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A novel stereochemical control
A NOVEL STEREOCHEMICAL CONTROL
As a con
of shtdks
related I0 Ibe bromo-
came under scrutiny. We feel that the work report4 here adds a third facet to the understandbqt of the bomane framework,the other two beii, the weti studied eiectrophik acceptance of 2-bomene-24 (II) or its salts to cxmphor-which preferentially takes ml exe course2 &B-o-S(IV) was ppepared in 55% and the thoroughly documented cmuse of addition of nu&opliiles to can&&or 0 which shows ml snso yields from camphor oxime (V) and hypobromi&.’Our work as well as that from x-ray auidysis‘ have ~~~.3~s~~a~~)~a variety of bus lwc&-entiy accepts If+ and Br+ ~~~~~~~~0~~~. from the bxo side has emerged from the present study. The form&on of IV demonstrates a clear preference to theexoacceptanceofBr”bytheiatumedi&Va.
kX=HorNa Va
IV 2-~~~~~~~~~
by sodii borohydride reduction of XV that involves the qumcbiag of the &mate 1(X= Naj witb liydroxybuniae hy&tchMk.* Tbe’preference is for 811 QD proton ~*~~~~ contain& I(x=Na).was poured onto bromiae water. The PncipitaM so&i was &own to be exchmivety 2. ~brom*2emfo nitrobomane IV (IR, NMR). titative yields
Until 1%7it was gene&y believed that substitutionin bomanes would show an endo preference due to the sbkldbu i&ence of tk c7-gemdimethyi gMlps? In$ieedtbisconceptwassodl!eplyentR&dthat ~k~~t~~w~n~~~ camphorwas sbowa to cxcbangeachy Gl-0:T&e ~y~~~~a~~~t~ ~~a~~~~~ pbiieaccep&nccfortypeIIsyatmll8.Thevkwwas&o expressed that this effect k inc4mHqlmntialfor processes iavofviae the gt!lm&n
or de-
of em 9r 3I28
Under unequivocallyhinetic conditions also the preference is for the formation of &-2-m-. Thus, the potassium salt 1(X= K), pmpared using shit excess of KOtBu, was poured onto 3NHdiOJ and then extracted with ether. careful anldysis of the reaction mixture showed that the product was ado 2&trobornane (VI).- In another ex~~ the potassium sah was poured onto bromii water. The p&p&ted product was 2-exe ~rn~2-~-~~ bomane (IV). Nip of camphor oxime with fuming HNOl is reported to yield 2-zdinitrobornanc m-p. 107”.”To our surprise the reaction gave a 37% yield of camphor nitrimiue (Xl and a 7% yield of VII m.p. 21C! The structural assignmentfor VII is fully supported by spectralandanalyticaldata.
VI
,o- K*
k(.)_
x 37%
Iv
No,
+ Lzi+
‘NO b?
The mdo assigmncnt for VI is supported by its NIUK spectrum.” Further, on hydroget&n VI furnished VII 7% bomylamine. It appears that of the two possible 2. Hydrogenolysis of VII, gave as the sole isohtble nitrobomanes. the end0 isomer enjoys thermodynamic preference. This is brou&t out with the exchtsive product, in 66% yields, endo nit&ornak (VI). There formation of 2-e&o nk&xmme (VI) in 32% yields was no evidence for the forinatiou of any of the isomeric from IV with ethan&c KOII.
w
VI
VI
In a novel etfort to discern preferences for the tic ~(1)~2-~~~~h~~ of2~~~s~~*It~~o~~ gem dinitro us undeqo rapid hy~ys~ at normal pressure to giwe nioskonib compollllds. The
reduction viTtuauy stops at this St@@alld led? to
hineticany co&rolled @oducts as exetuplihed whh the VIII4IX change.‘z
VIII
Wer~~~y~c~ basis of active ~ function.
IX
onthe of the mueduced nitro
We believe that the VII+VI change constitutes an elegant ~0~s~ of preference for kinetic 40 proton acceptance. Keactiotlof bornaue’4*‘Jwith dik HNo3 in sealed tube ~~n~~~~2-~‘6In~ hands, however, the reaction was found to lead to a complex mixture” containing n&o and carbonyl functions. The only pure compound that could be isolated was errdonitrobornane.The isolation of VI was not entirely unexpected, since the reaction most prob ably proceeds via I. Thus, 2+x0 nitrobornane remains elusive.
pmduct-like tgatmitiott state wber&t t&n&ant bond formationwith the ekbophile occur8 only when the mlcleophilicc-* centre has c-e s-cb which w&d place the Ssubstitucntin a progressively
matmid was s~poseble with that of 2-exe-bromo_2+rdonitrobmuane, prqmred fran cmphamiie with potassium hypobmn&:furthsr~theNlURwasakoidenticalwitbthatofan autbenticsampk.
finer descriptions‘may bc4avours cxo entry, and a start& materWike transitionstay an eMi substitu~n”~~~s~~~~~t invckvesag at 2 and 3 positions of bomanes
Isolorion of endo-2-Arn8togornaneIn a Parr hydrogenation qmamtu& a sok of 2-endo-nhtwcamphanein BtGAc (0.28Og, oAol~ntole,2oml)~b~ovarpt4catetystatan ~~~~~~~~S~,~rnk~~%~, ~~~E~~~~~~%~ evaporated to give 0.128Og(71%)uf essentially pure bomylamine. IR: v,, (CHU,) (em-‘): 330&3150(NH, due to hydrogenbmrdi@. Ne w 6.88(broad -NH&cxcbangnd in D@), 342 (do, non_bndsrbsrd tqotou), 1.86(s. C-CH& 8.91 (s, C-CHk 6 protons).
c&d bo ex@&tod ott this basis.
To a mechanicallystirred soIn of NaB& (2.711;0.0713mole)in MeGIi: water (7MJ; SOml).warmedwith hot water. was introdueed a soltl of bromotdtrobomane’(3.51; 0.01335mole) in h&M (17.SmB.At t%st.a few droos wem added czawhslv. ~~~~~~~~~~, causing the &OH to dux. subsequentlytbe remainkg sok was intrwdd rapidly. After additionalt&ring for 3 hr at room ~p.~rn~~w~rn~~y~by~~ KOHaq,and steam distiikd to remove most of the &GIL The
Reaction of IV w&huhondic
KOIi
J,rolor& of 2endo &obontsne (VI). An aqueoussob of KOH (I a, amount of waterwas addedto -. O-018mok) in ~~ a sob of bomonikw@mw
(Sg, aOl~mok)
in EtoH
(12.5ml). The mixture was rethtxedon a water bath overnight, concentmU diluted witb watar and steam distilled.Crystals of 2~~~. accumtdatedon the wails of the condenser ware co&cted and dri& yieki Llg (32%); m.p. 1cT (lit.‘* 14614m. IR: viu (KBr) (cm-‘): 1545@I@,asym.), 180 @It&, tilktion. ‘Dm2-eado Nitrobuman~crysta&wI on the walls of ;yn&86S CC+ NIUk &-: 4.62 (i8da8ned tnpkt, I= non-bnlgeh#d t-proton), 1.08(s. C-CH,), 0.93 (s, Cthe condansar and was collected and dried; yield 1,758 (92%) m.p*1m @it.146-147q.‘9Tic singk spot (JQ: 0.7 m 0.6 d& 6 ;tons) 2 2-~~~ (VII).To a hand stirred sobt of camphoroxBenxene:hexane 1:l) IRz a+w&IiC!U(cm-‘): II45 (I$&, asym), 1388(NOI, sym.), 865 (C-N). NMR: i&r,): 4.65 (ii &fined hue (log, O.obmok)in gkciai AcGH (150ml)was added pure triplet. J = 7.50Hz. nonbridgebead t-proton), 1.10 (II, C-CHs), fuming HN4 (dlml, sp. g. 15ooo)in the absence of direct liit After 10mitt, water (508ml) was added and the blue ppt 0.976. C-C&, 6 protons). An diquot after NaBH4resction was addedto excess Br-water colkcted. wasbedliberallywith water and exposedto air for 8 hr and 3~~~~ drkd in vacumn; yiehi. 7.5g; m.p. 86-959,The ~~~~~~W~W~~~~ over SiIii gel 08g). I&to give sampieidenticalin aRrespects (tk, IR and NMR)to that crude pmduct was ~~~ tkn with benzene: hexane (2.5:75)gave pure 2&linitrobomane; of authentic 2.era-bromo-2-endo-nitmbornane. yiald, Log (7%); m.p. 21+ (sealed capill) (lit. 107.S-188.5@)~‘s TJXz Situ& spot (Jf,: 0.79, banxmmzhexane (1:l)). hound: c, Acid qrmoc&g of poressiam~~C*2-~~ (M,Wt.Zzs): C, JsoMox of VL To a stirtnd soln of t-BuGK in dry t-B&M 52% H. 730; N, 1240. Celc. for Cafe, l~(N~~yrn.), (0.6868g, 0.80535mok 2 ml) was added a sok of 2-emfo-nitro. ~H,7.01;N,122896.IRp,,(RBrfIcgi^’): 1.3o.1.03,0.%!@, bomane, in t-BuGH (0.9159op. 0.80.5mok, 1ml). After an ad- 1365(NCh.sym.),848CGN). NlUk I-: C-CH~. ditiomdOJhrofstirring,themixturewaspouredonto3N Further ektion using benzene-hexane (MO) gave materiai IIsSG, (loomi). The mixture was extmeted witb ether, the which was su~~n~~ identilkd as c~p~~~, yield: ~~~WaS~~~~~~U~~~,~ Of&Od and cvapomtcd and the crude product chromatographed 4.5g (37%).TLC: Singk spot (J&:0.65,knxene: hexane fl:l)). 00 silica. Ehttion with petroleum ether, benxeae IE9o:lO) gave W: v, (neat) (cm-‘): 1648(CaN), lJ78 (NO, asym.). 1325 unchanged 2.end&nitrobornane. One of the early fraction (NOS.sym.).NMR: &~a,: 1.86,1.80,0.91(s, C-CH,). IR and NMR spectraof this samplewas identicalto thatof an contained traces of isomer as evidenced by the presence of a 1570cm-’ in additkmto themajorbandat 1540an-’ attributedto authentic sampleof c~~~~. N4 asymof thestartiq material. Reactionof potadtn
bomoas-2-nitnnterew& bmminr-wohu Jsolerion of IV. To a stirred sok of 2-~-~ (0.9138.0805 mole) in drv t-BuGH (15ml) was added subRmed t-BttGK (0.728Og,~.~jrnok~ After additiomdujhr stirring the mixture was poured onto Br-water(3g, 0.019mole, 188ml), the precipitatedcrude bromonitrobomanewas collected,washsd with water and dried: yield, 1827Og(66%). The IR of this
Hy&vgwwlysis of 2&aWtmhomane
IsoMua of VI. In a semi-microhydrogenationset-up a soln of diniiboraano in EtGAe (0.132&b0.088378mok, 38ml) was ~~~a~~~~~~~~~(lOrnl) ~~rH~~~~t~~~~~~too~ nitro group was consumed in fmin. The mixture wss twice filtered.wasbsd thoroughlywith EtOAc and evaporatedto give 0978Og(66%)of c&e 2-e&-m, cryst&mion from hot aqueous EtGH gave 0.05888of pure product; m.p. 146-F (lit.” M-7?. T&n was no evidencefor the formationof anvI of the isomerk 2-exe-nitrocamphane. TIC: Single spot (RI: 0.52, benxene: bexane (MB. IR: vnu (CHCI~(cm-‘): lSS0(Not, nsym.), 1378Ox, sym.).865(C-N); ~~ on that of the 2~0~~~ obtainedby ~~~~~0~~~.
%.psweretakenon a Fisher-Jobn melting point lppurtus and are uncorrected. Capillary m.ps were tahen in a Thomas Hoover capillary melting point apparatus. IR spectra were recordedeither on a Per&Elmer 708or 137or Perhin -Elmer 521 ~~~~. NMJt spectra wcn detem&& with CIICI~drICck sohttionson a Vatian-A60w MODspsctrometer using TMS as internal standard. silica gel G (Stabi)with calcium sulfate bii was used for tic. Mumu chromatogtnphywas Ac&wl&emw#s-We are most grateful to Dr. Nityanandand ~~~~wi~~~~~~~~~ Ib. hf. hi. Dhar, CDRI, Luehnowand to Dr. S. Rajappa,CUBA, repormd here, are optically bmctive. Whemver possii, the Bombay for providing spectai facikks. &an&al assistance reactionswere monitoredby tic. from CSIR, New Defhiis grataftdlya&nowkdged.
S. RhueAuATHAuerel.
3132 umwNcE8
‘S. Ranganathanand II. Rantan. Tefmbed~ 38.63 (1974). ‘A. P. Thomas and B. Willhahn. Tetmhedmn Letfers I309 (1965): A. F. Thomas, R. A. Schneiderand J. Meinwakl. 1. Am. C/rem. Sot. g9.68 (1%7); M. Lipp and D. Bernstein, Nafurewirsmscbeffat 42. 378 (1955): Chem. Abstr. 51. 11293 (1957): E. Avela, Ann. Aced. Scieul. Fennicae,Srr. AH, No. 77. p. 84 (1956). Cbem. Absfr. 51. 10430 (1957): 0. C. Joshi. Ph.D. Thesis, University of Western Gntario. Can& (1968). ‘P. J. Ma&en, S&omen Kern.. Us, 250 (l%2) Cbem.Abrtr., 51. II404 (1963): 0. A. Nyman and A. M. Kuvaja. Amt. SJI. I8 (1939): J..M. Coxon. hi. P. Hartshorn and A. J. Lewis, Cbem. & lnd.. I I45 (1970); P. hf. L. Capmau M. M. W. Chodkiewicxand P. G&t Tetmhedfvn Letters 1619 (1965): L Y. Bruysova, 1. Geu. Chem. USSR 9,905 (1939).Ghan. A&r. 34.404 (1940):
P. Lerivcrend and J. hi. Conia, Bull. SW. Chim. Fr. 2715
(1970): J. Gripenherg, Suomen Kern. 189. 53 (1945). Chem. Abstr. 41,739(1947); J. Houhen and E Pfankuch Ber. Dlach C&m. 0~. Uft 588 (l927k L. W. Trevoy and W. G. Brown, 1. Am. Chem. Sot. 71.1675 (i%9); D. S. Noyce and D. B. Denny, ibid., 72.5743 (1950): II. Toivonen. Ann. Acad. Scient. Furniroe. Ser. A.11. No. 72,49 (1956). Chem. Abstr. 52.2806 (1958): P. Hiijarvi. Ann. Acud. Scient. Fcnnicae,Ser. A. No. 81. I6 (1937). Cbem. Abstr. 52. II09 (1958): G. Russo and G. Ricea. Chin. Ind. Mifex 46, I85 (1964). Chem. Abstr. 61. 1914 (1964): W. G. Da&en. R. E. Boxak. R Fliss and I? Willey. Reu. Chbn. Acad Rep. Popvlaim Rownanine 1,803 (1%2) Cbem.Abslr 61. 4424 fl964k I. Wolinskv. D. R. Dimmel and T. W. Gibson. L 0;. ?himl.32.2087 (1967): W. Hue&l and 0. Fechtig. Ann. (62. 87 (1962): J. Susyko and W. 2. Antkowiak, Bull. Acod. Polon. Sri.. Ser. Sci. Chim. 13. 447 (1965). Chem. Abrtt. 64. 2131 (1966): S. Beckmann and R Mexgar. Chem. Ber. 89.2738 (1956): E. Avela. Ann. Acod. seirnt. ~euniacae, Srr. A.11: No. 77. 84 11956). Chem. Ab;fr. 51. 10438 (1957): T. Kuusinen, S~o&1’&~3lB. 358(1958).Chem. Absir. 15114(1959): A. F. Thomas and B. Willhalm. Tetmhedron titers 1309(1965): J. P. Freeman. Chem. & Ind. 1624 (l%l): J. Katsuhara. H. Yamasaki. K. Hashintoto and M. Kohayashii. Kogyo Kagaku Zesshi 79.1265 (l%7). Chem. Abstr. 68.2995 (1968): B. Kubota and T. Havashi. Bull. Chem. Sot.. laoan 1.67 (1926). Chem. Abstr. # 2487 (1926): G.-Vavon and P: Pcig&r.~C. R. Acad. Sci. Paris 181. 183(1925). Cbem. Abstr., 19.3267 (1925): M. tipp, and E. Bund.. Eer Dsch Chem. Ga. 68B. 249 (1935): T. G. Traylor and C. L. Perrin. J. Am. Chem. Sot. 88. 4934 (l%6). See however. I. N. Naxarov and M. S. Burntistrova.Zh. Gbsbchei Khim. 28 2173 (1950). Chem. Absfr. 0. 7061 (1951); L. F. F’ieser and G. Ourisson. BMIL Sot. Chim. Fr. 1152 (1953): E. Cuingnet. Ibid. 91 (1955): V. I. Esafov and N. I. Novikov, Zh. dbschchei Khim. 26.2758 ~~_~ (1956). Chei. Abstr. 51.7330 (1957): -__. _~~~ R. Golsc. C.R. Acad; Sri.. &II& 249.1912 (1959), Chem. Absfr. 51. 14297 (1960): W. F. Erman and T. J. Flautt. I. Org. Chem. 27, 1526 (1%2). 4.. . . . . . . A different steric situation prevails in the Camphane System where the exe face of the mokcuk is stronglyscreened by the gem diithyl group at Cr. As a result, this system is generally approachedby reagentsfrom the endo side.. . . . .“,
E. L. Eliil. Steruocbabtry of Carbon Compounds,p. 304. McGraw-Hill Book Co., Inc., New York (1%2). 5.6. . . . ..Thep~~nanofuohy~excharyeinthecrsc of camphor must re8ect the operation of some as yet unap preciatedsteric or stereoelectroniceffect, It takes an additional, although rqmewhat vicarious, interest hecause this apparently general tendency of hiiyclo 22.1 heptan-2.onesto suffer exe protonation in a group of reactions wlticb certahuy cannot involve carhoniumions mimiis the tendency of 2-hkyclo 22.1 heptyl carhoniumions to yield exe suhstitutedproducts. . . . .“. (Ref.2). 6p. V. R. Schleyer. 1. Am. Chem. Sot. $9.699 (1967): P. V. R. Schleyer. Ibid...89.701 (1%7). ‘F. A. Carey and H. S. Tremper. J. Otg. Chem. 344 (1969): C. A. Burton.C. O’Connor and-D. Wit&r. Ibid.. 32.2881 (l%7): R. Baker and T. J. Mason. Chem. Coins.. 120 (1969k P. D. Bartlett, G. N. Fiikes. F. C. Haupt and k He&es&. Act. Chem. Res. 3,177 (1970): A. 0. Davies and R. Tudor. J. Chem. Sot. B. I815 (l97Ok S. P. Jindall and T. T. Tklwell. Tetmhuimn bte& 783 (1971); J. M. Mellor and C. I? Webb. Ibid. &5 (1971); P. C. Moews. J. R Knox and W. R. Vaughan, X Am. cbau. sot. Ice, 268 (1978). ‘D. A. Brueckner,T. A. Hamor. J. M. Robertson and 0. A. Sii. 1. Chem. Sot. 799 (1962). b. C. Ililand and 0. X. Criner. 1. Am. Chem. Sot. 75. 4047 (1953). ‘s2-Bomans nitronic acid readily tautomerisespreferentially to the endo isomer (Toivonen. Heikki, &omen Kern.. B 1971. 44(2). 54-60, Cbem:Absfr. 7s. 6l2Oj (1971). “NMR data given in “experimental”.The endo nitm assignment is supportedby the appearanceof the hrklge methyls as a single peak. Additionally, in the case of 23diiitm homane.whereone of the nitro groups must he exe-these peaks are clearly separated. ‘J. R Bull, E. R. Ii. Jones and G. D. Meakiis, 1. Chem. Sot. 2681 (1965). I$. Mitchell and R. Gordon, Ibid. 853 (1936). “L. Wolf, Ann. 394.86 (1912). “It was felt that desulfurixation of 2&ornanon&iiketal will provide a very desirableroute to hornane.comparedto the one availabk, namely, the Wollf-Kishner reduction of hornanone under drastic conditions.The novel 2-homanonethioketal was prepared in 85% yields by refluxing for 30hr a mixture of camphor (6.0 g), ethane dithiol (I7 ml), PTSA (0.8~) in dry benzene (160ml). Filtration followed by evaporation and diitillation gave 7.7 g of the thioketal bp. 122V0.5 mm (NMR &a: 3.44-3.10 (m, 4H), 1.07, 1.02, 0.95 (CH,). Surprisingly the thioketal could not be desulfurixed. ‘?I. S. Nametkin, J. Phys. Chem. Sot. 47. 409 (1915). Chm. Absk 10.45 (1916). “For a similar observation see Ref. 10. IsThe fact that tautomerization of humane-3nitronic acids proceeds with equal stereochemical preference is in excellent agreement with this observation (see Ref. IO). “J. L. Siionson. Tire Terpenes. Vol. II, p. 436. Canthridge University Press (1957).
As a con
of shtdks
related I0 Ibe bromo-
came under scrutiny. We feel that the work report4 here adds a third facet to the understandbqt of the bomane framework,the other two beii, the weti studied eiectrophik acceptance of 2-bomene-24 (II) or its salts to cxmphor-which preferentially takes ml exe course2 &B-o-S(IV) was ppepared in 55% and the thoroughly documented cmuse of addition of nu&opliiles to can&&or 0 which shows ml snso yields from camphor oxime (V) and hypobromi&.’Our work as well as that from x-ray auidysis‘ have ~~~.3~s~~a~~)~a variety of bus lwc&-entiy accepts If+ and Br+ ~~~~~~~~0~~~. from the bxo side has emerged from the present study. The form&on of IV demonstrates a clear preference to theexoacceptanceofBr”bytheiatumedi&Va.
kX=HorNa Va
IV 2-~~~~~~~~~
by sodii borohydride reduction of XV that involves the qumcbiag of the &mate 1(X= Naj witb liydroxybuniae hy&tchMk.* Tbe’preference is for 811 QD proton ~*~~~~ contain& I(x=Na).was poured onto bromiae water. The PncipitaM so&i was &own to be exchmivety 2. ~brom*2emfo nitrobomane IV (IR, NMR). titative yields
Until 1%7it was gene&y believed that substitutionin bomanes would show an endo preference due to the sbkldbu i&ence of tk c7-gemdimethyi gMlps? In$ieedtbisconceptwassodl!eplyentR&dthat ~k~~t~~w~n~~~ camphorwas sbowa to cxcbangeachy Gl-0:T&e ~y~~~~a~~~t~ ~~a~~~~~ pbiieaccep&nccfortypeIIsyatmll8.Thevkwwas&o expressed that this effect k inc4mHqlmntialfor processes iavofviae the gt!lm&n
or de-
of em 9r 3I28
Under unequivocallyhinetic conditions also the preference is for the formation of &-2-m-. Thus, the potassium salt 1(X= K), pmpared using shit excess of KOtBu, was poured onto 3NHdiOJ and then extracted with ether. careful anldysis of the reaction mixture showed that the product was ado 2&trobornane (VI).- In another ex~~ the potassium sah was poured onto bromii water. The p&p&ted product was 2-exe ~rn~2-~-~~ bomane (IV). Nip of camphor oxime with fuming HNOl is reported to yield 2-zdinitrobornanc m-p. 107”.”To our surprise the reaction gave a 37% yield of camphor nitrimiue (Xl and a 7% yield of VII m.p. 21C! The structural assignmentfor VII is fully supported by spectralandanalyticaldata.
VI
,o- K*
k(.)_
x 37%
Iv
No,
+ Lzi+
‘NO b?
The mdo assigmncnt for VI is supported by its NIUK spectrum.” Further, on hydroget&n VI furnished VII 7% bomylamine. It appears that of the two possible 2. Hydrogenolysis of VII, gave as the sole isohtble nitrobomanes. the end0 isomer enjoys thermodynamic preference. This is brou&t out with the exchtsive product, in 66% yields, endo nit&ornak (VI). There formation of 2-e&o nk&xmme (VI) in 32% yields was no evidence for the forinatiou of any of the isomeric from IV with ethan&c KOII.
w
VI
VI
In a novel etfort to discern preferences for the tic ~(1)~2-~~~~h~~ of2~~~s~~*It~~o~~ gem dinitro us undeqo rapid hy~ys~ at normal pressure to giwe nioskonib compollllds. The
reduction viTtuauy stops at this St@@alld led? to
hineticany co&rolled @oducts as exetuplihed whh the VIII4IX change.‘z
VIII
Wer~~~y~c~ basis of active ~ function.
IX
onthe of the mueduced nitro
We believe that the VII+VI change constitutes an elegant ~0~s~ of preference for kinetic 40 proton acceptance. Keactiotlof bornaue’4*‘Jwith dik HNo3 in sealed tube ~~n~~~~2-~‘6In~ hands, however, the reaction was found to lead to a complex mixture” containing n&o and carbonyl functions. The only pure compound that could be isolated was errdonitrobornane.The isolation of VI was not entirely unexpected, since the reaction most prob ably proceeds via I. Thus, 2+x0 nitrobornane remains elusive.
pmduct-like tgatmitiott state wber&t t&n&ant bond formationwith the ekbophile occur8 only when the mlcleophilicc-* centre has c-e s-cb which w&d place the Ssubstitucntin a progressively
matmid was s~poseble with that of 2-exe-bromo_2+rdonitrobmuane, prqmred fran cmphamiie with potassium hypobmn&:furthsr~theNlURwasakoidenticalwitbthatofan autbenticsampk.
finer descriptions‘may bc4avours cxo entry, and a start& materWike transitionstay an eMi substitu~n”~~~s~~~~~t invckvesag at 2 and 3 positions of bomanes
Isolorion of endo-2-Arn8togornaneIn a Parr hydrogenation qmamtu& a sok of 2-endo-nhtwcamphanein BtGAc (0.28Og, oAol~ntole,2oml)~b~ovarpt4catetystatan ~~~~~~~~S~,~rnk~~%~, ~~~E~~~~~~%~ evaporated to give 0.128Og(71%)uf essentially pure bomylamine. IR: v,, (CHU,) (em-‘): 330&3150(NH, due to hydrogenbmrdi@. Ne w 6.88(broad -NH&cxcbangnd in D@), 342 (do, non_bndsrbsrd tqotou), 1.86(s. C-CH& 8.91 (s, C-CHk 6 protons).
c&d bo ex@&tod ott this basis.
To a mechanicallystirred soIn of NaB& (2.711;0.0713mole)in MeGIi: water (7MJ; SOml).warmedwith hot water. was introdueed a soltl of bromotdtrobomane’(3.51; 0.01335mole) in h&M (17.SmB.At t%st.a few droos wem added czawhslv. ~~~~~~~~~~, causing the &OH to dux. subsequentlytbe remainkg sok was intrwdd rapidly. After additionalt&ring for 3 hr at room ~p.~rn~~w~rn~~y~by~~ KOHaq,and steam distiikd to remove most of the &GIL The
Reaction of IV w&huhondic
KOIi
J,rolor& of 2endo &obontsne (VI). An aqueoussob of KOH (I a, amount of waterwas addedto -. O-018mok) in ~~ a sob of bomonikw@mw
(Sg, aOl~mok)
in EtoH
(12.5ml). The mixture was rethtxedon a water bath overnight, concentmU diluted witb watar and steam distilled.Crystals of 2~~~. accumtdatedon the wails of the condenser ware co&cted and dri& yieki Llg (32%); m.p. 1cT (lit.‘* 14614m. IR: viu (KBr) (cm-‘): 1545@I@,asym.), 180 @It&, tilktion. ‘Dm2-eado Nitrobuman~crysta&wI on the walls of ;yn&86S CC+ NIUk &-: 4.62 (i8da8ned tnpkt, I= non-bnlgeh#d t-proton), 1.08(s. C-CH,), 0.93 (s, Cthe condansar and was collected and dried; yield 1,758 (92%) m.p*1m @it.146-147q.‘9Tic singk spot (JQ: 0.7 m 0.6 d& 6 ;tons) 2 2-~~~ (VII).To a hand stirred sobt of camphoroxBenxene:hexane 1:l) IRz a+w&IiC!U(cm-‘): II45 (I$&, asym), 1388(NOI, sym.), 865 (C-N). NMR: i&r,): 4.65 (ii &fined hue (log, O.obmok)in gkciai AcGH (150ml)was added pure triplet. J = 7.50Hz. nonbridgebead t-proton), 1.10 (II, C-CHs), fuming HN4 (dlml, sp. g. 15ooo)in the absence of direct liit After 10mitt, water (508ml) was added and the blue ppt 0.976. C-C&, 6 protons). An diquot after NaBH4resction was addedto excess Br-water colkcted. wasbedliberallywith water and exposedto air for 8 hr and 3~~~~ drkd in vacumn; yiehi. 7.5g; m.p. 86-959,The ~~~~~~W~W~~~~ over SiIii gel 08g). I&to give sampieidenticalin aRrespects (tk, IR and NMR)to that crude pmduct was ~~~ tkn with benzene: hexane (2.5:75)gave pure 2&linitrobomane; of authentic 2.era-bromo-2-endo-nitmbornane. yiald, Log (7%); m.p. 21+ (sealed capill) (lit. 107.S-188.5@)~‘s TJXz Situ& spot (Jf,: 0.79, banxmmzhexane (1:l)). hound: c, Acid qrmoc&g of poressiam~~C*2-~~ (M,Wt.Zzs): C, JsoMox of VL To a stirtnd soln of t-BuGK in dry t-B&M 52% H. 730; N, 1240. Celc. for Cafe, l~(N~~yrn.), (0.6868g, 0.80535mok 2 ml) was added a sok of 2-emfo-nitro. ~H,7.01;N,122896.IRp,,(RBrfIcgi^’): 1.3o.1.03,0.%!@, bomane, in t-BuGH (0.9159op. 0.80.5mok, 1ml). After an ad- 1365(NCh.sym.),848CGN). NlUk I-: C-CH~. ditiomdOJhrofstirring,themixturewaspouredonto3N Further ektion using benzene-hexane (MO) gave materiai IIsSG, (loomi). The mixture was extmeted witb ether, the which was su~~n~~ identilkd as c~p~~~, yield: ~~~WaS~~~~~~U~~~,~ Of&Od and cvapomtcd and the crude product chromatographed 4.5g (37%).TLC: Singk spot (J&:0.65,knxene: hexane fl:l)). 00 silica. Ehttion with petroleum ether, benxeae IE9o:lO) gave W: v, (neat) (cm-‘): 1648(CaN), lJ78 (NO, asym.). 1325 unchanged 2.end&nitrobornane. One of the early fraction (NOS.sym.).NMR: &~a,: 1.86,1.80,0.91(s, C-CH,). IR and NMR spectraof this samplewas identicalto thatof an contained traces of isomer as evidenced by the presence of a 1570cm-’ in additkmto themajorbandat 1540an-’ attributedto authentic sampleof c~~~~. N4 asymof thestartiq material. Reactionof potadtn
bomoas-2-nitnnterew& bmminr-wohu Jsolerion of IV. To a stirred sok of 2-~-~ (0.9138.0805 mole) in drv t-BuGH (15ml) was added subRmed t-BttGK (0.728Og,~.~jrnok~ After additiomdujhr stirring the mixture was poured onto Br-water(3g, 0.019mole, 188ml), the precipitatedcrude bromonitrobomanewas collected,washsd with water and dried: yield, 1827Og(66%). The IR of this
Hy&vgwwlysis of 2&aWtmhomane
IsoMua of VI. In a semi-microhydrogenationset-up a soln of diniiboraano in EtGAe (0.132&b0.088378mok, 38ml) was ~~~a~~~~~~~~~(lOrnl) ~~rH~~~~t~~~~~~too~ nitro group was consumed in fmin. The mixture wss twice filtered.wasbsd thoroughlywith EtOAc and evaporatedto give 0978Og(66%)of c&e 2-e&-m, cryst&mion from hot aqueous EtGH gave 0.05888of pure product; m.p. 146-F (lit.” M-7?. T&n was no evidencefor the formationof anvI of the isomerk 2-exe-nitrocamphane. TIC: Single spot (RI: 0.52, benxene: bexane (MB. IR: vnu (CHCI~(cm-‘): lSS0(Not, nsym.), 1378Ox, sym.).865(C-N); ~~ on that of the 2~0~~~ obtainedby ~~~~~0~~~.
%.psweretakenon a Fisher-Jobn melting point lppurtus and are uncorrected. Capillary m.ps were tahen in a Thomas Hoover capillary melting point apparatus. IR spectra were recordedeither on a Per&Elmer 708or 137or Perhin -Elmer 521 ~~~~. NMJt spectra wcn detem&& with CIICI~drICck sohttionson a Vatian-A60w MODspsctrometer using TMS as internal standard. silica gel G (Stabi)with calcium sulfate bii was used for tic. Mumu chromatogtnphywas Ac&wl&emw#s-We are most grateful to Dr. Nityanandand ~~~~wi~~~~~~~~~ Ib. hf. hi. Dhar, CDRI, Luehnowand to Dr. S. Rajappa,CUBA, repormd here, are optically bmctive. Whemver possii, the Bombay for providing spectai facikks. &an&al assistance reactionswere monitoredby tic. from CSIR, New Defhiis grataftdlya&nowkdged.
S. RhueAuATHAuerel.
3132 umwNcE8
‘S. Ranganathanand II. Rantan. Tefmbed~ 38.63 (1974). ‘A. P. Thomas and B. Willhahn. Tetmhedmn Letfers I309 (1965): A. F. Thomas, R. A. Schneiderand J. Meinwakl. 1. Am. C/rem. Sot. g9.68 (1%7); M. Lipp and D. Bernstein, Nafurewirsmscbeffat 42. 378 (1955): Chem. Abstr. 51. 11293 (1957): E. Avela, Ann. Aced. Scieul. Fennicae,Srr. AH, No. 77. p. 84 (1956). Cbem. Absfr. 51. 10430 (1957): 0. C. Joshi. Ph.D. Thesis, University of Western Gntario. Can& (1968). ‘P. J. Ma&en, S&omen Kern.. Us, 250 (l%2) Cbem.Abrtr., 51. II404 (1963): 0. A. Nyman and A. M. Kuvaja. Amt. SJI. I8 (1939): J..M. Coxon. hi. P. Hartshorn and A. J. Lewis, Cbem. & lnd.. I I45 (1970); P. hf. L. Capmau M. M. W. Chodkiewicxand P. G&t Tetmhedfvn Letters 1619 (1965): L Y. Bruysova, 1. Geu. Chem. USSR 9,905 (1939).Ghan. A&r. 34.404 (1940):
P. Lerivcrend and J. hi. Conia, Bull. SW. Chim. Fr. 2715
(1970): J. Gripenherg, Suomen Kern. 189. 53 (1945). Chem. Abstr. 41,739(1947); J. Houhen and E Pfankuch Ber. Dlach C&m. 0~. Uft 588 (l927k L. W. Trevoy and W. G. Brown, 1. Am. Chem. Sot. 71.1675 (i%9); D. S. Noyce and D. B. Denny, ibid., 72.5743 (1950): II. Toivonen. Ann. Acad. Scient. Furniroe. Ser. A.11. No. 72,49 (1956). Chem. Abstr. 52.2806 (1958): P. Hiijarvi. Ann. Acud. Scient. Fcnnicae,Ser. A. No. 81. I6 (1937). Cbem. Abstr. 52. II09 (1958): G. Russo and G. Ricea. Chin. Ind. Mifex 46, I85 (1964). Chem. Abstr. 61. 1914 (1964): W. G. Da&en. R. E. Boxak. R Fliss and I? Willey. Reu. Chbn. Acad Rep. Popvlaim Rownanine 1,803 (1%2) Cbem.Abslr 61. 4424 fl964k I. Wolinskv. D. R. Dimmel and T. W. Gibson. L 0;. ?himl.32.2087 (1967): W. Hue&l and 0. Fechtig. Ann. (62. 87 (1962): J. Susyko and W. 2. Antkowiak, Bull. Acod. Polon. Sri.. Ser. Sci. Chim. 13. 447 (1965). Chem. Abrtt. 64. 2131 (1966): S. Beckmann and R Mexgar. Chem. Ber. 89.2738 (1956): E. Avela. Ann. Acod. seirnt. ~euniacae, Srr. A.11: No. 77. 84 11956). Chem. Ab;fr. 51. 10438 (1957): T. Kuusinen, S~o&1’&~3lB. 358(1958).Chem. Absir. 15114(1959): A. F. Thomas and B. Willhalm. Tetmhedron titers 1309(1965): J. P. Freeman. Chem. & Ind. 1624 (l%l): J. Katsuhara. H. Yamasaki. K. Hashintoto and M. Kohayashii. Kogyo Kagaku Zesshi 79.1265 (l%7). Chem. Abstr. 68.2995 (1968): B. Kubota and T. Havashi. Bull. Chem. Sot.. laoan 1.67 (1926). Chem. Abstr. # 2487 (1926): G.-Vavon and P: Pcig&r.~C. R. Acad. Sci. Paris 181. 183(1925). Cbem. Abstr., 19.3267 (1925): M. tipp, and E. Bund.. Eer Dsch Chem. Ga. 68B. 249 (1935): T. G. Traylor and C. L. Perrin. J. Am. Chem. Sot. 88. 4934 (l%6). See however. I. N. Naxarov and M. S. Burntistrova.Zh. Gbsbchei Khim. 28 2173 (1950). Chem. Absfr. 0. 7061 (1951); L. F. F’ieser and G. Ourisson. BMIL Sot. Chim. Fr. 1152 (1953): E. Cuingnet. Ibid. 91 (1955): V. I. Esafov and N. I. Novikov, Zh. dbschchei Khim. 26.2758 ~~_~ (1956). Chei. Abstr. 51.7330 (1957): -__. _~~~ R. Golsc. C.R. Acad; Sri.. &II& 249.1912 (1959), Chem. Absfr. 51. 14297 (1960): W. F. Erman and T. J. Flautt. I. Org. Chem. 27, 1526 (1%2). 4.. . . . . . . A different steric situation prevails in the Camphane System where the exe face of the mokcuk is stronglyscreened by the gem diithyl group at Cr. As a result, this system is generally approachedby reagentsfrom the endo side.. . . . .“,
E. L. Eliil. Steruocbabtry of Carbon Compounds,p. 304. McGraw-Hill Book Co., Inc., New York (1%2). 5.6. . . . ..Thep~~nanofuohy~excharyeinthecrsc of camphor must re8ect the operation of some as yet unap preciatedsteric or stereoelectroniceffect, It takes an additional, although rqmewhat vicarious, interest hecause this apparently general tendency of hiiyclo 22.1 heptan-2.onesto suffer exe protonation in a group of reactions wlticb certahuy cannot involve carhoniumions mimiis the tendency of 2-hkyclo 22.1 heptyl carhoniumions to yield exe suhstitutedproducts. . . . .“. (Ref.2). 6p. V. R. Schleyer. 1. Am. Chem. Sot. $9.699 (1967): P. V. R. Schleyer. Ibid...89.701 (1%7). ‘F. A. Carey and H. S. Tremper. J. Otg. Chem. 344 (1969): C. A. Burton.C. O’Connor and-D. Wit&r. Ibid.. 32.2881 (l%7): R. Baker and T. J. Mason. Chem. Coins.. 120 (1969k P. D. Bartlett, G. N. Fiikes. F. C. Haupt and k He&es&. Act. Chem. Res. 3,177 (1970): A. 0. Davies and R. Tudor. J. Chem. Sot. B. I815 (l97Ok S. P. Jindall and T. T. Tklwell. Tetmhuimn bte& 783 (1971); J. M. Mellor and C. I? Webb. Ibid. &5 (1971); P. C. Moews. J. R Knox and W. R. Vaughan, X Am. cbau. sot. Ice, 268 (1978). ‘D. A. Brueckner,T. A. Hamor. J. M. Robertson and 0. A. Sii. 1. Chem. Sot. 799 (1962). b. C. Ililand and 0. X. Criner. 1. Am. Chem. Sot. 75. 4047 (1953). ‘s2-Bomans nitronic acid readily tautomerisespreferentially to the endo isomer (Toivonen. Heikki, &omen Kern.. B 1971. 44(2). 54-60, Cbem:Absfr. 7s. 6l2Oj (1971). “NMR data given in “experimental”.The endo nitm assignment is supportedby the appearanceof the hrklge methyls as a single peak. Additionally, in the case of 23diiitm homane.whereone of the nitro groups must he exe-these peaks are clearly separated. ‘J. R Bull, E. R. Ii. Jones and G. D. Meakiis, 1. Chem. Sot. 2681 (1965). I$. Mitchell and R. Gordon, Ibid. 853 (1936). “L. Wolf, Ann. 394.86 (1912). “It was felt that desulfurixation of 2&ornanon&iiketal will provide a very desirableroute to hornane.comparedto the one availabk, namely, the Wollf-Kishner reduction of hornanone under drastic conditions.The novel 2-homanonethioketal was prepared in 85% yields by refluxing for 30hr a mixture of camphor (6.0 g), ethane dithiol (I7 ml), PTSA (0.8~) in dry benzene (160ml). Filtration followed by evaporation and diitillation gave 7.7 g of the thioketal bp. 122V0.5 mm (NMR &a: 3.44-3.10 (m, 4H), 1.07, 1.02, 0.95 (CH,). Surprisingly the thioketal could not be desulfurixed. ‘?I. S. Nametkin, J. Phys. Chem. Sot. 47. 409 (1915). Chm. Absk 10.45 (1916). “For a similar observation see Ref. 10. IsThe fact that tautomerization of humane-3nitronic acids proceeds with equal stereochemical preference is in excellent agreement with this observation (see Ref. IO). “J. L. Siionson. Tire Terpenes. Vol. II, p. 436. Canthridge University Press (1957).