FORMATION OF NORTRICYCLENE
July 5 , 1955 [CONTRIBUTIOX FROM THE
DEPARTMENT OF
3583
CHEMISTRY, UNIVERSITY OF M I C H I G A S ]
Formation of Nortricyclene Derivatives by Bromination of exo-2,5-Methylene- 1,2,5,6-tetrahydrobenzoicAcids BY CHARLESD. VER NOOY'AND CHRISTIAN S. RONDESTVEDT, JR. RECEIVED DECEMBER 16,1954 Bromination of several derivatives of ero-2,5-methylene-l,2,5,6-tetrahydrobe11zoic acid in aqueous bicarbonate solution forms derivatives of 3-bromonortricyclene, as well as rearranged bromolactones, bromohydrins, etc This novel reaction is interpreted as a type of trans elimination. Iodolactonization has been used as a method for removing the endo isomer from a mixture of endo and exo isomers and as a method for the analysis of such mixtures
Attention was then turned to the stereoisomeric The Diels-Alder reaction of truns-2-phenylethene-1-sulfonic acid derivatives with cyclopentadi- 3,6-methylene-l,2,3,6-tetrahydrophthalic acids. ene forms a mixture of stereoisomers -1and B. The endo-cis form VI11 is known to give the bromoThe percentage of endo-sulfo isomer (B) was deter- lactonic acid IX,6while the trans isomer X forms a mined quantitatively by bromosultonization in neu- different bromolactonic acid XI .6,7 Bromination tral aqueous solution.2 I n an extension of this of the exo-cis-acid XI1 has been reported to give study to trans-cinnamic acid derivatives, bromo- only a poorly characterized mixture.x The anhylactonization was found to be inapplicable, since dride of XI1 has been brominated in non-polar solnot only did the endo-acids I form neutral bromo- ventsg-" to form dibromides, while the exo adducts lactones as expected, but also the exo-acids I1 of furan and maleic anhydride or maleic acid have formed neutral material as well as the expected been brominated in aqueous solution. l 2 , I 3 1Vhen acidic bromination products. In the present paper, we brominated XI1 in aqueous bicarbonate meit is demonstrated that some exo-bicyclo [2,2,1]-5- dium, the bromonortricyclenecarboxylic acid XI11 heptene-2-carboxylic acids are converted in part t o was formed in 22-3G% yield. Eoth XI11 and its bromonortricyclenes by bromine in aqueous bicar- amide exhibited strong infrared absorption a t 12.2bonate; a minor amount of rearranged bromolac- 12.5 p ; it has been shown previously that nortricyclene derivatives exhibit strong absorption in the tone is formed in some cases. Acrylic acid adds t o cyclopentadiene to give pri- 12.0-12.5 p region.".'? The structure of XI11 was established by reductive dehalogenation to the marily endo-2,5-methylene-l,2,5,6-tetrahydrobenzoic acid (111) contaminated by the exo isomer IV.4 known solid nortricyclene-3-carboxylicacid (XIV) The percentage of exo isomer may be increased by which was identical with an authentic s a ~ n p l e . ~ alkaline isomerization of the endo-methyl ester, fol- A second product was a bromolactonic acid which lowed by saponificati~n.~In the present work, it was neither IX nor XI. It was identified by reducwas found t h a t the isomerized acid was a mixture tive dehalogenation t o the known lactonic acid containing about 6070 exo- and 40% endo-acids. XP, identical with authentic samples prepared in Pure exo-acid could not be obtained by crystalliza- two different ways. The structure XVI is consisttion of the mixture, but after removal of the endo ent with these observations. contaminant as the iodolactone by treatment with The remainder of the bromination product of XI1 iodine in aqueous bicarbonate s o l ~ t i o n ,the ~ ex0 was a mixture of stereoisomeric dibromides and isomer was readily crystallized in pure form. The bromohydrins, judging from the neutral equivaiodolactonization did not affect the exo-isomer, lents. These were not investigated in detail. hence it was possible to show t h a t the original The exo-carboxyl adducts I1 of cinnamic acid a i d crude endo-acid was about 7.57, endo and 2570 exo. p-nitrocinammic acid with cyclopentadiene were The known4 bromolactone Va formed readily prepared from the mixed adducts bv removal of the from I11 in 74'34 yield. However, when the pure endo isomers by iodolactonization. They formed exo isomer IV was brominated by the same pro- the corresponding nortricyclene derivatives XVII cedure (aqueous bicarbonate), the acidic bromohy- in about 65yoyields when brominated in bicarbondrins and dibromides were accompanied by 3-bro- ate solution. Both exhibited characteristic nortrimonortricyclene VI and a rearranged bromolactone cyclene absorption in the 12-12.3 p region. They Vb in respective yields up t o 8 and 6y0. The acidic were accompanied by acidic dibromides and 'or material was usually glassy, but in one case a pure bromohydrins. crystalline bromohydrin acid (VI1 or an isomer) Discussion was isolated. The structure of VI was proved bv comparison with an authentic sample. The identity The nortricyclene system is not well known. I t of Vb was inferred by its non-identity with Va, by has been formed by the action of N-bromosuccinithe similarity of its infrared spectrum and that of (1:) K. Alder and G . Stein, A n n . , 6 0 4 , 217 (1933). Va, and by analogy to the case considered below. i 7 ) H. Kwart and L. K a p l a n , T H I SJ O U R N A L 1 ,6 , 4078 (1054) (1) E a s t m a n K o d a k Fellow, 1953-1954. Abstracted from t h e Ph.D. Dissertation of C. D. V . , University of Michiqan, 195.5. (2) C. S. R o n d e s t v e d t , Jr., and J C W y g a n t , T H I S J O U R N A L , IS, 5785 (1951); J . O u g . C h e w . , 11, 975 (1952) !3) C S Rondestvedt, J r , a n d C . D F'tr Nuiiy '1 tiis Jounh.AL, 11,
iii press I l 0 . i . i l . ( 4 ) I I> R'ibercs, 1.: K. 'l'runilmll, I r , \Y. Beuliett ant1 I A i
(8) Reference 6 , p. 230. 19) H. K w a r t a n d L . Kaplaii. THISJ O U R ' V A IS, L , 3356 11953). 110) D Craig, ibid, 1 3 , 4881) ( 1 Y 5 l ) (11) la) P. D Bartlett and .4.Schneider, i b i d , 68, t i i l Y 4 f i ) : J . h Berson, i b i d , 1 6 , 5748 tlY5.I) 1121 R B. n'oodward arid H h e r . i 6 i d . IO, l l ( i l , 1 4 4 8 ) . ( 1 3 1 I A Brr\im and K S w i d l F r , ihi,! , I S , 1721 I I!( 4Ot;ll (l4:J.); J . A. ,Bervm, ~hic/, 1 6 , .IC109 f l S T , 4 ) tI-11 Ii I5 c r h u v , r \ r r ref I d for d , a ~ u \ a i o nof hnndrdncr I t ) Ii 1 1 d d d ~ t n r ~ b , IJJ I\ i l d r r - 1 ~ 1 1L ~ I C I U 4 u n 615 Isti i l Y 3 ; ) 626 183 1V.wJ)
FORMATION OF NORTRICYCLENE
July 5 , 1955
formation, and (4) the exo location of the carboxyl group would prohibit lactonization. Further work will be necessary to confirm this assignment. The reactivities of halonium ions differ markedly. 9 bromonium ion, which forms bromolactone or bromonortricyclene, depending upon the carboxyl configuration, is evidently a much more energetic species than an iodonium ion, which can form iodolactone but not iodonortricyclene. This fact is of considerable value in separating endo and exo isomers and forms the basis of a convenient analytical method for mixtures of the twos3 We are extending this investigation to other electrophilic reagents18and other bicyclic systems in order to establish the scope of this ring closure. Experimental'
3555
(reported4 32.5-35'). T h e melting point !vas unchanged by another crystallization or by sublimation, but it was depressed strongly on admixture of 111. Anal. Calcd. for C8H1002: C , 69.54; H , 7.30. Found: C , 69.43; H, 7.29. exo-3,6-Methylene-l,2,3,6-tetrahydro-cis-phthalicAcid (XII).-The corresponding anhydride was prepared by isomerization of t h e endo-cis isomer as described by Craig'o; m.p. 1415-142' after three crystallizations (reported6,'0 142-143"). T h e anhydride was boiled with water for 15 min. The hydrate crystallized upon cooling; m.p. 147148" dec. (reported m.p. 148' dec.6f1iand 153-154' dec.'o), neut. equiv. 100 (calcd. 100). T h e hydrate lost its water when heated for 30 min. a t 0.5 mm.; the anhydrous acid melted a t 159-160" dec. (reportedlo161-162" dec.).
endo-2-Phenyl-3,6-methylene-l,2,3,6-tetrahydro-exo-benzoic Acid (IIa).-The pure exo-acid was prepared from t h e mixed Diels-Alder adduct by removing the endo isomer by iodolactonization.a
endo-2-p-Nitrophenyl-3,6-methylene-l,2,3,6-tetrahydro-
exo-benzoic Acid (IIb).-The pure em-acid was prepared endo-2,5-Methylene-l,2,5,6-tetrahydrobenzoic Acid (111). from the mixed adduct by removing the endo-isomer by iodo-A sample was prepared by t h e method of Alder20; b,pd lactonization.* Bromination of exo-2,5-Methylene-l,2,5,6-tetrahydroben121.5' (9 mm.), n26.2D1.4934 (reported' b.p. 118.5-120.5 (5.7 m m . ) , T Z ~ ~ 1.4931). D -4 sample was recrystallized zoic Acid (IV).-In a 300-ml. 3-necked flask, 9.60 g. (0.07 several times from petroleum ether (30-40') by cooling in mole) of IV was neutralized t o phenolphthalein with sodium hydroxide solution, and 100 ml. of 5% sodium bicarbonate D r y Ice; m.p. 45.7-46.2' (reported m.p. 39OZ0and 44.145.0'4). A sample of the distilled adduct before crystalli- solution and water were then added to make a volume of zation (12.50 g., 0.0905 mole) was treated with iodine in about 250 ml. Bromine, 11 g., was added with vigorous aqueous bicarbonate solution,6and it formed 17.67 g. (74%) stirring until a tinge of yellow persisted. T h e mixture was cloudy with some insoluble heavy oil. I t was extracted with of oily iodolactone; the aqueous layer upon acidification deposited 2.91 g. (23%) of crystalline exo acid. Roberts4 three portions of ether, and the extracts were dried with calreported t h a t the crude adduct contained 10% exo isomer cium chloride and evaporated a t reduced pressure. T h e t a n oil, 0.65 g., slowly deposited 0.17 g. of solid ( V b ) which on the basis of infrared analysis involving the impure "exo" was collected and washed with petroleum ether (60-75'). isomer as a reference compound. The known bromolactoiie was prepared from crude endo- T h e residual oil obtained from the filtrate and washings was largely 3-bromonortricyclene ( V I ) (crude yield 0.48 g., acid by bromination in aqueous bicarbonate solution. After crystallization from petroleum ether (60-75'), it 4%). After two distillations, b.p. 70-71" (18 mm.), n2lD 1.5220 (reported4 b.p. 70-74.5' (19 mm.), n Z 51.5269). ~ melted a t 67.5-68.5' (reported4 64.8-65.9'). T h e yield was 56y0 based upon total acid, 74% on the actual endo T h e infrared spectrum of this material and t h a t of a sample of VI prepared by N-bromosuccinimide bromination of norcontent. bornylene4 were almost identical, except that a weak hyexo-2,5-Methylene-l,2,5,6-tetrahydrobenzoicAcid (IV).droxyl band was present in the former spectrum, indicating The crude acid was prepared as described by Roberts,4 b.p. 77" (0.3 mm.) (reported, 103.5-104° (22 m m . ) ) . I n a sepa- that some hydrolysis had occurred. Carbon-hydrogen ratory funnel, 55.6 g. (0.403 mole) of crude acid was neu- analysis reinforced this belief. Highest purity could not tralized with 10% sodium hydroxide solution. Then 10 g. be obtained with t h e quantities at hand. T h e above solid (bromolactone Vb, crude yield l.l%), of sodium bicarbonate was added, followed by excess iodine solution (about 300 ml.). T h e dark oil was extracted with was dissolved in ethyl acetate and diluted with petroleum ether (60-75") t o give white crystals, m.p. 8'7.5-88.5'. three portions of ether, and the ether extract was washed with 10% sodium thiosulfate and dried over calcium chlo- T h e melting point was raised t o 89.0-89.5' by a second ride. T h e ether was evaporated (the last traces a t 20 mm.), crystallization. This melting point was depressed to 40leaving 44.6 g. (42yo) of yellow iodolactone which solidified 55" on admixture with Va. Anal. Calcd. for CsHoOzBr: C , 44.26; H , 4.18. Found: on standing. The crude yield in a duplicate run was idenC, 44.43; H , 4.20. tical. I t was recrystallized by dissolving in ethyl acetate, T h e aqueous layer after the original ether extraction was treating with Norit, and diluting with petroleum ether (6075"). White crystals formed on chilling; m.p. 58-59", un- acidified and extracted continuously with ether for 24 hr. After drying and distilling the ether, the residue was 13.5 g. changed after a second crystallization. of a light brown glass, neut. equiv. 261 (calcd. for bromoAnal. Calcd. for CsHgOd: C, 36.39; H, 3.44. Found: hydrin, neut. equiv. 235; for dibromide, neut. equiv. 298). C, 36.63; H, 3.51. I n other experiments with pure IV, the yields of VI were T h e aqueous layer from the iodolactonization was treated high as 8% and of Vb as high as 6%. When crude with 10% sodium thiosulfate solution, acidified, and ex- as IV (the 60:40 mixture) was brominated, the yield of VI tracted with three portions of ether. The ether was washed varied from 1.5-4%. Vb could not be isolated, but Va was with water arid 1% sodium thiosulfate solution, dried with found (30-33% yield based on crude IV, 7 5 4 2 % based on calcium chloride, and evaporated. T h e crude crystalline the 40% of I11 actually present in crude 1 x 7 ) by distillation acid (34.0 g., 61%) was distilled, b.p. 89" (0.25 mm.) (re- of the crude oil followed by crystallization from ethyl aceported4 b.p. 103.5-104° (2.2 mm.)). T h e product was tate-petroleum ether (60-75'); m.p. 67.5-68.5", undccrystallized from petroleum ether (30-40') by cooling in a pressed by a sample (m.p. 67.5-68.5", reported 64.8Skau tube in Dry Ice. The white solid melted a t 44-45O 65.9") prepared as described by R o b e r t ~ . ~ I n one experiment with crude IV, in which the aqueous (18) X I . Gates and S. P. Xlalchick, THISJ O U R N A L , 76, 1378 (1954); layer was acidified carefully and allowed t o stand, a crystalH. hl. \Vdlhorsky a n d D. P. Loncrini, ibid.,7 6 , 5397 ( I Q a 4 ) ; H. K w a r t line product, m.p. 125-127', separated. After two rea n d W. G. Vosburgh, i b i d , , 7 6 , 5400 (1931). These workers have crystallizations from ethyl acetate-petroleum ether (60studied hydroxylation. a n d have observed rearrangement. Perhaps 75'1, it melted a t 132.5-133.0'. T h e yield was 13.8% I V and X I 1 will form nortricyclene derivatives upon t r e a t m e n t with a based on crude IV, 23% based on the SOY0 of pure IV acperacid. tually present, if the structure is assumed to be bromohy(19) hlicroanalyses b y Anna Griffin, University of Michigan, b y &in VI1 or a stereoisomer. Spang hlicroanalyticfli I,ahoratory, Plymouth, Mich., and MicroAnal. Calcd. for Ca€illO:,Rr: C, 40.87; 11, 4.72; neut. Tech Laboratories, Skokie, Ill. Melting points are uncorrected. I n equiv., 235. Found: C, 40.72; H , 4.67; neut. equiv., frared spectra were taken on a Perkin-Elmer model 21 spectropho23.5. tometer as capillary films or at; X i i j o l miill.: (for solids) ; w c are indehlcrl t o Masao Yoshiiniiic f o r ohtainiriK the ciIr's.c\ Bromination of i~.\-o-3,6-Methylene-l,2.3,6-tetrahydro-~i~(20) K. Aldcr, ci i i i , A u > L , ,614, 1!17 (1931). phthalic Acid (XII).-lti :I 30~1-111l.:j-~iecliccl f l : t k , 5.Oo
35XG
CHARLES D. VER Noov
AND
CHRISTIAN S . KONDESTVEDT, JR.
g. (0.025 mole) of X I 1 monohydrate was neutralized to phenolphthalein with sodium hydroxide solution; 2.0 g. of sodium bicarbonate and water t o make 200 ml. were added. With vigorous stirring, 4.0 g. of bromine was added dropwise. The exothermic reaction was terminated when a tinge of yellow persisted. The clear solution was acidified slowly with dilute hydrochloric acid and allowed to stand in the refrigerator. The oily solid crystallized, m.p. 120-200". It was sublimed at 100" (0.1-0.5 mm.), giving a white solid ( X I I I ) , m.p. 121.5-123.5', in yields of 22-36%. ( I n one experiment, the pure acid separated during the acidification in 30yo yield.) Two recrystallizations from ethanol-water gave white plates, m.p. 123.0-123.5". I t s infrared spectrum showed strong absorption at 12.20 and 12.55 p . Anal. Calcd. for CsHgOZBr:C, 44.26; H , 4.18; neut. equiv., 217. Found: C, 14.19; H, 4.31; neut. equiv., 216. The amide was prepared by refluxing the acid with thionyl chloride and pouring the mixture onto ice-cold concd. ammonium hydroxide solution. The solid was recrystallized from ethanol-water and benzene-petroleum ether (60-75") as white plates, m.p. 117.0-117.5". The infrared spectrum had the characteristic absorption a t 12.25 p . A n d . Calcd. for CgHloOSBr: C, 44.41; H , 4.79. Found: C, 44.46; H , 4.66. The bromo acid XI11 (1.0 g . ) was hydrogenolyzed by stirring under hydrogen with 4 g. of sodium carbonate, 3 g. of fresh Raney nickel, and 75 ml. of water for 15-30 min. at room temperature. The mixture was acidified and extracted with ether, giving 0.5 g. of oil which, after sublimaThis product was identical with tion, melted at 51-53'. 3-nortricyclenecarboxylic acid2I as shown by mixture melting point and comparison of the infrared spectra. The residue from which XI11 had been sublimed varied in amount and melted over a wide range (190-235'). In one run as described, 1.36 g. (25y0) of XI11 was obtained as sublimate, and the crystalline residue weighed 2.32 g., m.p. 190-235", neut. equiv. 171. Continuous ether extraction of the aqueous solution from which the crude acid had been filtered produced a n additional 2.36 g. of a colorless glass, neut. equiv. 19.5. These by-products are thought to be mixtures of dibromides (neut. equiv. 171), bromohydrins (neut. equiv. 140) and bromolactones (neut. equiv. 261). I n one experiment with 0.15 mole of X I I , 12.0 g. of acidic material separated from the acidified solution. The solid nortricpclene derivative was isolated by sublimation. The aqueous solution was concentrated, and 1.1 g . (3%) of crystalline rearranged bromolactonic acid ( X V I ) separated. The analytical sample was crystallized from methanolwater, m.p. 212.5-213.0'. I n another run, the yield of XVI was 11%. .Inul. Calcd. for CgHsOaSBr: C , 41.40; H , 3.47; neut.equiv.,261. Found: C,41.30; H,3.56; neut.equiv., 261. Authentic X I was prepared from trans-3,6-methylene1,2,3,6-tetrahydrophthalicacid ( X ) by bromination in bicarbonate solution. The white solid (from ethyl acetatepetroleum ether (60-76") or hot water) melted at 183.,i184.5' (reported 186'), neut. equiv. 256 (calcd. 261). It depressed t h e melting point of XVI t o 162', and the infrared spectra have many differences. No nortricyclene derivative was found. Authentic I X was prepared from the endo-cis isomer VI11 (m.p. 191-192" dec., reported 178-17906 and 193-194°10) by bromination in aqueous bicarbonate solution. I t melted a t 158-160O after vacuum drying (reported 157°,6 155.5l.i707), neut. equiv 263 (calc:. 261), and it depressed the melting point to XVI t o 140 . The infrared spectra were different. KOnortricyclene was detected. Hydrogenolysis of the bromolactonic acids I X and XVI (21) A sample was kindly furnished h y Dr. John D . Roberts.
Vol. 7 ;
in aqueous sodium carbonate with Kaney nickel as described above produced the same lactonic acid XV, m.p. 19R.5-200.5°, which was identical with a sample prepared by lactonization of VI11 as described by Alder arid Stein; m .p. 199.5-200.5' (reportedz2203' ). I n one experiment, the crystalline residue ( m . p . 190-23.j0) from the sublimation of X I I I , 1.15 g., was refluxed for 2 hr. with acetic anhydride. The mixture n a s evaporated a t 20 mm. to remove volatile materials. The residue was dissolved in ether and extracted with two portions of sodium bicarbonate solution. The aqueous layer was acidified and evaporated in an air jet, giving 0.35 g. of XVI, m . p . 209-211'. The ether was evaporated and the residual oil was dissolved in 50cc aqueous acetone and warmed on the steam-bath for 2 hr. After treatment with S o r i t , the solution was evaporated, giving 0.85 g. of white solid, softens at 210", decomp. about 240". After tlvo recrysobtained 0.3 g. tallizations from water-ethanol, there $%-as of a white solid, m . p . 255-256' dec., possibly an acetoxybromobicyclo/2,2,1] heptanecarboxylic acid. I t was 1-ecovered unchanged after boiling with dilute acid. S o acidic products were formed upon attempted deacetylation by treatment with excess tetraisopropgl titanate. It was not investigated further. A,nal. Calcd. for C11Hla06Br:C, 41.14; H , 4.08;neut. equiv., 321. Found: C, 41.06, 41.20; H , 3.44, 3.59; neut. equiv., 269. Bromination of cndo-Z-Phenyl-3,6-methylene-l,2,3,6tetrahydro-em-benzoic Acid (IIa).-In a separatory funnel, 2.14 g. (0.01 mole) of I I a was neutralized with sodium hydroxide solution, and 10 mi. of Sc,;', sodium bicarbonate solution was added. Then I .6 g. (0.01 mole) of bromine it1 water mas added until a faint color persisted. The precipitated oil was extracted with ether, and the solution was dried with calciu*ii chloride and evaporated. The residue, 1.63 g. (64y0), of crude, oily solid XVIIa, was crystallized by dissolving it in ethyl acetate, treating with Korit, and diluting with five volumes of petroleum ether (30-40°). Upon cooling in Dry Ice, white plates separated, m.p. 5253", unchanged by a second crystallization. The infrared spectrum of pure XVIIa showed prominent ahsorptions a t 12.20, 12.40 and 1 2 . 3 p . Anal. Calcd. for C13HI3Br: C, 62.66; €I, 5.26. Found: C, 62.62; H , 5.22. The aqueous layer was acidified and ertracted with ether. After drying and evaporating the ether (100' (20 m m . ) ) , 1.03 g. of a dark glass remained, neut. equiv. 33.7, 300 on different samples. It is probably a tniiture of dibromide (neut. equiv. 373) and bromohydrin (neut. equiv. 310j. Bromination of endo-2-p-Nitrophenyl-3,6-methylene1,2,3,6-tetrahydro-exo-benzoicAcid (IIb).-In a 40-nil. centrifuge tube, 0.568 g. of I I b was dissolved in about 2 ml. of ethanol and neutralized with sodium hydroxide solution. Then 10 ml. of 5 5 sodium bicarbonate solution and 5 ml. of water were introduced. Bromine water !\-as added until a faint yellow color persisted. The light yellow precipitate neighed 0.421 g . (66c;), m.p. 116-118'. After recrystallization from methanol-water, it melted a t 118.q5-119.00. A 72yo yield of XVIIb \vas obtained in another run. Its infrared spectrum exhibited prominent absorption at 12.4 p . Anal. Calcd. for C13HI?O?SBr: C , 3.08; IT, 4.11; Y-,4.76; B r , 27.1'7. Found: C , 53.08, .:2.XI; H , 4.21. 4.07; ?;, 4.89; Br, 27.34. The aqueous filtrate \\--asacidified and extracted twice Lvitli ether. T h e extract was dried and evaForated (100° (20 nun.)), leaving 0.222 g. of a yellowish, glassy solid, n e u t . equiv. 335 (calcd. for bromohydrin, 3 5 5 ) . h
N
ARBOR,MICHIGAN
