Organic Chemistry
THE JOURNAL OF
@Copyright 1963
Volume 28, Number 3
March 22, 1963
b y lhr American Chemical Society
Ring Enlargements. IX. The Reactions of Cycloalkanones Carrying Three-carbon Side Chains Containing Potential Diazoalkyl Moieties’
c. DAVIDGvrscm A S D DEXIShf. B A I L E Y ~ Department of Chemistry, Washington University, St. Louis 30, Jlissouri Received November 16, 1962 The syntheses of cyclopentanone, cyclohexanone, and cycloheptanone carrying a -CH&H2CH2N( NO)COCH< moiety in the 2-position are described. Base-catalyzed decomposition of these compounds converts the nitrosoaniide group to a diazo group which reacts intramolecularly with the cycloalkanone to yield the bridged ring ketones 8-ketobicyclo [3.2.l]octane, 9-ketobicyclo [4.2.1]nonane, and 10-ketobicyclo [5.2.1]decane, respectively.
Chemists have long been fascinated by molecules which catch their own tails.3 This and the following paper4 add further examples to the collection of such sportive substances and describe cycloalkanones (11) which contain a diazoalkyl tail capable of being intramolecularly caught in the jaws of the carbonyl group and ingested into the ring. To isolate and directly study compounds of type 11, however, is difficult because of the facility with which the intramolecular di“Bisdiazoalkane Method”
1
method” by means of which compounds of type 1 can be synthesized and actually isolated. .Compounds of the general typo I containing a threecarbon side chain (VII) were synthesized in the following manner. Cyanoethylatioii of the pyrrolidineenamine prepared from the appropriate cycloalkanone6 (111) yielded the 2-(P-cyanoethyl)cycloalkanone (IV); protection of the carbonyl by formation of the ethylene keta iV) followed by reduct ve acetylation7 and selective hydl-olysis yielded the (y-acetylaminw propy1)cycloalkanone (VI) from which the corresponding N-nitroso conipound (VTI) was obtained by nitrosation with dinitrcgen tetroxide.8 In spite of the several steps involved, the conversion of the cycloalkanone to the ketonitrosoamide (VII) is an easy and efficient one; the intermediates need not be isolated
cH-cHzN -C~=O c&=o /NO
/
c=o
Cll2
I
“Diazoalkyl Bide Cha!n
CH-CHNz
‘COR
I1
n
Method”
azoalkane-carbonyl interaction takes place. Consequently, it is necessary to prepare compounds of type I in which a potential diazoalkyl group [ie., -CH,N(KO)COR] is present from which, under suitable conditions, the free diazoalkanes can be generated in situ. One approach to this problem has been outlineil in a previous paper of this series5 which discussed the reaction between bisnitrosourethanes (as sources of bisdiazoalkanes) and cycloalkanones. Although compounds of type I were not isolated from the reaction mixtures encountered in that study, it is almost certain that they were present as transient intermediates. The present paper outlines as an alternative to the “bisdiazoalkane methcd” the “diazoalkyl side chain
IIIa ( n = 0 ) b ( n = 1) c (n = 2 )
IVa ( n = 0) t) ( n = 1) b (n = 2 )
VIIa (n = 0) b ( n = 1)
(1) Thls work was supported, in part, b y a grant-in-ald from t h e National Science Foundation (G-6282). (2) Universal Match Company Fellow, 1959-1961. (3) See, for instance, 4. Kekule, Ber., 23, 1306 (1890). (4) D. M. Bailey, J. E. Rowers, a n d C. D. Gutsche, J . O,.Q. Chem.. 28, 610 (1963). ( 5 ) C . D. Gutsche a n d T. D. Smith, J . Am. Cbem. Soc., 82, 40137 (1960).
c (n
=
2)
Va ( n = 0) b (n = 1) b (n = 2 )
VIa ( n = 0 ) b ( n = 1) c (n = 2 )
( 6 ) G. Stork, R. Terrell, and J. Ssmuszkovicz. ibid., 76, 2029 (19.54): G. Stork and H. K. Landesrnan, ibid.. 78, 5128 (1956). (7) F. E. Gould. G. S. Johnson, and A. F. Ferris, J. O r g . Chem.. 26, 1658
(1960). (8) E. J. White, J. Am. Chem. Soc.. 77, 6008 (1988).
607
GETSCHE ASD BAILEY
608
and purified, and the over-all yields from cyclopentanone, cyclohexanone, and cycloheptanone to VI1 are 45-65 Since VIIb is the most accessible of the compounds in this series. its behavior on base-catalyzed decomposition was studied in some detail. Employing the previouslydescribed conditions for carrying out the ring enlarge, ~ addition of ment reaction via the in situ m e t h ~ d viz. the nitroso compound to a cold mixture of the ketone, methanol and potassium carbonate, a reaction took place with the quantitative evolution of nitrogen. The volatile product consisted of a mixture (total yield ca. 60%) of IXb and Xb in a ratio of 6 : 1. On the basis of an earlier observationlo that the ratio of ring enlargement product to solvolysis product increased with decreasing temperature, the decomposition of VIIb a t lower temperature was studied. Contrary to expectation, however, the ratio of IXb to X b decreased somewhat as the temperature was decreased to -30' and -60'. Although it was interesting that the nitroso compound underwent any decomposition a t these low7 temperatures, l1 the product ratio was disappointing from the standpoint of a useful synthesis of IXb. On the other hand, when the reaction temperature was increasetl to 60°, the ratio of IXb to X b increased to ca. 10 : 1, The higher reaction temperature also allowed a reduction in the amount of methanol necessary for the decomposition of VIIb, and this led to a further improvement in the ketone to ether ratio. It was subsequently ascertained that sodium methoxide could be used in place of potassium carbonate, that refluxing ethanol containing sodium ethoxide was equally as effective, that refluxing isopropyl alcohol containing sodium isopropoxide was completely ineffective,'* and
s.
0
/
VIIIa ( n = 0) b ( n = 1) c (n = 2)
VII,
I X a ( n = 0) b ( n = 1) c (n = 2 )
YOL.28
Thus, the method provides a definite advantage over the previously reported procedure whereby IXb was obtained in only 10% yield from the reaction of cyclopentanone with the bisnitrosourethane from butane1,4-diamine.5 The decomposition of VIIa also proceeded very smoothly in a refluxing solution containing ethanol and sodium ethoxide to provide an 88% yield of 8-ketobicyclo [3.2.l]octane (IXa) contaminated with only a small amount of the keto ether (Xa, R = OEt), the identity of which is inferred from the analogy with similar ring enlargement mixtures. In aqueous-alcoholic solvents 2-allylcyclopentanone (XIa) mas also produced, its identity being established through an independent synthesis. The structure of the ketone IXa was verified by a comparison with material obtained by another route.13 In this instance, also, the present method provides a reasonably easy route to the bridged ring ketone XIa. The decomposition of VIIc in refluxing methanol containing sodium methoxide proceeded smoothly and with quantitative nitrogen evolution, but the product contained mainly the keto ether Xc. The yield of IXc was improved by carrying out the reaction at 10' in methanol containing suspended potassium carbonate but only to the extent that the product, obtained in 80% yield, consisted of 10-ketobicyclo[5.2.1]decane (IXc) and ether (Xc) in a ratio of 3 :2. To obtain pure ketone from this mixture is rather difficult and inefficient, and in this instance the synthesis from cyclohexanone and the bisnitroso compound from butane-1 ,4-diamine5 is the method of choice. The base-catalyzed decomposition of compounds of the type VI1 thus provides a useful method for the synthesis of bridged ring ketones of the type IX. Extensions of this method to compounds of the type VI1 which are substituted in the cycloalkanone ring and/or the side chain will be reported at a later time. Extensions to compounds carrying side chains of other lengths and to compounds carrying the side chain at other positions in the cycloalkanone ring are reported in the following paper.4
Experimentall 4 01-6-3SeriesI5 [Synthesis of Q-Ketobicyclo[4.2.l]nonane (IXb)]
