper, W. published an article in 1915, the title of the article was p-Chloro- and p-bromo-m-cresols. I.Recommanded Product: 39503-58-7 And the article contains the following content:
Halogenated cresols have powerful antiseptic properties; p-chloro-m-cresol surpasses all other analogous phenol derivatives in this respect and therefore derivatives of this substance are of special interest. While the chlorination of o- and p-cresol with the formation of monosubstitution products proceeds with comparative case (cf. Ber. 16, 1598), m-cresol shows a great tendency to take up 2 atoms of Cl and it is only by protecting the OH group or observing special precautions as to temperature and dilution that the formation of dichloro-m-cresol can be avoided. By chlorinating m-HOC6H4Me (a) in glacial or 90% AcOH both at room temperature and at 100°, the following compounds were isolated by W. and Z.: 2,4,6-trichloro-m-cresol (b), 1-methyl-2,4,5-trichloroquinone dichloride (c), 1-chloromethyl-2,4,5-trichloroquinone dichloride (d), and 2,4,5-trichlorotoluquinone (e). (b) seps. in prisms when (a) in glacial AcOH is saturated cold with Cl; faintly yellow needles in clusters, m. 45° (cf. C. A. 6, 354; 7, 2546). When the filtrate from (b) is again saturated with Cl and allowed to stand, (d) seps.; prisms from alc., m. 117°. (e) is obtained when (a) is saturated at 100° with Cl. Some (d) seps. on cooling, which is filtered off, the solution again saturated with Cl, cooled, and diluted with H2O, when an oil seps. which deposits (e), yellow leaves from alc., m. 238° (decomposition). This m. p. is somewhat higher than that ascribed by previous investigators (cf. Ann. 168, 268; 172, 210; 237, 145) and lower than that of Michaelis (Ann. 293, 275). When (a) in the least quantity of 90% AcOH is saturated with Cl at 100°, a yellow oil and a crystalline solid sep. on cooling. The latter consists of (c), (d) and (e), which may be separated by crystallization from alc. 4,6-Dichloro-3-cresol (f), probably the dichloro-m-cresol obtained by Claus and Schweitzer (Ber. 19, 927) on chlorinating (a) hot and considered to be the 2,4-Cl2 compound, was obtained by W. and Z. from 6-chloro-3-cresol (p-chloro-m-cresol) (g), when treated in warm aqueous Na2CO3 with the calculated quantity of Cl and allowed to stand. The yellow oil which seps. on dilution with H2O is probably a mixture of mono-, di- and trichloro-m-cresols; on long standing (f) crystallines from this mixture, needles from Et2O, m. 45-6; FeCl3 gives no phenol reaction. Contrary to the finding of C. and S., neither this product nor any other dichloro-m-cresol was ever obtained by W. and Z. by the direct chlorination of (a) in AcOH. 6-Bromo-3-cresol (h) is obtained smoothly in 83% yield when (a) in CCl4 is treated slowly with the calculated amount of Br at -5° to -10°; needles from H2O or ligroin, volatile with steam, m. 62°; 100 cc. H2O dissolves 0.1713 g. at 19°. Benzoyl derivative, from BzCl in C5H5N, needles from alc., m. 83-83.5°. 6-Chloro-4-bromo-3-cresol (i) is obtained in needles when (g) in CCl4 is treated with Br in CCl4 in portions and the solvent evaporated; needles from petr. ether, m. 70-70.5°. When (g) in glacial AcOH is treated with Br until the red color persists, a brownish red oil seps., from which 6-chloro-2,4-dibromo-3-cresol (j) is extracted by 50% AcOH; needles from petr. ether, m. 70°-70.5°, b17 177°; yield, 67%. 6-Chloro-3-hydroxy-4-toluic acid (p-chloro-m-cresotinic acid) (k), previously prepared by Gattermann (Ber. 26, 1851), is obtained in 95% yield when dry Na (g) is heated at 160-75° with an excess of CO2 at high pressure for 6 hrs. The brown product is dissolved in NaOH, largely diluted, decolorized hot with SnCl2, filtered and precipitated by HCl; leaves from CHCl3, needles from alc., m. 206-7°; it is volatile with steam and sublimes readily; 100 cc. H2O dissolves 0.0120 g. at 12°. (The Na salt of (g) is much more readily decomposed than PhONa; in the presence of a trace of H2O, it chars as low as 180°.) (k) is also formed in almost quant. yield by the action of Cl (calculated amount) on m-cresotinic acid (l) in glacial AcOH. (c), (d) and (e) are also formed in small quantities, but there was no tendency to form polyhalogenated cresotinic acids when AcOH, CCl4, CHCl3, C6H6 or Me2CO were used as solvents. Alc., AcOEt, Et2O, ligroin and CS2 are not suitable mediums; H2O leads to the formation of (e). Sodium salt of (k), seps. in leaves from 96% alc.; potassium salt, needles from H2O; lithium salt, clusters of needles from alc.; ammonium salt, needles from alc.; neutral calcium and neutral barium salts, leaves from H2O; silver salt, fine needles; lead, mercury and aluminium salts, all very difficultly soluble; magnesium salt, leaves from H2O; manganese salt, bright violet needles from H2O; basic copper salt, green leaves, insoluble in H2O; bismuth salt, very difficultly soluble With FeCl3 (k) gives a violet coloration; when the chloride is in excess a brownish red precipitate seps. Hexamethylenetetramine p-chloro-m-cresotinate, (CH2)6 N4.C8H7O3Cl, prisms from alc., m. 170° (decomposition) and gives a weak blue fluorescence in aqueous NaOH; antipyrine salt, C8H7O3Cl.C11H12ON2, needles from H2O, m. 128°; quinine salt, C8H7O3Cl.C20H24O2N2, an oil from H2O, crystallizing in indefinite form; cinchonine salt, C8H7O3Cl.C19H22ON2, indefinite crystals from H2O. Methyl ester of (k), (m), leaves from MeOH, m. 55°; ethyl ester (n), faintly yellow leaves from 96% alc., m. 52-3°; propyl ester (o), prisms, m. 21°, b18 168-70°. Methyl 2-methoxy-4-methyl-5-chlorobenzoate (p), from the Na salt of (m) with EtI or from the Na salt of the (l) with Me2SO4 in NaOH solution, faintly yellow needles from MeOH, m. 53-4°, b14 160°. Methyl 2-ethoxy-4-methyl-5-chlorobenzoate b11 170°; precipitated from MeOH by H2O in faintly yellow needles, m. 54°. Methyl 2-propyloxy-4-methyl-5-chlorobenzoate, b24 188°. Methyl 2-isopropyloxy-4-methyl-5-chlorobenzoate, a highly refractive oil, b19 173°. Methyl 2-butyloxy-4-methyl-5-chlorobenzoate, faintly yellow refractive oil, b20 194°. Methyl 2-isobutyloxy-4-methyl-5-chlorobenzoate (q), refractive oil, crystallizing in prisms, b14 187°. Methyl 2-isoamyloxy-4-methyl-5-chlorobenzoate, faintly yellow refractive oil, b18 197°. 2-Methoxy-4-methyl-5-chlorobenzoic acid, obtained by saponification of (p), prisms from alc., m. 130°; sodium salt, needles; the salts of the alkali metals and the ammonium salt are soluble; calcium, barium, lead, silver, the yellow ferric and the blue copper salts are all difficultly soluble 2-Ethoxy-4-methyl-5-chlorobenzoic acid (r), needles from H2O, m. 143°, 2-propyloxy-4-methyl-5-chlorobenzoic acid, broad prisms from CCl4, m. 112° (sodium salt, needles), 2-isopropyloxy-4-methyl-5-chlorobenzoic acid, long prisms from ligroin, m. 121°, 2-butyloxy-4-methyl-5-chlorobenzoic acid, needles from ligroin, m. 96.5°, and 2-isoamyloxy-4-methyl-5-chlorobenzoic acid, leaves from ligroin, m. 94°, are all obtained by saponification of the corresponding esters. Saponification of (q) with alc. NaOH gave a mixture of 2-isobutyloxy-4-methyl-5-chlorobenzoic acid and (r), m. 117°, which could not be separated 3-Methyl-4-chlorophenyl salicylate, C6H4(OH)CO2C6H3MeCl, is formed when o-HOC6H4CO2H is heated at 135-40° with (g) in the presence of POCl3; fine needles from alc., m. 74°. 3-Methyl-4-chlorophenyl p-chloro-m-cresotinate, from (k), (g), and POCl3 at 140°, small needles from MeOH, m. 142°. Phenyl p-chloro-m-cresotinate (s), needles from MeOH, m. 88°. β-Naphthyl p-chloro-m-cresotinate, prisms from Me2CO, m. 137.5°. Saponification of these new “salols” shows a behavior similar to C6H4(OH)CO2Ph; their therapeutic application is thus possible. Acetyl-p-chloro-m-cresotinic acid, clusters of needles from CCl4, m. 146°. 5-Chloro-4-methyl-2-hydroxybenzoyl chloride (t) is easily obtained on heating (k) with SOCl2 at 80°; long needles from petr. ether, m. 48°; it cannot be distilled without decomposition Treated with PhOH, (t) gives (s). The amide of (k), leaves from alc., is formed when (t) is treated in Et2O with dry NH3; anilide, leaves from alc., m. 222°; p-phenetidide, from (t) and p-NH2C6H4OEt, leaves from 96% alc., m. 215°. 6-Bromo-3-hydroxy-4-toluic acid (p-bromo-m-cresotinic acid) (u) is obtained in theoretical yield when 106 g. Br in 300 g. CCl4 is slowly dropped into 100 g. (l) in 1 kg. CCl4 and let stand 24 hrs.; prisms from 96% alc., which give a bluish violet coloration with FeCl3 and m. 221° (not 211°, as Gattermann, Ber. 26, 1851, gave it); ammonium salt, needles from H2O; the alkali, cobalt and magnesium salts are all easily soluble while the barium, silver, mercury, lead, gold, bright yellow platinum, brownish violet ferric and yellowish green copper salts are all difficultly soluble Both (k) and (u) are more powerful antiseptics than o-HOC6H4CO2H. Methyl 2-methoxy-4-methyl-5-bromobenzoate, formed when (u) is treated with Me2SO4 and MeONa, seps. from dilute MeOH in leaves, in 45-6°; the yield is small as the chief product is methyl 2-hydroxy-4-methyl-5-bromobenzoate, needles from MeOH, m. 48°. Acetyl-p-bromo-m-cresolinic acid seps. in leaves from CHCl3, m. 155°. When (g) in 80% AcOH is treated cold with dilute HNO3, a yellow substance seps. from which 6-chloro-4-nitro-3-cresol (v) is obtained on crystallization from alc. in yellow leaves, m. 133.5°; ammonium salt, orange yellow leaves from H2O, m. 146° (decomposition); sodium salt, red needles; potassium and barium salts, red leaves; calcium salt, orange-red needles; mercury salt, brownish yellow leaves; copper salt, bright green leaves; lead salt, brick red; ferric salt, yellowish to dark brown, featherlike crystals; aluminium salt, yellow featherlike crystals; chromium salt, bright green; silver, gold, and platinum salts, yellow leaves; aniline salt, yellow leaves from alc., m. 134°; p-toluidine salt, bright yellow leaves, m. 133°; o-toluidine salt, yellow leaves, m. 132°. On evaporating the alc. mother liquors from (v), 6-chloro-2,4-dinitro-3-cresol (w) seps.; yellow leaves from ligroin, m. 69°. If heat is applied during the nitration of (g), (w) is the only product of the reaction. Ammonium salt, orange needles, m. 190-224° (decomposition); sodium salt, orange; potassium salt, orange needles; calcium salt, golden yellow scales; barium salt, microscopic orange needles; mercury salt, reddish brown needles; copper and lead salts, brown needles; ferric and aluminium salts, brown leaves; chromium salt, leaves; silver, gold and platinum salts, yellow needles; aniline, p-toluidine and o-toluidine salts, orange needles, m. 136°, 145° and 78°, resp. Reduced with H2SO3 in boiling H2O, (v) is converted into 6-chloro-4-amino-3-cresol, which seps. on cooling in leaves, m. 143°; yield, 80%. The experimental process involved the reaction of Methyl 5-bromo-2-methoxy-4-methylbenzoate(cas: 39503-58-7).Recommanded Product: 39503-58-7
Methyl 5-bromo-2-methoxy-4-methylbenzoate(cas:39503-58-7) belongs to organobromine compounds. Most organobromine compounds, like most organohalide compounds, are relatively nonpolar. Bromine is more electronegative than carbon (2.9 vs 2.5). Consequently, the carbon in a carbon–bromine bond is electrophilic, i.e. alkyl bromides are alkylating agents. Recommanded Product: 39503-58-7
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary