CHESTERW. MUTII,JOHN C. ELLEKSAND 0. FREDFOIAIUR
6500
tensity changes. This statement is not intended t o preclude minor changes in band shape on m-substitution. However, it may be noted t h a t frequently emax and oscillation strengths are directly related one t o another (cf. ref. 2 5 ) . (25) B M. Wepster, Rec. Irav. c h i m . , 76, 336 (1957).
[COSTRIBUTION FROM THE
\'ol. 79
knowledge t h i receipt of research gr&ts fro& the Research Of Canada and the Research Corporation of New York. ST. JOHS'S, N E W F O U N D L 4 X D , CAS14DA
DEPARTMEST O F CHEMISTRY, \brEST
\JIRGISIA
CNIVERSITY]
A Novel Ring Closure Involving a Nitro Group ; Preparation of Phenanthridine-5-oxidel BY CHESTERW.MUTH,JOHX C. ELLERS AND 0. FRED FOLXER RECEIVED JULY 3, 1957 I n the biphenyl series a nitro group in the 2-position will react with an activated methylene group in the 2'-position in the presence of sodium hydroxide or sodium methoxide to form substituted phenanthridine-5-oxides. Cyano, carbomethoxy and carbamyl groups are activating groups; hydrogen, hydroxyl, bromo aiid carboxyl do not serve as activators.
Discussion An unexpected reaction was observed when methyl 2-(2'-nitropheny1)-phenylacetate (I)2 was warmed with methanolic sodium hydroxide in an effort to saponify it. The product obtained was not the parent acid of I, but was compound A, an acid, which had no nitro group and which decomposed with gas evolution to yield compound B. Compound B could be treated with zinc and hydrochloric acid to produce compound C.
A
4J
I
Compound C was identified a s phenanthridine by comparison of its picrate with t h a t of an authentic sample. Compound B was identified as phenanthridine-5-oxide (111) by m.m.p., infrared spectrum and by its picrate. Since the gas given off in the decomposition of compound X was carbon dioxide, the structure postulated for compound A is 6-carboxyphenanthridine-%oxide (11). M-ith this information the foregoing reactions may be rewritten
1
+
i
4
--+
C, phenanthridine
0 A or I1
Since the reaction was very rapid under mild coliditions and since the literature did not disclosc such a reaction, a further investigation appeared profit(1) Supported by t h e S a t i o n a l Science Foundation. Research Grant G-1581, whose help we wish t o gratefully acknowledge. From the P h . D . dissertation of 0 . F. F . ,1!157, and l I . S . thesis of J , C. Is.. 1058, both from Tl'est Virginia University. Presented in part a t t h e 130th hIeeting of t h e A.C.S., Atlantic City, X . J . , September, 1LI36 (2) C. 1%'. Liuth, W. L. Sung and Z . B. Papanastassiou, THIS J O U R K A L . 77,3393 (195.5).
able. The further study of this reaction was approached along two lines. First, the reaction of ester I was investigated under a variety of conditions to learn more about the yields, the structure of the acid material and the mechanism of the rcaction. Secondly, the carbomethoxy group was replaced by other groups and the resulting conipounds were tested for this cyclization. The bases used which effected the cyclization of ester I were sodium hydroxide in methanol or water and sodium methoxide in methanol. The results are summarized in Table 11. 115th low base concentration ester I yielded G carbomethoxyphenanthridine-%oxide (IV), whereas ester I with high base concentration and longer reaction time produced acid -1aiid I11 or acid I1 and 111. Acid A evolved a gas a t 120-138" and melted a t about 200°, whereas acid I1 inclted a t about 200" with no previous gas evolution. Both acids X and I1 reacted with diazomethane to give the same ester; both yielded phenanthridine-5oxide when warmed with dimethylformamide and their infrared spectra were nearly identical. The use of a nitrogen atmosphere3 or an equal molar quantity of hydroquinone had no effect on the reaction, hence i t is assumed t h a t the cyclization is not an oxidation-reduction process. Since the cyclization is not affected by acids (concentrated or dilute sulfuric acids) or by dehydrating agents (acetic anhydride or thionyl chloride) nor by ammonium hydroxide, b u t only by strong bases (sodium hydroxide and sodium methoxide) it seems likely t h a t the cyclization is a base-catalyzed reaction similar to an aldol condensation. T h a t hydrolysis of the ester group is not a necessary condition for the cyclization is shown by the production of the cyclized ester, 6-carbonicthoxyphenanthridine-3-oxide (IV), This is also shown by the fact t h a t the parent acid, ~-(2'-nitrophenyl)phenylacetic acid (I7),of cster I does not cyclize. Seven model compounds were subjected t o basic conditions to determine whether Cyclization would oc.cur. These compouricls were the same as methyl 2-(2'-riitrophenyl)-phenylacetate (I) except t h a t the carboinethoxy group was replaced (see V-XI). If3th I< as carboxyl (IT),hydrogen (\:I), hydroxyl (IT) and bromine (VIII) no cyclization (3; T. Tsuruta, T. Fueno and J. Furukawa, ibid., 77, 3205 (1953J.
Dec. 20, 1957
occurred under the conditions which caused cyclization of ester I. Qualitative evidence indicated t h a t t.he compound with R as nitro was prepared. If this is valid then the compound with R as nitro also does not give cyclization.
3””’ I
6501
PREPARATION O F PHENANTHRIDINE-5-OXIDE
YIII. R = Br I X ,RR == CN X, KOq XI, R = COKHz
iVith R as cyano (X) or carbamyl (XI) cyclization does take place. Table I shows t h a t the cyano group causes the cyclization to occur more rapidly than does the carbomethoxy group which in turn causes the cyclization to occur more rapidly than does the carbamyl group. This rate order is the same as the order of decreasing meta-directing power4 of the three groups and thus adds credibility to the base-catalyzed type mechanism.
During attempts a t infrared measurements on the amide X I reaction products it was observed t h a t part of the reaction mixture was very insoluble in chloroform. The chloroform-soluble part was phenanthridine-5-oxide. The chloroform-insoluble part was identified as the cyclized amide by its infrared spectrum and by synthesis from the cyclized nitrile X I I . The differences in chloroform solubility probably are due to the intrahydrogen bonding in the cyclized amide X I I I , whereas the phenanthridine-5-oxide hydrogen bonds with the solvent, chloroform. It was believed t h a t 2- (2’-nitrophenyl)-benzyl bromide (VIII) could be made to react with sodium cyanide to produce 2-(2’-nitropheny1)phenylacetonitrile (X) which would be a model compound and, also, an intermediate for the preparation of ester I. However, as is shown in Table IV the major product was G-cyanophenanthridine-5-oxide (XII) .
TABLE I COXPARISOS OF CYCLIZATION RATES 6 : 1 ratio of base t o reactant a t 37’ in methanol
1: 1 ratio of base t o reactant in refluxing methanol
. ..., .. . Nitrile, X 87% cyclization in 1 min. Ester, I 87, cyclization 27y0Cyclization after 9 23y0 recovery after 3 min. niin. Amide, X I 88-937, recovery after 10 min. , , . .. , .
VI11
XI1 (50%)
XI11
In one run a t room temperature a 28% yield of crude 2-(2’-nitropheny1)-phenylacetonitrile (X) was obtained; however, even in this case the major product was the cyclized nitrile. The explanation It is significant that G-cyanophenanthridine-5- must be that the open chain nitrile (X) is being oxide (XII) was obtained in nearly quantitative formed in the foregoing reactions and then it yields from 2-(2’-nitrophenyl)-phenylacetonitrile cyclizes to form XI1 because of the base produced (X) a t 35” in about 1 minute, whereas X a t reflux by the hydrolysis of the potassium cyai1ide.j temperature and with the same base-nitrile ratio The 2-(2’-nitropheny1)-phenylbromomethane and concentration gave little or no cyclized nitrile (VIII) was prepared from the corresponding alcoX I I . I n the later case the cyclized nitrile X I 1 hol, 2-(2’-nitropheny1)-phenylmethanol(VII), and appeared to form instantaneously and then reacted hydrobromic acid in 79% yield, and the alcohol was further as the heating was continued for four prepared from 2-(2‘-nitropheny1)-benzoic acid by minutes. way of the acid chloride and subsequent reduction With R = CX the cyclization reaction is base with sodium trimethoxyborohydride in 767, yield. catalyzed, because with X and a 0.1 111 quantity of 2-(2’-Nitropheny1)-phenacetonitrile(X) was presodium hydroxide the yield of cyclized nitrile X I 1 pared in good yields by methods which did not inwas 3.3 times that expected assuming the sodium volve any base stronger than ammonium hydroxhydroxide and nitrile X are required in a 1:1 ratio. ide. Methyl 2-(2’-nitropheny1)-phenyl acetate The structure of 6-cyanophenanthridine-5-oxide (I) was converted to 2-(2’-nitropheny1)-phenyl(XII) was established by elemental analysis, in- acetic acid (V) (91%) by acid hydrolysis and this frared absorption and degradation to phenanthri- was in turn converted to the amide X I (‘727,) by dine4-oxide (111). consecutive reactions with thionyl chloride and am\Yith 2-(2’-nitropheny1)-phenylacetamide (XI) monium hydroxide. The amide X I was dehyas shown in Table I11 and one mole of base no ap- drated to the nitrile X (71yo)with thionyl chloride. preciable cyclization occurred in 10 minutes. Four attempts using the method of Kornblum, With the base and amide in a G : l ratio approxi- et aZ.,6 were made to convert 2-(2’-nitropheny1)mately the same types and amounts of products phenylmethyl bromide (VIII) to 2-(2’-nitropheny1)were obtained regardless of whether the heating phenylnitromethane (IX) . Qualitative tests inditime was 10 minutes or 5.5 hours. However, the cated that I X had been prepared, but it was not longer reaction times gave the better quality prod- obtained pure. The product formed did not ucts. Cyclized amide XI11 and phenanthridine- cyclize when warmed with methanolic sodium 5-oxide (111) were the only products which could hydroxide. be isolated; it was surprising that no G-carboxy(5) C. W. Muth, D. 0. Steiniger and Z . B. Papanastassiou, THIS phenanthridine-5-oxide (11) could be found. JOURNAL, 77, 1006 (1955). (4) L. F. Fieser and M. Fieser, “Organic Chemistry,” D. C. Heath a n d Co., Boston, Mass., 1056, p. 5,57.
(6) N. Kornblum, H. 0. Larson, R K. Blackwood, D D Ifooberry. E. P. Oliverto and G. E. Graham, ibid., 78, 1497 (1956).
6502
CHESTERW. MUTH,JOHN C. ELLERS AND 0. FRED FOLMER
Experimental' Methyl 2-(2'-Nitropheny1)-phenylacetate(I) and Sodium Hydroxide.-The following procedure is typical of those runs listed in Table I1 in which sodium hydroxide was used except for the differences noted in the table
REACTIOY OF
Bkw NaOH hTaOH KaOH NaOH CHaOKa CHaONa CH30hTa CHaONa
?r$ETHYL
Ratio of base Time to1 min 1:l 0 .1 1i.l
6.1 1:l
1:l 6:1 6.1
0 8* 5 83'
7.2 10.4 25
23
TABLE I1 2- (2'-SITROPHENk (I) ~ I T HBMFS Cyclized ester IT' (mp,'C)',
2 7 (170-174) 8 (17:S-lib) ,.
..
. . .. . . ....,.
39 (171-177) 5 5 (170-176)
..,.... . , ..
.....
L)-PHENYLACETATE
Cyclized liecovacid (A) ered o r I1 and 111 eiter I Imp " C ) " ' , '&
. .... . . , . ... . . . .. 3G-57 (214-225) 4 1 (210-317)
. . .. . . . . .
220.5° with 110 depressioii i i i in.1n.p. with authentic XII. In another run duplicating the above except that tlie rcaction mixture was refluxed for 5 Inin., a yelliiw precipitate formed instantaneously but it dissolved aiitl no pure XI1 could be isolated by the above procedure. ~IORGASTOUX, IY.I-A.
CHEMICAL LABORATORIES O F NORTHWESTERS USIVERSITI']
Rearrangements of a-Halogenated Ethers. I. 2,2,3,3-Tetrachloro-p-dioxane BY R.K. SURI~IERBELL AND D.INIELR.BERGER' RECEIVEDJULY 25, 1957 The compound previously assigned the structure 2,S,3,3-tetrachloro-p-dioxane (111) has been shown to be (2-chloroethoxy)-dichloroacetyl chloride (IV). I11 has been synthesized, its structure proved, and the formation of I V from 111 by a thermal rearrangement has been demonstrated
Discussion aliquots for spectral examination, the infrared specSome ten years ago the high temperature chlori- trum of I11 was observed t o change slowly to t h a t nation of tvans-2,3-dichloro-p-dioxane2 was de- of IV, the apparently first-order reaction requiring scribed,3 and the liquid product, obtained in 55%; approximately 30 hours for the disappearance of yield, WRS assigned the structure 2,2,:3,3-tetra- 111. Finally, on heating IT: at 190' without solchloro-p-dioxane. This assignment seemed justi- \-ent, there was a very slow distillation, the prodfied as solid derivatives of both ethylene glycol a1.1~1 ucts being ethylene chloride and oxalyl chloride. oxalic acid were isolated from the hydrolrsate ; On the basis of these observations, the liquid IV is but rather must no other tetrachlorodioxane could gi.i-e these de- not 2,2,3,3-tetrachloro-p-dioxane, rivatives. \Ye recently have had occasion to pre- be (2-chloroethoxy)-dichloroacetylchloride. I t is pare this compound, and a routine examination of entirely possible t h a t in t h e previously described its infrared spectrum revealed a strong absorption a t 5.55 p , entirely inconsistent with its formulation as tetrachlorodioxane. I n order t o resolve this inconsistency, the tetrachlorodioxane was prepared by an alternate route. I I1 Addition of chlorine t o 2-chloro-p-dioxene gave 2,2,3-trichloro-$-dioxane (I). Removal of hydrogen chloride from I by means of sodium hydroxide gave 2,3-dichloro-p-dioxene (II), which upon addition of chlorine gave the desired 2,?,3,3-tetrac1 C l chloro-p-dioxane (111). However, I11 is entirely IV different from the previously described liquid, I\-. IT1 is a stable white solid melting a t 140°,whereas preparation of IV3, I11 is actually formed as an IT: is a water-white mobile liquid boiling a t 20.5'. intermediate. Howex-er, the reaction temperature Cornpourid IV reacts "violently" with water and (153') and the time taken for the reaction (3-1 alcohols ; 111 can be recrystallized successfully hours) are more than are required to permit essenfroni aqueous ethanol a n d is stable to a. humid a t - tially complete isomerization of 111 to IIT; should mospliere. Furthermore, 11I does riot absorb in any I11 still be present a t the end of the reaction, the region of 5-6 p . i t would be isomerized in the atmospheric disThe structural relationship between 1I1 and IV tillation used in the purification scheme for IV. was established as follows: Both gave correct an- Confirmation of this was obtained by heating I11 alyses for CdH40?C14,and after hydrolysis both gave a t 210' for 30 minutes. On cooling, the liquid did derivatives of oxalic acid and ethylene glycol. not solidify, and the infrared spectrum of I11 was \Then 111 was heated under reflux in tetrachloro- no longer present, having been replaced by t h a t of ethane solution, with the periodic withdrawal of TY. The observation t h a t both I11 and IV could be (1) Northwestern University Fellow, 1955-1~5(1: .4llied Chemical and Dye Corp. Fellow, 195fi-1957. hydrolyzed to yield derivatives of ethylene glycol ( 2 ) See R. K. Summerbell and H. E.Lunk, THISJOURXAI.. 7 9 , requires some comment. Hydrolysis of 111 would 4802 (1937), for t h e structures of cis- and Irails-~,3-dichlorti-p-dioxane. be expected to yield t h e glycol, whereas the hydrol( 3 ) R . K . Summerhell, R . 12. TJmhoefer a n d G. R . T.appin, i h i d . , \.si? of I\' should instead give ethylene chloro69, 1332 (19471.
