Elimination and addition reactions. Part XXVII. Addition of amides to electrophilic alkenes

摘要

1976Elimination and Addition Reactions. Part XXVIIJ Addition of Amidesto Electrophilic AlkenesBy John W. Batty, I.C.I., Organics Division, Blackley, Manchester M9 3DAPeter D. Howes and Charles J. M. Stirling," School of Physical and Molecular Sciences, University Collegeof North Wales, Bangor, Gwynedd LL57 2UWTreatment of amides from primary amines with strong bases and electrophilic alkenes (acrylonitrile or p-tolyl vinylsulphone) gives products derived from N-alkylation of the amide. When amides without an N-H bond are used,no reaction occurs unless the amide gives a stabilised carbanion on proton abstraction ; C-alkylation then occurs.When N- and C-alkylation can compete, N-alkylation i s preferred.Dialkylation of diamides occurs readily, and evidence for alkylation of a low molecular weight polyamide has beenobtained.Alkylation of Nylon 6 and Nylon 66, however, does not occur to an appreciable extent under the condi-tions used for the other amides.NUCLEOPHILIC addition to electrophilic alkenes is an im-portant and versatile reaction 2*3 and is particularly suc-cessful when the alkene bears a cyano- or sulphonyl 4*5group. Addition of amides to electrophilic alkenes has,however, received only scant attention6-* and we nowreport on the reactivity of simple mono-, di-, and poly-amides towards p-tolyl vinyl sulphone and acrylonitrile.Part XXVI, M. J. van der Sluijs and C. J. M. Stirling, J.C.S.P. F. Butskus. Russ. Chem. Rev., 1961, 30, 583; H. ,4.a H. 0. House, ' Modern Synthetic Reactions,' 2nd edn.,A.T. Kader and C. J. M. Stirling, J . Chem. SOC., 1962, 3686,S. M. McDowell and C. J. amp;I. Stirling, J . Chewz. SOC. (B),Pevkin 11, 1974. 1268.Bruson, Org. Reactions, 1949, 5, 79.Benjamin, New York, 1972.and references cited therein,1967, 343.Neutral amides show only very restricted nucleo-philicity; the site of protonation is variable9 and ininter- lo and intra-molecular l1 nucleophilic displace-ments in which the neutral amido-group is the nucleo-philic centre, oxygen is the nucleophilic site.Simple amides which possess an ionisable N-H bondare weak acids12 with pK, values in the region of 15.Under suitable basic conditions, nitrogen anions derivedR. P. hiaridla and R. J. Johauskas, J . Opg. Chew., 1958, 23,923.euro;3.P. 875,135 (Chem. Abs., 1963,59,6420).B. P. 920,213 (Chem. Abs., 1962, 58, 14148).M. Liler, Adv. Plzys. 0p.g. Chem., 1975, 11, 267.l o M. G. Ahmed, R. W. Alder, G. H. James, M. L. Sinnott, andl1 C. J. M. Stirling, J . Chem. Soc., 1960, 255.l2 S. Kaae and -4. Senning, Acta Chem. Scand., 1968, 22, 2400.M. C. Whiting, Chem. Comm., 1968, 1533J.C.S. Perkin Ifrom amides can take part in intra-l1,l3 or inter-molecular l4 nucleophilic displacements with halides.Addition of simple amides of aromatic carboxylic acids toacrylonitrile under catalysis by Triton B has been accom-plishedJ6 and alkoxide-catalysed addition of lactams toseveral electrophilic alkenes has been claimed.' In base-catalysed nucleophilic addition of amides to electrophilicalkenes, the base used to generate the anion must notitself compete in the addition process. In the presentwork we have mainly employed potassium t-butoxide int-butyl alcohol as the solvent-base system.Thismedium is sufficiently basic to give significant equilib-rium concentrations of ions derived from the amidesused, and t-butoxide ion is feebly nucleophilic towardselectrophilic alkenes.Yields of adducts obtained from simple mono-amidcsand either $-tolyl vinyl sulphone or acrylonitrile aregiven in Table 1. In several reactions, separation of theAmideAcNHBu (3)AcNHBu (3)AcNHBu (3)AcNHBu ( 3 )AcNHBu (3)AcNHBu (3)AcNHBu (3)AcNHBu (3)(AcNHCH,), (7)(AcNHCH,), (7)PhCH,CO-NHMe (4)PhCH,CO.NMe, (5)AcNMe, (6)Alkene aArSO,*CH=CH,ArSO,CH=CH, cArSO,CH=CH, cArSO,CH=CH,NC*CH=CH,NCCHXH,ArSO,CH=CH, eArSO,CH=CH, eNCCH=CH,ArSO,CH=CH ~9 gArSO,CH=CH, cArSO,CH=CH, cArSO,CH=CH, eIn all amides which possess an N-H bond, alkylationoccurs at nitrogen.The acyl groups are clearly notsufficiently acidic to allow competitive reaction via acarbonyl-stabilised carbanion. This is true even ofN-methylphenylacetamide (4), in which the carbanionwould be additionally stabilised by the phenyl group;the products are solely derived from N-alkylation. Inan NN-dialkylamide, such as dimethylacetamide (6) noreaction occurs under conditions in which N-mono-substituted amides are alkylated. In NN-dimethyl-phenylacetamide ( 5 ) , however, C-alkylation occursreadily.Recent 1 y , C-alkylation of dimethylace t amideby P-nitrostyrene in the presence of lithium amides hasbeen a~conip1ished.l~Yields of N-alkylated product in all reactions aremodest. In recent work,16 reactivity of amido-groups asleaving groups in activated P-eliminations has been deter-mined. The amide (8) reacts slowly with ethanolicTABLE 1Addition of amides to alkenesCatalyst bButOK (0.2)RutOK (1.0)ButOK (1.5)NsOH (0.8)NaOH (1.0)ButOK (0.5)ButOK (0.26)ButOK (0.26)ButOK (0.15)ButOK (0.25)ButOK (0.5)ButOK (0.8)ButOK (0.8)SolventButOHButOHButOHPhHPhHButOHDMA jButOHButOHButOHButOHButOHDMA-But OH ( 1) bYield ofadduct38 d42 Ether ( 2 8 ) , alcohol (20), amide (59)375640 h Amide (43)31 Amide (48)11 hIk2937 Amide (57)4343650Other products (yo) (IAmide (57), alcohol (35,) ether (16)Alcohol (61), ether (30) Jamide (77)J4 Molar proportions (amide : alkene) 1 : 1 unless otherwise stated.b Molar proportions in parentheses. Ar = fi-tolyl. 'HN.m.r. analysis of adduct-alcohol mixture. e ArSO,CH,CH,.OBut. f ArSO,CH,CH,*OH. 2 mol per mol of amide. 'HN.m.r. analysis of amide-adduct mixture. I1H N.m.r. analysis of adduct-ethermixture. * C-Alkylated product.f Dimethylacetamide. k No proton donor.amide-alkene adduct either from t-butoxide-alkeneadducts or from unchanged amide was not attempted;such product mixtures were analysed by lH n.m.r.spectroscopy. In reactions with p-tol~7l vinyl sulphone,the ether (1) and the alcohol (2) were usually formed.The alcohol (2) presumably arises by p-elimination in theether (1) derived from the addition of t-butoxide ion tothe alkene.ArSO2*CH2*CH2-O -CMe2 4 ArSO2*CHfCH2*OHrJ(1 1 ( 2 )The structures of alkene-amide adducts were authen-ticated by syntheses involving acylation of the readilyformed amine-alkene adducts .5l3 M.S. Manahas and S. J. Jeng, J . Org. Ckeriz., 1967, 32, 1246.l4 J. D. Park, R. D. Englert, and J. S. Meek, J. Amev. Chenz.Soc., 1952, 74, 1010.sodium ethoxide (Kelim = 2.3 x 1 mol-l s-l at 40 "C)to give the products (9) and (10) derived from initialelimination of the corresponding amide anion. In theamide alkylation reactions, therefore, equilibration prob-ably occurs between adduct and free amide, and part ofthe electrophilic alkene is diverted to addition reactionswith the base-solvent system.Support for this view isfound in the observation that when C-alkylation occurs,yields are substantially higher than in the N-alkylationreactions (Table 1). Elimination of carbon leavinggroups in activated p-eliminations occurs only slowly,and diversion of the electrophilic alkene to other productsis therefore disfavoured.Alkylation of the diamide (7) (Table 1) occurs at bothnitrogen atoms, but surprisingly yields of dialkylatedproduct were not sensitive to the alkene-amide ratiowhen this was varied from 2 : 1 to 1 : 1.l5 D. Seebach and H. F. Leitz, Angow. Chem. Internat. Edn.,l6 D. R. Marshall, P. J. Thomas, and C.J. M. Stirling, J.C.S.1971, 7, 501.Chem. Conatn., 1975, 9401976 1545Formation of a stable addition product in these re-actions requires the presence of a proton donor. Thusalkylation of N-butylacetamide in dimethylacetamidewith t-butoxide as base but without added proton donorgives a yield of alkylated product only one-third of thatobtained in the presence of an equimolar proportion ofReactions with Polymeric Amides.-Reactions withcommercial polymers, even to very limited extents, mayproduce technologically valuable changes such as modi-fication of surface properties. We were interested todiscover whether such changes could be effected byt-butyl alcohol.decomposition. The importance of a proton donor isclearly seen in reactions with polymers also; in theabsence of t-butyl alcohol, the degree of sulphur in-corporation in t-butoxide-catalysed reactions is reducedby 90.Reactions with polyamides of much higher molecularweight (Nylon 6 and Nylon 66) were not successful.Calculated values for complete sulphonylet hylation arehigher but extents of incorporation were small as onsublimation most of the sulphur incorporated was lost,suggesting that little alkylation occurs. Mutual solubil-isation of the reagents under conditions in which a protonPhS02*CH2*CH2*NMeAc - PhS02*CH=CH2 + HNMeAc(8) (9) (10)N-alkyIation of polymeric amides with electrophilicalkenes.The only reported example of this type ofreaction is the cyanoethylation of Nylon 6 catalysed bysodium hydroxide in dioxan.8 No proof of chemical in-corporation was given.Two difficulties arise in re-actions with polymers; mutual solubilisation of the re-agents and proof of chemical rather than purely physicalincorporation of the reagent.Preliminary work was carried out with a simple poly-amide, Ultramid lC, which(11)-(14) in a polymer ofPolymerUltramid 1C{ Kylon 66Xylon 6contains the four componentsmolecular weight ca. 20 000.donor is present constitutes a severe problem and thetightly hydrogen-bonded structure of the polymers prob-ably contributes to their low reactivity.EXPERIMENTALReagents.-+-Tolyl vinyl sulphone had m.p. 64" (lit.,1763-66'), N-butylacetamide had b.p. 118" at 10 Torr., n, l71.4417 (1it.,l8 b.p. 135' at 18 Torr., nDZ0 1.4412) ; "'-ethyl-enediacetamide had m.p.173" (lit.,l9 173") ; N-methyl-cc-phenylacetamide had m.p. 57" (lit.,20 57") ; NN-dimethyl-a-phenylacetamide had m.p. 42-43' (lit.,21 43.5").TABLE 2p-Tolylsulphonylethylation a of polyamidesSolvent Proton donor BaseDMA C-ButOH (10 : 1) ButOH KOButDMA e-ButOH (4 : 1) ButOH KOButDMA Et,NDMA KOButButOH ButOH KOButButOH KOButPhCH,*OH PhCH,*OH NaO.CH,PhPhCH,.OH-ButOH PhCH,*OH KOButButOH-DMSO S Incorporated2.2,2.6, 1.5 d2.90.00.28.6,e 1.26.1,g 2.0(0.20.2j C O . 2 ka Sulphone : amide group ratio 1 : 1. 0.1-0.2~. Dimethylacetamide. After sublimation at 21OOC and 0.1 Torr. e At b.p.Dimethyl sulphoxide. g 4 h at 140 "C. 6 h a t 135 "C. j 5 h at 175 "C. At b.p.The polymer is soluble in dimethylacetamide and theresults of reactions with p-tolyl vinyl sulphone are shownin Table 2.The extent of reaction is gauged by thedegree of incorporation of sulphur into the recoveredpolymer. The calculated value for complete sulphonyl-The extent of sulphur in-corporation is reduced only slightly by reprecipitationTypical AZkyZation Procedures.-(a) AlkyZution of N-butyl-acetumide with p-tolyl vinyZ suZphone in t-butyl alcohol. Theamide (1.15 g, 10 mmol) was added to solution of potassium(O.39 gJ 10 mg atom) in t-buql alcohol (50 ml). P-TolYlsulphone (10 mmol)j in t-butyl alcohol (50 ml), wasadded with stirring. After 6 h, the mixture was neutralised(AcOH) and water (200 ml) was added. The product was is about lo yo.-~and by sublimation under Severe Conditions.In the IS w. E. Backmann, w. J. Horton, E. L. ~ e n ~ e r , N. w. Mac-latter case, some loss of sulphur Content may be due to Naughton, and C. E. Maxwell, J . Amer. Chern. SOC., 1950, 72,3132.G. D. Buckley, J. L. Charlish, and J. D. Rose, J . Chem. SOL, 2o F. F. Blicke and H. Zinnes, J . A w w . Chew. Soc., 1955, 77,1947, 1514. 4849.21 H. J. Taverne, Rec. Trav. chim., 1897, 16, 33. l 8 M. V. LockandB. F. Sager, J . Chem. SOC. (B), 1966, 6901546 J.C.S. Perkin Iextracted with dichloromethane and distilled to give threefractions: (i) N-butylacetamide (59y0), nD1*.5 1.4422, b.p.73' at 0.05 Torr, (ii) 2-t-butoxyethylp-tolyl sulphone (28) ,nD22 1.5131, b.p. 133' at 0.01 Torr (Found: C, 60.6; H, 7.9.C13H2,03S requires C, 60.9; H, 7.8), vmx 1 320 and 1 145cm-1 (SO,), z (CC1,) 2.15-2.8 (4 H, m), 6.2-6.95 (4 H, m),7.6 (3 H, s), and 9.0 (9 H, s); (iii) a mixture of 2-p-tolyl-sulphonylethanol and N-butyl-N-p-tolylsulphonylethylacet-amide (1.56 g), b.p.181-184' a t 0.05 Torr (1: 3 by lHn.m.r.).(b) NN'-Etlzylenediacetamide and acrylonitrile. Acrylo-nitrile (20 mmol) in t-butyl alcohol (10 ml) was added drop-wise with stirring to potassium (6.4 mg atom) and the di-amide (10 mmol) in t-butyl alcohol (100 ml). After 3 days,neutralisation with acetic acid, concentration, and filtrationgave the biscyanoethylamide (37y0), m.p. and mixed m.p.NCCHsCH,*NHBu t ArSO,.CHz.CHa~NH-CH,),NC.CHsCHs*NH.CH2)2ArSO,-CH,-CH,.NHMeNC.CH,-CH,-NAcBuArSO,CH,.NAcBunD'O1.43791.47841.54271.46281.5275and the precipitated polymer was taken up in methanol andreprecipitated with acetone.The analytical figures for theproduct (1.2 g) were: C, 67.6; H, 9.5; S, 2.9. The poly-mer was then kept a t 210 "C and 0.1 mmHg for 3 h. Afterthis time the S content had fallen to 1.5. An attempt toobtain recognisable fragments from the N-alkylated poly-mer by acidic hydrolysis (~M-HC~; 8 h; 130 "C) andchromatography of the hydrolysate failed.Sodium (0.3 g) and Nylon 6 (2.5 g) weredissolved in benzyl alcohol and the mixture was kept at120 "C to dissolve the nylon. p-Tolyl vinyl sulphone (3.6 g)in benzyl alcohol (75 ml) was added, and the mixture waskept a t 135 "C for 6 h. Neutralisation was carried out withacetic acid, and after steam distillation of the mixtureaddition of dichloromethane to the residue gave a solid(2.3 g) (Found: S 0.2).(b) Nylon 6.TABLE 3Properties of amine- and amide-alkene adductsFound () Required ()M.p.("C) Yield ,-----h---bsol; -7B.p./Torr () C H N Formula C H N115/18 82 (1it.p b.p. 103" a t 10 Torr)152/19 80 (lit.,a b.p. 152' a t 20 Torr)86 88 56.4 6.4 15.3 c C2,,HZ8N,O,S2 56.6 6.6 1 5 . 1 ~150/0.15 99 56.9 6.8 C1,Hl,N02S 56.4 7.0106/0.05 83 64.4 9.4 16.8 C,H,,N,O 64.3 9.5 16.5192/0.1 62 60.3 7.6 C,,H,,O,NS 60.6 7.7lH N.m.r. (7)2.1-2.7 (4 H, m), 6.6-7.2 (4 H, m),7.4 (2 H, s), 7.6 (3 H, s), 8.35 (1 H, s)2.0-2.6 ( 4 H, m), 6.5-7.15 (4 H, m),7.55 ( 3 H,s), 7.6 (3 H, s), 8.0 (1 H, s)6.6(4H,q,J6Hz),7.4(2H,t,J6Hz),8.0 (3 H, s), 8.3-9.2 (7 H, m)2.1-2.7 (4 H, m), 6.4-6.9 (6 H, m),7.6(3H,s),8.2(3H,s),8.4-9.4(7H,m)(NC.CH,CH2.NAcCH,), 143 57 57.2 7.0 CI2Hl8N,O, 57.6 7.2 6.3 ( 4 H, m), 7.2 (2 H, m), 7.7 (3 H, s)(ArSO,-CH,CH,.NAc.CH ,) 191 78 56.5 6.2 12.9C C,,H,,NOamp; 56.7 6.3 12.6 2.0-2.6(4H,m),6.0-6.9(6H,m),7.5( 3 H, s), 8.0 (3 H, s)PhCH,CO.NMeCH,*CH,.SO,Ar 83 99 65.0 6.1 C,8H,lN0,S 65.3 6.3 2.0-2.8 ( 3 H, m), 6.2-6.6 (2 H, m),6.95 (1 H, s), 7.5 (1 H, s)ArSOI*CH9CHsCHPhC0.NMe, 121 65 d 66.6 6.8 C1,H,,NO3S 66.1 6.7 2.1-2.7 (9 H, m), 5.9 (1 H , t, J 7 Hz),6.75-7.2 (8 H, m), 7.55 (3 H, s),7.8 (2 H, m)b A.E. Martell and S. Chaberek, J. Antar. Chem. SOC., 1950, 72, 5375. c S Analysis. d From vinyl sulphone a A.E. Frost and A. E. Martell, J . Org. Chem., 1950,15,51.and amide.141-143". The mother liquors yielded unchanged amidePreparation of Authentic Amide-Alkene Adducts.-Thegeneral procedure is illustrated for NN'-bis-p-tolylsulphon-ylethyl-NN'-ethylenediacetamide. p-Tolyl vinyl sulphone(20 mmol) in benzene (75 ml) was treated dropwise with1,2-diaminoethane (10 mmol) in benzene (25 ml). After24 11, evaporation gave the amino-sulphone (87), m.p.85-86' (from ethanol) (details in Table 3). The amino-sulphone (5.6 mmol) in acetic acid (25 ml) was treated withacetic anhydride (9 mmol). After being kept a t 25 "C for1 h and at l0O'C for 1 h, the mixture was poured intoaqueous sodium hydrogen carbonate and extraction withdichloromethane gave the diamide, m.p. 190-192" (detailsin Table 3).Examples of Reactions with Polyaunides.-(a) (with R.PEAK) Ultramid 1C. The polymer (1.6 g) in dimethylacet-amide (320 ml) at 70 "C was treated with p-tolyl vinyl sul-phone (4.6 g), t-butyl alcohol (32 ml), and then potassiumt-butoxide (2.8 g). The mixture was kept at 65-70 "C for20 h and was then added to aqueous 4 acetic acid (500 ml),(57).(c) Nylon 66. The polymer (4.0 g) was stined underreflux with t-butyl alcohol (100 ml) for 18 h, then potassiumt-butoxide from potassium (0.9 g) in t-butyl alcohol (100ml) was added. After 1 h, p-tolyl vinyl sulphone (6.3 g,1 equiv. per amide group) in t-butyl alcohol was added, andafter a further 4 h refluxing the mixture was cooled andneutralised with acetic acid. Decantation left a residuewhich was washed with t-butyl alcohol (150 ml) and thenwith acetone (2 x 150 ml). The remaining solid (4.05 g)(Found: N, 10.3; S, 8.6) was sublimed at 160 'C and 0.01Torr; the S content of the residue was 1.2. The residuefrom evaporation of the decantate and washings combined(5.8 g), on extraction with dichloromethane, left a residue(2.2 g) (Found: S, 6.9; N, 0.5). Evaporation of theextracts gave a mixture (3.6 g) of the alcohol (2) and theether (1).We thank the S.R.C. for a C.A.S.E. studentship (toP. D. H.) and Mr. R. Peak for the experiments with Ultra-mid 1C.6/062 Received, 9th January, 1976