COMMUNICATIONS TO THE EDITOR
July 20, 1964
acyl insertion" reaction of aminoacylated salicylamide As shown below the postuand related c0mpounds.j latedj mechanism involves initially a 1,5-dicarbonyl compound.
OH
aoH CONHCHRCONHz
The thermal isomerization of 7-methoxycycloheptatriene to 3-methoxycycloheptatriene and related isomerizations6 may also be postulated to proceed via the 3,2,l-bicyclicpath in which the two carbons forming the leaving and arriving sites for the migrating hydrogen are the bridgehead atoms. OCH3
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dec., Xmax 280 ( E 10,100) and 406 mp (24,750); [ c y ] 6 9 0 7 ~ , -468°.3 Diazotization of the latter followed by the reduction of the diazonium salt with 507, aqueous hypophosphorous acid gave the 3-methoxy- l-p-nitrophenylazo compound (89y0 yield), m.p. 223-224' ; Amax 279 ( t 9500) and 350 r n p (16,200) ; [ ( Y ] B ~ oH,~ -348'. Reductive cleavage of the azo compound with zinc dust and glacial acetic acid provided 1-amino-3-methoxyestra-l,3,5(10)-trien-17-one ( I I I b , 7 3 7 , yield), m.p. 213-214'; Amax 245 (sh, t 6720) and 291 mp (3000); [ a ] ~ +301°.4 The free l-amino-3-hydroxy-17-one I I I a was obtained by demethylation of I I I b with pyridine hydrochloride (66yG yield), m.p. 280-288' dec., Amax 212 ( E 40,000), 240 (sh, 7850), and 292 m p (3080) ; 3412, 3380, 1725, and 828 cm.-'; [ c Y ] * ~ D$264' (pyridine). The 1-amino-3-methoxy compound I I I b on diazotization a t -25' (sodium nitrite, glacial acetic acid, and 1 iV sulfuric acid) followed by the addition of sodium azide in water at -25' was converted inta the 1-azide (85% yield), m.p. 147-149'; Amax 218 ( E 23,000), 255 (6500),293 (3620), and 303 mp (sh 3000); :,"v 2100 and 831 cm.-'. The latter, on being heated in n-hexadecane for 5 min. a t 200', gave the indoline, 1 , l l a -
N HZ We are carrying out other studies to test the generality of this path.7 ( 5 ) M. Brenner and J, P. Zimmermann, Heiv. Chim. Acla, 40, 1933 (1957); 41, 467 (1958); M. Brenner and J. Wehrmuller, ibid., 40, 2374 (1957); H . Dahn, R. Menasse, J. Rosenthaler, and ?VI. Brenner, i b i d . , 44, 2249 (1959). We thank Dr. F. Kagan of the Upjohn Company for bringing this reaction t o our attention. (6) E . Weth a n d A. S. Dreiding, Pvoc. Chem. Soc., 59 (1964). We thank Dr. N . Nelson of t h e Upjohn Company for bringing this reaction to our attention (7) This work has been supported by a grant from the Sational Science Foundation
RO
HN---
CHs0 IIIa, R = H b, R = CH3
IV
imino-3-methoxyestra-1,3,5(lO)-trien-l7-one (IV, 65% yield),j m.p. 199-201'; Amax 212 ( e 28,000), 235 (sh, 5800), and 293 mp (3550); vt;: 3300, 824, and 728 cm.-'; [ a ] +164'. ~ Dehydrogenation of IV with palladium-charcoal in xylene (1 hr. reflux) gave the indole, 1,1l-imino-3-methoxyestra-1,3,5( 10),9(11)-tetraEVASSCHEMISTRY LABORATORY MELVINs. S E W h f A S OHIOSTATEUSIVERSITY COXSTASTISOS COURDUVELIS en-17-one (Ib, 90% yield), m.p. 203-205'; Xmax 229 COLUMBCS, OHIO 43210 RECEIVED MAY2 , 1964
The Synthesis of a Novel Steroid Heterocyclic System
Sir : We wish to report the synthesis of a novel heterocyclic steroid, 3-hydroxy- 1 , ll-iminoestra-l,3,5(10),9(11)-tetraen-17-one (Ia) by a pathway whose key feature was the generation of a nitrene intermediate appropriately situated for ring formation.
RO
CHs0 Ia,R=H b, R=CH3
2"
I1
4-Amino-3-methoxyestra-l,3,5 (10) -trien-17-one (11) in acetic acid was coupled with p-nitrophenyldiazonium chloride to give directly the 4-amino-3-methoxy-l-pnitrophenylazo compound (87yGyield), m.p. 243-244' (1) S. Kraychy, J . A m . Chem. SOL.,81, 1702 (1959). ( 2 ) T h e yields reported are for material after initial purification.
( 3 ) The ultraviolet absorption spectra are for a methanol solution. T h e optical rotations are for a chloroform solution a t 2.5' unless noted otherwise. .411 new compounds reported here gave satisfactory elemental analyses The n m.r. spectra were taken in deuteriochloroform, and the chemical shifts were measured with respect t o TMS. (Varian A60 spectrometer) (4) The n.m r . spectrum of the 1-amino-3-methyl ether I I I b showed two aryl protons barely separated from one another a t 366 and 367 C.P.S. In contrast the C - l and C-4 protons of the corresponding 2-amino-3-methyl ether' were seen as singlets a t 388 and 397 c.P.s., and the 4-amino-3-methyl ether I1 showed a single sharp line a t 400 C . P . S . which had a n integrated value of two protons (.5) G. Smolinsky, J . A m . Chem. Soc., 84, 4717 (1960), has shown t h a t aryl azides on thermal or photolytic decomposition yield nitrenes which, either by a direct insertion (singlet process) or by abstraction of hydrogen and subsequent closure of the resulting diradical (triplet process), yield cyclic products An examination of molecular models indicates t h a t , in t h e formation of I V , insertion could occur either l l a or I l p , with the former being slightly favored when ring B assumes a normal half-chair conformation. However if the biradical two-step process pertains then C - l l a - K bond formation would he favored since the '2-18 methyl group would be expected to exert a stronger orienting effect than in the singlet process. The n.m.r. spectrum of I V does not indicate whether the C-Y and -11 hydrogens have a CIS or t r a n s relationship, which feature was not resolved by a n initial a t t e m p t with spinspin decoupling IS. L. M a n a t t and D . D . Elleman, ibid., 83, 4095 (1961)l. However, it is known t h a t an Ilp-hydroxyl group6,' shifts the C-18 methyl absorption ca. 15 c.p s. downfield from its normal position while an 11 ahydroxyl group6 produces a similar shift of only 2 c.p s The position of the C-18 methyl group of IV ($59c.P.s.) is shifted only 2 c p s. downfield from t h a t of the unbridged precursor I I I b (57 c P.s.) which supports the a assign. ment of the C-11-N bond. (6) Y . Kawazoe, Y Sato, M . Natsume. H. Hasegawa, T. Okamoto, and K. Tsuda, Chem. Pharm. Bull., 10, 338 (1962). ( 7 ) E. Capsi, T. A. Wittstruck, and P. K . Grover, Chem. Ind (London), 1716 (1962).
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COMMUNICATIONS TO THE EDITOR
Vol. 86
34,000), 272 (5470), and 298 mp (3690); Amin 252 4280) and 286 mp (3250)*; vz,”: 3350, 819, and 802 cm.-’; [ a ] D +225.9 Demethylation of I b with pyridine hydrochloride gave 3-hydroxy-1,ll-iminoestra1,3,5(10),9(11)-tetraen-17-one(Ia, 81% yield), m.p. 290-300’ dec. ; A,, 229 ( e 32,000), 270 (5050), and 301 ml.c (3530); vf;: 3380, 1725, and 828 cm.-’; [ a ] ~ 4-331 ’ (pyridine). Further work is in progress on the synthesis of steroids containing an indole nucleus. (E
(E
( 8 ) T h e ultraviolet absor1)tion spectrum of I b compared very favorably with t h a t of 2,3-dimethyl-6-methoxyindole:N A’euss. H . E . Boaz, and J . W. Forbes, J. A m . Chem. Soc., 1 6 , 2463 (1954). (9) Additional support for t h e structure Ih as well as for IIIb and IV was obtained by mass spectrometric analysis, which will be discussed in the full length paper on this synthesis.
ORGANIC CHEMICAL RESEARCH SECTION E. W. CANTRALL LEDERLE LABORATORIES R. B. CONROW CYANAMID Co. SEYMOUR BERNSTEIN A DIVISIONOF AMERICAN PEARLRIVER,NEWYORK RECEIVED MAY19, 1964
f(Y)
Fig. 1.-Correlations
of u ( Y ) with
UI
and
u
for YCsH4S02.
0.4
Electronic Effects of the Sulfonyl Group in Aromatic Systems. Relationships between Inductive and d-Orbital Resonance Contributions’
Sir: Recent reports2 have discussed possible relationships between resonance and induction parameters of substituted benzenes. Although Tafta proposed U R and U I as independent parameters which in general are not directly interrelated, McDaniel’s correlations4suggested that in benzoic acids a linear meta-para relationship may exist for families of substituents bonded to the ring through a common atom, e.g., SCH3, SH, SC(O)CH3, S ( 0 )CH3, S02NH2, and S02CH3. The corresponding phenols, however, deviated substantially from linearity. Subsequently, TaftZademonstrated that better linearity is realized if comparison is restricted to series of more closely related substituents, e.g., m- and pF C ~ H ~ S O Z(X X is F, C1, CH3, CzHs, “2, 0-).Significantly, S(O)CH3 and SF5 did not qualify for the S 0 2 Xline. We now report that for acetic acids, benzoic acids, and phenols substituted with S02CsH4Y1b~5~6 the parameters of SO2X and relative influence of Y can be correlated for each series; other factors influencing the S-X bond remain virtually constant (cf.above). From the data (Table I)7 several significant relationships become apparent. (1) (a) Supported by grants from the Petroleum Research Fund and Army Research O 5 c e (Durham); (b) preceding paper: C. Y. Meyers, Gnez. chim. i l d , 98, 1206 (1963). (2) (a) R . W. T a f t , E. Price, I. R . Fox, I. C. Lewis. K . K . Andersen. and G. T. Davis. J . A m . Chem. Sac., 86, 3146 (1963); (b) L. A. Cohen and W. M. Jones, ibid., 86, 3397, 3402 (1963); (c) D. R . Eaton and W. A. Sheppard, ibid., 86, 1310 (1963); (d) 0 . Exner, Telvahedvan Lellevs. 815 (1963). (3) R. W. T a f t , J . Phys. Chem., 64, 1808 ( 1 9 6 0 ) . (4) L). H . Mcllaniel, J . O r g . Chem., ‘26, 4692 (1961). (.5) C. Y . Meyers, G. hloretti, and I*, Maioli, ibid., 41, 626 (1962), B. Cremonini. Doctoral Dissertation, University of Bologna, 1962. ( 6 ) C . Y. Meyers. G. 1,ombardini. and I*. Bonoli. J. A m . Chem. SOL., 84, 4603 (1902). ( 7 ) I-effects from m e l a and para positions were considered equivalent; by definition, R-effects reflect all influences of =-interaction between the substituent and the system into which it is introduced: 6. ref. 2b, 2d. 3, K . W. Tart and I . C. I,ewis, Telvahedvon, 6 , 210 (19591, and M. J . S. Dewar and P J Grisdale, J A m Chem Sac., 84, 3529 (19621, el seq
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