Amide derivatives of γ-substituted paraconic and aconic　acids have been　synthesized. Ultraviolet spectra of the aconic acid derivatives showed characteristic　fine structure in the region of 245 to 280 mμ

Isikawa, Tatsuo

Takeda, Akira

Torii, Sigeru

English

Okayama University Digital Information Repository

Biologically Active Compounds. II. The Synthesis of　β-CarboxY-γ-butyrolactone Derivatives

Okayama University Scientific Achievement Repository

MEMOIRS OF THE SCHOOL OF ENGINEERING, OKAYAMA UNIVERSITY, Vol. 3, No. I, SEPTEMBER, 1968Biologically Active Compounds. II. The Synthesis ofp-CarboxY-r-butyrolactone DerivativesSigeru TORII and Tatsuo ISIKAWA*Department of Indu5trial Chemi5tryAkira TAKEDADepartment of Synthetic5 Chemi5try(Received March 14, 1968)Amide derivatives of I-substituted paraconic and aconic acids have beensynthesized. Ultraviolet spectra of the aconic acid derivatives showed charac-teristic fine structure in the region of 245 to 280 mil.For the purpose of studies designed to inves-tigate biologically active substances, a num-ber of the title new compounds were synthe-sized. Certain of the r -lactone derivatives asare shown in Table I and II showed, to someextent, antibacterial, antifungal, and herbi-cidal activity.In order to avoid the formation of pyrroli-done derivatives by the reaction of intramolec-ular ester group such as lactonic linkage withamines,1) the amides of r-substituted paracon-ic and aconic acids (5 and 7)2),3; were prepar-ed by the reaction of equimolar amount of thechloride of the acids (5 and 7) with amines. 4)The general preparative ways of amides (6 and8) are shown in Scheme I.The infrared spectra of amides (6 and 8)5)show an absorption band at 1750-1760 (forlactone carbonyl) and an absorption band at1650-1680 (for amide carbonyl) as are shownin IR Charts I and IV. The ultraviolet spectraof aconic acids (5) exhibit characteristic bandsin the region of 245 to 280 m,l! as are shown inUV Charts.Table I I-Alkyl-I-methylparaconic Acids and Their AnilidesCH3 R'"C---C// I I "CO--R"R 0 CH2,,/CIIoR R" FormulaCalcd., %IH INFound, %C I H I NC2H5 I H 2,4-CI2CsH3NH 135 40 C14H15C12N03 53.18 4.78 4.43 53.33 4.6913.98IC2H5 H 2,5-C12CsH3NH 120 37 CI4H15C12N03 53.18 4.78 4.43 53.24 4.79 4.48C2H5 H 3,4-CI2CsH3NH 157 72 C14H 15CI2N03 53.18 4.78 4.43 53.18 4.72 4.76C2H5 H 4-CICsH4NH 128 61 C14H16CIN03 59.68 5.72 ... 59.69 5.79 ...i50-C4Hg Br OH I 166 90 CloH15Br04 43.02 5.43 ... 43.27 5.63 i ...i50-C4Hg H 3,4.CI2CsH3NH 195 66 C16H19C12N03 55.82 5.56 4.07 55.76 5.50 4.07i50-C4H9 H 2-CICsH4NH 102 53 C16H2QCIN03 62.03 6.51 4.52 62.66 6.50 4.34i50-C4Hg H 4-CICsH4NH 184 60 C16H20CIN03 62.03 6.51 4.52 62.33 6.68 4.83* Present Address: Isihara Sangyo Co. Ltd., Kusatzu Institute, Kusatzu-Si, Siga Prefecture.7374 S. TORII, T. !SIKAWA, and A. TAKEDA (Vol. 3,Table II 7-Alkyl-'l-methylaconic Acids and Their AnilidesCHg CO-R'"C--C//1 IIROC"'" / "-C HIIoICalcd., %IFound, 915R R' °C % FormulaI I I I-~---I C H N C H NC2H5 4-CICsH4NH 154 59 C14H14CINOg 60.1215.01 5.01 60.40 4.94 4.46C2H5 2,4-ClzCsHgNH 125 65 C14HlgClz:"lCg 53.5214.14 4.46 53.57 4.16 4.25C2H5 3,4-ClzCGHgNH 190 44 CI4HlgClzNOg 53.5214.14 4.46 53.27 4.17 4.00iSO-C4H9 OH 85.5 90 I ClOH1404 I 60.541 7. 12 ... 1 60 .60 7.20 ...ScheDle IRIR'-CH=C-CH-COOHICH2COOHR BrI IR'-CH2-C--C-COOHI Io CH2"-/CIIo(5)(4)(3)(2)-HBr11+(6)RIR'-CH2-C--C-COOHI IIo C"-/"'"C H/ g/ I. SOClz, pyridine2. ArNH2----- .._-~RIR'-CH2-C--C-CONH-ArI IIo C""'/"'"C HIIoRi! HBrin aq. AcOH(8)(I)R'-CH-C-C-COOEt"-H'ICH2-COOHRIR'-CH2-C --CH-COOHI Io CH2""'/CIIo! I. SOCh, pyridine2. ArNH2RIR'-CH2-C--CH-CONHArI Io CH2""'/CIIo1968) Synthesis of /3-Carboxy-7-butyrolaetone DerivativesIR Charts: I, N-(p-chlorophenyl)-7-methyl-7-isobutylparaconamide; II,7-methyl-7-isobutyl-B-bromoparaconic acid; III, 7-methyl-7-isobutylaconicacid: IV, N-(p-chlorophenyl)-7-methyl-7-isobutylaconamide, nujol mull.75Experhnental SectionAll melting and boiling points are uncor-rected. Microanalyses were performed by MissTeruko Nisi of our department.r, r-Dialkylparaconic Acids.2)- The ac-ids were prepared by the lactonization of theStobbe half. esters obtained in the usual way. 6)r, r-Dialkyl-lJ-broIlloparaconic Acids.-The B-bromoparaconic acids were prepared bybromination of a-alkylidenesuccinic acids ac-cording to the procedure of Fittig and Kraen-cker. 7) r -Methyl-r-ethyl-B-bromoparaconic ac-id melted at 162-5° (lit. 8) mp 163°). The in-frared spectrum of B-bromoparaconic acid (4,R = CH3 and R' = (CH3)zCH), mp 166°, isshown in IR Chart II. These acids (4) wereused for the preparation of aconic acids (5).3)r, r-Dialkylaconic Acids. - Y, r -Dialkyl-B-bromoparaconic acid (0.05 mole) in 200 mlwater was heated to 80-90° for 1hr. Upon cool-ing to room temperature the oily material cry-stallized (from water or n-hexane). The physicaland analytical data of aconic acid (5, R' =(CH3)z CHCHz) are indicated in Tabe II. Theinfrared spectrum of 5 (R' = (CH3h CHCHz) isshown in IR Chart III. r -Methyl-r-ethyl-aconic acid melted at 118° (lit. 8) mp 117-119°).General Procedure for Preparation ofAnilides. - To a mixture of a r, r-substitut-ed paraconic (or aconic) acid (0.02 mole), py-ridine (2 ml), and thionyl chloride (1. 4 ml)primary amine (0.03 mole) was added withstirring for 4-5 hr. The mixture was washedwith water and taken up in ether. The ethersolution was washed with sodium bicarbonatesolution, with water, and dried (NazS04).Removal of the solvent afforded crude anilide.The resulting product was recrystallized fromthe appropriate solvent. The physical con-76 S. TORn, T. !SIKAWA, and A. TAKEDAW 301EUV -1-(AI---- (61 UV-2200 250 300200stants, yields, and analytical data are given inTables I and II.ReferencesI) W. KOrTING: "Uber die Einwirkung von Aminen aufUV Charts: UV-I, ";-meth1'I-'Y-eth1'laconicacid; UV-2, (.-\) "t-pentylaconic acid, (B)j'-hexylaconic acid; 3) UV-3, aconic acid.Lactonmonocarbon,i£uren", Doctor Theses, 1958.2) K. SISIDO, S. TORn, and M. KAWANISI: J. Org.Cl:em. 29, (1964) 904.3) A. TAKEDA, K. TAKAHASI, S. TORn, and T.MORIWAKE: ibid. 31, (1966) 616.4) A. TAKEDA an:l S. TORn: This Memoirs I, (1966)44.5) L. T. BELLAMY: "Thg Infrared Spectra of ComplexMolecules", 2nd ed., John 'Viley and Sons, Inc.,New York, l\'. Y., 1958; K. Nakanishi: "InfraredAbsropt;on Spectroscopy", I.\an\odo Co. Ltd., '1'0:'1'0,1960.6) W. S. JOHNSON and G. H. DAUB: Org. Reac-tions 6, (1951) I.7) R. FITTIG and J. KRAENCKER: Ann. 331, (1904)88.8) H. STOBBE: ibid. 321, (1902) 83.

TAKEDA an:l S. TORn: This Memoirs I,

Theses,

Thg Infrared Spectra of Complex Molecules&quot;, 2nd ed., John 'Viley

Biologically Active Compounds. II. The Synthesis of　β-CarboxY-γ-butyrolactone Derivatives

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Biologically Active Compounds. II. The Synthesis of β-CarboxY-γ-butyrolactone Derivatives

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Biologically Active Compounds. II. The Synthesis of　β-CarboxY-γ-butyrolactone Derivatives