4072
CALVIN L. STEVENS AND A
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[CONTRIBUTION FROM THE DEPARTMEST O F CHEMISTRY O F \vAYSE STATE
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Epoxyethers. XVI. A Bicyclo Epoxyether',' BY CXLVIKL. STEVEIGS AND -ILFRED J. WEINHEIWER:' RECEIVED MAKCH18, 1958 2,2,6-Tritnethylcyclohesanoiie (111) w,s prepared in 69yoover-all yield from carbethoxycyclohexanoiie. Hal(igeiiatiuii of the ketone I11 gave the haloketones IV and V in excellent yield. The chloroketone IV was converted in 839% yield t o
the bicyclo epoxyether \TI which was characterized by hydrolysis and reaction with p-nitrobenzoic acid to give the h y droxyketone IX and the ketoberizoate VIII. The structure of the hydrosyketone IX was proved by peracid midation to geronic acid.
Recently an investigation was initiated in this in alcohol solution the conformational isomer preLaboratory to establish methods for the deter- dominated in which the halogen was axially oriented. mination of the stereochemistry of the epoxyethers This form was considered to be the preferred form as well as the stereochemistry of the ring-opening for reaction with methoxide ion to give epoxyether reactions of them.4 h bicyclo epoxyether such as (ziaVI). VI1 has been sought for some time for this stereoIn alcohol solution the parent ketone 111 had chemical investigation since the stereochemistry , , ,A at 292 mp with log E 1.44. The chloroketone of this particular type of epoxyether would be IV had Xmax at 312 mp (A 20 m p ) with log E 1.60 known with certainty (the epoxide could only be ( A 0.16 log E). The bromoketone V had Xmax a t fused cis to the cyclohexane ring). The present 320 mp (A 28 mp) with log E 2.01 (A 0.57 log E ) . investigations resulted in the successful synthesis From these data the conformational structure of the and characterization of such a bicyclo epoxyether bromoketone V is clear since Cooksong has shown (YII). from a number of steroid and triterpenoid a-bromoThe most general method for preparation of ketones that an axial bromine of an a-bromocycloepoxyethers is the reaction between an a-halo- hexanone causes a shift in the ultraviolet absorp ketone and a sodium alkoxide. However, this re- tion of about +28 mp with the correspondiiig action, when applied to the a-halo derivatives of change of about $0.6 log t . Although the number of examples of a-chlorothe more common cyclic ketones, led to a variety of products other than the desired epoxyethers. ketones presented by Cookson was small, direct Thus depending on solvent and conditions, so- comparison of certain chloroketones with the cordiurn rnethoxide reacted with the a-halo derivatives responding bromo derivatives showed that neither of cyclohexanone,j in~lanone,~ tetralone' and alkyl- the AXmax nor the A log E is as great for the chloro tetralonesj to bring about variously, simple compounds, which data support the axial conforenolization, Favorski rearrangement, aromatiza- ination for the chlorine in IV. The infrared spectioti to phenols and the formation of cr-hydroxy- trum further supports IV since the parent ketone, ketals. Epoxyethers were presumed to be inter- 111 had a carbonyl band a t 5.S;{ p (liquid filni) :iiid iiiediates in the hydroxyketal formation, but coultl the chloroketone IV had identical absorption, .5.X% iiot be isolated. The alternate method for the p (liquid film). Xxial a-halocyclohexanories arc I)rel)aratioii of epoxyethers, which involved eposi- knowti to exhibit little shift of wave length of thc ahsorptioii bands. I " ?'lit% solid (latioil of an enol ether, has been showti not to he infrared c~~rbciriyl ;jpplicablc for the sy~ithesisof the simple bic.ycIo brornoketone 1. was cotiiparecl t o the liyuid chloroc.1)oxyetht.r froni cyclohexanone enol ether.' .Ill ketotic by mc';itis of spectra i n cThloroforrn solutioii. (if these undesired reactions were circumveri trtl i i i T h e fact that the ahsorpticm oi I*,>.Xi p , was c's thc present study by the use I)!' the halo deri1.a t i v c sentially idciitical w i t h I i ? , .-).s:! p , supl)(irtrcl the o f the highly substituted ketonc, 2,2,(i-triiiiethyl- ultraviolet data ior the coiilortiiHticiiia1 structurc. ( i f the hroinoketotit~ V. cyclohexanone (TIT). 'The bicyclo epoxyether \ - I I was 1xepareti i i i good T h e trirnethylcyclohexa~lorlc (111) reactctl huioothlv with chlorinc arid bromirie in acetic. acid to vield (83(i;) from the ch1t~rol;etorieIV l>y rcactioii give the tu-chloro (11;)a i i t l (2-brorno (Vlderivatives with sodium niethoxide i i i iiiethaiiol solution 13). ;Lllowing the tt,riiperaturcx oi' t h c reaction t o .;t;rr( i i i !N iiiid R4';;, yields, rrsprctive a t 0' aiid slowly rise t o i ~ o i ~ i iteiiil)eraturc,. i 'l'ht, ariwlysis oi each of these haloketorle epoxyether vas stable t o :ilcciholysis uiitlcr t hest* , I ) S u i n l w r Xl'i n this ~ l r r ~ 1, oi t 1 'I 111h I o ~ ' K conditions a i i t l . the product (lit1 iiot slion. c~viclc~iicc .\ iirelirninary annt?itnccment o f this u < v k ~ a -m;i { b f Lhc a r i t l by rcactioii with /~-iiitrobt.nzciicacid to give S a t i o n a l Cancer I n s t i t u t e , 19;;-195fi. the a-!etobenzoate V I I I . T o show that 1 1 0 carbon (4) C. 1 , . Stevens a n d T. 1%. Coffield J . O v p . C h r m , 23, 336 ( I ! i h ) . skeleton rearrangeinent had occurred in these re( 5 ) C. L. Stevens and J. Tazunia, Tais J O U K N A L , 1 6 , 715 (1934). (1;) K-. G. Rutherford and C. L. Slcvens. ibid., 17, 3278 (1955). actions the a-ketobenzoate \vxs hy-drolyzed to tht. ( 7 ) C. L. Str\,ena, 1. J. Uecrelmom. j r . , ; m d i;.G I
