ratentamt JcuropaiscnesEuropean Patent Office ® Publication number: 0108 294 vsrriceOffice europeeneuroDeen aesdes Drevetsbrevets B1 ® EUROPEAN PATENT SPECIFICATION (45) Date of publication of patent specification: 06.02.91 (g) int. CI.5: C 01 B 21/14, C 07 C 51/41, C 07 C 249/04< C 07 C 259/04 ® Application number: 83110342.9 (22) Date of filing: 17.10.83 w> preparation trom nyaroxyiammomum suirate ot alcoholic hydroxylamine solutions and of oximes, hydroxamic acids and other hydroxylammonium salts via alcoholic hydroxylamine solutions. & rriorixy: ui.il.tsz US 437920 (73) Proprietor: ALLIED-SIGNAL INC. (a Delaware 23.09.83 US 534292 corporation) 23.09.83 US 534291 Columbia Road and Park Avenue P.O. Box 2245R Morristown New Jersey 07960 (US) g) Date of publication of application: 16.05.84 Bulletin 84/20 ® I nventor: Mathew, Chempolil Thomas 9 Openaki Road tandolph New Jersey 07869 (US) ruDiication ot the grant of the patent: nventor: Ulmer, Harry Edwards 06.02.91 Bulletin 91/06 !6 Ellsworth Avenue /lorristown. New Jersey 07960 (US) HJ Designated Contracting States: BE CH DE FR GB IT LI NL SE J5) Representative: Brock, Peter William et al URQUHART-DYKES & LORD 91 Wimpole Street London W1M8AH (GB) nererences citea: DE-B-1247284 JS-A-2483252 JS-A-3420 621 JOURNAL OF ORGANIC CHEMISTRY, vol. H,May 1946, pages 207-214, Washington, US; ID. HURD et al.: "Hydroxamic acids from iliphatic dicarboxylic acids" wie. vviuiim nine monms rrom Tne puDiication or the mention of the grant of the European patent, any person may jive notice to the European Patent Office of opposition to the European patent granted. Notice of opposition shall )e filed in a written reasoned statement. It shall not be deemed to have been filed until the opposition fee has been >aid. (Art. 99(1) European patent convention). ouner rress, Leamington Spa, England. tr w IUO £94 D I chloridl V th7X XHn,the f°7 °f S3,tS SUCh 88 hydroxylammonium sulfate, or * hydroxylammonium oham!J^ch^Z V 35 3 reagent f0r preparing various 5 m USld industrial- sPeciality susceoSe SSES™ Pr°dUCtS oxime or substituted to ^ c°.ntaiAnln9 hydroxylamine groups are not 3!fJ5,« fh 1qUe°US med'a- Accordingiy, such materials are normally prepared by , Chl0n'de th" SSn^Mnl?™n^^a^m0?Um in °rganiC S0'VentS SUCh as methano1 with or9anic sulfate cSid sufflc,en,t base to neutralize *e by-product HCI. Because sulfate (also(a so caNed hln , hydroxylammonium hydroxylamine sulfate) is not soluble in methanol, however, the cheaper sulfate ^^0^^reaoent preX tLn^^rSlVd'fh6 TV^""" hVd-Vlammonium ZZZ £nnn,^T£ i V- lSCh'9 pr0CeSS) and therefore would desirab|y be ™de from the uS^^T^iT^^'^ eXC'USi0n °r 6XtraCti0n C0,Umn a- contained in Hydroxylammonium salts of organic acids are made in US-A-2483252 " by reaction of hvdroxvl- sirwX"heSSionCthl°ride a,mm°niUm °r 3,kali metal SaltS 0f such acid< added LcS o^made situ with the reaction as in temperature being usually 40— 70°C. (see col. 2, lines 1—37) A process for producing hydroxylammonium perchlorate is for disclosed in US— A— d<W0W1-3420621 A Processnrocpss producing alcohol hydroxylamine slution is disclosed in DE-B-1247284 hvdrox^S^M^T di,SCOhVe,red ™hich enahles solid hydroxylammonium sulfate v to be used to provide amZntm Sr3£m i S°iVt,0.ns and t0 Produc« oximes, hydroxamic acids and other h^lroxyl. wte the MnTri^JtS^S Accord'n9ly, present invention in its first form includes a 'process atCOh0li° soliJlXnvlio ^Ut]0n 0f sodium hydroxide, or a sodium alkoxide having EP 0 108 294 B1 may be as high or about 30°C, is preferably no greater than 20°C and more preferably no greater than 10°C. Comparative Example 3, below, illustrates the significantly lower yields obtained at 35 — 40°C compared to those obtained at 22— 25°C (e.g., Example 2) and at 5 — 10°C (e.g., Example D.The concentration of sodium hydroxide in methanol or ethanol is not critical, but it is preferred to operate as near to the solubility limit of s sodium hydroxide in the alcoholic solvent as possible without creating so viscous a solution that agitation becomes difficult. Larger amounts of the solvent may also be used if tolerable in subsequent reactions. Various of the examples illustrate the use of relatively concentrated methanolic and ethanolic solutions of sodium hydroxide in the present process. The amount of sodium hydroxide should be at least that required to neutralize 50% of the hydroxylammonium sulfate reacted, preferably at least that necessary to neutralize 10 all of the hydroxylammonium sulfate. It is contemplated that greater amounts of sodium hydroxide than that stoichiometrically required may be used and, as indicated in Example 9 below, such excess sodium hydroxide may increase the reaction rate without detracting from reaction yields. Excess sodium hydroxide is normally to be used, however, only if the product alcoholic solution is to be used as a reagent in processes where more base would normally be charged at a later time. In other cases, the excess base can 15 be neutralized before the solution is used further. Thus, the product solution can be formed at any desired pH such as from 5 to 12. In using sodium hydroxide in ethanol as the solvent, lower temperatures are still preferred, with reaction being below 30°C, preferably below 20°C and more preferably no greater than 10°C. It appears, however, that the reaction in ethanol is less temperature dependent than the reaction in methanol (see 20 Examples 11 and 12 below). While isopropanol or propanol may be used as solvents with NaOH, the limited solubilities of the hydroxide and of the product hydroxylamine in these solvents makes these embodiments less preferred to those described above. In using sodium hydroxide, pressure is not a critical factor since neither the base nor the solvent is very 25 volatile. Alkoxides, i.e. sodium methoxide, ethoxide, isopropoxide, propoxide, butoxide and pentylate may be used in place of the hydroxide, having the advantage of not producing water as by-product. Therefore, when a substantially water-free hydroxylamine solution is desired, these more expensive alkoxide bases should be used. Normally, the solvent will correspond to the anion (e.g., sodium methoxide in methanol), 30 but mixed systems (e.g., sodium butoxide in methanol) may be used if the solvent later present (after the hydroxylamine-consuming reaction) is not to be recovered and recycled or can be distilled. While the anion may be larger than three carbons, the solvent is a 1 — 3 carbon alkanol (and is preferably methanol or ethanol) because free hydroxylamine is more soluble in these lower alkanols. If the product hydroxyl- ammonium salt is organic (e.g. the acetate) and the anion is present initially (e.g. by reacting sodium 35 acetate), then the solubility of free hydroxylamine becomes less critical and higher alcohol solvents, e.g. isopropanol or n-propanol, become more suitable. Alkoxides are more expensive than hydroxides and are, therefore, normally not used unless the 3% or so water in the product solution of the above reactions of hydroxide cannot be tolerated for a particular use. The present invention, using alkoxides, still makes available the use of cheaper hydroxylammonium sulfate 40 for such water-sensitive uses. In each case, one preferred mode of conducting the reaction is to first dissolve (or slurry) the base in the alcohol and then react the alcoholic solution with hydroxylammonium sulfate. As illustrated by Examples 1 and 8, below, essentially identical results can be achieved either by adding the solid hydroxyl- ammonium sulfate to the alcoholic solution or by adding the alcoholic base to the solid hydroxyl- 45 ammonium sulfate. Furthermore, it is contemplated that the two may be mixed in any conventional batch or continuous process scheme normally used to react a solid with a liquid. A less preferred method of conducting the present invention is to mix the base (solid) with the hydroxylammonium sulfate first, and then to add the alcohol. This scheme is less preferred because the process of dissolving the base in the alcohol (which is required before the reaction can occur) is normally an exothermic reaction. Since high so temperatures are to be avoided it is desirable that the act of dissolving base in alcohol be conducted first, that the alcoholic solution be cooled and that the cooled alcoholic solution be reacted with the hydroxyl- ammonium sulfate. Another less preferred method is to add the base slowly to hydroxylammonium sulfate slurried in alcohol. In the second form of the invention, once the reaction between alcoholic base and hydroxylammonium 55 sulfate is complete, or while it is proceeding, the alcoholic solution containing hydroxylamine values is further reacted with either a mineral acid (inorganic acid) or an organic acid. In one mode, this reaction is conducted after separating the by-product sulfate (e.g., sodium sulfate) from the alcoholic hydroxylamine solution. Thus, as illustrated in certain Examples below, the separated hydroxylamine-containing liquid phase is reacted with acids such as HCI, nitric acid, phosphoric acid, perchloric acid, oxalic acid, acetic acid, 60 formic acid or benzoic acid to produce the corresponding hydroxylammonium salt (e.g., hydroxyl- ammonium chloride, hydroxylammonium nitrate, dihydroxylammonium oxalate ortrihydroxylammonium phosphate). In addition to these acids exemplified, one can use, for example, arsenic acid, fluoboric acid, propionic acid, toluenesulfonic acid, benzenesulfonic acid. In general, because of the ease of reacting alcohol hydroxylamine solutions, any such acid can be used even if the product is slightly unstable, such as 65 is the case for the formate, nitrate and perchlorate.