The Chemistry of 3-Acetyl-3, 4-Phenacylidenecoumarin Gerald Eugene Risinger Iowa State University
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Iowa State University Capstones, Theses and Retrospective Theses and Dissertations Dissertations 1961 The chemistry of 3-acetyl-3, 4-phenacylidenecoumarin Gerald Eugene Risinger Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/rtd Part of the Organic Chemistry Commons Recommended Citation Risinger, Gerald Eugene, "The chemistry of 3-acetyl-3, 4-phenacylidenecoumarin " (1961). Retrospective Theses and Dissertations. 1983. https://lib.dr.iastate.edu/rtd/1983 This Dissertation is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Retrospective Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. This dissertation has been 62-1367 microfilmed exactly as received RISINGER, Gerald Eugene, 1932- THE CHEMISTRY OF 3-ACETYL-3,4-PHENACYLI- DENECOUMARIN. Iowa State University of Science and Technology Ph.D., 1961 Chemistry, organic University Microfilms, Inc., Ann Arbor, Michigan THE CHEMISTRY OF 3-ACETYL-3 , ^-PI-ENACYLIDENECOUKARIN by Gerald Eugene Risinger A Dissertation Submitted to the Graduate Faculty in Partial Fulfillment of The Requirements for the Degree of DOCTOR OF PHILOSOPHY Major Subject : Organic Chemistry Approved: Signature was redacted for privacy. In Charge of Major Work Signature was redacted for privacy. head of Major Department Signature was redacted for privacy. Iowa State University Of Science and Technology Ames, Iowa 1961 il TABLE OF CONTENTS PAGE I INTRODUCTION 1 II HISTORICAL 2 III DISCUSSION 49 IV SPECTRA 87 V EXPERIMENTAL 100 VI SUMMARY 116 VII LITERATURE CITED .. 11? VI11 ACKNOWLEDGEMENT 124 1 INTRODUCTION The Darzens reaction has been extensively studied since the turn of the Twentieth Century. The scope and limitations of the reaction were determined by Darzens In the early 1900's, and In recent years, the stereochemistry and mechanism of the condensation have received ample investigation. The vinylogous Darzens reaction, on the other hand, has received sparse attention, and indeed, its existence Is still In doubt today. The purpose of this research was to investigate the chemistry and constitution of 3-acetyl-3,4-phenacylldene- coumarln, and the validity of the vinylogous Darzens reaction In the condensation of 3-acetylcoumarln with phenacyl halldes. HISTORICAL The Darzens Reaction The Darzens reaction le defined as the condensation of a haloraethylene compound with an aldehyde or ketone In the presence of base to yield an oxlrane ring (I) by the elimination of hydrogen hallde, 1,e., H A — C =» 0 -+• X—C — •+ : 0 — C — C — •+• HB®+• X ® I I I I In 1892, Erlenmeyer (1) announced the first synthesis of an epoxy or glycidic ester (II) by the condensation of benzal- dehyde with ethyl Ct-chloroacetate (III) In the presence of sodium: VCO.ET •f NaCL HE I The condensation was extensively investigated by Darzens ( 2-14) in the early 1900'e, as a consequence of which the reaction was given his name. Darzens (2) demonstrated the generality of the condensation in regard to the use of ketones in 1904: V +- CL R + NaCL 0 R-" r."thyl, ieohexyl, heptyl, nonyl, phenyl, j8~ph~nylethyl and p-1 sobutylphenyl 3 In 1906, Darzens (4) investigated the condensation of al dehydes with a-haloesters, and demonstrated the reaction to be general for aldehydes also. The aromatic aldehydes, benzaldehyde, anisaldehyde, plperonal and furfural, gave high yields of the corresponding epoxyesters. On the other hand, the aliphatic aldehydes, formaldehyde, acetaldehyde, proplonaldehyde and 1sovaleryaldehyde, were found to give low yields of the epoxyesters. The condensation of (2,^9 -unsaturated ketones with ethyl Œ-chloroacetate was also studies by Darzens and other investigators. Darzens and Host (9) reported the prep aration of the glycidic ester of 1-acetyl-l-cyclohexene (IV) by the condensation of ethyl Œ -chloroacetate with 1-acetyl- l-cyclohexene (V). p, ,OET _ ./V^T 0 V IV In recent years, Hellbron and coworkers (15), and Linnell and Shen (16) have investigated the condensation of CL, ft-unsaturated ketones with Œ haloesters. Hellbron, et al have reported the preparation of the glycidic esters of Q-lonone (VII)., ft -ionone (VI), and mesityl oxide (VIII): ^A^co2ET CO,, ET ^ ^t-CO,ET VI VII VIII 4 Linnell and Shen have also prepared the glycidic ester of benzalacetone (IX) by the condensation of benzalacetone (X) with ethyl fit-chloroacetate: + CL T0 - - L x ix In recent years the German chemists, Merdel and Frtihlich (17) have investigated the condensation of m-methoxyacetophen- one and p-methoxy-acetophenone with ethyl a-chloroacetate, and have obtained a satisfactory yield of the glycidic esters, ethyl ft-methyl- ft-(m-methoxyphenyl) - Cl,ft-epoxypropionate (XI) and ethyl ft -methyl-ft-methyl- ft -p-raethoxyphenyl)-a,ft - epoxypropionate (XII). Nerdel and Frtihllch have also pre pared ethyl ft -methyl-^(m-nltrophenyl)- a,ft-epoxypropionate, and ethyl ft -(m-nltrophenyl)-Q ,/5-enoxyproplonate by the con densation of rn-nitroaoetophenone and m-nltrobenzaldehyde with V^V/C02'ET ^ CO^ET OCH3 XI ethyl a -chloroacetate. The Russian workers, i'artynov and 01 'man (18) have supi'lein-;nted the work of Nerdel and Frtihlioh by condensing ethyl a -chloroacetate wl!.h several substituted benzal- 5 dehy&es. The Russians have prepared the glycidic esters of o-nitrobenzaldehyde, m-nltrobenzaldehyde, p-nitrobenzalde- hyde, and p-chlorobenzaldehyde. In I905, Darzens (3,4) Investigated the condensation of ethyl a -ohloroproplonate with aldehydes and ketones, and found this O-chloroester to exhibit the same behavior in condensations as ct-chloroacetates. Darzens has pre pared the a-methyl glycidic esters of acetone, methyl ethyl ketone, methyl propyl ketone, methyl hexyl ketone, and acetophenone. Aldehydes such as benzaldehyde, anisaldehyde, piperonal, furfural, acetaldehyde, propionaldehyde and isovalerylaldehyde have also been found to condense favor ably with ethyl g-ohloroproplonate. In 1952, Dullaghan and Mord (19) have employed ethyl a -ohloroproplonate and methyl CZ-chloroacetate in the pre paration of the glycidic esters of 2-thenaldehyde and sub stituted 2-thenaldehydes (XIII): 0 XIII 6 XIII a) R^-hydrogen b) Ri-ethyl c) R]_:ethyl d) R%=chloro Rgzmethyl Rgshydrogen Rgzhydrogen Rgzbydrogen R^zmethyl R^zhydrogen R^rmethyl R^thydrogen R/p ethyl Rj^imethyl R^z ethyl R^Zmethyl e) Rliohloro f) R^-hydrogen g) Rirhydrogen h) Ri^hydrogen R2=hydrogen R^hydrogen Rgthydrogen Rgzmethyl R^zmethyl Rirhydrogen R^Zmethyl R^zhydrogen Rijiethyl R^zmethyl R^ethyl R^r methyl In recent years, Morris and Young (20) have investigated the Œ -chloroesters, ethyl a-chloroproplonate, ethyl Cf-chlorobutyrate, ethyl a -chlorovalerate, and ethyl a-chlorocaprdate by preparing the substituted glycidic ester (XIV a-d) of acetone. XIV a) R = methyl b) R r ethyl C02ET c) R = propyl R d) R = butyl XIV Although ethyl 0 -chloroacetate has become the most popular halo component in the Darzens reaction, df-bro- rcoacetate and Œ-lod.oacetate have also been used (21). The yields of glycidic esters are somewhat lower if- the a-bromo- or a -iodoesters are employed; the lower yields have been explained by the greater reactivity of the bromo-and lodo- esters to SH2 displacement. Rallcr and. Ranart - Lucas (22) have illustrated the fact that aIky1at Ion of the carbonyl component is enhanced by usinr; ethyl Œ -bromoacctate and ethyl a -iodoacetate. When ieopropyl phenyl ketone (XV) is condensed with ethyl Q -chloroacetate, the Darzens product (XVI) prevails, Q ___ OET + CL^V/ 0 XV XVI however, when ethyl Q -chloroacetate in replaced by ethyl Q -bromoacetate or ethyl a -lodoacctate, only the alkylated ketone (XVII) is recovered: OET XV 4- X-^V^ CO2ET 0 XVII X; Br, I Stetter, Dierichs, and Siehnhold (23, 24) have alco reported O-alkylation to be the predominate reaction in the conden sation of ethyl Ct -bromoacetate with dihyciroresorcinol (XVIII). OET + BR^V^ • COOET 0 OH -ôc XVIII 8 The condensation of ethyl Œ-bromophenylacetate with acetone has been shown by Morris, et al. (25) not to afford a glycidic ester. An analysis of the reaction mixture dis closed that the bromoester was degraded to a mixture of ethyl phenylacetate, ethyl 2,3-diphenylmaleate, and ethyl 2,3-dlphenylsuccinate. The Darzens reaction with complex Gt-haloesters has proven to be unsuccessful. Yarnall and Wallis (26) have- attempted to condense ethyl 0^3 dichloroproplonate with oyolohexanone and have found no evidence of a Darzens product. Apparently, the ethyl Ctij9 dichloroproplonate undergoes elimination to yield ethyl flt-chloroacrylate. The Darzens reaction between acetophenone and ethyl Ot-chlo- ro- j3j3-dlethoxypropionate has also been unsuccessful, as Oroshnlk and Spoerrl (27) were unable to isolate products. The Darzens reaction involving an Q-haloketone as the haloraethylene component was first discovered by Fritz (28) in 1895» In attempting to prepare a-ethoxyaceto- phenone by the solvolysis of Gt-bromoacetophenone, Fritz discovered that Œ-bromoacetophenone condensed with itself. Fritz named the condensation product, diphenacyl bromide, and assigned the structure of the compound as 1,5-cllphenyl- 2-bromo-l,4 butadlone (XIX). 9 XIX Paal and coworkers (29, 30) studied the condensation in 1903, and discovered that two isomeric diphenacyl bromides were formed In the reaction; the isomeric diphenacyl "bromides were designated as a-and /3-diphenacyl bromides. Paal then extended the condensation by preparing the a -and ft -diphenacyl chlorides, and the GE-and ^-diphenacyl iodides. In 1913 » Wldman (31) investigated the diphenacyl halldes and rejected the structure proposed by Fritz. 'ildman discovered that if he treated ^6-diphenacyl bromide with acetyl chloride, he obtained a product that was Identical with a product obtained by treating ft-diphenacyl chloride with acetyl bromide. On the strength of this reaction, and other degradative evidence, Wldman proposed the tetrahydrofuran structure, 2-b.romo-3 ,4-epoxy-3 ,5 diphenyltetrahydrofuran (XX).