摘要:
1976 2505Preparation of Macrocyclic Ether-Esters, Thioether-Esters, and Ether-ThiolestersBy Jerald S. Bradshaw,' Clark T. Bishop, Steven F. Nielsen, R. Elliott Asay, David R. K. Masihdas,E. Dean Flanders, Lee D. Hansen, Reed M. Izatt, and James J. Christensen, Department ofChemistry and Chemical Engineering and Center for Thermochemical Studies, Brigham Young University,Provo, Utah 84602A series of macrocyclic ether-esters, thioether-esters, and ether-thiolesters [(I )-(I O)] have been prepared bytreating various oligo-ethylene glycols and sulphur-containing oligo-ethylene glycols with malonyl, succinyl. andglutaryl chlorides.WE have previously reported the synthesis 2-5 and cation-complexing properties of several oxathiapentadecanesand thio-crown compounds.Several of the thio-(crown-5) compounds were shown to form more stable(as measured by log K ) complexes in aqueous solutionwith Ag+ and Hg2+ than with TI+ and Pb2+. Also,metal-ligand complexes of 1 : 2 stoicheiometry werefound for the reaction of Ag+ and Hg2+ with several ofthe thio-crown ligands.6 We present here the synthesisof compounds (1)-(lo), containing ether, ester, thio-Preliminary communication, J. S. Bradshaw, L. D. Hansen,S. F. Nielsen, M. D. Thompson, R. A. Reeder, R. M. Izatt, and3. J. Christensen, J.C.S. Chew. Comna., 1975, 874.J . S. Bradshaw, J. Y. Hui, B. L. Haymore, J. J. Christensen,and R. M. Izatt, J . Heterocyclic Ckem., 1973, 10, 1.J. S. Bradshaw, J. Y . Hui, Y. Chan, B. L. Haymore. R. M.Izatt, and J. J.Christensen, J . Heterocyclic Chena., 1974, 11. 45.J. S. Bradshaw, B. L. Haymore, R. M. Izatt, and J. J.Christensen, J . Org. Chem., 1975, 40, 1510.ether, and thiolester groups. A calorimetric investi-gation of the cation-complexing properties of thesecompounds has been started.The formation of macrocyclic esters has been reportedpreviously. Drewes and his co-workers have studied anumber of macrocyclic di- and tetra-esters from phthalicand maleic acid systems. They treated the dipotassiumsalts of phthalic and maleic acid with a series of alkyland alkynyl dibromides to make 10-34-membered ringSimilar compounds have been reportedJ. S. Bradshaw, R. A. Reeder, M. D. Thompson, E. D.Flanders, R. L. Carruth, R. M. Izatt, and J. J. Christensen, J .Org. Cnem., 1976, 41, 134.R.M. Izatt, R. E. Terry, L. D. Ilansen, A. G. Avondet,J. S. Bradshaw, N. K. Dalley, T. E. Jensen, B. L. Haymore, andJ. J. Christensen, in preparation.S. E. Drewes and P. C. Coleman, J.C.S. Perkin I , 1972,2148.8 S. E. Drewes and B. G. Riphagen, J.C.S. Perkin I, 1974, 323.S. E. Drewes and B. G. Riphagen, J . C . S . Perkin I , 1974,19082506 J.C.S. Perkin 1( 1 1O Y - - Y 0 co 0 O>L 0 J 0( 6 1co O 7 e, .i L/0 n o A s t i + o y bowsH CIby other workers.lO However, macrocyclic esters con-taining the oxyethylene unit like those described herehave not been reported.The macrocyclic esters and thiolesters were preparedby treating the appropriate glycol or dithiol withmalonyl, succinyl, or glutaryl chloride.The oligo-( 8 1C Iethylene glycols are available commercially, and theirthio-analogues can be prepared in the laboratory. Thereaction was run at high dilution by adding the startingmaterials from separate dropping funnels to benzene atlo See reference 7 for a review of other macrocyclic ester syn-theses1976 250750 "C. Yields were generally in the range 27-91%.The thiolesters (4) and (8) appeared to be unstable.The structures proposed for the macrocycles areconsistent with i.r. and n.m.r. spectra, elementalanalyses, and molecular weights. The esters all exhibiti.r. bands at 1730-1 740 cm-l and the thiolesters (4)and (8) bands at 1690 cm-l. All the malonate esters[(1)-(3) and (5)] exhibit n.m.r. peaks at 6 3.42 5 0.01(O,C*CH,*CO,) .l1 The corresponding peak for com-pound (4) is shifted to 6 3.75, by approximately the sameamount as observed in comparing the acetate methylpeaks for S-ethyl thioacetate and ethyl acetate.ll Thesuccinates [(6), (7), and (9)] exhibit n.m.r. peaks at8 2.70 & 0.02 (O,CfCH2],-C0,) .ll Corresponding peaksfor the thiolester (8) are shifted by much the sameamount as mentioned above for compound (4).Com-pound (10) exhibits n.m.r. peaks similar to those ofdiethyl glutarate.ll The CO-0-CH, groups of the estersexhibit n.rn.r. peaks with similar chemical shifts to thoseat 6 4.22 for diethyl mdonate l1 [(l)-(3) and (5)]; at6 4.15 for diethyl succinate l1 [(6), (7), and (9)]; and at6 4.15 for diethyl glutarate l1 [(lo)]. The SCH, groupsof compounds (5) and (9) exhibit peaks at 6 2.8 & 0.1 aspreviously repor ted.,?3 The SCH, signals for com-pounds (4) and (8) were at 6 3.1 0.1.The etherOCH, groups all exhibited peaks at 6 3.7 & 0.1.Methylene groups p to sulphur or to an ester group gavepeaks at lower field, as previously reported.lP2The thiolesters (4) and (8) appear to be unstable.Repeated chromatography on alumina always gave aproduct which exhibited small i.r. bands at 2 550 cm-1and an n.m.r. triplet at 6 1.6 (SH). We were able topurify compound (4) well enough for a satisfactorycombustion analysis.EXPERIMENTAL1.r. spectra were obtained with a Hilger and WattsH 1200 Infragraph. N.m.r. spectra were obtained withVarian A60-A and EM390 spectrometers.Elementalanalyses and molecular weight determinations were per-formed by MHW Laboratories, Garden City, Michigan, andby Galbraith Laboratories, Inc. , Knoxville, Tennessee.Starting MatwiaZs.-Most of the starting glycols and acidchlorides were used as purchased : ethanedithiol (Aldrich) ,2-( 2-chloroethoxy)ethanol (Parish), triethylene glycol(Baker), tetraethylene glycol (Aldrich), pentaethyleneglycol (Columbia), malonyl chloride (Aldrich) , succinylchloride (Aldrich), and glutaryl chloride (Aldrich) . 3,6,9-Trioxaundecane-1, ll-dithiol, vmX. 2 560 m-l (SH), wasprepared. from tetraethylene glycol by the thiourea m e t h ~ d . ~3,12-Dioxa-6,9-dithiatetradecane- 1,14-diol was prepared(757;) by treating ethanedithiol with 2-(2-chloroethoxy)-ethanol and sodium ethoxide in ethanol; the productexhibited 6 2.85 (8 H, m, S-CH,) and 3.70 (14 H, m, O*CH,and OH).General Procedure f o y Synthesis.-The glycol and acidchloride, each dissolved in benzene (200 ml) were slowlyadded simultaneously to stirred benzene (600 ml) at 50 "C.A nitrogen atmosphere was maintained where sulphurSee Sadtler n.m.r.spectra nos 11 242 (diethyl malonate),10 391 (ethyl acetate), 21 182 (S-ethyl thioacetate), 183 (diethylsuccinate), and 4 258 (dkthyl glutarate).compounds were used. The mixture was stirred at 50-GO "C for at least 2 days. Longer reaction periods gavehigher yields. The atmosphere over the mkture was foundt o be acidic. After the reaction was stopped, benzene wasremoved under vacuum.The crude product was thenpurified by recrystallization or by chroniatography onalumina with hexane containing increasing amounts ofchloroform as eluant. Specific details are given for eachcompound.1,4,7,10-Tet~aoxacyclotridecane- l l , 13-dione (1). Tri-ethylene glycol (10 g, 0.067 mol) and nialonyl chloride(9.38 g, 0.067 mol) were used. The product (4.8 g, 34%)had m.p. 51.5-52.5 "C (from chloroform-hexane) ; v,.1710 cm-1; 6 3.40 (2 HI s, CO*CH,-CO), 3.64 (4 H, s,OCH,CH,*O), 3.75 (4 H, t, CO,CH,*CH,), and 4.35 (4 H,t, CO,*CH,) (Found: C, 49.75; H, 6.657;; -W, 232.C9H,,0, requires C, 49.55; H, 6.45%; AT, 218.2).Tetraethylene glycol (15.0 g, 0.077 Inol) and inalonylchloride (10.9 g, 0.077 mol) were used. The product (5.5 Q,27%) had m.p.67-68 "C (from chloroforni-hesane) ;v,, 1 720 cm-1; 6 3.43 (2 H, s, COCH,-CO), 3.65 (8 H, s,O-CH,CH,*O), 3.75 (4 H, t , CO,*CH,*CH,), 4.34 (4 H, t,CO,*CH,) (Found: C, 50.3; H, 6.85%; fM, 247. CllH,,O,requires C, 50.4; H, 6.9%; M , 262.26). Tlic same productwas isolated in 1-2% yield by refluxing nialonic acid andtetraethylene glycol in benzene with a trace of toluene-p-sulphonic acid.1,4,7,10, 13,16-HexaoxacycEolaonadecane-1iJ lg-dio9ze (3).Pentaethylene glycol (15 g, 0.063 mol) and nmlonyl chloride(8.88 g, 0.063 mol) were used. The product (7.5 g, 38%)had 1n.p. 57-58 "C (from chloroform-hexane) ; vmxa1720 cm-l; 6 3.43 (2 H, s, COCH,*CO), 3.67 (12 H, s,O*CH,*CH,*O), 3.77 (4 H, t, CO,*CH,*CH,), and 4.33 (4 H,t, CO,*CH,) (Found: C, 50.75; H, 7.15%; Ji, 291.C,,H,,O, requires C, 51.0; H, 7.25% ; M , 306.31).1,4,7-Trioxa-10J 1PdithiacycZohexadecane-11, lbdioute (4).3,6,9-Trioxaundecane-1, ll-dithiol (17 g, 0.076 mol) andmalonyl chloride (11.5 g, 0.076 mol) were used.Theproduct was purified on an alumina column (yield < 1 g) ;it decomposed when heated, as shown by the appearanceof an i.r. band at 2 550 cm-l. Compound (4) exhibited vmU.1 690 cm-l; 6 3.15 (4 H, t, CO-SCH,), 3.63 (8 H, s,O*CH,CH,*O), 3.68 (4 H, t, CO*S*CH,CH,), and 3.75(2 H, s, CO*CH,*CO) (Found: C, 44.75; H, 6.45; S,21.55%; M , 279. Cl,H,,0,S2 requires C, 44.9; PI, 6.15;S , 21.8%; M , 294.39).1,4,13,16-Tetraoxa-7,1O-ditlaiacyclononadecane- 17,lg-dione(5). 3,12-Dioxa-6,9-dithiatetradecane-l, 14401 (27 g, 0.10mol) and malonyl chloride (14.1 g, 0.10 mol) were used.The viscous product (28.1 Q, 85y0), was purified by chro-matography on alumina; vmax. 1 740 cm-l; 6 2.78 (8 H, m,SCH,), 3.47 (2 H, s, CO*CH,*CO), 3.72 (8 H, m, OCH,),and 4.35 (4 H, t , CO,*CH,) (Found: C, 45.95; H, 6.65; S,18.75%; M , 350.C,,H,,O,S, requires C, 46.15; H, 6.55;S, 18.95%; M , 338.45).1,4,7,10,13-Pentaoxacyclohe~tadeca~ae- 14,l'i-diow (6).Tetraethylene glycol (15 g, 0.077 mol) and succinyl chloride(11.4 g, 0.077 inol) were used. The light yellov: s-iscous oilwas purified on alumina; yield 0.80 (20°', based on theamount of product purified) ; v,, 1 735 cn1-l; 8 2.72 (4 H,s, COCH,CH,*CO), 3.68 (8 H, s, OCH,*CH,*O), 3.72 (4 H,t, C0,*CH2*CH,), and 4.32 (4 H, t, CO,.CH,) (Found: C,52.35; HI 7.4%; M , 289.C1,H2,,0, requires C, 32.15;H, 7.3%; M , 276.03).1,4,7,10,13-Pentaoxacyclohexadeca.~ze- 14,16-dione (2)2505 J.C.S. Perkin I1,4,7,10,13,16-Hexaoxacycloeicosane-17,20-dioize (7)-Pentaethylene glycol (19 g, 0.08 mol) and succinyl chloride(12.4 g, 0.08 mol) were used. The mixture was stirred a t50 "C for 6 days. The crude product was filtered througha small amount of alumina, and the alumina was washedwith chloroform (25 ml). The product (25 g, 90%) was aviscous oil; vmx. 1 740 cm-1; 6 2.68 (4 H, s, COCH,*CH,*CO),3.68 (16 H, s, ether OCH,), and 4.28 (4 H, t, CO,*CH,)(Found: C, 52.4; H, 7.45%; M , 339. C14H2408 requiresC, 52.5; H, 7.55; M , 320.15).1,4,7-T~ioxa-l0,15-dithiacycEoheptadcane-ll,l4-dione (8),3,6,9-Trioxaundecane-l, 11-dithiol (18.1 g, 0.08 mol) andsuccinyl chloride (12.4 g, 0.08 mol) were used.Theproduct was dissolved in chloroform and repeatedlyextracted with water. The final product (ca. 5%) was alight yellow viscous oil; vmX. 1690 cm-l; 6 2.85 (4 H, s,COCH,*CH,*CO), 3.10 (4 H, t , SCH,), and 3.62 (12 H, m,OCH,). Good elemental analytical results were notobtained.1,4,13,16-Tetraoxa-7,10-dithiacycloeicosane-17,20-dione (9).3,12-Dioxa-6,9-dithiatetradecane-l, 14-diol (27 g, 0.1 mol)and succinyl chloride (17.1 g, 0.1 mol) were used. Theproduct was chromatographed on alumina to yield a lightyellow viscous oil (28 g); vmrc 1 735 cm-l; 6 2.65-2.85(12 H, m, COCH,CH,-CO and SCH,), 3.72 (8 H, m, etherOCH,), and 4.28 (4 H, t , CO,*CH,) (Found: C, 47.85; H,6.95; S, 18.25. C,,H,,O,S, requires C, 47.7; H, 6.9; S ,18.2%).1,4,7,10,13,16-HexaoxacycZolie~~eicosane-17,21-dione (10).Pentaethylene glycol (19.1 g, 0.08 mol) and glutaryl chloride(13.6 g, 0.08 mol) were used. The mixture was stirred a t50 "C for 6 days. The crude product (27 g, 80%) wasdissolved in chloroform and filtered through alumina(10 g); v,,, 1735 cm-l; 6 1.98 (2 H, m, CH,*CH,*CH,),2.41 (4 H, t , CH2*CH,*CH,), 3.68 (12 H, s, O*CH,*CH,*O),3.72 (4 H, t , CO,*CH,CH,*O), and 4.25 (4 H, t , CO,*CH,)(Found: C, 53.85; H, 7.75. Cl,H,,08 requires C, 53.9;H, 7.85:/,).We thank G. E. hlaas for the preparation of one of thethio-glycols. We also thank the associated studentgovernment of B.Y.U. for student grants (to C. T. B.,S. F. N., and E. D. I?.).[6/87S Received, 21st June, 1978
ISSN:1472-7781
DOI:10.1039/P19760002505
出版商:RSC
年代:1976
数据来源: RSC