J . Am. Chem. SOC. 1994,116, 1016-1026
1016
The Schmidt Reaction of Dialkyl Acylphosphonates’ Milon Sprecher*vt and Daniel Kost*** Contribution from the Departments of Chemistry, Bar-Ilan University, Ramat Gun 52900, Israel, and Ben-Gurion University of the Negev, Beer Sheva 841 05, Israel Received September 13, 1993’
Abstract: The scope of the Schmidt rearrangement of ketones has been extended to dialkyl acylphosphonates (lla-111). Surprisingly, it was found that lla-lld and l l g , in which the acyl moiety was benzoyl alone or benzoyl bearing an electron-attracting or mildly electron-releasing substituent, yielded an overwhelming portion of products resulting from C-to-N migration of the aryl group (N-arylcarbamoylphosphonates,12, and N-arylformamides, 15). Contrariwise, the arenecarbonylphosphonates,which carry a powerful electron-releasing p-alkoxy group, yielded products resulting from phosphonate group migration from C to N or elimination (dialkyl N-arenecarbonylphosphoramidates,13, and arenecarbonitriles, 17, respectively). These counterintuitive results are rationalized by application of the concept of “degree of electron demand” to this area of intramolecular rearrangements. The possible existence of an additional pathway for the Schmidt rearrangement, involving protonation of the iminodiazonium ion, is proposed.
Introduction Despite the large amount of work which has been reported on both the synthetic and the mechanistic aspects of the Schmidt rearrangement of ketones? the balance of factors effecting the outcome in any particular case is still poorly understood. In many cases product composition is unpredictable even in a qualitative sense, and a posteriori and ad hoc rationalizations abound in the l i t e r a t ~ r e .Scheme ~ 1 depicts possible pathways for this reaction. Most authors have favored the iminodiazonium (ID) pathway, ‘a’ (via 3 or 3’), vigorously expounded by Smith,2‘.8 including the provision based on indirect evidence that C N migration is concomitant with N2 releasee2v3It must therefore involve the group antiperiplanar to the diazonium function, in analogy with the well-established stereochemical requirement of the Beckmann rearrangement of ket0ximes.2.~ While calculations confirm that E -.Z isomerization (3 F! 3’) by lateral shift of
-
t Bar-Ilan University.
t Ben-Gurion University of the Negev. Abstract published in Aduance ACS Abstracts, January 1, 1994. (1) The experiments reported here were performed in the laboratories of the Department of Chemistry, Tel Aviv University, Ramat Aviv, Tel Aviv, Israel. (2) (a) Kyba, E. P. In Azides andNitrenes: Reacriuity and Utility;Scriven, E. F. V., Ed.; Academic: Orlando, FL, 1984;pp 2-34. (b) Brossi, M.; Kaenel, H. R. SLZ, Schweiz Lab.-Z.l983,40,59-64. (c) Abramovich, R. A.; Kyba, E. P. In The Chemistry of the Azido Group; Patai, S.,Ed.; John Wiley and Sons: London, 1971; pp 221-329. (d) Banthrope, D. V. In The Chemistry ofthe Azido Group; Patai, S.,Ed.; John Wiley and Sons: London, 1971; pp 405 ff. (e) Uyeo, S.Pure Appl. Chem. 1963, 7, 269-283. (f) Smith, P. A. S. In Molecular Rearrangements; de Mayo, P., Ed.; Wiley-Interscience: New York, 1963;Vol. l,pp507ff. (g)Smith,P. A.S.;Antoniadu,E.P. Tetrahedron 1960, 9, 210-229. (h) Wolff, H. Org. React. 1946, 3, 307-336. (3) (a) Adam, G.; Andrieux, J.; Plat, M.; Viossat, B.; Rodier,N. Bull. SOC. Chim. Fr. 1984, 2, 101-108 and references cited. (b) Arcus, C. L.; Coombs, M. M.; Evans, J. V. J . Chem. SOC.1956,1498-1 506 and references cited. (c) Evans, D.; Lockhart, I. M. J . Chem. SOC.1965,4806-4812. (d) Tomita, M.; Minoni, S.; Ugio, S.J . Chem. SOC.C 1969, 183-188. (e) Flemming, C. A.; Gandhi, S.S.; Gibson, M. S.;Ruediger, E. H. Can. J. Chem. 1982,60,624628. (f) Hunter,N. R.;Khan,M.Z.;Marat,K.;El-Kabbani,O.A.L.;Delbaere, L. T. J. Can. J . Chem. 1987, 65, 137-149. (9) Di Maio, G.; Permutti, V. Tetrahedron 1966, 22,2059-2067. (h) Duddeck, H.; Brosh, D.; Koppetsch, G. Tetrahedron 1985, 41, 3753-3762. (i) Lansbury, P. T.; Manusco, N. R. J . Am. Chem. SOC.1966,88,1205-1212. (j) Campaigne, E.; Huffman, J. C.; Yodice,R. J. Heterocycl. Chem. 1981,18,135-142.(k) Fikes,L. E.;Shechter, H. Tetrahedron Lett. 1976,2525-2528; J. Org. Chem. 1979,44,741-744. (I) Georg, G . I.; Kant, J.; Guan, X . Tetrahedron Lett. 1988, 29, 403-406. (m) Yeh, M. Y.; Tien, H. J.; Nonaka, T. J . Org. Chem. 1983,48,1362-1364. (n) Levai, A. Acta Chim. Acad. Sci. Hung. 1980, 104, 385-387; Chem. Abstr. 1980,94, 192295k. ( 0 ) Siddiqui, A.; Memariani, M.; Ramesh, D.; Siddiqui, A. H. U.; Rao, V.; Uma, M. J. Indian Chem. SOC.1990,67,39-42; Chem. Abstr. 1990, 113, 1724158. (p) Abraham, J.; Jindal, D. P.; Sing, H. Indian J. Chem., Sect. B 1989,28B, 1051-1052; Chem Abstr. 1989, 113,6670s.(9) Hassner, A.; Ferdinandi, E. S.;Isbister, R. J. J . Am. Chem. SOC.1970, 92, 1672-1675. e
the diazonium group would be too slow to occur under the usual reaction conditions,4such equilibration could certainly be achieved by rapid hydration to an azidohydrin and redehydration28,3k4,5(3 s? 2 3’) or an equivalent process involvinganother nucleophile). The isolation, in the case of highly sterically congested reactants, of the products of N insertion into C-H bonds shows that in certain circumstances the release of N2 from the ID ion and the formation of a divalent nitrogen (nitreniumion) species, 5, precede C N migration.6 The proposal of the ID intermediate was supported by the isolation, in many cases, of tetrazole byproducts (7, Scheme 2), which were assumed to be formed by the reaction of a second mole of hydrazoic acid with the rearranged iminium ion (4 or 4’).2 Moreover, the Schmidt reaction with ketones had been found to proceed with hydrazoic acid but not with alkyl azides.’ This was consistent with the necessary intermediacy of an ID ion (3 or 3’). Other researchers focused on the fact that the “migratory aptitudes” which they found in the Schmidt reaction of ketones did not reflect the findings in the Beckmann rearrangement. They therefore opted for the protonated azidohydrin (AH), 1, as the species undergoing decompositionrearrangement (Scheme 1, path ‘b’),3bJthough this proposal, too, proved far from satisfactory in rationalizing product composition data. Yet othersfound that theratioofthe twoproductsstemming from the migration of different groups (6 or 6’) was affected by the identity and concentration of the acid catalyst used.3dLJ This led to the obviously simplest, but at present not very edifying, postulate that both pathways are operative c ~ m p e t i t i v e l y . ~In ~+g,~~~ other words, they generally have rather similar energy barriers, the relative rates along them being determined in any specific case by experimental conditions and the interplay of the particular electronic and steric factors. Recently Aub6 discovered the conditions necessary for the Schmidt rearrangement of ketones using alkyl azides rather than hydrazoic acid: thus dispelling the long-standing myth that only the latter is effective and supporting the competency of an A H structure (8, Scheme 3) as an intermediate which may suffer C -.N migration upon N2 release. Amyes and Richard have lately reDorted for the first time a direct demonstration of the formation
*
-
~
~~~~~
(4) Bach, R. D.; Wolber, G. J. J . Org. Chem. 1982, 47, 239-245. The barrier is, of course, subject to modification by substituent. ( 5 ) Amyes, T. L.; Richard, J. P. J . Am. Chem. SOC.1991,113,1867-1869. (6) Reference 3c; cJ Gudmundsen, C. H.; McEwen, W. E. J. Am. Chem. SOC.1957, 79, 329-334 and references cited. (7) (a) Briggs, L. H.; De Ath, G. C.; Ellis, S. R. J . Chem. SOC.1942,6143. (b) Smith, P. A. S. J. Am. Chem. SOC.1948, 70, 320-323. (8) (a) Aub6, J.; Milligan, G. L.; Mossman, C. J. J . Org. Chem. 1992,57, 1635-1637. (b) Aub6, J.; Milligan, G. L. J. Am. Chem. SOC.1991,113,89658966.
0002-7863/94/1516-1016$04.50/00 1994 American Chemical Society
The Schmidt Reaction of Dialkyl Acylphosphonates
J. Am. Chem. SOC., Vol. 116, No. 3, 1994 10 17
Scheme 1
I Rl
kl Ill
//
N@
-< '.
t
H H
?
I
R2
Scheme 2 R
R-c==$-R
I
R 4
+
N N '
c''
&
\\
N-N
7 I
7
H-N=N=N
Scheme 3 e.
c+
N, +
R'
E)
'R
a
and the reactivity of ID ions (Le., a-azido carbocations, 3 and 3') and have set limitations on the competency of such species as intermediates in the Schmidt reaction5 They calculated rate constants of approximately 107 and 105 s-l for the addition of solvent to benzylidene and p-methoxybenzylidene iminodiazonium ions, respectively, in neutral aqueoussolution a t 25 OC, the reaction with azide ion to give a gem-diazide (9) being diffusion limited. The equilibrium concentrations of ID ions were extremely small, and no N2 release or decomposition products were found. As gem-diazides have now been shown to be respectable, though perhaps capricious, compounds9 which may also be produced in solution from ID ions,5 or possibly even directly from AHs under Schmidt conditions, it is no longer necessary to conclude that tetrazoles must originate from the addition of hydrazoic acid to the iminium ion 4. They may possibly be formed via the acidcatalyzed monodecomposition of a gem-diazide (9) to an N-diazonioamidine ion (10) which cyclizes (Scheme 4). The new experimental findings and their implications have undermined much of the ratiocination upon which the identification of the ID ion (3 or 3') as the one undergoing decomposition-rearrangement was based. Regarding theoretical work, early calculations concluded that the release of N2 from an ID ion unaccompanied by C N migration would be highly endothermic, and that an IDintermediate could be reasonably entertained only if the energy gain due to concomitant rearrangement was very con~iderable.~ In contrast, a recent report based on a higher level of theory (though lacking the extensive configuration interaction calculations which are generally considered necessary for really high quality results for such decompositions) finds that the decom-
-
(9) (a) Nishiyama, K.; Oba, M.; Watanabe, A. Tetrahedron 1987, 43, 693-700. (b) Nishiyama, K.; Watanabe, A. Chem. Lett. 1984,455458.
position of H2C=N3+ to H2C=N+ and N2 hasa calculated energy barrier in the gas phase of only 4.6kcal/mol.1° Solvation effects should lower it, while conjugating electron-donating substituents should raise it. In any case, this report, if qualitatively relevant to the usual solution conditions, would support the viability of the ID pathway 'a' (with the possibility of 5 as a distinct high-energy intermediate). These new contributions to the area prompt us to report the details of work on the Schmidt rearrangement of dialkyl acylphosphonates" which, while undertaken at the time as part of our research to elucidate characteristics of the dialkyl phosphonate function,12 extends the scope of said rearrangement and bears on its mechanism.
Results and Discussion The dialkyl acylphosphonates used in this study were readily prepared by reaction of the corresponding acyl chlorides with trialkyl phosphites (eq 1) according to the procedure of Berlin
RCOCl + (R'O),P
-
RCOPO(OR'),
+ R'CI
(1)
et al.I3and were thoroughly characterized (Experimental Section). Though the reactions of dialkyl acylphosphonates with most nucleophilic reagents parallel those of ketones,*2a.cJ4the hydrolytic behavior of dialkyl acylphosponates is reminiscent of that of acyl halides or esters.14J5 Since the Schmidt reaction must be carried out in strongly acidic and potentially hydrolytic media, it was satisfying to find conditions for the reaction of the substrates in question which did not lead tosignificant hydrolysis. In the event, the chloroform solutions of the acylphosphonates were treated at 0 OC for 10-30 min with a 5 mol % excess of hydrazoic acid in the presence of concentrated sulfuric acid. The resulting product mixtures were divided by extraction into neutral, acidic, and basic fractions, and these were further separated and the individual compounds purified by column chromatography and appropriately characterized (Experimental Section) and identified. (10) Hoz,S.; Wolk, J. L. Tetrahedron Lett. 1990, 31, 40854088. (1 1) Kost, D.; Sprecher, M . Tetrahedron Lett. 1970, 2535-2536. (12) (a) Sprecher, M.; Nativ, E. Tetrahedron Lett. 1968,44054408. (b) Sprecher, M.; Kost, D. TetrahedronLett. 1969,703-706. (c) Kost, D.; Sprecher, M. Tetrahedron Lett. 1975,4483-4486. (13) (a) Berlin, K. D.; Taylor, H. A. J. Am. Chem. SOC.1964,86, 38623866. (b) Berlin, K. D.; Hellwege, D. M.;Nagabushanam, M. J . Org.Chem. 1965, 30, 1265-1267. (14) Zhadnov, Yu.A.; Uzlova, L. A,; Glebova, 2.I. Vsp. Khim. 1980,49, 1730-1750; Rum Chem. Rev.(Engl. Transl.) 1980, 49, 843-853. (15) Narayanan, K. S.; Berlin, K. D. J. Am. Chem. SOC.1979,101, 109120. CJ Mitchell, A. G.; Nicholls, D.; Walker, I.; Irwin, W. J.; Freeman, S. J. Chem. SOC..Perkin Trans. 2 1991, 1287-1303.
Sprecher and Kost
1018 J . Am. Chem. SOC.,Vol. 116, No. 3, 1994 Scheme 4
Table 1. Schmidt Reaction of a-Ketophosphonates [RCOPO(OR')2, 111" and Product Distributionb
product compd
R Ph p-CIPh m-C1Ph p-tolyl p-CHaOPh p-CH3OPh p-CH3OPh p-CH3OPh m-CH3OPh 3,4-methylenedioxyphenyl 2,6-dimethoxyphenyl mesityl 2,6-dimethyl-4-methoxyphenyl (CH3)zCH
lla llb llc 1Id 1l e
lled llf 11fC 1lg llh 1l i lljh llk 111
R' Et Et Me Et Me Me Et Et Et Et Et Et Et Me
12
13
9 19
3.1 1.8 1 3.3 46 45 30 31 2 28
11.4
14
15
16
1 1.3
53 65 39 70
14 4 6.5 6.5
0.8
59
8.5
1.5
17
7 47 51 62 54 6 51 62
18
19
0.2 4
1.8
XC
0.4
Y 17g
43 50
0.5
57
4V 0.7'
a Unless otherwise indicated the reactions were carried out for 10-30 min at 0 'C using concentrated H2S04 and 1.05 equiv of "3. b In mol % based on a-ketophosphonate. Other compounds isolated. In the presence of 1 equiv of diethyl phosphite. In the presence of 1 equiv of dimethyl phosphite. fm-CHsOC6H4COOEt. g Unreacted starting material. Reaction for 20 h at room temperature. Under the usual reaction conditions, 76% of unreacted starting material and 16% of 16j were isolated. (CH&CHCONHCH(CH3)2.
Scheme 5 "3
,p
RCOPO(0R')Z 11
*
R"COPO(OR')2 12
-
+ HPO(OEt),
-
C,H,NHCOPO(OEt),
(2) fraction. They are further distinguished from those of type 13 by their IR spectra (N-H stretching -3200 cm-1, C=O stretching 1660 cm-1, doubling of P-0 stretching absorption band at 1220, 1255 cm-1;16 cf. Table 2) and their N-H 1H N M R spectra. In compounds 13,the NH grouping flanked by carbonyl and phosphonate functions shows the expected imidetype acidity due to stabilization of the conjugate anion, as well as the consequent spectral shifts. The -PO(OR')2 substituent on the N reduces the nitrogen-electron pair delocalization into the carbonyl group, strengthening the double bonding in the latter. (16) 16.Corlinidge, D.E.C . Topics Phosphorous Chem. 1969,6,235-
-- -
365.
I R-NHCONHPO(OR')2
14
QWOR?2 RNHCHO I R N Y I RCN I RCOOH I RCKPO(OR')2 16 17 18 19 IS
Table 1 lists the dialkyl acylphosphonates (lla-111) used in this study and the variety and yields of products isolated in each case. In all, eight types of products (12-19,Scheme 5) were found. The diethyl N-arylcarbamoylphosphonates(12)and the diethyl (or dimethyl) N-arenecarbonylphosphoramidates(13)are the primary products of Schmidt rearrangements involving C N migrations of the aryl or dialkyl phosphonate groups, respectively. For confirmation of identity, an authentic sample of 12a was prepared by reaction of phenyl isocyanate with diethyl phosphite (eq 2). Compounds of type 12 appear in the neutral
C,H,N=C=O
I RCONHPO(OR'), 13
The assignment of structures 13 was confirmed by preparation of authentic samples from the corresponding benzamides by reaction with phosphorus pentachloride followed by ethoxide/ ethanol treatment (eq 3).17
RCONH,
+ PCl,
-
-
+
[RCON=PCl,] EtOH/EtONa RCONHPO(OEt), (3)
In four cases, minor quantities of products of type 14,N-arylN'-dialkyloxyphosphinoylurea (a dialkyl arylcarbamoylphosphoramidate), were found in the sodium hydroxide extracts of the reaction mixtures. Structure assignment rests both on elemental analysis, IR, and lH N M R spectra which show, inter alia,the presence of two N H groups and C O and PO functions, and on the characteristic mass spectral fragmentations appropriate for 14. Furthermore, the unsubstituted 14s had been reported in the literature1*and comparison was possible. Formally, 14 is derived from the starting a-ketophosphonate by the insertion of two N H groups, one on each side of the carbonyl, and might be thought to be the product of a second Schmidt rearrangement of either 12or 13. However, amides are not known to undergo such a reaction, and, in fact, only unchanged 12a and 13a were recovered from control experiments under the reaction conditions; (17)Almasi, L.; Paskucz, L. Chem. Der. 1967,100,2625-2632. (18)Kirsanov, A. V.;Levcbenko, E.S. Zhur. Obshchei. Khim. 1956,26, 2285-2289; Chem. Abstr. 1957,51, 1875f.
The Schmidt Reaction of Dialkyl Acylphosphonates
J . Am. Chem. SOC., Vol. 116, NO. 3, 1994 1019
Table 2. Selected Spectral Properties of Dialkyl N-Arylcarbamoylphosphonates[RNHCOPO(OR')z, If], Dialkyl N-Arenecarbonylphosphoramidates[RCONHPO(OR')z, 131, and N-Aryl-N'-dialkoxyphosphinoylureas[RNHCONHPO(OR')z, 141 IR (KBr), cm-*
compd 12a 12b
1M 13a 13b 13bb' 13c 13cc' 13d 13dd" 13e 13f 13g 13gg 13b 14a 14c 14d 14g
R
R' Et Et
Ph p-CIPh p-tolyl Ph p-CIPh p-CIPh m-ClPh m-CIPh p-tolyl p-tolyl p-CH3OPh p-CHsOPh m-CH3OPh m-CH1OPh
Et
Et Et Me Me Et Et Me Me Et Et Me Et Et Me Et Et
3,4-(methylenedioxy)phenyl
Ph m-C1Ph p-tolyl m-CHjOPh
NH
co
PO
3160-3215 3150-3210 3205 3125 3100,3140 3105 3120 3150 3085-3130 3100-3160 3120-3140 3140 3160 3170 3120 3125,3180-3265 3170,3225 3165,3240-3270 3180,3220
1665 1660 1655 1677 1680 1685,16706 1680 1680 1680 1680 1680 1665 1680 1680 1665 1675 1700 1670 1690
1220,1255 1220,1250 1225,1255 1222 1230 1225 1230 1230 1237 1235 1230 1235 1240 1255 1230 1230 1230 1230 1220
'H NMR (CDCl3) 6" 9.25 (br s) 9.28 (br s) 9.10(br s) 9.22(d, 8) 9.81 (d, 9) 9.79 (d, 9) 9.84(br s)
(mult, J in Hz)
9.68 (d, 9) 9.22 (d, 8) 9.56 (br s) 9.23 (d, 9) 9.40(d, 9) 9.61 (d, 8) 9.55 (br s) 9.40 (br s) 7.72 (br s), 8.92 (s) 7.80(br s), 8.85 (s) 8.15 (br s), 8.79 (s) 7.90 (br s), 8.90(s)
Synthesized;not isolated from Schmidt reaction. 1685 cm-' in CHC13 solvent.
Scheme 6 R-CZ=N 17
/\
I
N II
e Hy R'
H@
I 7 H f l PO(0Rh !El
\N
