,. 2,868,787 United States Patent 1C6 Patented Jan. 13, 1959 1 conditions and localized areas of high bromine concen tration. 2,868,787 The following equation will illustrate the preparation of PROCESS OF PREPARING N-BROMINATED N-bromo succinimide from succinimide by this prior art HALOGEN COMPOUNDS, process: Laurene 0. Paterson, Adrian, Mich., assignor to Drug II Research, Inc., Adrian, Mich., a corporation oliMichi C Biz-C gall ' ' NH + Bra + NaOH ----->v No Drawing. Application August 6, 1956 Serial No. 602,466 10 112-0 ‘ 4 Claims. (Cl. 260-248) O CHr-(ii _ U This invention relates to new methods of preparing NBI‘ + NaBr + 1120 15 organic halogen carriers and speci?cally relates to new H's-C methods of preparing organic halogen carriers contain ' ii u) ing bromine alone or both chlorine and bromine and is di rected particularly to the class of halogen carriers char From this equation it is readily seen that one-half of’ the acterized as N-halogen compounds. bromine introduced into the reaction mixture is lost as Generally, the class of compounds which may be pre 20 by-product. Since bromine is a costly reagent, it would pared by the present process are characterized as halo be advantageous‘ to provide a process for preparing N genating agents containing at least one N-halogen radical 'brominated halogen carriers which does not involve the in which structure .the halogen atom is loosely bound to loss of by-product alkali bromide. ' the nitrogen atom and is readily available for chemical Accordingly it is an object of the present invention to reaction. Speci?cally, the products produced by this 25 provide a process for preparing N-bromo halogenating process arethose which contain at least one N-bromo radi agents which completely utilizes the bromine reactant. cal and may also contain additional N-bromo or N-chloro Another object is to provide a process for preparing N groups. Thus compounds such as N-bromo succinimide, bromo halogen carriers which employs mild reaction con- ‘ N-bromo phthalimide, N-bromo-cyanuric acids, N-bromo ditions. melamines, N,N-dibromo-S-substituted hydantoins, N A further object is to ‘provide a process for preparing brorno-toluene-sulfonamide, N-bromo-3a,6a-substituted N.-bromo halogen carriers which may be carried out in the _ glycolurils, N-bromo-S-substituted barbiturates and .the absence of strong base. like are contemplated as products which may be prepared A further object is to provide a process for preparing : by this process. In addition, one may also prepare the N-halogen carriers which does not employ elementary 35 mixed dihalo-(N-bromo-N-chloro) compounds where 'bromine.. - more than a single nitrogen atom is in the carrier mole A still further object is to provide a process for making cule, such as for example, N-chloro-N-bromo-S-substitut mixed N-bromo-N-chloro halogen carriers. ed hydantoin. Further and additional objects will appear from the The compounds which are particularly preferred as N following description and the appended claims. halogen carriers are classi?ed as N-cyclic imides and are 40 In one broad aspect of this invention there is provided represented by the hydantoins, succinimide, phthalimide, a processfor preparing N-bromo halogen carriers con cyanuric acid, the glycolurils, and the like. I taining only bromine which comprises treating an N The properties and methods of manufacture for many chloro organic nitrogen compound with a bromine pro of these compounds have been described in the chemical ducing compound such as a bromide. Generally the or literature: N-bromoacetamide, Behrend and Schreider, ganic nitrogen compounds which are suitable starting Ann. 318, 373 (1901), N-bromo succinimide, Ziegler, materials to prepare the N-bromo derivatives are N Ann. 551, 109 (1942),. N-mono- and N-N-‘dibromodi chloro organic nitrogen compounds containing at least methyl hydantoin, Orazi, Anales, Asociacion Quemica one radical selected from the group consisting of: Argentina, vol. 37, 192 (1949), and vol. 38, 5 (1950). In ‘the preparations as described, the carrier is usually reacted in alkaline medium with bromine, and the N brominated compound isolated in a solid crystalline form. “Halogen carriers which contain both bromine and chlorine are also known, being described in my copend 55 ing application Serial No. 438,633, ?led June 22, 1954, now U; S. Patent No. 2,779,764.. That prior application describes methods of preparing N-bromo-N-chloro-S-sub stituted: hydantoins and N,N-dibromo-S-substituted hy The bromine producer may be a bromide such as a bro d'antoins. . a . 60 mine salt of the character of sodium bromide, potassium 'Generally, the methods employed in the prior art to bromide, and the like. The process of the present inven prepare these N-brominated carrier compounds comprise tion may be carried out in an aqueous media, or if desired reaction of the unsubstituted carrier with elementary bro may ‘be carried out in inertorganic solvents such as mine in an aqueous alkaline media. In such a reaction heptane, hexane, carbon tetrachloride, and the'like. one-half of the bromine molecule (Br-2) substitutes for (S5 The amount of bromine producer or bromide which is the ‘hydrogen atom in the >N—H radical and‘the remain utilized in this particular embodiment of the vprocess der combines with that hydrogen atom to form hydrogen should be at least one equivalent of bromide for each re bromide (HBr). This acid then reacts with the alkali ' placement of a removable chlorine atom contained in the I present to form the alkali bromine salt as a by-product. >N'—Cl radicals in one mole of the halogen carrier start- 1 The carrying out of this reaction by these prior art meth ing materials. Thuswhere a carrier starting material con-' " odsjis sometimes rendered dif?cult since the carrier com 70 tains but a-‘single >N-—Cl group an equivalent of a bro pounds. areoften. adversely. affected by strongly>alkaline ' trnide-such asNaB'r (or-one mole) would be required per 2,868,787 4 mole‘ of "starting'material. Similarly, where the carrier in 500 milliliters of iced water containing 40 grams of ' starting‘material contains two >‘N-chloro'groups, two‘ sodium hydroxide and ‘55 grams of sodium carbonate. equivalents of bromide are required per mole of carrier To this were added 320 grams of bromine with agitation. starting material.. Thus, to produce an N,N-dibromo-5 When all the bromine had been taken up, 197 grams of substituted hydantoin,‘one would react one mole of N,N— N,N-dichloro-dimethyl hydantoin were stirred in, and dichloro-S-substituted hydantoin with at least-two-moles of agitation continued until the bromination of the N,N-di a bromidesuch‘ as.N-al3r. if a divalent. salt such as chloro-dimethyl,derivative was also complete. The re CaBrz were‘ used, two equivalents or one mole would be sultant Washed and dried product weighed 550 grams, ‘and required. analyzed 55 .1 %“ bromine. It had a melting point of 188° The overall process may ‘be exempli?ed by the follow 10 C. The reactions-involved in this process are: ing equation:

15

(2) As may be seen from‘ the above equation, this particular 20 embodiment results in the production of an N-bromo halogen carrier without the use of elementary bromine or alkali. It is also apparent thatall of the bromide react ant is utilized and the only by-product is the low cost NaCl. 25 It is also contemplated as an embodiment of this present. process the production of N-bromo halogen carriers The aboveE'quations 3 and 4 illustrate the sequenceof‘: wherein the carriers also contain unsubstituted N-hydro the reaction which may be described in its overall aspects‘ gen radicals. According to this modi?cation one may according to the following equation: treat a carrier starting material which contains both N 30 chloro radicals and N-hydrogen radicals with a bromide to replace the chlorine atoms with bromine. Thusfor. ex ample one may react N-monochloro-S-substituted hy dantoins with an equivalent of a bromide such as sodium bromide to produce an N-monobromo-S-substituted hy-. 35 dantoin. It will be noted that in this particular. embodi ment, as well as the foregoing broad process wherein all of the N-‘chlororadicals are changed to N-bromo, radicals, all of the bromide reactant is utilized to produce a bromine carrier compound. It is also apparent that by this‘modi 40 It is also contemplated as an embodiment of thepresent. ?cation one may produce N-bromohalogenating agents invention, theprovision of a process for producing N— under mild reaction conditions characterized by the ab bromo-N-chloro halogen carriers by reacting an..N sence of strong reagents such as elementary bromine. or chloro carrier compound of the character previously de alkali. scribed with a bromide. It has beenfound that by av The following examples will illustrate the foregoing modi?cation of the broad process one may obtain these. embodiments of the process of the present invention: mixed chloro-bromo carrier compounds by utilization.of_ Example 1 the broad concepts disclosed for the production .of..N bromo halogenating agents. Generally to prepare these 103 grams of sodium bromide were dissolved in 200 mixed halogen carriers one reacts an N-chloro. halogen. milliliters of water. To this were added, with agitation, carrier containing at least 2-N-chloro radicals with. .a 134 grams of N-chloro succinimide; Stirring was con- ' bromine salt. I The amount of bromide required. ,to pro-i tinned for 15 minutes, at'which time the N-bromo-succini duce ,these mixed chloro-bromo halogen. carriers is. less... mide was?ltered 'o?, washed free of sodium chloride, and thanthat which is requiredfor complete replacementof dried. It weighed 169 grams, analyzed 44.6% active all-of the N-chloro substituents. Thus, for. example; by bromine, and had a melting :point of 173°- C. reacting. a mole of N,N-dichloro-5-substituted hydantoin Example 2 with one equivalent of a bromide such as KBr, a mixed An aqueous slurry of 63 grams of melamine in a liter chloro-bromo hydantoin . is produced- Generally the of water was prepared, and a stream of chlorine bubbled amount of bromide required to carry out this reaction may through the mixture until 71 grams had been taken up. vary but in all cases it will be less than an amount which: The resultant chlorinated product was ?ltered oil and 60 would be required to completely substitute all of the N washed. It was resuspended in water, treated with a solu chloro substituents. It is also possibleto prepare .N tion of sodium bicarbonate to adjust the pH to 6.7, and chloro-N-bromo-N-hydrogen carrier compositions byte 100 grams of calcium bromide added. The resultant acting a carrier molecule which contains at least. three. available irnide groups of which only two are chlorinated. N,N-dibromomelarninc was removed on a ?lter, Washed free of salts, and dried. It analyzed 55.8% bromine. 65 Thus, for example, one may react N,N-dichloro cyanuric . acid Withsodium bromide to produce N-chloro-N-bromo . Example 3 cyanuric acid. The N-chlorinated carrier may also be used in conjunc The following examples will illustratethe various.-.em¢.' tionwith elementary bromine to make available all the‘ bodiments ofthe process, of the present inventionas .ap-% bromine added to the process. In this method of manu‘ 70 plied to making. mixed chloro-bromo halogenatingagents-l. facture, the; carrier, is treated‘ with bromine and sufficient . from ,N-chloro starting materials. . _ . alkali to . take, up the. hydrogen bromide. The.correspond-.~ Example '4 ~' ing. .N-chlorinated ‘carrier... is then... added 'to displace, fth?x bromine}from.=the by-product .bromine;salt. . Thusz. 273 ' grams - of _‘N-,N,N.-trichloro-3a,6a dimethyl' : ‘glyLa-v 12,8-i-_j.gramsof1 5,-5-dimethyl, hydantoin-1 were dissolved» 575 colurihwere'jsuspended in- ‘water; to form :a ‘heavy: slurryzl' 2,868,787 v5 To this were added 533 grams of a crude concentrated product is comprised of equal parts of N-chloro-N-bromm solution of alkali and alkaline earth bromides analyzing 5,5-dirnethylv hydantoin and N,N-diBromoliS-dimethyl _ 30% bromine. When all the bromine had been taken up, hydantoin. ' . the slurry was ?ltered oil, washed and dried. The prod From the foregoing it is apparent that two di?erent uct consisted of N-chloro-N,N~dibromo-3a,6a-dimethyl _ types of what might aptly be termed “'multi-halogenated" glycoluril. It contained theoretical amounts of active substituted hydantoins can exist, and can ‘be made by the halogen. methods herein described. The bromine may be attached Example 5 to the nitrogen atom in the .1-position which is vicinal to the S-Substituted carbon atom,‘or may be attached-to the To a solution containing 119 grams of potassium 10 nitrogen atom in .the 3-position. Thus there may be N-l bromide, 211 grams of N,N-dichloro-S-ethyl-S~methyl hy bromo-N-3-chloro, or N-1-chloro-N-3-bromo compounds. dantoin were added with constant agitation. The result It has not been de?nitely established that the N-chloro-N ant product, after ?ltering, washing and drying, weighed bromo compounds produced in accordance with the here 245 grams and contained 31.7% bromine and 14% chlo in described methods are not mixtures of such isomers. rrne. 15 In the subjoined claims, both types of chloro-bromo or Example 6 bromo-chloro products are claimed. 232 grams of N,N,N-trichloro-cyanuric acid were added It is a particularly preferred embodiment of the pres with constant agitation to a solution of 103 grams of ent invention to utilize S-substituted hydantoi'ns and 3a,6a F. sodium bromide in 1 liter of water. When the bromine substituted glycolurils as starting materials. Thus, with had been completely taken up, the product was removed 20 reference to the S-substituted hydantoin, the radicals on on a ?lter, washed and dried. It consisted of N,N-di the carbon atom in the number 5 position are given in the chloro-N-bromo-cyanuric acid, and contained theoretical examples as being methyl, dimethyl, methyl-ethyl, ethyl, amounts of these halogens. phenyl, diphenyl, or the like. It is to be understood that Another embodiment of the process of this invention considerable variations are possible in the substituents in is the provision of a process for preparing admixtures 25 the number 5 position, and compounds such as 5,5-di of IN-chlorodN-bromo halogen carriers with N,N-dihalo propyl, 5,5-phenyl, ethyl may be prepared. Combina halogen carriers, wherein the dihalo materials contain tions of aliphatic and aromatic radicals containing up to either chlorine or bromine. For example, referring about 10 carbon atoms in eachof the respective radicals speci?cally to 5-substituted hydantoins it is contemplated are contemplated as preferred starting materials, as is that admixtures of an N-chloro-N-bromo-S-substituted 30 disclosed in my copending application, Serial No. hydantoin with either an N,N-dichloro or an N,N-di 593,047, ?led June 22, 1956. bromo-S-substituted hydantoin may be prepared by re With respect to 3a,6a-substituted glycolurils it is pre acting an N,N-dichloro-S-substituted hydantoin with a ferred that these substituents be of the same character bromine salt. The amount of bromide required will vary as those substituents in the number 5 position of the with the particular end product desired. For example, to 35 hydantoin starting materials, but for the sake of economy prepare the mixed dihalo with N,N-dichloro less than it may be desirable to use only the methyl or ethyl sub one equivalent of a bromide per mole of N,N-dichloro stituted N-chloro-glycolurils. hydantoin starting material is required. Thus the bromide In summary, it is apparent that the process of the forms mixed chloro-bromo hydantoin and to the ex present invention is broadly applicable to the production tent that the bromide utilized is less than an equiva 40 of N-brominated halogenation agents speci?cally charac lent per mole of starting material, there remains un terized as being prepared by bromination of N-chloro reacted N,N-dichloro-S-substituted hydantoin present in organic nitrogen compounds containing at least one radi the admixture. Similarly, if one reacts more than one cal selected from the group consisting of: equivalent but less than two equivalents of a bromide with a mole of N,N-dichloro-S-substituted hydantoin, an ad 01 mixture of N-chloro-N-bromo-S-substituted hydantoin 0 Cl 0 G10 01 llIH 0 Cl 0 with N,N-dibromo-S-substituted hydantoin will be formed to the extent that the bromide exceeds one equivalent per ilhlm, Jail-2L, _SO.NH, 4‘): _, —-('3—llI—"—— mole of starting material. Other mixed halogen carriers and may also be prepared by a modi?cation of this process, C 0 Cl it merely being required that less than the stoichiometric Mail-11am amount of bromine salt be reacted with the N-polychloro starting material. Thus for example to prepare such an admixture using N,N,N-.trichloro-cyanuric acid one would Exemplary of compounds containing such groups or radi utilize a bromide in an amount ranging from less than one cals are N,N-dichloro-S-substituted hydantoins, N-chloro equivalent to somewhat less than three equivalents per 55 succinimide, N-chloro-acetamide, N-chloro-phthalimide, mole of starting material, the stoichiometric amount re N-chloro-cyanuric acids, N-chloro-toluene-sulfonimides, quired for complete bromination being at least three N-chloro-melamines, N-chloro-S-substituted barbiturates, equivalents per mole of trichlorocyanuric acid. Therfol N-chloro-3a,6a-substituted glycolurils, and the like. lowing examples will illustrate the above described modi While several particular embodiments of this invention ?cation. 60 are shown above, it will be understood, of course, that Example 7 the invention is not to be limited thereto, since many modi?cations may be made, and it is contemplated, there To an aqueous slurry of 197 grams of N,N-dichloro fore, by the appended claims, to cover any such modi?ca 5,5-dimethylhydantoin is added with constant stirring 51.5 tions as fall within the true spirit and scope of this in grams of NaBr. After addition is complete the resultant 65 vention. product is recovered by ?ltration, washing and drying. I claim: The product is an admixture of equal parts of N,N-di 1. A process for preparing N~brominated halogen com chloro-5,5-dimethyl hydantoin and N-bromo-N-chloro pounds which comprises treating an N-chlorinated com 5,5-dimethyl hydantoin. pound selected from the group consisting of N,N-di 70 chloro~5-lower alkyl substituted hydantoins, N~chloro I Example 8 succi'nimide, N-chlorinated cyanuric acids, N-chlorinated To a slurry of 197 grams of N,N-dichloro-S,S-dimethyl melamines, and N-chlorinated-3a,6a-lower alkyl substitut hydantoin in water is added 154.5 grams of NaBr while ed glycolurils with at least about ‘0.5 equivalent of an in maintaining constant stirring. The resultant product is organic bromide selected from the group consisting of recovered by ?ltration, washed with water and dried. The sodium bromide, potassium ‘bromide, calcium bromide and 8 'mixtures-zthereof, .per mole of: N-‘chlorinated; compound. References Cited inzthe‘?le of patent I2; pm‘cessnf'claim :1 wheIeim-saidshlorjuated.com- _ , . , pound is an N,N-dichloro-5-lower alkyl substituted -hy- UNITED STATES PATENTS dantoin: 2,779,764 Patterson ______Jan. 29, 1957 '3: The‘ process of claim v1 .whereinssaid chlorinated com- 5 pound. is an Nfchlorinatedcyanuric acid. OTHER REFERENCES 4. The process ofclaim 1 whereinsaid:chlorinated'com- Chattaway et aL; Journal of the Chemical Society. pound .is an N-ch1orinated-3a,6a-l0wer :alkyl substituted (1902), vol, 81, pages 200-202, glycoluril.