J . Org. Chem., Vol. 39, No. 24, 1974 3559
Condensations Effected b y 2,6-Dimethoxyphenyllithium 2.4 g of acetic acid was treated as described in the last experiment up to the point of drying the reaction mixture over calcium chloride. The dried solution was evaporated to give 2.2 g of a viscous residue, whose ir spectrum showed that it consisted of unreacted a-(9-acridanyl)propionitrile and some unknown carbonyl-containing materials. The acidic aqueous extracts and washings from above were treated with aqueous ammonia to liberate the free base which was filtered, washed with water, and dried to give 3.0 g of a mixture of two compounds, mp 50-90’. Repeated crystallization of this mixture from ether-petroleum ether gave 1.9 g (41%) of a-(g-acridiny1)propionitrile (A), mp 115.5-117’ (yellow crystals from heptane containing a small amount of pyridine), and 0.4 g (8.5%) of acyano-a-methyl-9-methyleneacridan (B), mp 197-199O from ether-petroleum ether. Anal. of A. Calcd for C 1 6 H d 2 : C, 82.73; H, 5.21; N, 12.06. Found: C, 82.81; H, 5.39; N, 12.38. Anal of B. Cnlcd for C16P112N2: C, 82.73; H, 5.21; N, 12.06 Found: C, 82.35; H, 5.18; N, 11.97. The ir spectrum of A showed a weak C=N band a t 4.43 p and a strong aromatic band at 13.27 p. There were no N-H bands present and there was no absorption in the 6.0-6.2-p region. The ir spectrum of a-cyano-a-methyl-9-methyleneacridan (B) showed an N-H band at 2.96 p, a strong C z N band at 4.52 F , a strong, sharp band at 6.20 p (indicative of a conjugated double bond), and various aromatic bands. Heating A briefly above its melting point converted it quantitatively to B. This conversion also occurred when A was kept a t room temperature for 6 months. These conversions were verified from their ir spectra and melting points. 3. Dehydrogenation of a-(9-Acridanyl)phenylacetonitrilc. Lead tetraacetate (8.8 g, 0.02 mol) containing acetic acid (2.6 ml) was added slowly at room temperature to a stirred solution of a(9-acridany1)phenylacetonitrile(5.9 g, 0.02 mol) in 300 ml of benzene. After stirring at room temperature for 1 hr, the lead salts were filtered and the benzene filtrate was washed with four 100-ml portions of water and was dried over calcium chloride. The benzene solution was concentrated to 80 ml and was diluted with 250 ml of ether. The resulting solution was extracted with three 100-ml portions of 6 N hydrochloric acid and was then washed with four 100-ml portions of water. After drying over calcium chloride, the solvents were evaporated to give 3.2 g of a residue, mp 45-200’; its ir spectrum showed that it contained unreacted a-(g-acridany1)phenylacetonitrile and some unknown materials containing carbonyl functions which were not characterized further.
The combined acidic aqueous extracts and washings from above were treated with aqueous ammonia to liberate the free base which separated as an oil. This product was dissolved in ether and, after washing with water and drying (calcium chloride), the ether was evaporated to give 2.7 g of reddish, gummy solid, mp 35-55’; its ir spectrum showed an N-H band a t 2.91 p, a strong C=N band at 4.53 p, and various aromatic bands and agrees with the structure of a-cyano-a-phenyl-9-methyleneacridan. The very crude product was repeatedly recrystallized from benzene-petroleum ether to give 0.5 g (7.5%) of pure a-cyano-a-phenyl-9-methyleneacridan, mp 209.5-210.5’ [literature value for a-(9-acridinyl)-a-phenylacetonitrile, 210°4]. Anal. Calcd for C21H14N2: C, 85.69; H, 4.79. Found: C, 85.65; H, 5.08. Its ir spectrum was identical with that described above. The dehydrogenation of a-(9-acridany1)propionitrile gave a mixture of two products. (a) a-Cyano-a-methyl-9-methyleneacridan (8.5%, mp 197-199’ from ether-petroleum ether). Anal. Calcd for C16H1&2: C, 82.73; H, 5.21; N, 12.06. Found C, 82.35; H, 5.18; N, 11.97. (b) a-(9-Acridinyl)propionitrile(41% 115.5-117’ from heptane). Anal. Calcd for C16H12N2: C, 82.73; H, 5.21; N, 12.06. Found: C, 82.81; H, 63.9; N, 12.58.
Registry No.-2 (R = R’ = H, 22409-47-8; 2 (R = H; R’ = C&5), 52673-98-0; 2 (R = H; R’ = CH5) 1:l adduct with acridine, 52673-99-1; 2 (R = H; R’ = CH3), 52674-00-7; 3 (R = H; R’ = CH3), 62674-01-8; 4, 52674-02-9; 5, 52674-03-0; 6, 52674-04-1; 7, 5267405-2; acridine, 260-94-6; acetonitrile, 75-05-8; phenylacetonitrile, 140-29-4;propionitrile, 107-12-0;isobutyronitrile, 78-82-0.
References and Notes (1) F. Krohnke and H. L. Honig, Ann., 624,97 (1959). (2)C.S.Sheppard and R. Levine, J. Heterocycl. Chem., 1, 61 (1964).
(3) R. M. Acheson and L. E. Orgel, “Acridines,”interscience Publishers, New York, N.Y., 1956. H. Lettre, P. Jungman, and J. Salfield, Chem. Ber., 85, 397 (1952). Y. Mizuno, K. Adachi, and K. Ikedo, Pharm. Bull. Jap., 2, 225 (1954); Chem. Absfr., 50, 1035 (1956). We thank one of the referees for pointing out these spectral correlations and suggesting the importance of structure 9. For a complete discussion of the ir spectra of the acridines and acridans see “Acridines,” R. M. Acheson, Ed., 2nd ed., Interscience, New York, N.Y., 1973, Chapter 11, pp 665-685.
Certain Condensations Effected by 2,6-Dimethoxyphenyllithium R o b e r t Levine* and J a y R. Sommers
Department of Chemistry, Uniuersity of Pittsburgh, Pittsburgh, Pennsyluania 15260 Received May 30,1974 2,6-Dimethoxyphenyllithium (2,6-DMPL) can be acylated with several aromatic and heterocyclic esters to give ketones. The use of methyl isonicotinate gave 2,6,2’,6’-tetramethoxydiphenylcarbinoland no ketone. Methyl anisate and 2,6-DMPL gave a mixture of 2,6,4’-trimethoxyhenzophenone and 4-(2,6,2’,6‘-tetramethoxydiphenylmethylene)-2,5-cyclohexadienone.Several aliphatic esters were used to give ketones, carbinols, or a mixture of the two. With the three esters, ethyl acetate, ethyl propionate, and ethyl phenylacetate, which contain a-hydrogen atoms, small amounts of P-keto esters (for the first two esters) or the ketonic cleavage product of the P-keto ester (for the third ester) were formed. While 2-picoline, 4-picoline, and methylpyrazine can be benzoylated using 2,6-DMPL at their methyl groups with methyl benzoate, this reaction fails with 3-picoline and 2,6-dimethoxybenzophenone is formed. Resorcinol dimethyl ( R D M E ) was first metalated by Wittig and Pockels b y reaction with phenyllithium at room t e m p e r a t u r e for 60 hr to give 2,6-dimethoxyphenyllit h i u m (2,6-DMPL) which was treated with gaseous carbon dioxide t o give a mixture of 2,6,2’,6’-tetramethoxybenzop h e n o n e (25%) a n d 2,6-dimethoxybenzoic acid (20%). Several o t h e r condensations have been effected with 2,6DMPL including its reaction (1) with N - methylformanilide2 t o give 2,6-dimethoxybenzaldehyde(55%); (2) with
benzophenone3 t o give 2,6-dimethoxydiphenyIcarbinol; (3) with a series of a,w-dibromoalkanes t o give a,w-bis(2,6dimethoxyphenyl)alkanes4 (50-90%); (4) with aliphatic a n d aromatic nitro compounds5 t o give a series of nitroxides; and (5) with t h e sterically hindered ketone 2,6,2’,6’tetramethoxybenzophenone6 t o give 2,6,2’,6’,2’’,6’’-hexamethoxytriphenylcarbinol in 77.8% yield. Of particular interest i n connection with t h e present problem ( d e infra) is t h e work of Limaye a n d cowork-
3560 J . Org. Chern., Vol. 39, No. 24, 1974
Levine and Sommers
ers7-lQwho studied the reactions of coumarin derivatives as This scheme is somewhat analogous to the two mechaa route to 2,6-dimethoxyacylbenzenes.Their route involves nisms proposed bs7 Filar and Winstein” for the conversion a six-step synthesis starting with resorcinol. of 3,5-dimethyl-4-hydroxybenzylchloride to 2,6-dimethylThe present study was undertaken to determine whether 4-methylene-2,5-cyclohexadienone. The cleavage of the 2,6-DMPL can be acylated with a series of aliphatic, aropara ether function in the conversion of 1 to 4 in an acidic matic, and heterocyclic esters to give directly sterically hinmedium is not without precedent since it has been redered ketones, the 2,6-dimethoxyacylbenzenes in a oneported12 that the reaction of p - methoxytriphenylchlorostep process and to ascertain whether these reactions give methane with sulfuric acid gives 4-diphenylmethylene-2,5any carbinols, which would also be sterically hindered. Ancyclohexadienone and methyl chloride. other aim was to determine, in those cases where the acylC1 ating esters have a-hydrogen atoms, whether the esters self-condensed to an appreciable extent to give the corresponding P-keto esters. Finally, it was of interest to determine the feasibility of using 2,6-DMPL as the condensing agent in the benzoylation of certain methylated heterocyCF(IT)=C(C&), -t C H J 1 clic nitrogen compounds. The required 2,6-h)MPL was prepared in 70% yield by Elemental analysis and spectral methods were used to the interaction of equivalents of resorcinol dimethyl ether elucidate the structure of 4. The ir spectrum shows a car(RDME) and a- butyllithium in refluxing ether for 2 hr. bonyl band a t 1628 cm-l, which indicates the presence of a The conversion of RDME to 2,6-DMPL was determined by quinoidal system and is in good agreement wit,h the recarbonation and isolating the 2,6-dimethoxybenzoic acid. ported values for the carbonyl peak of 2,6-dimethyl-4methylene-2,5-cyclohexadienone(1625 cm-l)ll and other As an orienting experiment both commercial and freshly quinoidal systems (1605 cm-l).13 prepared 2,6-DMPL were acylated with methyl benzoate to give 2,6-dimethoxybenzophenonein 36.3% yield with the The nmr spectrum integrates correctly for the indicated former and in 81.0% yield with the latter source of 2,6structure. There is a doublet at T 3.75 (2 H) which is asDMPL. In all other experiments the 2,6-DMPL was freshly signed to the protons ortho to the disubstituted 4-methylene group. This value agrees with the reported average prepared prior to use. Although 2,6-dimethoxybenzophenvalues for a proton bonded to a quinone ring.I4 one was prepared by IAimaye’s7-lomultistage synthesis, an Martin and Smith16 have found that when overall yield was not reported. 2,6,2’,6~,2’’,6’’-hexarnethoxytriphenylcarbinol is dissolved With methyl anisate there was obtained the new ketone, in dilute hydrochloric acid, a purple color arises due to the 2,6,4’-trimethoxybenzophenone(55.8%) as well as 17.5% yield of 4-(2,6,2’,6’-tetramethoxydiphenylmethylene)-2,5- formation of the 2,6,2’,6‘,2‘’,6’’-hexamethoxytriphenylmethyl carbonium ion, which they propose exists to an apcyclohexadieneone (4). This unsaturated ketone appears to preciable extent in a highly nonplanar or an exaggerated arise from the gross loss of the elements of methanol from the initially formed 2,6,2’,6’,4/’-pentamethoxytriphenylcar- “propeller” conformation. Similarly, we have found that when 4 is dissolved in 6 N hydrochloric acid a purple color binol, (1) when the reaction mixture is processed in the is formed probably by the formation of the carbonium ion presence of hydrochloric acid. 5 , which is the protonated form of 4 and which also probably has an appreciable amount of nonplanar character.
\
‘OCH,
1%
2
0
L
3
OCH, 3 -3 c1- CH,]Cl -I-
( + C O O
OCH3 4
The cyclohexadienone, 4, gives ,a, ,A at 510 mp in 6 M hydrochloric acid and its calculated A, using 4-diphenylmethylene-2,5-cyclohexadie1~one as the parent chromophore (A,, 470 mp in 100%hydrochloric acid)16 and allowing 7 mp for each o-methoxy gsoup17 is 498 mp (Amp = -12). Although this calculation is in reasonably good agreement with the observed data, the steric contribution of the methoxy groups has not been taken into consideration. Triphenylcarbinol has a A,, a t 435 my in sulfuric acid,ls while the carbonium ion derived from 2,6,2‘,6‘,2‘/6‘‘-hexamethoxytriphenylcarbinol in 0.5 A4 hydrochloric acid has a A,, at 522 mw.l5 This represents a difference of 87 mp or a contribution of 14.5 mp for each 0- methoxy group including steric hindrance. Therefore, the four methoxy groups in 5 (the carbonium ion derived by protonating 4) add 58 mp to the, , ,A of the parent chromophore to give a calculated A,, of 528 (Amy = +18). From these calculations it is concluded that there is some steric contribution from the four o-methoxy groups in 5 but it is not as great as the steric contribution of the six 0 - methoxy groups in the carbonium ion derived from 2,6,2’,6’,2”,6’’-hexamethuxytriphenylcarbinol. It has been reported that the effect of twisting the aryl groups out of the central plane of the carbonium ion by the
J. Org. Chem., Vol. 39, No. 24, 1974 3561
Condensations Effected by 2,6-Dimethoxyphenyllithium 0-methoxy groups is a shift to longer wavelengths with the accompanying lowering of the extinction ~0efficient.l~ This trend can be seen in the two quinoidal compounds: 4-diphenylmethylene-2,5-cyclohexadienone , ,A,( 472 mp, log e 5.03) and 4-(2,6,2’,6/-tetramethoxydiphenylmethylene)2,5-cyclohexadienone,,A,( 510 mp, log t 4.11). The carbinol, 1, which is the proposed precursor of 4 may be envisioned as arising by two paths. OLi
(a) RLi 6
+ R’CO,CH, 7
-
philic displacement reaction at carbon with 6 to give 11, the precursor of 4, which is obtained in 17.5% yield, and not exclusively 10, which arises in 55.8% yield. From the reaction of 2,6-DMPId with ethyl picolinate and methyl nicotinate only the corresponding ketones were obtained in yield of 30.6 and 19.6%, respectively. Because of the proximity of the nitrogen atom to the lithium atom in the intermediate adduct which is formed between the ester and the 2,6-DMPL (shown below in 13 for the ethyl
I I
R-C-OCH, R \
8 0
route 1
LiOCH,
OLi
+ R--C-R1
6 -+
I R
10 (b)a
