JOURNAL OF RESEARCH of the National Bureau of Standards-A. Physics and Chemistry Vol. 68A, No.3, May- June 1964 Cyclic Polyhydroxy Ketones II. xylo-Trihydroxycyclohex­ enediolic Acid and Keto-Inositols Alexander J. Fatiadi and Horace S. Isbell (J anuary 30, 1964) A new crystalline compound, Dlrxylo-t rihydroxycyclohexenediolic acid (oL-xylo-penta­ h ydroxy-2-cyclohexen-1-one) (1), has been isol ated from the products of oxidation of myo­ inositol with nitric acid, and its structme has been established. Compound (1) r educes Tillmans reagen t, reacts with iodine in neutral or sli ghtly acidi c solution, produces a blue color with ferric chloride solution, and exhibits other properties cha racteri stic of an enediolic acid. On catalyt ic reduction, it gives both scyllo-inositol and m yo-inositol. On oxidation, it yields a new t riketo-inositol, xylo-4,5,6-trihydroxycyclohexane-1 ,2,3-tri one (II). U nder acidic conditions, catalytic acetylation of 1 gives two pentaacetates, t he infrared spectra of which arc simila r but not id entical. One of these acetates exists in two forms, both of whi ch, on deacetylation, yield the pa ren t acid 1. The product formed by deacetyla­ tion of the other pentaacetate has not been identifi ed. Benzoylation of I gives a crystalline p en taben zoate. Under basic conditions, acetylation of I proceeds with simultaneous a romatization, resulting in the formation of pentaacetoxybenzene, from which pentahydroxybenzene is obtained by h ydrolysis. xylo-4,5, 6-Trihydroxycyclohexane-1,2,3-trione (II) gives a crystalline bis(phenylhydra­ zon e). By acetylation under basic conditions, it yields hexaacetoxybenze ne. M echanisms are presented for t he aromatization of keto-inositols by enoli zation and beta elimination-reactions, and certain observations reported in t he li teratme a re rationali zed. Infrared and ult raviolet a bso rption spectra are reported for the new compound . 1. Introduction 4 Tho term j'c ncd iol ic acid" is used here for a,.8-11Jl saiuratcd, c1 ihydroxy aId £'­ h ydes and ketones having the SLr ueture R- C= C- C- R '. The cc m- Cyclic polyhydroxy ketones, obtained by the H ~ ~ rr ~ pounds belong to the group that have bren classifled by their chem ical reactions oxidation of inositols, yield enolic compounds of as "aci-rccl uctoncs" [6, p. 3} . T'il e cll eci ioli c acids arc relatecl to tl1 e carboxylic acids in that they have a carbonyl group in co nju gati on with a hyd roxyl group. value in the study of oxidation- reduction phe­ T ypica l examples are nomena and molecular structure. Prior workers n c = c - Cl[ have established that oxidation of myo-inositol (III) with nitric acid gives DL-epi-inosose-2 (V), H ~ 6n ~ PropencdioJic acid tetrahydroxy-p-benzoquinone, rhodizonic acid, and (2,3 -d ih ycJ l'oxy-2- propenal, reductone) a residue weighing approximately half the weight n ,c-C=C-ClI of the parent myo-inositol [1 to 5].3 It has now I I II been found that, after treatment with potassium n6 on 0 carbonate, this residue gives a crystalline potassium BlItencdioJic acid salt of a new enediolic acid (1) 4 in a yield of 10 per­ (2,3-cJ ih yd roxy· 2- bu tenal) cent (based on the weight of myo-inositol taken). On oxidation, the salt gives a new crystalline tri­ hydroxycyclohexanetrione (II). The tructures and properties of I and II have been investigated, and certain characteristic derivatives have been pre­ Cyclopentenedioli c acid pared. (2,3·dihydroxy·2·cyclopenLen·[-one, reductic acid) Encdiolic deri vatives of tetrah ydrof uran are more conveniently named as ascorbic acid s, for example: n no n I I I 1 This work was supported, in part , by the Division of Air Pollution, Public no 9 - 9 - 9 - 9=9-~- 1 Health Servicc, U . D epartm ent of Health, EduCc'l tion, and 'Vel fare. IT II 0 no OR 0 'Presented, in I)art, before the Division of Carbohydrate Chemjstry at the 141st Meeting of the Ameri can Chemical SOCiety, Washington, D .C., M arch 26, I 1962. Abstracts Papers, Am. Chern. Soc. 141,60 (962). Paper I was published in J. Res. N BS 67A, (Phys. and Chem.) N o.2, 153 (1963) . L·threo·Hexoascorbic acid [71 3 Figures in brackets indicate the li terature references at tl,e end of tbis paper. (L·threo· hexo no ·2-ene·1 ,4·Iacton e) 287 2. DL-xy10-4,5,6- Trih ydroxycyclohexenediolic JI hI-IO1r-< "- OlI 1 Acid (I) K "orr The structure of (I) was established from the no ""~~ following considerations: The equivalent weight and II1 '" 0 chemical analysis of the acid correspond to the I DL-xylo-4,5,6-'r rihydroxycyclohexenediolic acid formula C6H g0 6 ; analysis of the potassium salt of the acid is in agreement with the formula n o 0 C 6H 7KOo' H 20; both the acid and the salt react with 1--1 two equivalents of either iodine or Tillmans reagent rrK~ I '" and give a deep-blue color on admixture with ITO OIl )=0 methanolic ferric chloride. "I~ A compound having structure I may arise by rr 0 enolization of either an ortho- or a meta-dike to­ II xylo-4,5,6-Trihydroxycyelohexane-l,2,3-trione inositol.5 Compound I might have anyone of several configurations: the actual configuration was established by studying the reduction products. HO~ On catalytic reduction with hydrogen, I gave a mixture of myo-inositol (III) and scyllo-inositol ' (IV). The latter has an alternating arrangement of the hydroxyl groups around the ring ([9], p. 138; HO~OH [10]). Hence, the new enediolic acid (I) likewise III 1nyo-I nositol must have an alternating arrangement of its three hydroxyl groups and must be DL-xylo-trihy droxy­ HO~OH cyclohexenediolic acid. In nonionic derivatives formed from the acid, the configuration is D- and L-xylo (racemic, unless diastereomers are formed). However, in the anion (fig. 1), C1 and C3 are HO~OH ~dentical because of resonance, and the configuration IS IV scyllo-Inositol meso. JlO 0 I-IO 0 - / 1 HO~OH II J[-" " T(f //1-<) II 1~ "fon <---+ 1 OR no " 0 ][ #' HO ""Oil "1-"]I 0- 1I1---< 0 ~OH \\0 FIGURE 1. Anion of xylo-4, 5,6- trihydroxycyclohexenediolic o acid. ~ // The potassium salt is particularly suitable for isolating and purifying the compound. The isolation of I do es not establish the structm e of the parent diketo-inositol. Thus, as depicted in HO~OH figure 2, all of the diketo-inositols are theoretically V DL-e]Ji-Inosose-2 interconvertible by reversible enolizations, to yield a mixture of isomeric trihydroxycyclohexenediolic acids. Compound I is t he only isomer thus far HO~HOH isolated. Acetylation of I , catalyzed by mild acidic catalysts, gave a pentaacetate, mp 111 to 113 ec, which solidi­ HO OH fied above 113 ° and then remelted at 134 to 136 °C. \\o Recrystallization of the higher-melting acetate from ethanol produced the lower melting. The infrared VI 1nyo-Inosose-2 spectra of the two compounds are identical, and hence they are polymorphic modifications of the I same compound. Deacetylation of both modifica­ tions regenerated I; therefore, the acetylation had not altered the configuration, and the compound is , After oxi dizing (the D isomer of) DT.-ep;·inosose-2 with Acetobacter suboxydans, M agasanik and ChargatI [8] found that th c oxidation product had "acidic prop­ erties ... in agrccJnent with the expected behavior of an enolized ,B-di-kctonc." rrhis cOlllpouncl, which was not isolated, may bave been the enec1iolic acid c1e­ VII 2,4,5,6-'l'etraaoetoxy-2-eyclohexen-l-onc scri bed bere. 288 o o o n,OH II B,OTT II n ,on II lI,on()u ,O JI n ,on()lI,OlI n ,Ol Ir-\U, on n)m-{ ~I o ][M'1I o 1l o o II,OH II ID,OTT I II,OII . - Oll IJ,OIIO = O n , . I n,OH ]l,on on F IGUR E 2. I nterconvel'sion oj diketo-inositols by enolization. DL-xylo-pent aacetoxy-2-cyclohexen-1-one. Benzoyl­ 3. xylo-4,5,6-Trihydroxycyclohexane-l,2,3- ation of I , with zinc chloride as catalyst, gave a trione (II) pentabenzoate shown to be DL-xylo-pentabenzoyloxy- 2-cyclohexen-1-one. When oxidized with concentrated nitric acid, the Ace tylation of J, catalyzed by sulfuric acid , gave a ne\y enediolic acid (I ) gave a crystalline product (II). pen taacetate (mp 154 to 155°C) presumably having The analysis, molecular weight, and other properties an altered confIguration. The substance differs from ofthelatter howthat it is xylo-4,5,6-trihydro:,,:ycyclo­ that de cribed above in its rnelLing point, in its infrared spectrum, and in the fact that, on deace­ hexane-1 ,2,3-trione. Cry talline II, Lhe fu'st triketo­ tylation, iL does no t yield 1. However, it has inositol to be isolated, provides a promising new area essen tially Lhe same ultraviolet spectrum. for inve tigation , The relationship of I to II is the Acetylation of I under b asic conditions gave same as that of ascorbic acid to dehydroascorbic acid. ptntaacet oxybenzene, pre umably by the series of Acetylation of II under basic conditions gave enolization and beta-elimin ation reacLion depicted hexaacetoxyben zene [15, 16, 17], presum.ably by the in figure 3 [11 , 12]. On deaceLylation, the penta­ acetate gave pentahydro:\.'Yben zene, an important process depicted in flgum 4.