Patent GB-510683-A (GB)
Title: Improvements in or relating to the production of amino-substituted aryloxy-alkanol arseno compounds
IPC: C07F9/74
Filed: 1938-02-04
Abstract: 510,683. Organo-arsenic compounds. PARKE, DAVIS, & CO. Feb. 4, 1938, No. 3597. Convention date, Sept. 2, 1937. [Class 2(iii)] Water-soluble derivatives of diamino-di (hydroxyalkoxy)-arsenobenzenes are prepared by treating the arsenobenzenes with an alkali metal formaldehyde-sulphoxylate or formaldehyde-bisulphite. The products, which are substituted in one or both amino groups, are useful therapeutically. Examples describe the preparation of (1) sodium 3:31-diamino-4:41- di - # - hydroxypropoxy - arsenobenzene N - methylenesulphinate by reducing 4-arsenic acid - 2 - aminophenoxy - # - hydroxypiopanewith hypophosphorous acid and treating the product with sodium formaldehyde-sulphoxylate; (2) sodium 3:3<1>-diamino-4:4<1>-d- #- hydroxyethoxy - -arsenobenzene - N - methylenesulphinate by treating with sodium formaldehyde-sulphoxylate the product of the reduction of 4 - arsonic acid - 2 - aminophenoxyethanol with hypophosphorous acid ; (3) disodium 3:3<1>diamino-4:4<1>4di-#-hydroxypropoxy disodium 3:3<1> - diamino - 4:4<1> - di - # - hydroxy - propoxy - arsenobenzene - N:N<1> - dimethylenesulphinate by warming the arsenobenzene with sodium formaldehyde-sulphoxylate; disodium 3:3<1> - diamino - 4:4<1> - di - # - hydroxyethoxy - arsenobenzene - N:N<1> - dimethylenesulphinate is simarly prepared ; (4) disodium 3:3<1> - diamirio - 4:41 - di - # - hydro - ethoxy or propoxy - arsenobenzene - N:N<1> - dimethylenesulphonate by treating the corresponding arsenobenzene with sodium formaldehyde-bisulphite; (5) sodium 3-3<1> - diamino - 4:4<1> - di - G - hydroxypropoxy - arsenobenzene - N - methylenesulphinate and N:N<1>-dimethylenesulphinate by first reducing 4-arsonic acid-2-aminophenoxypropanol with hypophosphorous acid to the arsenobenzene and then reacting the latter with sodium formaldehyde-sulphoxylate ; (6) disodium 3:3<1> - diamino - 4:4<1>- di - y - hydroxypropoxy - arsenobenzene - N:N<1> - dimethylenesulphonate from the corresponding arsenobenzene and sodium formaldehyde-bisulphite ; (7) the methylenesulphinates and methylenesulphonates of 3:3<1>-diamino-4:4<1>-di (#G-dihydroxy - n - propoxy) - arsenobenzene by treating the arsenobenzene, obtained by reduction with hypophosphorous acid of 4-arsonic acid-2- aminophenoxy-glycerol, with sodium formaldehyde-sulphoxylate and -bisulphite respectively. The operations are usually carried out in an air-free atmosphere ; whilst in the case of (1) and (2), acid is added to hydrolyze any di-sulphoxylate formed and liberate the monosulphinic acid, from which an alkali salt is obtained by use of caustic alkali. Other specified hydroxyalkoxy groups that may be present in the products are the oxy-gamma-butanol and oxy-#-isopentanol groups. Specification 444,882 is referred to. The Specification as open to inspection under Sect. 91 also describes products containing aryl nuclei, such as' naphthyl, as well as products containing in one nucleus a different oxyalkanol group from that present in the other nucleus ; it further describes compounds in which the methylene-sulphinic or -sulphonie group is replaced by a -CH2.COOH residue, together with salts thereof. The arseno compounds containing the -CH2COOH residue are obtained by reacting a halogen-acetic acid with one or more of the amino groups of an aminoaryl-oxyalkanol-arseno compound or by reduction of the corresponding arsonic acids, arsenoxides or arsine dihalides. Additional methods are also described of making the arseno compounds containing a methylenesulphinic group, viz., by the action of excess of formaldehyde-sulphoxylate on the corresponding arsonic acids, arsenoxides or arsine dihalides, reduction to the arseno stage then taking place simultaneously with the introduction of the said group ; by using in this process the calculated quantity of formaldehyde-sulphoxylate, reduction to the arseno stage is simultaneous with the oxidation of the sulphoxylate to bisulphite and the introduction of the latter as a methylene-sulphonic group. Examples describe the preparation of (1) sodium 3:3<1>-diamino-4:4<1>-di<1>-p-hydroxypropoxyarsenobenzene-N-methylenesulphinate by heating 4-arsonic acid-2-aminophenoxy-#-hydroxypropane or its sodium salt with sodium formaldehyde-sulphoxylate and glacial acetic acid ; sodium 3:3<1>-diamino-4:4<1>-di-#-hydroxyethoxy-arsenobenzene-N-methylenesulphinate is similarly obtained from 4-arsonic acid-2-aminophenoxyethanol or its sodium salt; (2) disodium 3:3<1>-diamino-4:4<1>-di-#-hydroxyethoxy or propoxy - arsenobenzene - N :N<1> - dimethylenesulphinate by heating 4-arsonic acid-2-aminophenoxy-ethanol or -#-hydroxypropane or the sodium salt with sodium formaldehyde-sulphoxylate; (3) sodium 3:3<1>-diamino-4:4<1>-di-#- hydroxypropoxy -arsenobenzene - N methylenesulphihate by heating 4-arsenoxide-2-aminophenoxy-#-hydroxypropane, obtained by reducing the corresponding arsonic acid with hydriodic acid and sulphur dioxide, with sodium formaldehyde-sulphoxylate and glacial acetic -acid; sodium 3:3<1>-diamino-4:4<1>-di-#- hdyroxyethoxy -arsenobenzene - N - methylenesulphinate is similarly prepared ; (4) sodium 3:3<1>-diamino-4:4<1>-di-#-hydroxy-propoxy or ethoxy-arsenobenzene-N-methylenesulphonate by heating the corresponding N:N<1>-dimethylenesulphonate with dilute hydrochloric acid and topping up with caustic soda ; (5) sodium 3:3<1> - diamino - 4:4<1> - di - gamma - hydroxypropoxy - arsenobenzene-N-methylenesulphinate by heating 4-arsonic acid-2-aminophenoxypropanol with sodium formaldehyde-sulphoxylate and glacial acetic acid, the same product is obtained by treating the corresponding arsenoxide, prepared by reducing the arsonic acid with hydriodic acid and sulphur dioxide, with sodium formaldehyde-sulphoxylate; the corresponding N:N<1>-dimethylenesulphinate results when either the arsonic acid or the arsenoxide is heated with sodium formaldehyde-sulphoxylate; (6) sodium 3:3<1>-diamino-4:4<1>-di-gamma-hydroxypropoxy-arsenobenzene-N-methylenesulphonate by acidification of the dimethylenesulphonate ; (7) disodium 2:2<1>-di-#-hydroxyethoxy-5:5<1>- arseno-diphenylglycine by first reacting 4- arsonic acid-2-aminophenoxyethanol with chloracetic acid and reducing the product with hypophosphorous acid ; the corresponding 2:2<1>-di-# and gamma-hydroxypropoxy compounds are similarly prepared ; (8) sodium 3:3<1>-diamino- 4:4<1>-di-#-hydroxyethoxy or propoxy-arsenobenzene-N-methylene-carboxylate by reducing with hypophosphorous acid a mixture of 5-arsonic acid-2-#-hydroxy-ethoxy or propoxyphemylglycine and 4-arsonic acid-2-aminophenoxy-ethanol or -#-propanol respectively ; (9) sodium 3:3<1>diamino-4:4<1>-di (#gamma-dihydroxy-npropoxy-arsenobenzene-N-methylenesulphinate by treating 4-arsonic acid-2-aminophenoxyglycerol or the corresponding arsenoxide with sodium formaldehyde-sulphoxylate ; (10) 2:2'- di (#gamma-dihydroxy-n-propoxy)-5:5<1>- arseno - diphenyglycine by reacting 4-arsonic acid-2- aminophenoxy-glycerol with chloracetic acid and reducing the product with hypophosphorous acid ; (11) 3:3<1>-diamino-4:4<1>-di<1> (#gamma-dihydroxyn - propoxy) - arsenobenzene - N - methylenecar - boxylic acid by reducing a mixture of 2- (#gammadihydroxy-n-propoxy) -5-arsonic acid-phenylglycine and 4-arsonic acid-2-aminophenoxyglycerol with hypophosphorous acid. The compound obtained by reducing 3-amino-5- #-methylethoxy-phenylarsonic acid, as well as products containing additional amino groups, are also mentioned. This subject matter does not appear in the Specification as accepted. 4- Arsonic acid-2-aminophenoxyglycerol is prepared by treating sodium p-hydroxyphenylarsonate with glycerol-alpha-monochlorhydrin, nitrating the resulting 4-arsonic acid-phenoxyglycerol.with fuming nitric acid to give 2-nitro- 4-arsonic acid-phenoxyglycerol dinitrate, hydrolysing with sulphuric acid, and reducing the 2-nitro-4-arsonic acid-phenoxyglycerol so obtained with hydrogen under pressure in the presence of an. activated nickel catalyst prepared as described in U.S.A. Specifications 1,563,587, 1,628,190 and 1,915,473.