摘要:

1708 J.C.S. Perkin IAlkylation, Acylation, and Beckmann Rearrangement of Qximes in thePresence of an Qxidation-Reduction SystemBy Shmuel Bittner and Sarina Grinberg, Department of Chemistry, Ben Gurion University of the Negev,Beer Sheva, IsraelThe system triphenylphosphine-diethyl azodiformate (TPP-DAF) can interact with oximes in the presence of eithercarboxylic acids or alcohols. Reactions of benzophenone oxime with a variety of aromatic carboxylic acids leadto O-acyl derivatives which undergo spontaneous Beckrnann rearrangement. This modification of the Beckmannrearrangement takes place under very mild (0 "C), aprotic (tetrahydrofuran), and weakly acidic conditions, affordingNN-diacyl aromatic amines as final products. The reaction of benzophenone oxime with alcohols in the Dresenceof TPP-DAF gives O-alkyl ethers of the oxime.THE system triphenylphosphine-diethyl azodiformate(TPP-DAF) can interact with an alcohol (ROH) and anacidic component (ZH) to yield an alkylation product(ZR) (Scheme l).1-3 This reaction can be regardedTPP+ DAFZH -4- RQH XTPP0 Z- R + H2DAFSCHEME 1either as an intermolecular dehydration, in which amolecule of water is abstracted from the alcohol and0.Mitsunobu and M. Eguchi, Bull. Chem. SOC. Jafxzn, 1971,S. Bittner and Y . Assaf. Chem. and Ind.. 1975. 281.44, 3427.A mechanism is proposed.the acid, or as an oxidation-reduction in which tri-phenylphosphine is oxidized to triphenylphosphine oxide(TPPO) and the azo-compound is reduced to the appro-priate hydrazo-derivative (H,DAF) .Acidic componentsthat have been alkylated by this method includecarboxylic acids: phosphoric die~ters,~ cyclic imides,6phenols,2 and diketones.'Normal aromatic ketone oximes are weak acids(pK,. 11-12), and it might be expected that in thepresence of an alcohol they would act as an acidic0. Mitsunobu and M. Yamada, Bull. Chem. SOC. Japan, 1967,0. Mitsunobu, M. Yamada, and T. Mukaiyama, Bull. Chem.6 0. Mitsunobu, M. Wada, and T. Sano, J . Amer. Chem. SOC.,40, 2380.SOC. Japan, 1967, 40, 935.1972. 94. 679. 3 S. Bittner, S. Grinberg; and Y. Assaf, Proceedings XXVthIUPAC Congress, Jerusalem, 1975, p. 86. 7 M.-Wada and 0. Mitsunobu, Tetvuhedvon Letfers, 1972, 12791976 1709component (ZH), affording O-alkyloximes. On theother hand, in the presence of a stronger acid, the oximemight act as the hydroxylic component (ROH), yieldingO-acyloximes.The present paper describes the be-haviour of benzophenone oxime in such a system undervarious conditions.A cylation and Beckmann Rearrangement.-When equi-molar quantities of an aromatic carboxylic acid andbenzophenone oxime (1) reacted in dry tetrahydrofuran,in the presence of TPP and DAF, the oxime was con-sumed within several hours (at 0 “C), as indicated byt.l.c., with concomitant formation of a new compound.This first product was transformed slowly (12-24 h)into a second, stable compound. The existence of asecond reaction was supported by the i.r. spectra:initial samples showed vco at 1760-1 780 cm-l,characteristic of O-acyloximes, shifting to 1 680-1 710cm-1, suggesting transformation into an amide.Work-up and purification gave high yields of NN-diacylaniline(4), identified by elemental analysis and i.r. and n.m.r.spectroscopy.Efforts were made to isolate the intermediate; in onecase, with p-toluic acid, the reaction was quenched after2 h, when the conversion into (4) was still low. Rapidevaporation followed by silica gel chromatography gavebenzophenone O-p-toluoyloxime (2b) , identified on thebasis of spectroscopic properties and elemental analysis.The detection of the O-acyloxime (2) suggested that aBeckmann rearrangement was occurring. O-Acyloximesare known to undergo the Beckmann rearrangementreadily and in the absence of catalyst.8 The initialproducts are O-acyl imidic acid derivatives (3), whichundergo further spontaneous rearrangement involving a1,3 O-to-N shift of the acyl group.In the absence ofwater the final products are substituted diacylamines(4) (Scheme 2). No acylation reaction or rearrangementPh PhArC02H \ \C=NOH / C=NO*COArPh/ TPP-OAF ’ PhI 1 1 (2 1k p o n tPhspon tPhCO-N-COAr -’ ‘C=NPhI / IPh Ar C 0 . d( 3 1took place in the absence of the aromatic carboxylicacid : the benzophenone oxime was unchanged.Open Chain Nitrogen Compounds,’ Ben- 8 P. A. S. Smith injamin, New York, 1966, p. 47.In an analogous reaction NN-diethylhydroxylaminewas transformed in the presence of TPP-DAF andbenzoic acid into the O-benzoyl derivative. No re-arrangement is possible here, and the reaction is termin-ated after the first step (Scheme 3).SCHEME 3The i.r.and n.m.r. spectra of the diacylanilines(4a-g) are given in the Table.1.r.a and n.m.r.b data for diacylanilinesCompd. voo VAr a ~ r ~ h e .1 695, 1 600 7.25-7.80 (m)1 6551 680 1 595 7.05-7.64 (m) Me,2.33 (s)(4b) 1 680 1 590 7.20-7.75 (m)(4c) 1685 1590 7.15-7.71 (m)(4d) 1 710, 1 600 7.20-8.15 (m)(4e) I 6601 675 1600 7.20-7.75 (m)1 675 1 595 6.72-7.73 (m) OMe, 3.80 (s)(4a)(44(4g)0 vmsx. (Nujol)/cm-l. b 6 Values; solvent CDC1,.0.-:IEtO2C.N=N+CO2Et + Ph,P -% Et 02C-N-N-C*OEt(DAF) ’, TFP) +PPh3I( 5 )Ii i ArC02H .1Ph2C=N0.COAr + Ph,PO + Et02C-NH.NH-C02Et[ TPPO) ( H2DAF)( 2 iSCHEME 4The proposed mechanism of this acylation reaction isoutlined in Scheme 4.When TPP reacts with DAF itforms a labile adduct which is subjected to furtherreaction in situ. Owing to the high electrophilicactivity of the nitrogen of DAF, it is believed 9 that theadduct is formed by nucleophilic attack on the nitrogen,forming a quasi-l,3-salt (5). This internal quaternaryphosphonium salt is transformed in the presence ofacid into a second, external phosphonium salt (6). Thesalt (6) is attacked by the oxime, with fission of theP-N bond, formation of the stronger P-0 bond (7), andrelease of diethyl hydrazodiformate. Salts of type (7)are known to be powerful donors of the group attachedto oxygen. The presence of an excellent leaving group(TPPO) is the driving force of the reaction.In ourcase, this leaving group is attached to the oxime nitrogen,and could be easily displaced by the nucleophiliccarboxylate anion, forming the O-acyloxime (2). This9 E. Brunn and R. Huisgen, Angew. Chem. Internat. Ed%.,1969, 8, 5131710 J.C.S. Perkin Ifinal reaction (step iv) provides a rare example of N-0fission in an oxime brought about by nucleophilic attackon the nitrogen. A number of examples of nucleophilicattack on nitrogen have been reported,1°-12 and in allthese cases the nitrogen is hydroxylaminic in origin.The same is true in our case; however nucleophilicattack on an oxime nitrogen atom has not been reportedhitherto.The foregoing general procedure involves a Beckmannrearrangement under very mild (0 "C), aprotic (tetra-hydrofuran), and weakly acidic conditions.Almost allthe usual procedures for this rearrangement involve theuse of acidic reagents or of elevated temperatures,which induce isomerization of the oximes. In thepresent modification, the mild conditions precludeisomerization prior to rearrangement, and provide aconvenient route to asymmetric diacylated aromaticamines.AZkyZation.-We next investigated the reaction ofbenzophenone oxime with alcohols in the presence ofTPP-DAF. Oximes are poor nucleophiles, and react inthe un-ionized state with only very active alkylatingagents.l3 Under the present conditions, oximes under-went ready alkylation by alcohols. The reactions wereperformed at 0-5 "C in the alcohol as solvent withenough tetrahydrofuran added to dissolve the TPP.The O-alkyloximes (8) were obtained in 40-70~, yield,and unlike the general alkylation reaction of oximes, nosign of nitrones was detected (Scheme 5).Ph,C=N*OH +RQH P h, C = N.0 R( 1 ) ( 8 )a;R=Me d; R=Bub; R = E t e; R = Pr'c ; R = P r f ; R =PhCH2SCHEME 5The 0-alkyl ethers may arise from the sequenceBy analogy with the mechan- illustrated in Scheme 6.!J ..:IEt02C-N-N-COEt + Ph2C=NOH I'PPh3I 15) [ l l 19)ROH ~ I+ +Ph2C=N.0R + Ph3P0 & [ROPPhJ Ph2C=N6+ E t 3 C-NH.NH.C02Etei "91SCHEME 6ism proposed for the acylation, the key intermediate isthe zwitterionic salt (5) formed from DAF and TPP.This salt is in equilibrium with an external quaternaryphosphonium salt (9) in which the oximate ion is the10 L.A. Carpino, J . Org. Chem., 1965, 30, 321.11 T. Sheradsky, Tetrahedron Letters, 1968, 1909; T. Sheradskyand 2. Nir, ibid., 1969. 77.anion. The salt (9) is attacked by the alcohol in aprocess comprising fission of the N-P bond, release ofdiethyl hydrazodiformate, and formation of a newphosphonium salt (10). Within this salt, the nucleo-philic oximate anion at tacks, triphenylphosphine oxideis the leaving group, and benzophenone O-alkyloxime(8) is formed.O-Alkyloximes are important precursors of amino-oxy-compounds, and the present procedure provides aconvenient synthesis of O-alkyloximes from alcohols.Preliminary studies have indicated that, under theconditions described, aromatic and aliphatic aldehydeoximes undergo fast dehydration yielding nitriles.Thescope and mechanism of these reactions are underinvestigation.EXPERIMENTALM.p.s were taken with an electrically heated silicone oilbath (Thonias-Hoover). 1.r. spectra were recorded forNujol mulls with a Perkin-Elmer 357 spectrometer (slowscan speed) and 1H n.m.r. spectra for solutions in deuterio-chloroform with 1 yo tetramethylsilane as internal standard(Varian EM 360 spectrometer).All reactions were followed by t.1.c. on silica gel plates(Riedel-De-Haen AG DC lrarten SIF). Solvents were driedby standard techniques.NN-Dibenzoylaniline (4a) .-A solution of diethyl azodi-formate (1.74 g, 10.0 mmol) in dry tetrahydrofuran (5 ml)was added dropwise to a stirred solution of triphenylphosphine (1.96 g, 7.5 mmol), benzophenone oxime (0.98 g,5.0 mmol), and benzoic acid (0.61 g, 5.0 mmol) in drytetrahydrofuran a t 0-4 OC, in a current of nitrogen, atsuch a rate as to prevent warming.The mixture was thenwarmed to 25 O C , stirred for 18 h, and concentrated underreduced pressure. The semicrystalline residue was re-dissolved in hot methanol (10 ml), and on cooling NN-dibenzoylaniline (1.3 g, 88%) was precipitated; m.p. 163"(from methanol) (lit.,l4 161-162") (Found: C, 79.3; H,5.3; N, 5.05. Calc. for C,,H,,NO,: C, 79.7; HI 5.0;N, 4.65%).Similarly prepared from benzophenone oxime and otheraromatic carboxylic acids in dry tetrahydrofuran wereN-benzoyl-N-p-nitrobenzoylaniline (87 %), m.p. 176-1 77"(Found: C, 69.2; H, 4.0; N, 8.2.C,oHl,N,04 requiresC, 69.4; HI 4.0 ; N, 8.1 yo) ; N-benzoyl-N-p-toluoylaniline(74%), m.p. 158-159' (Found: C, 80.2; H, 5.5; N, 4.5.C,,H,,NO, requires C, 80.0; H, 5.4; N, 4.4%) ; N-benzoyl-N-p-chlorobenzoylanili~ze (76%), m.p. 128-129' (fromethanol) (Found: C, 71.9; H, 4.2; K, 4.05. C,,Hl4C1NO,requires C, 71.7; H, 4.2; N, 4.2%) ; IS-benzoyl-N-o-chloro-benzoylaniline (79yo), map. 126" (Found: C, 71.7; H, 4.2;C1, 10.9; N, 4.1%) ; N-p-anisoyl-N-benxoylaniline (770/,),m.p. 164-165' (Found: C, 75.9; H, 4.9; K, 4.0.C,,H,,NO, requires C, 76.1; H, 5.1; N, 4.2%); and K-benzoyl-N-m-nitrobenzoylaniline (92%), n1.p. 132-133"(Found: C, 69.5; H, 3.9; N, 7.88. Calc. for C,,H1,N,04:C, 69.4; H, 4.0; N, S.l:(,).O-Benzoyl-NN-diethylhydroxylamhze.-A solution of di-ethyl azodiformate (2.96 g, 0.017 mol) in dry tetrahydro-l2 F.Yamainoto and S. Oae, Bull. Chem. SOC. Japan. 1975, 48,77.13 P. A. S. Smith and J. E. Robertson, J . Amer. Chem. SOC.,1962, 84, 1197.l4 A. Mumm, Ber., 1910, 43, 8891976 1711furan (5 ml) was added dropwise to a stirred and cooledsolution of triphenylphosphine (3.93 g, 0.015 mol), NN-diethylhydroxylamine (0.89 g, 0.01 mol), and benzoic acid(1.22 g, 0.01 mol) in dry tetrahydrofuran, under nitrogen.The mixture was then left a t room temperature for 20 h.The solvent was removed under reduced pressure and theresidue was digested with hexane to remove most of thetriphenylphosphine oxide and diethyl hydrazodiformate.The soluble fraction was extracted twice with aqueous5% sodium hydrogen carbonate and the extracts weredried and evaporated.The resulting oil (1.2 g) waspurified by column chromatography [dry column of alumina(300 g ; 80-200 mesh; type F-20)]; elution with chloro-form-benzene (70 : 30) gave O-benzoyl-NN-diethylhydroxyl-amine (1.05 g, 54%) as an oil, v- 1 750 cm-l (CZO);6 1.05 (6 H, t), 2.9 (4 H, q), and 7.4-7.9 (5 H, m).Benzophenone O-p-ToluoyZoxime.-A solution of diethylazodiformate (1.74 g, 0.01 mol) in dry tetrahydrofuran(5 ml) was added dropwise to a stirred and cooled solutionof triphenylphosphine (1.96 g, 0.007 5 mol), benzophenoneoxime (0.98 g, 0.005 mol), and 9-toluic acid (0.68 g, 0.005mol), in dry tetrahydrofuran under nitrogen. After 2 hstirring a t 0 "C the solvent was removed under reducedpressure and the residue was digested with hexane toremove the product from triphenylphosphine oxide, diethylhydrazodiformate and some N-benzoyl-N-p-toluoylaniline.The hexane was evaporated off and the semicrystallineresidue was purified by column chromatography (silica gel).Elution with benzene gave benzoplaenone O-p-toluoyloxime(0.64 g, 41%), m.p.73-74' (Found: C, 80.1; H, 5.4; N,4.25. C,,H,,NO, requires C, 80.0; H, 5.40; N, 4.4y0),vmaX. 1 780 cm-l (GO).Benzophenone O-Methytoxime.-A solution of diethylazodiformate (3.48 g, 0.02 mol) in dry methanol (5 ml) wasadded dropwise to a stirred and cooled solution of tri-phenylphosphine (3.93 g, 0.015 mol) and benzophenoneoxime (1.97 g, 0.01 mol) in dry methanol (10 ml) and tetra-hydrofuran (3 ml; to dissolve the TPP).After 36 h atroom temperature the solvents were removed underreduced pressure and the residue was digested several timeswith dry hexane. The combined hexane solutions wereevaporated, and the residue was purified by columnchromatography on silica gel (150 g; 100-200 mesh).Elution with hexane and then with hexane-benzene gavebenzophenone O-methyloxime (1.18 g, 56%), m.p. 60'(Found: C, 79.6; H, 6.2; N, 6.6. C1,Hl,NO requires C,79.6; H, 6.2; N, 6.6%), 6 3.9 (3 H, s) and 7.2-7.35(10 H, m).Similarly prepared from benzophenone oxime andalcohols were benzoplzenone O-ethyloxime (67 yo), an oil(Found: C, 80.0; H, 6.6; N, 6.5. C,,H,,NO requires C,80.0; H, 6.6; N, 6.2%), 6 1.3 (3 H, t), 4.22 (2 H, q), and7.2-7.5 (10 H, m) ; benzophenone O-n-propyloxime (42%),an oil (Found: C, 80.2; H, 7.4; N, 5.7. C,,H,,NOrequires C, 80.3; H, 7.1; N, 5.8%), 6 0.9 (3 H, t), 1.62(2 H, m), 4.15 (2 H, t), and 7.35 (10 H, m); benzophenoneO-isopropyloxime (46%), an oil (Found: C, 80.4; H, 7.0;N, 6.1. C,,H,,NO requires C, 80.3; H, 7.1; N, 5.8%),6 1.1 (6 H, d), 4.15 (1 H, septet), and 7.0-7.35 (10 H, m);benzophenone O-butyloxime (62%) (Found : C, 80.3 ; H,7.3; N, 5.5. Cl,H1,NO requires C, 80.6; H, 7.5; N,5.5y0), 6 0.9 (3 H, t), 1.2-1.8 (4 H, ni), 4.2 (2 H, t), and7.0-7.4 (10 H, m) ; and benzophenone O-benzyloxime (32%),m.p. 58' (Found: C, 83.1; H, 5.8; N, 4.8. C,,H,,NOrequires C, 83.6; H, 5.9; N, 4.8%), 6 5.2 (2 H, s) and7.0-7.4 (15 H, m).We thank Dr. A. Pross for reading the manuscript andMrs. P. Kriaf for technical assistance.[6/193 Received, 29th January, 1976

ISSN:1472-7781    

DOI:10.1039/P19760001708

出版商:RSC    

年代:1976

数据来源: RSC