Acknowledgment.-The authors wish to acknowledge their great indebtedness to the National Science Foundation for financial support which made this research possible. Such support was
granted under the aegis of the National Science Foundation Uiidergraduate Research Participation Program as N.S.F. Grant 12635 and N.S.F. Grant 16131.
Aromatic Nuclei by the Sulfur Extrusion Reaction. Derivatives C. K. BRADSHER AND J. TI.'
I. Phenanthridixinium
3lc;Doxa~n~
DPpartment of Chemistry, Duke University, Durham, ,Vorth Carolina Received July 6, 1962 The action of an excess of hydrogen peroxide on pyrido[2,l-b]benzo[f][1,3]thiazepinium salts (I) a t 56' followed by heating a t 100" has been found to cause extrusion of the sulfur atom, yielding phenanthridisinium salts (11). The consumption of hydrogen peroxide a t 5 6 O , and analogy to related reactions suggest that a sulfoxide may be the intermediate.
Recently the first synthesis of pyrido [2,1-b]benzo If][1,3]thiazepinium salts (I) was described.2 When these salts were treated with 30% hydrogen peroxide and acetic acid, under essentially the condit,ion reported3 to effect the oxidation of diary1 sulfides to sulfones, crystalline sulfur-free products were obtained. The analytical results obtained for these products suggested that they might be substitut.ed phenanthridi~inium~ perchlorates (11). The correctness of the postulate was confirmed by direct comparison of the product I I a with a sample of 7-methylphenanthridizinium perchlorate prepared from an authentic sample5 of the bromide. The results of the sulfur-extrusion reaction are summarized in Table I. The procedure for carrying out the ring-contraction reaction involved an initial period of three to ten hours during which the thiazepinium compound (I) was heated at about 50' with acetic acid and an excess of hydrogen peroxide, followed by a period of about equal length during which a temperahre of 100' was maintained. Since it is known that certain dibenzo [b,f]thiepins (111)6and dibenzo [b,f]-l,4-thiazepines (IV)'s8 on heat'ing in the presence (or a b ~ e n c e of ) ~ copper (1) This research waa supported by research grants (NSF-6215 and NSF-G 19901) of the National Science Foundation. Taken in part from a thesis submitted in partial fulfillment of the requirements for the Ph.D. degree, Duke University. A preliminary report of a part of this work appeared as a Letter to the Editor, Chem. Ind. (London), 1797 (1961). (2) C. K. Bradsher, L. D. Quin, R. E. LeBleu, a n d J. W. McDonald, J . Org. Chem., 26,4944 (1961). (3) B. R. Baker, M. V. Querry, and A. F. Kadish, ibid., 16, 402 (1950). (41 The name phenanthridiainium has been proposed [ C . K. Bradsher and K. B. Moser, J . Am. Chem. Soc., 81, 1941 (1959)l for the benzo [alquinolizinium nucleus. (5) C.K. Bradsher and L. E. Beavers, ibid., 77,453 (1955). @ ) ( a ) J. D. Loudon, A. D. B. Sloan, a n d L. A. Summers, J . Chem. Soc., 3814 (1957); (b) C. I. Brodrick, J. S. Nicholson, and W. F. Short, i b i d . , 3857 (1954). (7) -4. D. Jarrett and J. D. Loudon, ibid., 3818 (1957). ( 8 ) R. H.B. Galt and J. D. Loudon, ibid., 885 (1959). (9) R. H.B. Galt, J. D. Loudon, and A . TI. B. Sloan, ibid., 1588 (19.58).
TABLE I PHENAKTHRIDIZINIUM SALTSBY SIJLFUR EXTRUSION
Rz
c10*@
c10,e I a b C
d
I1 R1
Rz
Yield, %
H CH3 H H
H H CH, OCH3
38 31 47 40
yield phenanthrenes (V) or phenanthridines (VI), respectively, it seemed important to determine first whether the extrusion of sulfur from phenanthridizinium (I) salts was not also purely thermal. Since 7-methylphenanthridizinium perchloraote (IIa) showed an absorption maximum at 35-18 A., R'
R 111. R = H, X = C-COOH IV. R = CeH,, X = S
R T'.
R
VI. R
=
=
H, X = CH CaH,, X = Ti
and the absorption of solutions obeyed Beer's law, it was possible to follow the thermal reaction spectrophotometrically. A solution of the thiazepinium salt (Ia) in acetic acid, with no hydrogen peroxide added, was heated for twenty-two hours at 100'. Under these extreme conditions there was definite indication of the formation of the
BRADSIIER AND M C ~ O N A L D
4176
-I
0.9
i
0.8 0.7 1o
0.6
3 $ 0.5 d 4
0.4
1
0.3
3600
3200
3400 Wave length, .4
Fig. 1.-Ultraviolet absorbance of samples withdrawn during oxidative sulfur extrusion reaction. After 0 hr. (thiazepinium salt) (-.--). After 5 hr. a t 56' (). After 9 hr. a t 56' and 19.5 hr. a t 100' (- - -).
-
phenanthridizinium system, but the yield did not exceed 10%. With regard to the two-stage process in which the thiazepinium salt (Ia) was heated at about ,50°, and then again a t 100' with acetic acid and hydrogen peroxide, it was not a t first clear what was accomplished a t each stage. It was certain that the higher temperature did destroy excess peroxide (and perhaps peroxy acid) present, and failure to observe this precaution led to low-order explosions during the subsequent vacuum evaporation. The process was next carried out under controlled conditions, with aliquots being examined spectrophotometrically and titrated for peroxide iodometrically. The results of such an experiment are recorded in Table 11. TABLE I1 SULFUR EXTRUSION FROM A TIiIAZEPINIUM SYSTEM ( I A ) Heating Optical Milliliters time, Temp., density of SzOr-' hr. OC. (3548 A.) (0.0102 M )
0
56
0.120
1
56 56 56 56 56 100
.118
100 100 100 100 100
.156
3 5 7 9 9.25 10 11
15.5 25.5 28.5
,098 ,085 .093
.OQ8 .28G
.759 .go9 ,916
24.7 23.0 17.7 12.7 10.2 8.7 5.5 0.0 0.0 0.0 0.0
The optical density readings indicate that at 56' very litt81eof the expected phenanthridizinium salt (IIa) is present after nine hours. There is actually
VOL. 27
a decrease in optical density at 3548 b. a n t although the change in optical density a t 3548 A. is only slight, examination of the complete ultraviolet absorption spectrum (Fig. 1) makes it clear that the decrease in optical density is even more evident at shorter wave lengths. Although all of the peroxide was destroyed in less than two hours a t 100°, the yield of phenanthridizinium salt continued to rise during the 19.5 hours heating a t that temperature. The final conversion of product, corresponding to the optical density 0.916, was 68%. Similar experiments carried out at higher initial temperatures, gave much poorer results, e.g., a t 64' the yield of phenanthridizinium salt being less than 10%. At an initial temperature of 40' yields comparable to those in Table I1 were obtained, but the time required for the initial oxidation step was nearly double that observed a t 56'. In the experiment described in Table I1 there was present 2.5 moles of hydrogen peroxide per mole of thiazepinium salt Ia. The data indicate that a t the end of the 56O-heating period approximately 1.5 moles of hydrogen peroxide had disappeared. To correct for the thermal decomposition of hydrogen peroxide in acetic acid at 56' the experiment described in Table I1 was repeated without the thiazepinium salt present. The data thus obtained was used to correct the values reported in Table 11. A plot of the results is shown in Fig. 2. The upper horizontal dotted line represents the calculated volume of thiosulfate if one mole of hydrogen peroxide had been consumed in the oxidation, and the lower represents the thiosulfate volume if two moles had been consumed. The data (Fig. 2) suggest that one mole of hydrogen peroxide is consumed in the oxidation and make it appear probable that the intermediate being formed a t 56' is a sulfoxide. The strongest support for the sulfoxide hypothesis is found in the work of Szmant and Alfonso,lov'l in which it was demonstrated that the monosulfoxide of 2,5-diphenyldithiadiene, when heated, would undergo sulfur extrusion (dethionylation) to yield 2,4-diphenylthiophene. Even more closely related is a more recently published12 example of the dethionylation of the seven-membered ring of dibenzo-1- thia-4,5-diaza-2,4,6-cycloheptatriene Soxide (VII), a structure closely related to the intermediate (VIII) proposed in the present study. A sulfoxide intermediate has been proposed9 to explain a t least one other example of sulfur extrusion brought about by the action of acetic acid and hydrogen peroxide. Szmant and Alfonso" have pointed out that the dethionylation reaction of sulfoxides might take (10) H. (1956). (11) H . (12) H. Kharasch,
H. Ssmant a n d L. Alfonso, J. Am. Chem. Soc., 18, 1064 H. Szmant and L. M. Alfonso, ibid., 79, 205 (1957). H. Szmant, "Organic Sulfur Compounds," Vol. 1, N. ed., Pergamon Press, New York, N. Y.Jl1961, p. 163.
DECEMBER, 1962
AROMATIC NUCLEIBY
THE
SULFUREXTRUSIOX REACTION. I
8
4477
25
20
VI1
CH3 (Not isolated) VI11
place either by a direct loss of sulfur monoxide, or via a bimolecular disproportionation reaction in which sulfur dioxide is eliminated, and a portion of the sulfoxide is reduced to the sulfide. While the majority of our preparative experiments have afforded a less than 50% yield of the sulfur extrusion product (11),no sulfide (I)has been recovered, and direct dethionylation of the thiazepinium salts (I) may actually be the predominant course of the reaction, especially in those systems providing high yields of phenanthridiainium products (11). To date efforts to isolate the proposed thiazepinium sulfoxide intermediate (VIII) have not, been successf ul. A factor of importance in determining ideal conditions for the sulfur-extrusion reaction of thiaaepinium salts (I) is the stability of the final product I1 in the presence of excess hydrogen peroxide. In an experiment in which 7-methylphenanthridizinium perchlorate (Ira) was exposed to the action of a large excess of hydrogen peroxide (about nine times the quantity used in the experiment recorded in Table 11),but otherwise under conditions usually used in the ring-contraction experiment, the destruction of not more than 25y0 of the phenanthridizinium salt occurred, as evidenced by the decrease in optical density a t 3548 A. From this experiment it seemed probable that in the normal sulfur-extrusion experiment, using relatively small quantities of peroxide, the destruction of the product (IIa) by the excess of the oxidant present would not be important, as it affects the total yield. Of the other oxidizing agents known to t>ransform the sulfide linkage to sulfoxide,12 nitric acid alone was tried. The thiazepinium salt (Ia) was unaffected when heated with 8 M nitric acid a t 100' (80% recovery), but with concentrated nitric acid it apparently undergoes nitration to yield what appears t o be a mononitrated product.
s 'n
15
54 10 5
2
4
6
8
Hours
Fig. 2.-Plot of peroxide titration data from Table I1 (corrected for thermal decomposition) for the 56"-heating period. Upper dotted line corresponds to consumption of one mole of peroxide; lower line, two moles.
commercial 30% hydrogen peroxide was added, and the total volume made up to 20 ml. by the addition of acetic acid. The flask w a ~heated at 56' in an acetone vapor bath, or a t 100' in a steam bath, and a t regular intervals (Table 11) I-ml. samples were withdrawn with the calibrated syringe. The aliquots were made up to 100 ml. with distilled water. Exactly one half of the 100-ml. solution was diluted to 500 ml. with distilled water for examination with the ultraviolet absorption spectrophotometer. The other half of the 100ml. solution was used in the peroxide determination. To it was added 100 ml. of water, 10 ml. of 4 N sulfuric acid, 1 g. of potassium iodide, and 3 drops of neutral 37, ammonium molybdate solution. The resulting solution waa titrated immediately with 0.0102 M sodium thiosulfate solution. 7-Methylphenanthridizinium Perchlorate (IIa).-A mixture containing 20 ml. of acetic acid, 0.45 ml. of 30% hydrogen peroxide, and 0.59 g. of 12-methylpyrido[2,1-b] benzo[f] [ 1,3]thiazepinium perchlorate ( Ia)2 was heated a t 56" (acetone vapor bath) for 12 hr. A t the end of this period it was heated at 100' (steam bathj for 10 hr. The mixture was concentrated on the steam bath under reduced pressure and the residual oil crystallized from methanol-ethyl acetate (Sorit). The product, 0.20 g. (3870) consisted of tan crystals, m.p. 252-254'. An analytical sample crystallized from methanol as light tan irregular needles, m.p. 260-263'. This was identical (ultraviolet and infrared absorption, m.p., and m.m.p.) with a sample obtained by action of perchloric acid on 7-methylphenanthridiziniumbromide.6 Anal. Calcd. for CI4H1pClNOa: C, 57.25; H, 4.12; S , 4.77. Found: C, 57.64; H,4.04; N,4.87. 7 , l l -Dimethylphenanthridizinium Perchlorate .-One benzo[f] [1,3]thiazepingram of 4,12-dimethylpyrido[2,1-b] ium perchlorate (Ib)*was suspended in 70 ml. of acetic acid and 1.5 ml. of 30% hydrogen peroxide added. The suspension waa magnetically stirred and heated at 56'. After a few minutes solution was complete, but heating waa continued Experimental for a total a t 3.5 hr. After an additional 10-hr. heating a t All elementary analyses were carried out by Dr. Ing. A. loo', the mixture was placed in the refrigerator for 24 hr. Schoellcr, Microanalytisches Laboratorium, Kronach, Ger- The resulting light brown crystals were collected and remany. Ultraviolet absorption spectra were taken with a crystallized from methanol-ether. affording 0.28 g. (31%) The analytical Cary Model 14 recording spectrophotometer using l-cm. of light brown crystals, m.p. 180-184'. matched quartz cells. All boiling and melting points are sample consisted of light yellow plates, m.p. 190-192'. uncorrected; the latter were determined by using the Mel- This was identical to the perchlorate prepared from an authentic4 sample of the bromide. Temp capillary apparatus. Anal. Calcd. for C15H1,CIN04: C, 58.53; H, 4.59; N, Analytical Procedure.-Six hundred and fifty-four milligrams (2 mmoles) of 12-methylpyrido[2,1-b]benzo[fl[l,31-4.55. Found: C, 58.54; H , 4.54; N , 4.55. 7,lO-Dimethylphenanthridizinium Perchlorate (IIc).thiazepinium perchlorate ( I a ) 2 waa dissolved in about 15 ml. of acetic acid in a 20-ml. volumetric flask. By use of a A mixture containing 0.63 g. of 3,12-dimethylpyrido[2,1-b]calibrated 1-ml. hypodermic syringe exactly 0.50 ml. of benzo[f] [1,3]thiazepinium perchlorate, 10 ml. of acetic acid,
-
and 0.5 ml. of 307, hydrogen peroxide was heated for 12 hr. a t 56", followed by 10 hr. a t 100'. Isolated and recrystallized as in the case of the isomer (IIb), it yielded 0.27 g. (47y0) of tan crystals, dec. aliout 340". The analytical sample crystallized from methsnol as light yellow irregular crystals, m.p. 340" dec., and was identical t o the perchlorate prepared from au authentic4sample of the bromide. Anal. Calcd. for ClaHlrCIPITO~:C, 55.53; H , 4.59; N, 4.55. Found: C, 58.44; H, 4.64; N, 4.60. 7-Methyl-10-methoxyphenanthridzinium Perchlorate (IId).-The procedure was the same as in the preparation of the 7,lO-dimethylphenanthridizinum perchlorate (IIc), except that the reaction time at 56 and 100" was 3 hr. each. From 0.36 g. of 3-methoxy-12-methylpyrido[2,1-b] benzo[f]. [1,3]thiazepinium perchlorate2 (Id), 3 ml. of acetic acid, and 0.5 ml. of hydrogen peroxide, 0.13 g. (40%) of a yellow crystalline material wm obtained, m.p 319-320'. The analytical sample crystallized as needles, m.p. 322-
323". This material was identical with the perchlorate salt obtained from an authentic sample of b r ~ r n i d e . ~ Anal. Calcd. for C16HllC1N06: C, 55.65; H , 4.36; N, 4.33. Found: C, 55.78; H , 4.42; N,4.37. Nitration of 12-Methylpyrido[Z,1-b] benzo[f] [ 1,3]thiazepinium Perchlorate (Ia).-A solution of 1 g. of 12-methylpyrido[2,1-b]benzo[f] [1,3]thiazepinium perchlorate in 20 ml. of concentrated nitric acid was heated a t 100' for 16 hr. The solution was concentrated under reduced pressure, then 20 ml of ethanol was added and the solution was once more concentrated. The residue was crystallized from methanol-ethyl acetate, atlording 0.43 0;. (38y0) of colorless crystals, m.p. 240-245" dec. The analytical sample con-' sisted of fine colorless needles, m.p. 255-257' and had the composition expected for a mononitration product, A, mp (log E ) 215 (4.30), 270 (4.21); 235 (4.03). Anal. Calcd. for C14H11C1N206: C, 45.36; H, 2.99; X, 7.56. Found: C, 44.97; H , 2.94; N,7.85.
Aromatic Nuclei by the Sulfur Extrusion Reaction. 1I.I Phenanthridizinium Salts with a Substituent i n Ring A
c. I
