IIII l‘I‘ I ‘II‘III I.II III II 01—: 00—8 I .mmm '4 I SYNTHETIC STUDIES IN THE PREPARATION OF VARIOUS PYRAZOPYRROMETHANES, PYRAZOPYRROMETHENES AND PYRAZOPYRROKETONES AS POSSIBLE ROUTES TO A 4,7:13,16 - DIIMINO - 2,26:18,20 - DIETHYLENE-O, 11 - N,N’ - HYDRAZINE - 22,24 - N,N'OIIMINE- 1,19 - DIAZA(26)ANNULENE Thesis for the Degree of M. S. MICHIGAN STATE UNIVERSITY JAMES EDWIN MACDONALD 1976 “L m- ' - ._"‘. . n‘ . u . . .- . - _ _ ,_-__ _"__ -_--_- - -qH—O_ ‘5‘- —--»—-” IIIIIIII IIIIIIIIIIII MICHIGAN STATE UNIVERSITY B 01591 3852 MIIIIII IIIIIIIIIIIII V ABSTRACT SYNTHETIC STUDIES IN THE PREPARATION OF VARIOUS PYRAZOPYRROMETHANES. PYRAZOPYRROMETHENES AND PYRAZOPYRROKETONES AS POSSIBLE ROUTES TO A 4,7:13,16-DIIMINO-Z,26:18,20-DIETHYLENE-9,TT-N,N'-HYDRAZINE-22,24- N,N'DIIMINE-T,T9-DIAZA[26]ANNULENE By James Edwin Macdonald The 4,7:l3,16-diimino-2,26:l8,20-diethylene-9,ll-N,N'-hydrazine- 22,24-N,N'diimine-l,l9-diaza[26]annulene is proposed as the object of a synthetic scheme, as it should have interesting physical and chemi- cal properties. The mode of approach is based on the precedence of known pyrrole chemistry. The methods employed involve the reaction of pyrroles that have free a positions with 3,5—disubstituted pyrazoleacid- chlorides, pyrazoleketones and pyrazolealdehydes or hydroxymethyl- pyrazoles under a variety of conditions. In no case investigated could the desired model condensations be achieved, and these methods do not appear to be a viable route to the proposed system. SYNTHETIC STUDIES IN THE PREPARATION OF VARIOUS PYRAZOPYRROMETHANES, PYRAZOPYRROMETHENES AND PYRAZOPYRROKETONES AS POSSIBLE ROUTES TO A 4,7:l3,T6-DIIMINO-2,26:lBJK¥DIETHYLENE-9,ll-N,N'-HYDRAZINE-22,24- N,N'DIIMINE-T,TQ-DIAZA[26]ANNULENE By James Edwin Macdonald A THESIS Submitted to Michigan State University in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE 1976 ACKNOWLEDGEMENTS The author wishes to express his sincere gratitude to Dr. Eugene LeGoff for his guidance and aid during the course of this research. Thanks are also due to my fellow graduate students, especially to Houston Brown, who contributed to making this degree possible and the last two years agreeable. ii TABLE OF CONTENTS LIST OF FIGURES ......................... INTRODUCTION .......................... DISCUSSION OF RESULTS ...................... EXPERIMENTAL SECTION ...................... 3-Diazo-2,4-pentanedione(ll) ............... 4-Methyl-3,5-diacetylpyrazole(l2) ............. Pyrromethenes(l3) from 4—methyT-3,5-diacetylpyrazole(l2) . 3,5-Dimethyl~4-carboethoxypyrromethene(l3a) of (12) . . . . 3,5-Dimethyl-2-pyrromethene(l3b) of (12) ......... 3,5-Dimethyl—4-ethyl-2-pyrromethene(l3c) of (l2) ..... 4-Methyl-3,5-dithioacetylpyrazole(l4) ........... Pyrrolidine fluoroborate(l5) ............... 3,5-Bis(acetylpyrrolidiniminium fluoroborate)-4- methylpyrazole(l6) .................. 3,5-Dicarboxaldehydepyrazole(l7) ............. 3,5-Bis(glyoxate)-4-methylpyrazole(l8) .......... 3,5-Bis(diacetatemethyl)pyrrole(l9) ............ 3,5—Pyrazoledicarboxaldehyde(l7) by an adaption of the method of McFadens and Stevens ............ Pyrazole,3,5—dicarboxaldehyde by the Sonn-Muller Method N-phenylamides from esters .............. B-Anilinoacrolein(22) ................... Diazoacetaldehyde(23) ................... 3-Carboxaldehyde-S-carbethoxyp razole(24)' ......... 2-Pyrro-3-(5-carboethoxypyrazoImethene(25) ........ Reduction of pyrazopyrromethene(25) with zinc ....... Reduction of pyrazopyrromethene(25) with SnCl ...... Reduction of the pyrazopyrromethene with NaBH4 ...... Oxidation of the pyrazopyrromethene(25) with ceric amonium nitrate .................... Pyrazole-3,5-diacid chloride ............... 3,5-Bis(2-pyrrocarbonyl)pyrazole(28) ........... l-Benzylpyrazole—3,5-dicarboxylate(29) .......... Benzylpyrazole-3,5-diacidchloride(30) ........... l-Benzyl-3,5-bis(2-pyrrocarbonyl)pyrazole(3l) ....... Bromination of 3,5-dimethylpyrazole(32) .......... 3,5-Dimethyl-4-carbethoxy-l-pyrazoleamide(33) ....... Bromination of 3,5-dimethyl~4-carbethoxy-l- pyrazoleamide(34) ................... 3,5-Bis(hydroxymethyl)pyrazole(35) ............ 3,5-Bis(methyleneacetate)pyrazole ............. 30 3-Hydroxymethyl-5-carbeth oxypyrazole(37) ......... 30 Pyrazopyrromethanes from pyrazole(37) ........... 30 3-Carbet hyoxy-Z,4-pentanedione(37) ............ 3l l ,5-Dibromo-3-carb etho xy-2 ,4-pentanedione(38) ...... 3l Nucliophilic displacement on (38) with pyrrole ...... 31 Nucleophilic displacement on (38) with hydrazine ..... 32 Nucliophilic displacements on (38) with acetate ...... 32 Nucleophilic displacement on (38) with methanol ...... 32 Tris(3-phenyl-2,4-pentanedionato)chromium III (39) . . . . 33 Tris(l,5-dibromo-3—phenyl-2,4-pentanedionato)- chromiumIII(40) .................... 33 BIBLIOGRAPHY .......................... 34 iv LIST OF FIGURES Figure Page 1 The proposed diaza[26]annulene ................ l 2 Pyrrole and pyrazole ..................... 2 3 Dipyrroleketone, dipyrromethene, and dipyrromethene ..... 2 4 Pyrazopyrroketone, pyrazopyrromethane, and pyrazopyrromethene ...................... 2 5 The synthetic scheme ..................... 3 6 The methene condensation ................... 5 7 Thioketones from ketones ................... S 8 Aldehydes from acetyl groups ................. 6 9 Thiele's method ....................... 7 l0 An acid chloride dimer .................... 9 ll The preparation of l-benzylpyrazole-3,5-diacid ........ l0 l2 Methane formation ...................... ll 13 Possible reaction of l,5-dibromo-2,4-pentane diones ..... l4 l4 A possible route to substituted pyrazoles .......... l5 15 A possible route to the macrocyclic ring ........... l5 16 A possible multistep route to the desired diaza[26]annulene . l5 INTRODUCTION Porphyrins are important hetrocyclic aromatic systems that have been intensively studied. An interesting and perhaps useful idea is to expand the porphyrin moiety into an extended ring structure like the diaza[26]annulene in Figure l. \\ '\\ ‘\\ ‘\\ \\ NH MEN HN \ H H \ N N—N N.» \ I / / / / Figure l. The proposed diaza[26]annulene This expanded [26]annulene would be novel in that it may form bimetallic compTexes. In that case mixed metal and mixed metal oxidation states with unusual physicaI properties could be observed. This might lead to the development of novel catalyst systems or to organic conductors. Annulenes of this size are unusual in that calculations show that they should show little if any aromatic charactor.2 Tests of this prediction could be interesting. The purpose of this work is to apply the methods developed in porphyrin chemistry to the formation of the proposed diaza- [26]-annulene. This was undertaken using pyrroles and pyrazoles as building blocks (Figure 2). The models for the reactions were [a 4/”) D11 N H H pyrrole pyrazole Figure 2 derived from the well studied coupling of pyrroles to form a,a' dipyrromethanes, methenes and ketones (Figure 3). \ \N NJ \ N~ H H H H dipyrroleketone dipyrromethene dipyrromethene Figure 3 Following these models the unknown pyrazopyrromethane, pyrazopyrro- methene and pyrazopyrroketone classes of compounds in Figure 4 might be synthesized by the condensation of pyrazoleacidchlorides, pyrazole ketones and aldehydes or hydroxymethylpyrazoles with ant: unsubstituted pyrrole. /\ // /I / /n \ \ N/N N N,N N/ N/N N\ H H H H H pyrazopyrroketone pyrazopyrromethane pyrazopyrromethene Figure 4 3 If any of the model systems tested work then the condensation in Figure 5 would be a reasonable approach to the diaza[26]annulene, (x is any group that is found to react well with pyrrole). Figure 5. The synthetic sceme The difficulties found in this approach will be discussed and other potential routes to this system will be considered as future possibilities. DISCUSSION OF RESULTS One approach to this proposed diaza[26]annulene system would be to condense two pyrromethanes with two properly functionalized pyrazoles as seen in Figure 5. The pyrromethanes are not difficult to form and are well known intermediates in porphyrin chemistry.5 The objective of this research then is to investegate the unknown con- densations of pyrroles with pyrazoles to give methene, methane or ketone linkages as this is the crucial step in the synthesis of the target macrocycle in Figure 5. This investigation can be approached with the least difficulty by first attempting the reactions with small model systems, and if their results are favorable then extend-- ing the reaction to the larger system as in Figure 5. One approach to the proposed macrocycle is exemplified by the model reaction between 4-methyl-3,5-bis(acetyl)pyrazole(12) and pyrrole which should lead to a 4-methyl-3,5-bis(a-pyrromethene) pyrazole(l3). C? ./ // / +_22 [Z713> ___;> ’/ ‘/’ ,/’ / ‘\‘ \\ HN"N N 6N, HN—N \ (12) (13) This reaction has many precedents in the reactions of pyrroles with other aIdehydes and ketones, for example, the formation of a pyrromethene salt by the acid catalyzed reaction of pyrrole and 6 3,4,5-trimethylpyrrole carboxaldehyde as in figure 6. HB H H Figure 6. The methene condensation The reaction of the pyrazole was carried out in hot ethanol, methanol or hot acetic acid. In all cases the mixture exhibited two peaks in the visible spectra, one at 485nm and one at 605nm. They arose from two different chromophores since the absorption ratio between the two peaks varied over a wide range as the reaction progressed. It was clear from this that the reaction gave a mixture of products. Attempts to separate the two products by crystalization did not succeed. Other pyrroles such as 2,4-dimethyl or 2,4-dimethyl-3-ethyl or 2,4-dimethyl- 3-carbethoxy pyrrole were tried with similar results. Each showed two or more peaks in the visible spectra with variable ratios. Another approach to pyrazopyrromethenes involves the activation of the ketones in 4-methyl-3,5-bis(acetyl)pyrazole to nucleophilic attack. One method of activating a ketone is to convert it to a thioketone, and this can be achieved by treatment with P255 in benzene, toluene or acetonitrite8 as in Figure 7. ~-——-— P s ,— 2 5 w -—-> W Figure 7. Thioketones from ketones 6 When these methods were used on the 4-methyl-3,5-bis(acetyl) pyrazole the starting diketone was recovered in low yield and intract- able, nonidentifiable products were obtained. Another way to activate a ketone is to convert it to its corresponding iminium perchlorate.9 Because perchlorates are danger- ous to work with tetraflouroborate salts were employed. The amine salt precursor and the iminium salt products proved to be very deliques- cent and thus difficult to purify. As a result a satisfactory sample of the 4-methyl-3,5-bis(pyrolidine iminium acetyl)pyrazole(l6) could not be prepared. In light of these results a pyrazole carbonyl compound that is more reactive than the 4-methyl-3,5-bis(acetyl)pyrazole is needed. Aldehydes are more reactive than ketones so some pyrazole aldehydes were investigated to see if they would form stable methenes with pyrroles. Ideally the 3,5-bis(carboxaldehyde)pyrazole (17) would be the best compound to test as it could be used to construct the de- sired annulene if its reactions with pyrrole were successful. This aldehyde is unknown so its synthesis was attempted. Collman's re- ]0 Use of agent is reported to reduce acid chlorides to aldehydes. the reagent on 3,5-pyrazolediacidchloride may have decarbonylated the pyrazole as well, as the product'slnmeshowed no aldehyde or acid. A different approach to form aldehydes is to oxidize methyl ketones to glyoxalates and decarboxylate them11 (as in Figure 8). KMnO Figure 8. Aldehydes from acetyl groups When 4—methyl-3,5-bis(acetyl)pyrazole was oxidized with permangenate in accordance with this method no product was isolated after extrac- tion of the aqueous media. 12 In An alternative oxidative procedure is that of Thiele. this method methyl groups on aromatic systems are oxidized to diace- tates with chromic anhydride in acetic anhydride (Figure 9). CFOB’ ACZO -— OAC \ / \ / OAC Figure 9. Thiele's method Product formed by application of this method to 3,5-dimethypyrazole could not be isolated from the aquious workup by extraction. The McFadyen and Stevens method13 and the Sonn and Muller 13 for making aldehydes out of carboxylic acids also ran into approach the problem of the solubility of pyrazoles in water. Their applica- tions did not succeed. Synthesis through functional group manipula- tion did not seem to be a useful procedure. The 3,5-dialdehyde would be approached directly by the 1,3- dipolar addition of diazoacetaldehyde on propyna], The synthesis of diazoacetaldehyde from B-anilinoacrolein(22) and tosyl azide is 14 The formation of the B-anilinoacrolein in reasonable reported. yields following the reported procedure was not possible. An alterna- tive route to the diazoacetaldehyde was attempted. Butylithium in THF will generate the acetaldehyde enolate.15 This enolate could be reacted with toluenesulfonylazide to yield the diazoacetaldehyde(23). An IR spectrum of the product from the reaction showed no diazo absorptions. O EilLli> (/ L? _T5 N3//\ M2 O Q" //7 (23) H H This could be due to a C or 0 attack of the enolate on the sulfiJr of the sulfonylazide with displacement of azide. Since the results of concurrent studies on pyrazole aldehydes showed their reaction products with pyrroles where unstable, the efforts to produce the dialdehyde were halted. 3-Ca rboxaldehyde-S-pyrazolecaboxylate ethyl ester16 was a reasonable model compound with which to test pyrazole aldehyde reac- tivity as the 3,5-pyrazoledicarboxaldehyde was not available. Its acid catalized condensation with pyrrole in ethanol or acetic acid rapidly gave a deep red solution with a single absorbance peak at 485 nm in ethanol. This product was precipitated and dried at room temperature over night in a vacuum. It then gave a much higher base line and broader peak in its visable spectra. The analogous pyrro- methenes slowly decompose, but the process is significantly faster in pyrazopyrromethenes. If the methene could be reduced to a methane or oxidized to a ketone it would still be of some use in synthesis. A reduction of fresh material was tried with sodium borohydride, zinc metal on tin- dichloride but a methane was not produced. An oxidation of the methene to a ketone was tried with ceric amonium nitrate (which is useful in forming dipyrroketoneslg) without obtaining the desired result. At this point it can be seen that pyrazolealdehydes or ketones will not serve as a route to the formation of a stable pyrazopyrromethene or 9 the formation of a methane or ketone by their oxidation or reduction. Pyrazopyrroketones could be a useful alternative route to diaza[26]annulene as the analogous pyrroketones3’ 5 are known and used in the synthesis of porphyrins. Pyrroketones are formed by the Friedel- Crafts catalized reaction of a pyrrole and an acid chloride,3 the reac- tion of a pyrrole magnesium bromide with an acid chloride or by the reac- tion of an amide by the Vilsmeier-Haack Procedure.5 These reactions of pyrroles could be extended to the pyrazole acid chlorides to determine if pyrazapyrroketones can be generated in the same manner. Pyrazopyrroketones formed from the known 3,5-pyrazolediacid- chloride19 would fit the requirements for the synthesis of the diaza- [26] annulene (Figure 5). In order to determine its reactivity to pyrroles several condensation methods were tested. First the uncatalyzed reaction between the pyrazolediacidchloride and pyrrole was run in refluxing ether. It gave results that did not warrant further investigation. In the next approach to ketone formation pyrrole magnesium bromide was added to the acid chloride in ether at -78°, and purified by chromat- ography. The mass spectra showed fragments up to 73l m.u., this is much higher than the expected 254 m.u. molecular ion of the anticipated pro- duct. The reaction appears to have resulted in a polymer. This is most likely due to the acidity of the proton on the l-position and the characteristic property of N-unsubstituted pyrazoleacidchlorides to cyclize4 (Figure lO). 2MC—e \\ N’\ W I N’N \ PI Figure To. An acid chloride dimer TO With two acid chlorides on each pyrazole the material formed polymers. The Lewis acid catalyzed acylation of pyrrole was tried to see if polymer formation could be avoided in this manner. Silicon tetra- 22 When used with chloride has been shown to be a mild Lewis acid. 3,5-pyrazoledicacidchloride and pyrrole it gave an impure tarry pro- duct which could not be purified by recrystalization or chromato- graphy. It appears that the N-unsubstituted pyrazoles potential for polymerization is the difficulty in the system. A suitably protected pyrazole should prevent polymerization. One potential protecting group would be benzyl, which can be added 2] It should to pyrazoles and removed from them with relative ease. prevent polymer formation due to the nucleophilicity of the pyrazole nitrogens. The l-benzylpyrazole-3,5-diacarboxylate can be made from the 3,5-diester (Figure ll). The acid chloride of this diacid can be formed with SOCl 2. 1.IVCIC)P¢H3 MeO C CO Me 2 Q 2 / 2 . CH Br HO CWO H / 2 ——> 2 2 W m. H H CH2¢ Figure ll. The preparation of l-benzylpyrazole-3,5-diacid Its reaction with pyrrole magnesium bromide however is not as expected. The product after chromatography is a yellow oil which did not Chrystal- iae out of ethanol at 20° and turned black over 24 hours. It would seem that the conditions necessary to form a pyrazo- pyrroketone are not the same as the conditions that have proven to work well in the formation of pyrroketones. Because of this ll pyrazopyrroketones do not seem to offer a viable approach to the proposed hetrocyCTic system. Another possible route to the diaza[26]annulene exists in the pyrazopyrromethanes based on the precedence of the analogous 20 dipyrromethanes. The route to the pyrromethanes involves the reaction of a hydroxymethylpyrrole or a halomethylpyrrole with a pyrrole (Figure 12).22 X OH,E3r / va Q‘im H H H Figure l2. Methane formation This might be adapted to a 3,5-bis(bromomethyl) or (hydroxymethyl)- pyrazole to form mixed methanes and ultimately diaza[26]annulene. The desired a-bromomethylpyrazoles are unknown, so it was neces- sary to synthesize the desired 3,5-bis(bromomethyl)pyrazole in order to test its reactivity. N—bromosuccinimide (NBS) in carbon tetrachlor- ide reacts with benzylic methyl groups. Its reaction with 3,5-dimethyl- pyrazole should yield 3,5-bis(bromomethyl)pyrazole with a potential side product being a 4—bromopyrazole. The reaction gave three pyrazole products. With bromine as the reagent the number of products was the same. Evaporation of the reactions did not yield crystals and the material formed a hard glass over the period of a week. The tendency to form polymers in these systems also has been observed in the case of 4-chloromethylpyrazole,2] so the decomposition of this bromopyrazole is unfortunately an analogous reaction. It would appear that the l2 nucleophilicity of the pyrazole is again a drawback. In order to block the brominations of the pyrazole at the 4-position and block the nucliophilic nitrogen, pyrazole(27) was made. CéEt N1 /// Me CONH Q” 2 It should brominate only on the methyl groups and give only one dibromo product, however, in reality it gave several products. Due to the multiplicity of products the reaction was not investigated farther. Based on these results it would seem that bromomethylpyrazoles are difficult to generate by direct bromination of pyrazoles. This has made it difficult to investigate their reactivity to pyrroles. Hydroxymethylpyrazoles could reasonably be expected to yield pyrazopyrromethanes in a manner similar to the hydroxymethylpyrroles 20 In order to approach the target forming dipyrrolemethanes. diaza[26]annulene in the most direct manner 3,5-bis(hydroxymethyl)- pyrazole(35) was made by reducing the diester. 7 LAHI . MeOQCWCOZMe I 4 XHOH2C // CHZOH H H mm This dialcohol was a wax that would not crystalize in methanol, ethanol or water. The diacetate was made in an attempt to purify the T3 diol but it was extremely deliquescent. The diol turned out to be unstable, a sample allowed to sit for two months became insoluble in ethanol or water. Due to the difficulties in handling the diol and purifying it, a more reasonable model system was investigated. The easily accessible 3-hydroxymethyl-5-carbethoxypyrazole(37) can be obtained by reducing 3-carboxaldehyde-5—carboethoxypyrazole with sodium borohydride. NOB H 802ch H O 4 % EtO2CflC H 20 H HN— lN—N H (37) The reaction of this hydroxymethylpyrazole with three different pyrroles was carried out by a modification of the method of MacDonald.20 In the case of kryptopyrrole the hydroxymethylpyrazole remained un- reacted over several hours while all the kryptopyrrole reacted and a red color developed. It appears that the solvent acetic acid was more reactive than the pyrazole to the pyrrole and the red color due to the methene formation. When the hydroxymethylpyrazole was reacted With pyrrole 0P 2a4-d1'methyl-3-carbethoxypyrrole the pyrazole reac- ted over a twenty-four hours but not with the pyrroles, which remained unreacted. This was unfortunate as it made the simple routes to pyrazopyrromethanes unatainable. These last results combined with those for attempted methene and ketone formations means that standard methods of porphyrin chemistry do not appear to be applicable to the formation of analo- gous systems of pyrazoles and pyrazoles such as the diaza[26]annulene. T4 Alternatives nay exist to the use of pyrazopyrromethenes, methanes or ketones, a possible approach to the synthesis of diaza- [26]annulene could be through the use of l,5-dibromo-2,4-pentane- diones. A nucleophile should displace the bromide and then the beta dione could be converted with hydrazine to form a 3,5-difunc- tional pyrazole (Figure 13). Mi. Nuc 2. N H A Nuc / Nuc EBF' E3F‘ P¢—- H/ Figure l3. Possible reaction of l,5-dibromo-2,4-pentaned iones Displacements on l,5-dibromo-3-carboethoxy-2,4-pentanodione with pyrrole, hydrazine, acetate or methanol did not yield l,5-difunctional- 2,4-pentanediones which could be isolated as copper complexes. A Favorski reaction could have occurred in the presence of base and re- sulted in the destruction of the dione. Some way of protecting the system from the Favorski reaction seemed to be needed, and a nonlabile metal complex might do it. The III III 25 chromium and cobalt complexes of l,5-dibromo-3-phenyl-2,4-pen- Itanedione have been made but their yields were not reported. In- vestigating the reaction showed the yields to be very low. No nucle- ophic displacements were attempted on the brominated compexes. Other possible routes to the diaza[26]annulene exist that were not investigated in the lab. One way is through substituted diazo- compounds reacting with substituted acetylenes to form pyrazoles, if the materials used are like those in Figure 14 then pyrazopyrro- methanes should be formed. 15 \ NaH 2 W+ QCH-CE—C-H—fi Fgi-N N// H 2 / H Figure l4. A possible route to substituted pyrazoles For Figure 14 the diazo is not known and the best reported yield of z- 26 this product after reaction with formalde- -(propyne)pyrrole is l5%, hyde might yield the desired macrocycle with oxidation. In Figure l5 the problem of precursor synthesis can be seen to be doubly more difficult. Figure l5. A possible route to the macrocyclic ring A different route can be visualized which avoids non stabilized diazo compounds and is shown if Figure 16. OHC ” ‘ <%L—”4§U2 VN__ *' —__—_> I QDEF3F' (;H:LJS)F+1 * PCDBBF‘ H” 7 H H H II FTCDEEBrr H Figure 16. A possible multistep route to the desired diaza[26]annulene 16 Figu re 16 con. 17 Figure l6 circumvents the problem of the formation of the diazo- pyrrole which would be a most difficult compound to make. These methods were not used due to their complexity and the amount of time available for the project. They are, however, poten- tial routes to the proposed diaza[26]annulene. EXPERIMENTAL SECTION 3-Diazo-2,4-pentanedione(ll): made by the method of M. Regitz.28 4-Methyl-3,5-diacetylpyrazole(12) made by the method of Wolf.29 Eyrromethenes(l3) from 4-methyl-3,5-diacetylpyrazole(12) 3,5-Dimethyl-4-carbethoxypyrromethene(l3a) of (l2)_4-methyl-3,5- diacetylpyrazole, (0.368 grams, 2 m mole) was disolved in 2 ml of methanol. Then 0.668 g of 2,4-dimethyl-3-carbethoxypyrrole was. added and followed by 1 ml of concentrated HBr. After stirring two hours at room temperature there was no change of color. It was then heated to 60° for ten hours. The reaction mixture became a deep green. The visable spectrum showed the development of two peaks, one at 485 nm and the other at 605 nm in ethanol. They showed a varia- tion in their absorption ratio as the reaction progressed. The reac- tion products were precipitated by the addition of 40 ml of water and collected by filtration. Attempts to seperate the two products by crystalization with ethanol, methanol or acetic acid were not successful. 18 l9 3,5-Dimethyl-2-pyrromethene(l3b) of4(12)_ To 10 m mole