1977 93Allenes. Part 362 Synthesis of 2,4,5-Trienamides as Potential Insecti-cides, by a Wittig ReactionBy Phyllis b. Landor, Stephen R. Landor,"? and Olwa Odyek, Department of Chemistry, Makerere University,Kampala, UgandaN-Substituted 2,4,5-trienamides have been synthesised by the reactions of a 4,4-dialkylbuta-2,3-dienal with diethylN-alkyl- and NN-dialkylcarbamoylmethylphosphonates, and characterised by i.r., u.v., and n.m.r. spectra. Anattempted Wittig reaction of hepta-2.3-dienal and diethyl N-isobutylcarbamoylmethylphosphonate resulted inmainly nucleophilic attack a t C-3 of the allenic aldehyde.MANY natural products of plant origin contain an iso-butylamide group conjugated with a trans double bond(-CHkH*CO*NHBui), for instance affinin and theisobutylamides from Chrysanthemum frutescens L.3Most of these amides possess considerable insecticidalactivity, and in some cases this is similar to that of thepyrethrins towards Musca domestica.We have, there-fore, synthesised a number of conjugated N-substitutedamides containing an allenic functional group in orderto have these tested for insecticidal activity.Previously allenic amides4 were prepared in ourlaboratory from allenic nitriles with hydrogen peroxide,and allenic N-t-butylamides were prepared by a Ritterreaction. This paper reports the synthesis of conjugatedN-substituted 2,4,5-trienamides from an a-allenic alcohol(I),5 as outlined in Scheme 1.MnO2MeEtC=C=CH.CHiOH hexanew MeE t C=C=CH.CHO( 1 ) I (11)+(III) INaH (EtO+PCICH-,CO.NR'R~ ,lo.( EtO),P(0).CHiC0.NR'R2(111 1t MeEtC=C= CH.CH= CH.CO.NR'R'(IY 12 - R'= H, Et.or CHiCH:CH2 R =Bu', Et,or CHiCH:CH,SCHEME 1The dlenic alcohol (I) was oxidised with activemanganese dioxide 1 in hexane and the reaction wasmonitored by i.r. spectroscopy to ascertain conditionsfor maximum yield of allenic aldehyde; the OHabsorption decreased while a new band (conjugatedGO) at 1 690 2m-l increased. When no further changeoccurred the product was worked up and the crudealdehyde used in the next stage. The crude productconsisted of a ca. 50 : 50 mixture of aldehyde (11) andalcohol (I), as shown by the integration of the allenicproton n.m.r. signals at T 4.1 and 4.71, respectively,and U.V. absorption at lmX. 224 nm (E 5 900) [ c j .Me,C:CH*CHO, A,,, 228 nm (E 14 2OO)J.The yield oft Present address : Department of Chemistry, University ofLagos, Lagos, Nigeria.3 Kindly donated by Hoff man-La-Roche, Basle, Switzerland.Part 35, S. R. Landor, V. Rogers, and H. R. Sood,. Tetra-L. Crombie, A . H. Krasinski, and M. Manzoor-i-Khuda, J .hedron, 1976, in the press.Cltem. Soc., 1963, 4970.oxidation product appeared to reach a maximum at thisstage, and further addition of active manganese dioxideeffected no change. Possibly an equilibrium involvingcomplexing of alcohol and aldehyde with hydridetransfer prevents further oxidation of the allenic alcohollsee (A)]. A series of N-substituted carbamoylmethyl-phosphonates (111) were prepared for use as modifiedc o- -CH-0( A )'0-Wittig reagents in 65-73% yield from triethyl phosphiteand the appropriate N-alkyl- or NN-dialkyl-chloro-acetamide.The n.m.r. spectra showed a distinctivecoupling constant, J 22 Hz, for -P(O)CH,-. The anionof the appropriate N-subs titu ted carbamoylmethyl-phosphonate in dimethoxyethane was treated with4-methylhexa-2,3-dienal to give a one-step Wittigsynthesis of the trienamides (IV). Column chromato-graphy on alumina gave the pure trans-amides, vwx.1940 (C:C:C), 1650-1 640 (amide C:O), 1610 and 980(trans-CX), and 1 510 cm-l (NH def.). High intensityU.V. absorption at A,, 257-264 nm was comparable tothat for alka-2,4-dienarnides.' The n.m.r. spectraresembled those of the trans-2,4,5-trienoates with J2,315 and J3,4 10 H z .~N-Isobutyl-6-methylocta-trans-2,4,5-trienamide wasalso prepared, in lower yield but spectroscopicallyidentical with the previous sample, by using N-isobutyl-carbamoylmethyl( tripheny1)phosphonium chloride 3 asthe Wittig reagent.The known naturally occurring isobutylamides arestraight-chain compounds, and in an attempt to preparea similar allenic isomer we used hepta-2,3-dien-l-ol (VI)as starting material (Scheme 2). The allenic alcohol(VI) was prepared by a modification of our publishedroute,5 via the acetylenic alcohol (V), obtained from theaction of propyl-lithium followed by formaldehyde on3-tetrahydropyran-2-yloxyhex-l-yne. This reaction wasfaster and cleaner than the Grignard method; reductionF. Bohlmann and R. Miethe, Chem.B e y . , 1967, 100, 3861.P. M. Greaves, P. D. Landor, S. R. Landor, and 0. Odyek,J . S. Cowie, P. D. Landor, and S. R. Landor, J.C.S. Perkin I ,Preliminary report of a similar oxidation, P. D. Landor, S. R.K. S. Burden and L. Crombie, J . Chent. SOC. (C), 1969, 2477.Tetrahedron, 1974, 38, 1427.1973, 720.Landor, and S. hIukusa, CAem. Comm., 1971, 163894 J.C.S. Perkin Iand oxidation then gave the corresponding crude allenicaldehyde. However on treatment with the anion of&ethyl N-isobutylcarbamoylmethylphosphonate, work-up and chromatography, only traces of trienamide wereobtained, and the main product appeared to be formedPrCH.CrCHIOThp1 ,Pr Li 2,HCHO If LiAl HqPrCH.C=C. CH i OH h PrCH=C=CH*CHjOHIOThp(V)I r CH.CO.NHBU' CH.CO.NHBU'I I Pr CH=C-CH s2 C H 0II ItPrCHi C=CH.CHO -& PrCH$=CH.CHO -+ PrCH2+CH-CH0I I NHBuiC=C* N HE u H-C-C.A N HB uI "3 I IO=P 0 &P,O-AE t 0 AoE t EtOAkt EtO OEt(V111)PrCH, 4 \Thp = tetrahydropyran-2-yl ,c=CH-cHo&cCSCHEME 2by a Michael addition at C-3 of the aldehyde [to give(VII) and (VIII) and degradation products such as(IX)]. Similar Michael additions of other ylides totwo a-allenic ketones have been reported.*EXPERIMENTAL1.r. spectra were determined for liquid films with aPerkin-Elmer 257 spectrophotometer. U.V. spectra wereobtained for ethanolic solutions with a Pye-Unicam 1800spectrometer. N.m.r. spectra were determined with aVarian T60 spectrometer for solutions in deuteriochloro-form, with tetramethylsilane as internal standard unlessotherwise stated.Ethereal solutions were dried overMgSOI.N-lsobutylchloroacetamide.-Chloroacetic acid (48.0 g,0.6 mol) and benzoyl chloride (140.5 g, 1.0 mol) wereheated under a fractionating column. The acid chloridewas distilled off into an ice-cooled receiver and the distillate8 G. Buono, G. Peiffer, and A. Guillemonat, Comfit. rend., 1970,271, 937.refractionated to give chloroacetyl chloride (47.8 g, 86%),b.p. 106" (lit.,O 105-107"), vmx. 1 800 cm-l (GO).The acid chloride (28.4 g, 0.25 mol), cooled to 0 "C, wasadded to a solution of isobutylamine (29.2 g, 0.4 mol) inanhydrous ether (50 ml) at 0 "C. The mixture was shakenvigorously and allowed to warm to room temperatureovernight.The crystalline amide was dissolved in chloro-form; the solution was washed with dilute hydrochloricacid, sodium hydrogen carbonate solution, and water,dried, and evaporated to give N-isobutylchloroacetamide(27.4 g, 73y0), m.p. 27-30" [recryst. twice from chloroform-light petroleum (b.p. 40-60 "C)], vmaX 3 300, 3 100 (NHstr.), 1660 (GO), and 1550 cm-1 (NH def.), T (CC1,) 9.07(6 H, d, Me2CH), 8.20 (1 H, m, CHMe,), 6.90 (2 H, t, col-lapses to a doublet on deuteriation, NH*CH,*CH), 6.00(2 H, s, ClCH,*CO), and 2.78br (1 H, s, disappears ondeuteriation, NH); g.1.c. (tR 10.5 min; 5% SE30 onCelite; 90 "C) showed a single peak. .NN-Diethylch1oroacetawzide.-Diethylamine ' (29.2 g, 0.4mol) and chloroacetyl chloride (28.4 g, 0.25 mol) in a similarmanner gave NN-diethylchloroacetamide (23.2 g, 62y0), b.p.130Oat 0.4 mmHg (Found: C, 48.0; H, 7.9; C1, 23.6; N,9.2.C,H1,CINO requires C, 48.2; H, 8.0; C1, 23.7; N,9.4y0), vm 1655 cm-l (GO), 'C 8.82 (3 H, t , CH,CH,),8.72 (3 H, t, CH,*CH,), 6.53 [4 H, q, N(CH,*CH,),], and5.83 (2 H, s, CH,*CO).NN-Diallylch1oroacetamide.-Diallylamine (50.0 g, 0.52mol) and chloroacetyl chloride (34.95 g, 0.31 mol) similarlygave NN-diallylchloroacetamide (30.51 g, 57%), b.p. 37' at0.5 mmHg (Found: C, 55.5; H, 7.0; Cl, 20.4; N, 8.1.C,H12C1N0 requires C, 55.4; H, 6.9; C1, 20.5; N, 8.1y0),vmx. 1660 ( G O ) , 1630 (C=C), and 990 and 925 cm-l(CHXH,), T 5.92 [6 H, m, CH,CO*N(CH,-CH:CH,),],4.80 [2 H, dt, (CHXHH),], 4.73 [2 H, dt, (CHXHH),], and4.13 [2 H, m, (CH:CH,)J.Diethyl N-Isobutylcarbamoylmethy1phosphonate.-Tr iethylphosphite (10.0 g, 0.06 mol) was maintained a t 110 "C, andN-isobutylchloroacetamide (8.0 g, 0.053 mol) was addedslowly.The mixture was then heated under reflux withstirring for 30 min. Low boiling material was distilled offa t 1.0 mmHg and the residue crystallised on cooling to givethe phosphonate (8.58 g, 65y0), m.p. 40", vmx. 3 290 and3 080 (NH, str.), 1 660 (CO), and 1 550 cm-1 (NH def.),T 9.07 (6 H, d, Me,CH), 8.63 [6 H, t, (CH,*CH,-O),P], 8.20(1 H, m, CHMe,), 7.10 (2 H, d, PCH,, J 22 Hz), 6.87 ( 2 H,t, collapses to d on deuteriation, NH*CH,*CH), 5.80 [4 H,dq, (CH,*CH,*O),P], and 2.87br (1 H, s, NH, disappears ondeuteriation) .Diethyl NN-Diethylcarbamoylmethyl~hos~honate.10-Tri-ethyl phosphite (10.0 g, 0.06 mol) and NN-diethylchloro-acetamide (7.5 g, 0.05 mol) similarly gave the phosphonate(9.2 g, 73%), b.p.170" at 0.04 mmHg (Found: C, 47.8;H, 8.7; N, 5.5; P, 12.2. CloH2,N04P requires C, 47.8;H, 8.8; N, 5.6; P, 12.4y0), v,, 1 645 cm-l (C:O), T 9.00-8.5 [12 H, m, (CH,*CH,),N and (CH,*CH,*O),P], 6.97 (2 H,d, PCH,, J 22 Hz), 6.52 (2 H, q, N.CH,*CH,), 6.57 (2 H,q, N-CH,*CH,), 5.83 (2 H, q, CH,*CH,*O), and 5.72 (2 H,q, CH,*CH,*O) .Diethyl NN-Diallylcarbamoylmethylphosphonate.lO-Tri-ethyl phosphite (16.6 g, 0.1 mol) and NN-diallylchloro-acetamide (15.62 g, 0.09 mol) similarly gave the phosphonate(16.6 g, 67y0), b.p. 130" a t 0.3 mmHg, vmx. 1 650 (C=O) and*O A. J. Speziale and R. C. Freeman, J . Org.Ckem., 1958, 23,H. C . Brown, J . Amer. Chem. SOL, 1938,60, 1325.18831977 951640 cm-' (C=C), T 8.67 [6 H, t, (CH3*CH2*O)2P], 6.97(2 H, d, P-CH,, J 22 Hz), 5.98 [8 H, m, (CH,*CH,*O), and(CH,CH:CH,),], 4.80 [4 H, m, N(CH,*CH:CH,),], and 4.13[2 H, m, N(CH,*CH:CH,),].4-Methylhexa-2,3-dienal.-Active manganese dioxide ( 18.0g; Hoffmann-La Roche) was added to a solution of 4-methylhexa-2,3-dien-l-016 (1.8 g, 0.016 mol) in n-hexane(100 ml). The mixture was shaken at room temperaturefor 3 h, then filtered and washed with hexane. Manganesedioxide (18.0 g, 0.21 mol) was added to the combinedfiltrate and the oxidation was continued for a further 2 h.The reaction was monitored by i.r. spectroscopy. Themixture was filtered, the solid washed with hexane, andthe filtrate evaporated at room temperature to give crude4-methylhexa-2,3-dienal (1.2 ,g, 68%), v- 3 360 (OH),1 945 (CCC), and 1 690 cm-1 (CZO), A,, 224 nm (e 5 900),T 7.4 (0.5 H, s, OH), 5.97 (1 H, d, CH,*OH), 4.70 (0.5 H, m,:CH*CH,*OH), 4.17 (0.5 H, m, :CH*CHO), and 0.50 (0.5 H,d, :CH*CHO).N-Isobutyl-6-methylocta-trans-2,4,5-trienamide.-(a) Di-ethyl N-isobutylcarbamoylmethylphosphonate (1.8 g, 0.007mol) was added to a slurry of sodium hydride (0.48 g,0.02 mol) in 1.2-dimethoxyethane (50 ml) and the mixturewas stirred for 30 min.Crude 4-methylhexa-2,3-dienal(0.4 g) obtained from oxidation of the alcohol (0.7 g, 0.006mol) was added, and stirring was continued for 3 h a t40-50 "C. The mixture was diluted with water and theproduct extracted into ether and dried.The solvent wasremoved and the crude product (0.64 g) chromatographedon alumina (100 g; Woelm acid, activity 11). Ethereluted N-isobutyE-6-methylocta-trans-2,4,5-trisnamide (0.5 1g, 40% based on the alcohol), m.p. 136-137" (Found: C,75.0; H, 10.0; N, 7.1. C13H2,N0 requires C, 75.3; H,10.2; N, 6.8%), vmX. 3 450, 3 320 (NH str.), 1 940 (C:C:C),1650 (CZO), 1610 (CC), 1510 (NH def.), and 980 cm-l(trans-C:C), Amax. 257 nm (E 24 700), T 9.00 (9 H, m,CH3*CH, and Me2CH), 8.20 (6 H, m, CH,*CH2, Me,CH, andCH3*C:), 6.80 (2 H, t , collapses to d on deuteriation), 4.10(3 H, m, NH, :CH*CO, and C:C:CH, collapses to 2 H ondeuteriation), and 2.83 (1 H, dd, trans-CH:CH*CO, J 2 . 3 15,JsB4 10 Hz), m/e 207.(b) Crude 4-methylhexa-2,3-dienal [0.8 g; obtained fromthe oxidation of the alcohol (1.4 g, 0.012 rnol)] in dryethanol was added to a solution of N-isobutylcarbamoyl-methyl(tripheny1)phosphonium chloride 3 (3.4 g , 0.009 mol),followed by sodium ethoxide [l ml of a solution fromsodium (2.3 g) in dry ethanol (30 ml)].The mixture washeated under reflux for 2 h, the solvent distilled off, and thecrude amide (0.8 g) chromatographed on alumina (100 g).Ether eluted the 2,4,5-trienamide (0.62 g, 24% based on thealcohol), m.p. 137", spectroscopically identical with theprevious sample.NN-Diethyl- 6-methylocta-trans- 2,4,5-trienamide .-Diethy1NN-diethylcarbamoylmethylphosphonate (5.4 g, 0.022 mol)and crude 4-methylhexa-2,3-dienal (1.5 g) obtained fromoxidation of the alcohol (2.6 g, 0.023 mol) treated as inmethod (a) above gave the crude amide (4.5 g). Chromato-graphy of the crude amide (1.9 g) on alumina (Woelm acid,activity 11) and elution with isohexane-ether (4 : 1) gavethe trienamide (0.74 g, 36% based on the alcohol) (Found:C, 75.3; H, 10.3; N, 6.7.C,,H,,NO requires C, 75.3;H, 10.2; N, 6.8%), vmSX 1940 (C:C:C), 1640 (CO), 1600(C:C), and 980 cm-1 (trans-C:C), hmK 263 nm (E 30000),T 8.97 [6 H, t , (CH3*CH2),N], 8.78 (3 H, t, CH,*CH,*C:),8.23 (3 H, d, CH,*C:), 8.08 (2 H, m, CH,.CH,*C:), 6.63[4 H, q, (CH,*CH,),N], 4.07 (1 H, m, C:C:CH), 3.75 (1 H,d, trans-CCHCO, J2.3 15 Hz), and 2.77 (1 H, dd, trans-NN-Diallyl-6-methylocta-trans-2,4,5-trienamide.- DiethylNN-diallylcarbamoylmethylphosphonate (6.10 g, 0.022 mol)and crude 4-methylhexa-2,3-dienal (1.2 g) obtained fromoxidation of the alcohol (2.5 g, 0.022 mol) similarly [method(a)] gave the crude amide (2.6 g).Chromatography of thecrude amide (1.3 g) on alumina (Woelm acid, activity 11)and elution with isohexane-ether (4 : 1) gave the trienamide(0.42 g, 16% based on the alcohol), vms. 1940 (C:C:C),1 640 (C:O), 1 600 (C:C), 990 and 920 (CHXH,), and975 cm-1 (trans-CC), A,, 264 nm (E 27 000), T 8.97 (3 H, t,CH3CH2), 8.23 (3 H, d, CH,*C:), 8.00 (2 H, m, CH,*CH,),5.93 [4 H, m, N(CH,*CH:CH,),], 4.80 [2 H, dt, (CH:CHH),],4.73 [2 H, dt, (CH:CHN),], 4.10 [3 H, m, C:C:CH andN(CH,*CH:CH2)2], 3.73 (1 H, d, trans-CH:CH*CO, J 2 . 315 Hz), and 2.70 (1 H, dd, trans-CH:CH-CO, J3.2 15,J3.4 10 Hz), m/e 231.4-Tetrahydropyran-2-yloxyhept-2-yn-l-ol. 3-Tetrahydro-pyran-2-yloxyhex-l-yne (59.7 g, 0.33 mol) in tetrahydro-furan (100 ml) was added dropwise to propyl-lithium [froml-bromopropane (48.3 g, 0.4 mol) and lithium (5.5 g, 0.79mol) in ether (1 60 ml) at - 5 "C under oxygen-free nitrogen].Gaseous formaldehyde generated from paraformaldehyde(16 g) was passed through a heated tube onto the surface ofthe stirred mixture.After 2 h the mixture was poured onaqueous ammonium chloride and the organic phase andethereal extracts of the aqueous phase were dried (K2C03-MgSO,). Evaporation left the heptynol (59 g, 85%).Hepta-2,3-dienul.-Active manganese dioxide (35 g) andhepta-2,3-dien-l-o15 (2.3 g, 0.02 mol) in n-hexane (60 ml)treated as described above gave crude hepta-2,3-dienal(0.8 g, 36%); vmX, 3 360 (OH), 1 945 (C:C:C), and 1 690cm-l (C:O), A,,,. 220 nm (E 10 400), T 7.03br (0.5 H, s, OH),5.97 (1 H, dd, CH,-OH), 4.78 (1 H, m, CH:C:CH-CH,-OH),4.28 (1 H, m, CHCCHCHO), and 0.60 (0.5 H, m,CH:C:CH*CHO) .Reaction of Hepta-2,3-dienaE with Diethyl N-lsobutyl-carbamoylmethy1phosphonate.-Diethyl N-isobutylcarbam-oylmethylphosphonate (2.2 g, 0.01 mol) was added toa slurry of sodium hydride (0.2 g, 0.011 mol) in dry 1,2-dimethoxyethane (50 ml) and the mixture was stirred for30 min. Crude hepta-2,3-dienal (1.5 g) was added dropwisewith stirring for 1 h, and the mixture then heated a t40-50 "C for 2 h. Work-up as described above gave acrude product ( 1.2 g) which on chromatography affordedvarious fractions ; spectroscopic examination showed onlytraces of allene ( i r . and n.m.r. spectra). The materialsappeared to be mixtures of the Michael addition products(VII) and (VIII) and the degradation product (IX).CH=CH*CO, J2.3 15, J3.4 10 Hz).[6/1283 Received, 2nd July, 1976