The Replaceonetit of Hydi*Oxyl by Bromine

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LXXXVIII:.- The ReplaceoneTit of Hydi*oxyl by Bromine.

By WILLIAM HENRYPERKIN, jun., and JOHNLIONEL SIREONSEN. Published on 01 January 1905. Downloaded by University of Windsor 26/10/2014 01:06:14. THEmethods available for the preparation of aliphatic compounds in which several atoms of bromine are combined with different carbon atoms are few in number. It is usually assumed that a substance containing one or more hydroxyl groups may be converted into the corresponding bromo-derivatives by treatment with hydrobromic acid, or phosphorus tri- or penta-bromide, but in attempting to use this method in the preparation of bromo-derivatives for the purpose of ring synthesis unexpected difficulties were encountered. The hydroxy -groups in such polyhydric alcohols as glycerol, erythritol, mannitol, ckc., are usually only partially replaced by bromine when these alcohols are treated with hydrobroinic acid, and if, by employing higher temperatures and a large excess of the halogen acid, the attempt is made to complete the substitution, decomposition usually takes place with much charring, and the yield obtained is consequently very small. The same remarks apply to the use of the View Article Online 856 PERKIN AND SIMONSEN :

bromides of phosphorus in such cases, the results obtained by the action of these reagents on the polyhydric alcohols being frequently most unsatisfactory." In investigating this matter, we found that a great improvement is achieved if the alcohol is first converted into the acetate and the latter is then heated with a solution of hydrogen bromide in glacial acetic acid (saturated at 0") at about 150'. By this process, which may be represented in a general way thus : R*O*C,H,O+ HBr = RBr + HO*C,H,O, the whole of the hydroxyl groups may usually be substituted by bromine, and the reaction proceeds smoothly without any separation of carbonaceous matter, consequently a good yield is obtained and the product is easily purified. We have investigated the following cases, which may serve to illustrate this process : I. Glycol diucetate is converted quantitatively into ethylene dibromide, when it is heated with ncetic-hydrobromic acid at 150". 11. GEycerol tricccetate (triacetin) is readily acted on by acetic- hydrobromic acid at 150°, and an almost quantitative yield of s-tribronzo- propawe, CH,Br*CHBr*CH,Br,is obtained. The behaviour of triacetin, when treated with a solution of hydrogen bromide in acetic acid, has lately also been investigated by R. de la Acena (Compt. rend., 1904, 139, 867), who found that at 0" and in the dark a monobromodiacetin is produced, whereas at 100' two acetyl groups are displaced with formation of a dibromomonacetin. 111. Ergthritol tetracetate reacts readily with acetic-hydrobromic acid at 1 50°, yielding s-trans-tetrabromobzct~~ze,CH,Br*CHBr*CHBr*CH,Br (m. p. llSo), and two oily substances which boil at 122-127' (25 mm.) and 164-165O (27 mm.), and which appear to consist of s-cis-tetrccbromobzctctlze and erythritol tribromohydriw, C,H,Br,*OH, Published on 01 January 1905. Downloaded by University of Windsor 26/10/2014 01:06:14. respectively. s-Tetrabromobutane had previously been prepared from erythritol by the action of phosphorus pentabromide (Colson, Bull. SOC.Cllirn., 1887, 48, 53), as well as by the following interesting indirect process. When erythritol is heated with formic acid (Henninger, Ann. Chint.

* The action of hydrobromic acid on glycerol does not appear to have been investigated, but, when treated with phosphorus pentabromide, glycerol yields dibromohydrin, CH,Br*CH( OH)'CH,Br (Aschan, Bey., 1888, 21, 2890). When erythritol reacts with aqueous hydrobromic acid, it yields a dibromohydrin, C,H6Br,(OH),, and Colson (Bull. Xoe. Chirn., 1887, 48, 53) found that s.-tra.ILs- tetrabromobutane, CH,Br*CHBr,'CHBr*CH,Br, is produced in very small quantity when erythritol is treated with phosphorus pentabromide. The action of hydrobromic acid on niannitol has been investigated by Champion (Zcitschrift, 1871, 348) and Bouchardat (Ann. Chim. Phys., 1876, [v], 6, 102), who showed that, when heated with a saturated aqueous solution of hydrogen bromide at looo, it is converted into a mannitoldibrornohydiiii, CBH,Br2(OH),. View Article Online THE REPLACEMENT HYDROXYL BY HROJIINE. 857

Plu~s., 1886, [vi], 7, ZlS), it yields erythrene, GH,:CH*CH:CH,, a hydrocarbon which has also been prepared by passing the vapour of fuse1 oil through a red-hot tube (Caventou, AnnaZen, 1863, 127, 93), and by distilling trimethylpyrrolidylammoniurn iodide with caustic potash (Ciamician, Magnaghi, Be?..,1886, 19, 570, and 1887,20, 3064). Erythrene combines readily with bromine, yielding a mixture of two isomeric tetrabromides, C,H,Br,, which melt respectively at 118" and 39". The former is identical with the tetrabromobutme, which we obtained from erythritol tetracetate in the manner just described. Grimaux and CloGz (Bull. Xoc. Cl~im,1887, 48, 32) have shown that this substance distils at about 260-270", and is, at the save time, partially converted iuto the isomeric tetrabromide melting at 39O, and in order to account for this they assume that change in constitution had taken place during distillation, and that the s-tetrabromobutane had been converted into a tetrabrorno-compound of the foriuula Cl-I;CBr,*CBr,*CH,. This view can hardly be accepted as correct, and it is much more probable that the two tetrabromides are cis- and ti.ans-iiiodifications :

and the broiiiide iiielting at 39" is probably the cis-iiiodificzttion, since it is produced from the less fusible (trccm-)modification by the action of heat. Ciamician seems to have held a similar. view of the isomerism of these tetrabroillo-compounds, since he suggested in 1887 (Ber., 20, 3064) that their relationship may be of the same kind as that of the inactive iriodificat ions of dibroniosuccinic and tartaric acids. The constitution of erythrene, CH,:CH*CH:CH,, is proved beyond Published on 01 January 1905. Downloaded by University of Windsor 26/10/2014 01:06:14. doubt, not only by its method of forination from erythritol, but also hy the fact that it yields s-tetrabromobutane when treated with broiiiine. This hydrocarbon contains the grouping -U:C*C:C-, and i Is behaviour towards bromine seems therefore to make it an exception to the generalisation of Thiele (Art,nden, 1898, 306, 87 ; 1901, 319, 129). IV. The tetracetate 01 pe?iteytlwitol, C(C H,*O*C,H,O),, yielded interesting results, since, when heated with acetic-hydrobromic acid at 160", it was converted into s-tetrabro/rt,otetrantet?~?lZrizet~t,La~e,C(CH,Br),, but the principal product of the reaction was tribl.on.Lotrimetl~ylcarbilzyZ ncetate, (CH,Br),C*CH2*O*C,H,0, one of the acetyl groups having escaped replacement by bromine. V. In the case of wic6n~itoZ hexcbcetate, it was found impossible to replace more than five of the acetyl groups by bromine, and the product of the reaction is pewtobromohexyl acetate, C6H8Br,(0.C,H,0), VOL, LXXXVIl. 3M View Article Online 858 PERKIN AND SIMONSEN :

a crystalline substance which melts at 13g3. It is remarkable with what tenacity one of the acetyl groups remains, not only in this case, but also in the case just mentioned of the tetracetate of pentaerythritol. We have also attempted to apply the method described above to the case of aromatic substances, but without success. When phenyl acetate, C6H,*O~C,H,0,for example, was heated with acetic-hydrobromic acid, profound decoinposition set in with much charring, and no trace of bromoberizene could be isolated froin the product. These negative results led us to investigate the aclion of phosphorus pentabromide at the ordinary temperature on the trihydric phenols, pyrogallol and phloroglucinol, but no substitution of hydroxyl by bromine could be observed. When the reaction was carried out in the presence of an indifferent solvent, such as benzene, pyrogallol yielded a di6ronzopyrogccZZoZ of the prolialde formula : OH

which had not previously been prepared. It melts at 150" and yields a triacetyl derivative, C,HBr,(O*C2H,0),, melting at 143". Phloroglucinol, under similar conditions, is converted into tribromo- phloroglucinol : 01-1 Br()Br OH\/OH ' Br

Published on 01 January 1905. Downloaded by University of Windsor 26/10/2014 01:06:14. which had previously been obtained by brominating phloroglucinol in acetic acid solution (Herzig, Jfoncctslb., 1885, 6, 885). That phosphorus pentabromide should exert such a pronounced brominating action at the ordinary temperature and in the presence of an indifferent solvent seems remarkable.

s-I'ribronzopropane (Tribrornohy drin), CH,Br CH Br *CH,Br. When glycerol is digested with acetic anhydride, it is readily converted into diacetin, but even when a large excess of the anhydride is employed very little triacetin is produced (Seelig, Bey., 1831, 24, 3467; Geitel, J. pr. Chem., 1598, [ii], 57, 117). We have found that the following method may conveniently be used in preparing pure triacetin (compare Erwig and Koenigs, Her., 1889, 22, 1464). Glycerol (20 grams) is digested for one hour with acetic anhydride (150 gram) and zinc chloride (1 gram), the product is mixed with View Article Online THE REPLACEMENT OF HYDROXYL BY BROMINE. 859

ether, rapidly washed with water, dried over calcium chloride, and fractionated. Almost the whole quantity distils at 258-259' (760 mm.) and consists of pure triacetin, since a second treatment with acetic anhydride and zinc chloride does not alter the properties of the substance. Triacetin (5 grams) was now mixed with the solution of hydrogen bromide in acetic acid (2s gra.ms) and heated in a sealed tube for 10 hours at 150-160", the product was then poured into water and distilled in steam. The volatile oil was extracted with ether, the ethereal solution dried over calcium chloride and evaporated, when almost the whole quantity distilled at 217-219' (73s mm.) as R colourless oil which solidified in ~b freezing mixture and consisted of p U~Qs- t riborrz opr op ane . 0.2015 gave 0.4071 AgBr. Br = 85.7. CaH,Br, requires Br = 85*8 per cent. The method just described yields a very pure product, but it is, of course, much too laborious to serve as a means of preparation, and as we required considerable quantities of tribromopropane for future experiments, we worked out the following convenient method for the preparation of this substance. Ally1 bromide (100 grams) is dissolved in an equal volume of chloroform and, after cooling in a mixture of ice and salt, a solution of bromine (44 c.c.) in an equal volume of chloroform is: slowly added, care being taken to keep the temperature below - 5O during the operation. The chloroform is then distilled off and the tribromopropane purified by distillation under reduced pressure.

s- l'etvccbromobutccne, CH,Br *CHBr CHBr *CH2Br. Erythritol is readily converted into its tetracetate when it ia digested for a few minutes with acetic anhydride and a small piece of Published on 01 January 1905. Downloaded by University of Windsor 26/10/2014 01:06:14. zinc chloride; on pouring the product into water, the tetracetate separates as a crystalline mass which, after crystallisation from acetic acid, melts at 89O. This tetracetate (20 grams) mas heated in aealed tubes with the solution of hydrogen bromide in acetic acid (100 grams) for 10 hours at 160-170°, the contents of the tubes, which contained only very sinall quantities of carbonaceous matter, were diluted with water and distilled in steam, when a colourless oil condensed which rapidly became semi-solid. The mass was collected at the pump, washed with water, and left in contact with porous porcelain until quite free from oil; it was then crystallised from glacial acetic acid. The crystalline mass, which was obtained in a yield of 15 gramsj melted at 118-1 19", and consisted of s-trans-tetsiccbromobutane,as the following analysis shows : 0*14@8gave 0.2815 AgBr. Br = 55.1. C4H6Br4requires Br = 85*5per cent. SM2 View Article Online 860 PERKIS AND SIMONSEN :

A considerable quantity of this tetrabroino-compound was submitted to clistillation under reduced pressure, when it was found that almost the whole passed over at 180-135" (30 mix) with scarcely any decom- 1)osition. No transformation of the trans- into the cis-modification had taken place during distillation (compare p. 857), as wits shown by the fact that the product, when fractionally crystnllised frorvi light l)ebroleum, yielded nothing but the tetrabromo-compound nielting at 118-119". Wlien the aqueous liynors from the tlistillation in stenin (see above) were extracted with ether, a considerable quantity of EL viscid oil was obtained ; this was added to the ethereal extract of the porous porcelain usccl in the purification of the crude tetrabromobutane and fractionated under reduced pressure. It was thus separated into a heavy, mobile oil boiling at 122-157' (26 mu), and ;t viscid, syrupy subbtttnce which distilletl at 164 -1 65" (27 nim.}. The former evidently consisted, for the most, part, of the cis- modification of tetrabromobutanc, although the analytical numbers (Br = €3.6 instead of 85.5) were hot very satisfactory. The oil boiling at 164-165' (27 inm.) is probably the tribrornohydrin of erythritol; but we were not successful in obtaining it in R state of purity . 0.1473 gave 0.0784 GO, aiid 0.0256 H,O. C = 14 5 ; H = 2.0. 0.2445 gave 0,4544 AgBr. Br= 79.0. C,H70Br3 requires C = 15.4 ; I€ = 2.2 ; Br = 7-7-1 per. writ.

is- l'et?'cc~i.os,~oteti.arnet~~~/lrnet~~ci116, C( CH,Br) 4, and l'r ib romotr i rrie t hy 1- ccwbinyl acetate, (CH,Br)3C* CH; 0 * C,H,O.

Published on 01 January 1905. Downloaded by University of Windsor 26/10/2014 01:06:14. The penterythritol employed in these experiments was prepared by the condensation of formaldehyde with acetaldehyde in the presence of milk of lime exactly according to the instructions of Tollens and Wigand (A~~nclZen,1891, 265, 319).* In order to obtain the tetr- acetyl derivative, the alcohol (20 grams) wtas digested with acetic anhydride (75 grams) and a small piece of zinc chloride, when a vigorous reaction set in and, after boiling for two hours, the product wac; cooled and shaken with three times its volume of water. The tetracetate, which separated in voluminous needles, is in thi5 form sufficiently pure for the experiments described in this paper; it crystallises readily from alcohol in glistening needles and melts at 84-86", Tollens and Wigand (Zoc. cit., p. 327), who prepared the same acetate from penterythritol by the action of sodium acetate and acetate anhydride, give the same melting point, and they proved by a * We are much indebted to Prof. W. J. Pop for a large supply of this valuable mateiial. View Article Online THE REPLACEMENT OF HYDROXVI, BY RROMTNE. 861

direct determination of the acetyl groups that the s ibstance is tetr- acetylpenterythritol. In investigating the b?haviour of this substance towards hjdrogen bromide, it was heated, in quantities of 5 grams, with the solution of hydrogen bromide in acetic acid (50 grams), in which it readily dissolves, in a sealed tube at 1603 for 8 hours. Very little discoloration had taken place and the tube was filled with crystals; after pouring into water, the mass was collected at the pump, washt d with water, and crystallised froin glacial acetic acid, from which s tetrccb~onzotet~rcnzeth@nethaneseparated in glistening, hafy masses.

0.2062 gnve 0,3998 AgBr. Rr = 82.6. C5H,Br, requires Br = 82.5 per cent. This interesting substance had already been obtained by Rave and Tolleiia (Annalen, 1893, 276, 61) by the action of phosphorus tri- bromide on penterythritol, and these authors state that it melts at 154-1 56' ; but, artier repeated recrystallisation from acetic acid, me fonnd that the correct melting point was 158". One of the most) characteristic properties of the tetrdbroinide is the fact that it is very sparingly solllble in the usual solvents ; it is, however, moderately soluble in boiling toluene or glacial acetic acid.* The acetic acid mother liquors from the pnrification of the tetrabromide yield, on dilution with water, an oil which soon becomes semi- solid, and if this is left in contact with porous porcelain until the oily impurity is absorbed, a colourlees mass remains which, on crystallisation from light petroleum, is readily separated into small quantities of tttrabromotetramethylmethane and into tribromoti~inaetlr~yZcarbil.L?/I acetate. After repeated crystallisation from light petroleum (b. p. 60-70') this latter substance yielded the following results on mdysis : Published on 01 January 1905. Downloaded by University of Windsor 26/10/2014 01:06:14. 0,1922 gave 0-1568 CO, and 0-0.519 H,O. C= 32.3 ; H = 3.0. 0.1748 ,, 0.2689 AgRr. Br= 65.4. 0.1638 ,, 0.2522 AgBr. Br = 65.5. C7H1,0,Br, requires B = 22.8 ; H = 3.0 ; Br = 66.4 per cent. Tr ibi.onzotrinaeth2ZcaTb~n~lacetcd e separates in large, glistening prisms

* A number of experiments on the action of s-trans-t~frnb~~motctrm~iiet-llyl- nirtliane on the sodiiim derivatiws of ethyl malonate, cyanoacetate, &c., were instituted, as vcry interesting results might be exprctecl from the study of snch reactions. The decomposition was, however, in each case most incomplete, aiid defiiiite products could not be obtained in sufficient qiiatitity for investigation. These ncgative resiilts seein to be due partly to the fact that s-tctrabromotetra- iriethylniethane is very sparingly so1ul)l~and partly to its unexpectedly stable nature. The ieactions were carried out iu the preseiice of various solve1lts, but, even when a large excem of the sodiiiin tlerivative was employed, mnrh of the tetrsh-t omotetia - methylmethane was always recovered from the product of the reaction. View Article Online 862 PERKTN AND STMONSEN :

resembling sugar crystals when its solution in light petroleum is allowed to slowly evaporate in the air. It melts at 44-45', and, unlike tetrabromotetramethylmethane, is readily soluble in most organic solvents.

Pentn bromohexy2: Acetate, C,H,Br,(O-C,H,O). The mannitol hexacetate reqnired in these experiments was prepared by heating mannitol (20 grams) with acetic anhydride (100 grams) and zinc chloride (1 gram) in a reflux apparatus for one hour. On pouring the cold product into water, the hexacetate was pre- cipitated as a crystalline solid and purified by recrystallisation from acetic acid, from which it separated in colourless needles of melting point 121-1 22'. In investigating the action of hydrogen bromide, the acetate (4 grams) was mixed with the saturated solution of hydrogen bromide in acetic acid (28 grams) and heated in a sealed tube in boiling water for one day and then for 10 hours at 130-140°. The product, which contained only a trace of carbonaceous matter, was poured into much water, when a heavy oil separated ; this was extracted with ether, the ethereal solution washed with water and then with sodium carbonate, dried over calcium chloride, evaporated, and the residue repeatedly extracted with boiling light petroleum. After filtering and evaporating, a pale yellow oil was obtained which, over sulphuric acid in an exhausted desiccator, gradually became semi- solid and, in contact with porous porcelain, the oily impurity mas soon removed, leaving an almost colourless mass of crystals. From light petroleum, the substance separates in stars and, after twice recrystallis- ing, the following results were obtained on analysis : Published on 01 January 1905. Downloaded by University of Windsor 26/10/2014 01:06:14. 0,1829 gave 0,1213 CO, and 0.0328 H20. C = 18.0 ; €€ = 2.0. 0,161 1 ,, 0,2806 AgBr. Br = 74.1. 0.1864 ,, 0.3262 AgBr. Br=74*4. C,H,,Br,O, requires C = 17.8 ; H = 2.0 ; Rr = 74.2 per cent, Pentabronaolzexyl acetate melts at 138-1 39'. Several attempts were made to convert this substance into hexa- bromohexane, CH,Br(CHBr),CH,Br, by the removal of the remaining acetyl group, but without success. In one experiment, the pentabromo- compound was heated with a very large excess of the solution of byclrogen bromide in acetic acid at 150-160O for 8 hours. The clear, pale yellow solution was poured into water, when a solid, crystalline substance separated, which was found to be iinchanged pentabrorno- hexyl acetate. View Article Online THE REPJ,ACEMENT OF HYDROXYTJ BY BROMINE. 863

DibromopyrogaZloZ, C,HBr,(OH)3. This substance is produced when pyrogallol (1 4 grams) is suspended in benzene (250 c.c.) and allowed to react, at the ordinary temperature, with phosphorus pentabromide (100 grams). Hydrogen bromide is evolved in quantity and, if after 24 hours the whole is shaken with water, a white solid separates. This is collected at the pump, mixed with a small quantity of the same substance which is obtained by evaporating the benzene solntion, and the whole purified by recrystallis- ntion from water. 0,2503 gave 0.2344 CO, and 0.0359 H,O. C = 25.5 ; H = 1.6. 0.1556 ,, 0.2057 AgBr. Br=56*3. C6H,0,Br2 requires C = 25.3 ; H = 1.4 ; Br = 66 3 per cent, Dibromopyrogallol does not appear to have been previously prepared. It is a colourless, crystalline substance which melts at 150' and is readily soluble in hot water or alcohol, but only sparingly so in benzene or light petroleum. It dissolves readily in caustic alkalis, yielding solutions which rapidly become brown in contact with the air. TriacetyEdi6ronzopyrognlEol, C,HBr,(O*C,H,O),.-This acetyl compound is readily obtained by digesting dibromopyrogallol (3 grams) €or one hour with acetic anhydride (20 grams) and a small piece of zinc chloride, The cold product is mixed with water, the solid which separates collected on the pump and purified by recrystallisation from acetic acid. 0.1736 gave 0.2226 CO, and 0.0401 H,O. C: = 35-1 ; H= 2.4. 0*1931 ,, 0.1'791 AgBr. Bl*=39*4. C,,H,,,O,Br, requires C = 35.1 ; H = 2.5 ; Br = 39.0 per cent. Published on 01 January 1905. Downloaded by University of Windsor 26/10/2014 01:06:14. Trir~cet~~~~bronzo~~yrog~~~~o~separates froiiz acetic acid in glistening plates and melts at 143'.

Tribromophlorog Zucinol, C6Br3(OH),. The phloroglucinol used in these experiments was first dried at 110-120°, in order to remove the water of crystallisation, and the anhydrous substance (14 grams) suspended in benzene was mixed with phosphorus pentabromide (100 grams) and allowed to stand at the ordinary temperature for 24 hours. The mixture mas poured into water, and the solid which separated collected at the pump and purified by recrystallisation from water. The brownish needles thus obtained contained water of crystallisation, which was removed by drying at 100-110". The anhydrous substance melted at 149--150°, and gave the following results on analysis : View Article Online 864 FRANKLAND AND GEBHA4RD: THE ETHEREAL SALTS ANT)

0.1912 gave 0.1396 CO, and 0.0202 H,O. C = 19.9 ; H= 1.1. C6H,0,Br, requires C = 19.9 ; H = 0.8 per cent. There can be no doubt that this substance is trib~~orno~~lorogluc~~~ol, since the trictcetyl compound, prepared by means of acetic anhydride and zinc chloride, melted at 180-183°, whereas Herzig (Momtsh., 1885, 6,887) gives the melting point of this siihstmwe as 181-183". Published on 01 January 1905. Downloaded by University of Windsor 26/10/2014 01:06:14.