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2052 J.C.S. Perkin IPolycyclic Systems. Part XV1.l Synthesis of 1 -Isopropyl-2,8-dirnethyl-phenanthreneBy Dhanonjoy Nasipuri * and Ila De Dalal, Department of Chemistry, Indian Institute of Technology, Kharagpur721 302, IndiaAn unambiguous synthesis of 1 -isopropyl-2,8-dimethylphenanthrene from 2-isopropyl-I ,3-dimethyl benzene isdescribed in which 3.4-dihydro-5-isopropyl-6-methylnaphthalen-I (2H)-one serves as a key intermediate. Thishydrocarbon i s different from one previously encountered by Short and Wang to which this formulation wasascribed. An error in the literature regarding the synthesis of this phenanthrene is corrected.SHORT and WANG~ in their attempt to synthesise adegradation product of the diterpene totarol, obtaineda hydrocarbon, C,,H,, m.p.168.5-170", by treatmentof methyl 2-methoxy-8-methylphenanthrene-1-carboxy-late with methylmagnesium iodide, which they formu-lated as 1-isopropyl-2, 8-dimethylphenanthrene (XVI) .The assignment was justified by the known propensity ofa methoxy-group to be replaced by methyl during reactionof an adjacent hindered carbonyl group with methyl-magnesium halide.4 Later, Bardhan and Nasipuri,during work on a general synthesis of alkylphenan-threnes,6 prepared what they believed to be this hydro-carbon by treatment of 3,4-dihydro-2,8-dimethylphenan-thren-1 (2H)-one with isopropylmagnesium iodide andsubsequent dehydrogenation and found it to be differentfrom that reported by Short and Wang. A reinvestiga-tion, however, showed that the synthetic hydrocarbonwas actually 1,7-&methylphenanthrene, arising fromreduction of the carbonyl group by isopropylmagnesiumiodide, a common reaction of hindered ketones.Twoother attempts to synthesise the title phenanthrene from2-isopropyl-3-methylcyclohex-2-enone (I) also failed,this ketone being unreactive towards phenethyl-magnesium bromide and also in attempted Reformatskyreactions with ethyl bromoacetate and with methyl7-bromocrotonate. Meanwhile, a procedure for thepreparation of 1 ,2-dialkyl-3-methylbenzenes from Hage-mann's ester was developed in our laboratory.6 We nowreport an unambiguous synthesis of 1-isopropyl-2,S-dimethylphenanthrene (XVI) from 2-isopropyl-l,3-di-methylbenzene (11), prepared by this procedure.2-Isopropyl-3-methylcyclohex-2-enone (I)' was treatedwith methylmagnesium iodide and the product dehydro-genated to afford 2-isopropyl-l,3-dimethylbenzene (11)in 85% yield. The latter was submitted to a convention-al series of reactions leading successively to the bromide(111), the cyanide (IV), the ester (V), and finally thecrystalline acid (VI) in an overall yield of 4.2%.Eachof the compounds including the amide (VII) obtained asa by-product in one of the reactions was characterised byn.m.r. spectra.Bromination of the hydrocarbon (11) with N-bromosuc-einimide also afforded 1,3-bisbrornomethyl-2-isopropyl-Part XV, D. Nasipuri and A. Bhattacharya, Indian J .Chem., 1972, 10, 799.For the synthesis of this degradation product, see D. Nasi-puri and A.C. Chaudhuri, J. Chem. SOC., 1958, 2579.R. C. Fuson and R. Gaertner, J . Org. Chem., 1948, 13, 496;and earlier papers.a W. F. Short and H. Wang, J . Chem. SOC., 1951, 2979.benzene in 12% yield, characterised by its n.m.r.spectrum. The ketone (I) was dehydrogenated to 2-isopropyl-3-methylphenol but an attempt to convert itinto l-bromo-2-isopropyl-3-methylbenzene by heatingwith triphenylphosphine dibromide * failed, thus frustrat-ing an alternative and possibly simpler approach to thealcohol (VIII). The ester (V) was reduced with lithiumaluminium hydride to the corresponding phenethylalcohol (VIII), and the latter converted into the arylbu-tyric acid (IX) by malonic ester synthesis. Cyclisationof the acid (IX) either by treatment of the derived acidchloride with anhydrous aluminium chloride or by heatingthe acid with polyphosphoric acid led t o a mixture ofthree tetralones (X)-(XII) as evidenced by g.1.c.Apparently the sterically hindered isopropyl group waspartly lost and partly rearranged during acid-catalysedring closure.The cyclisation was finally effected byreplacing aluminium chloride with tin(1v) chloride in theabove reaction and the tetralone (X) was obtained in 90%yield. The structure was confirmed by its n.m.r. spec-trum, which showed an AB quartet for the two aromaticprotons. The lability of the isopropyl group in thesystem precluded any conventional short synthesis byusing the phenethyl bromide derived from alcohol (VIII).l-Isopropyl-2,8-dimethylphenanthrene (XVI) was there-fore synthesised by appropriate transformation of thewell authenticated tetralone (X) (Scheme).The structures of the acid (XIV), the ketone (XV),and the phenanthrene (XVI) were supported by n.m.r.J.C. Bardhan and D. Nasipuri, J . Chem. SOL, 1956, 360.D. Nasipuri and I. De Dalal, J.C.S. Perkin I , 1973, 1764.D. Nasipuri, G. Sarkar, R. Roy, and M. Guha, J . IndianG. A. Wiley, R. L. Hershbowitz, B. 31. Rein, and B. C .Chem. SOC., 1966, 43, 383.Chung, J . Amer. Chem. SOC., 1964, 86, 961975spectra. The phenanthrene (XVI) had m.p. 80.5--81",formed a picrate, m.p. 176", and a trinitrobenzene deriva-iii 1(XYI) (XU 1SCHEME Reagents : i, BrCH,*CH=CH*CO,Me, Zn, C,H,; ii,heating with 10% Pd-C and hydrolysis; iii, PCl, followed bySnCl, in C,H,; iv, treatment with MeMgI, heating with 10%Pd-Ctive, m.p.198', and is entirely different from the hydro-carbon described by Short and Wang2 the structure ofwhich thus remains uncertain.EXPERIMENTALN.m.r. spectra were measured with a Varian T60 spectro-meter for solutions in carbon tetrachloride (unless otherwisestated), with tetramethylsilane as internal standard. G.1.c.was carried out using a column (6 f t x &in) of 10% polyesterof diethylene glycol adipate supported on Gas Chrom 2with nitrogen as carrier gas. 1.r. spectra were measuredfor films (unless otherwise stated). Petroleum refers to thefraction of b.p. 40-60". Solutions were dried over anhy-drous sodium sulphate.2-Iso~ro~yZ-3-methyZcycZohex-2-enone (I) .-2-Isopropyl-3-methylcyclohexenone (I), b.p.95-100" a t 12 mmHg, wasobtained by alkylating Hagemann's ester with isopropyliodide and hydrolysing the product with alkali7 Theunhydrolysed 1-alkylated product was left as a high boilingfraction (ca. 20%).@ The ketone (I) showed a single peakon g.1.c. and had nD30 1.4880; v-. 1 670 cm-1; T 7.00 (1 H,m, J 7 Hz, CHMe,), 7.69 (4 H, m, 4-H, and 6-H,), 8.02 (3 H,s, 3-Me), 8.05 (2 H, m, and 8.85 (6 H, d, J 7 Hz, CMe,).2-Isopropyl- 1,3-dimethyZbenzene (11) .-The foregoing ke-tone (24.3 g, 0.16 mol) was treated with methylmagnesiumbromide (0.52 mol) in ether (250 ml) for 10 h under reflux.The cooled solution was decomposed with aqueous am-monium chloride and the product after the usual work-upafforded 2-isopropyl- 1,3-dimethylcyclohexadiene (2 1.1 g ,88x1, b.p.73-75' at 10 mmHg. This was heated withpowdered sulphur (5.1 g, 0.16 mol) at 210-220 "C for 6 hand the dark liquid distilled in steam. The organic materialwas separated, dried, and distilled over sodium to give 2-isopropyl-1,3-diunethylbenzene (11) as a liquid (20 g , 85%),b.p. 200-201" a t 760 mmHg (Found: C, 88.7; H, 10.5.Cl,Hl, requires C, 89.2; H, 10.8%); n,35 1.5032; 7 3.22(3 H, s, ArH), 6.62 (1 H, m, J 7 Hz, CHMe,), 7.67 (6 H, s,2 x Me), and 8.67 (6 H, d, J 7 Hz, CMe,). It showed asingle peak on g.1.c.2-Iso~ro~yZ-3-methyZ~~nol.-2-Isopropyl-3-methylcyclo-hex-2-enone (I) (7.8 g) was heated with 10% palladium-charcoal (0.78 g) in p-cymene (16 ml) for 5 h under nitrogen.The product on extraction with aqueous sodium hydroxidefollowed by acidification afforded 2-isopro~yZ-3-methyl~henoZ(4.0 g), b.p.150" at 20 mmHg; m.p. 73-74' (from petro-leum) (Found: C, 80.1; H, 9.5. Cl0H1,0 requires C, 80.0; H,.9.3%); ~(CDCl,)2.90-3.60(3H,m,ArH),5.37(lH,s,OH),6.70 (1 H, m, J 7 Hz, CHMe,), 7.66 (3 H, s, 3-RIe), and 8.66(6 H, d, J 7 Hz, CMe,).A ttempted Preparation of 1 -Bromo-2-isopropyl- 3-mthyl-benzene.-Triphenylphosphine dibromide, prepared fromtriphenylphosphine (3.93 g, 0.015 mol), bromine, and aceto-nitrile (13 ml) was freed from solvent under vacuum andmixed with the above phenol (1.5 g, 0.01 mol) and heated at200 'C for 2 h. The product after usual work-up gave backthe original phenol quantitatively.2-Isopropyl-3-methyZbenzyl Bromide (111) .-2-Isopropyl-1,3-dimethylbenzene (14.8 g, 0.1 mol), N-bromosuccinimide(17.8 g, 0.1 mol), and benzoyl peroxide (0.1 g) in carbontetrachloride (45 ml) were heated under reflux for 1 h.Themonobromide (111) was obtained as an oil (15.8 g, 70%), b.p.105-110" a t 10 mmHg (Found: 57.8; H, 6.3; Br, 34.8.CllH,,Br requires C, 68.1; HI 6.6; Br, 35.2%). Someunchanged hydrocarbon was recovered as a lower boilingfraction which was rebrominated; the final yield of thebromide was 78%. The dzbromide, b.p. 160" at 10 mmHg,m.p. 84-85" (Found: C, 42.5; H, 4.7; Br, 52.8. CllH14Br,requires C, 43.1; H, 4.6; Br, 52.3%), was obtained in 12%yield; 7 (CDC1,) 2.70 (3 H, m, ArH), 5.33 (4 H, s, 2 xCH,Br), 6.43 (1 H, m, J 7 Hz, CHMe,), and 8.50 (6 H, d, J 7Hz, CMe,).2-Isopro~yE-3-methyZbenzyl Cyanide (IV) .-A mixture of2-isopropyl-3-methylbenzyl bromide (37.5 g), sodium cya-nide (26 g), potassium iodide (5.4 g), 95% ethanol (150 ml),and water (45 ml) was refluxed for 7 h.The product on usualwork-up, afforded the cyan.tde (IV) (24.5 g, 86%), b.p. 135-140' at 10 mmHg (Found: C, 82.8; H, 8.8. Cl,Hl,N re-quiresC,83.2; H,8.7%); ~2.95(3H,m,ArH),6.33(2H,s,CH,CN), 6.65 (1 H, m, J 7 Hz, CHMe,), 7.59 (3 H, s, ArMe),and 8.62 (6 H, d, J 7 Hz, CMe,).Ethyl 2-IsopropyZ-3-~nethyZ- 1-Phenylacetah (V) .-A solu-tion of the above cyanide (22.6 g) in absolute ethanol (110ml) cooled in ice was saturated with dry hydrogen chlorideand the mixture was heated under reflux in a current ofhydrogen chloride for 10 h.The solid that separated waspartly dissolved in water and the mixture filtered. Thefiltrate was worked up for the ester (V), which was obtainedas an oil (23.2 g, slyo), b.p. 143-145'at 10 mmHg (Found:C, 76.1; H, 9.2. C,4H,oO, requires C, 76.4; H, 9.1%).Hydrolysis with ethanolic sodium hydroxide afforded 2-isopropyl-3-mebhyZ- 1-phenylacetic acid (VI) (20.0 g) , whichcrystallised from petroleum in needles (18.0 g), m.p. 81"(Found: C, 74.8; H, 8.3. C1,H1,O, requires C, 75.0; H,8.3%); T (CDC1,) 0.37 (1 H, s, CO,H), 2.90 (3 H, s, ArH),6.24 (2 H, s, ArCH,), 6.65 (1 €3, m, CHMe,), 7.55 (3 H, s, Me),and 8.65 (6 H, d, CMe,). The purified acid was re-esterifiedand used for reduction.The solid collected by filtration crystallised from ethanolto give 2-iso~opyZ-3-m.ethyZ- 1-fihenylacetamide (VII) , m.p.124-125' (Found: C, 75.1; H, 9.1; N, 7.3.C1,H17N0requires C, 75.4; H, 8.9; N, 7.3%); T (CDCl,) 2.93 (3 H, m,@ D. Nasipuri, K. Mitra, and S. Venkataraman, J.C.S. PerkinI , 1972, 1836J.C.S. Perkin IArH), 3.90br and 4.66br (2 H, d, NH,), 6.37 (2 H, s, ArCH,),6.66 (1 H, m, CHMe,), 7.57 (3 H, s, Me), and 8.67 (6 H, d, J7 Hz, CMe,). The amide was also hydrolysed to the acid2-Isopropyl-3-methyl~henethyl A lcohol (VIII) .-The fore-going ester (18.4 g) was reduced with an excess of lithiumaluminium hydride in ether to yield 2-isopro$yl-3-methyl-phenyl alcohol (VIII) (14.2 g, 95y0), b.p. 151-153' at 15mmHg; nD3, 1.5220 (Found: C, 80.5; H, 10.3.C1,H1,Orequires C, 80.9; H, 10.lyo). The alcohol (14.2 g, 0.081mol) was treated with phosphorus tribromide (11.4 g, 0.042mol) to yield the corresponding phenethyl bromide (17.1 g,88%), b.p. 140-145" at 15 mmHg; nD3, 1.544".y-(2-IsopropyZ-3-methyl- 1-pheny1)butyric Acid (IX) .-Thepreceding bromide (17.1 g) was condensed with diethylmalonate in the presence of ethanolic sodium ethoxide inthe usual way to furnish diethyl2isopropyl-3-methylphenethyl-malonate (19.4 g, 85%), b.p. 178-180" a t 1.0 mmHg; nD341.4880 (found: C, 71.0; H, 9.0. C,,H,,04 requires C, 71.35;H, 8.75%). The ester (19.4 g) was hydrolysed with reflux-ing ethanolic 20% potassium hydroxide. The crude malonicacid (17.7 g) thus obtained was heated at 170-175OC tofurnish y-( 2-iso~ropyl-3-methyl- l-Phenyl) butyric acid (IX)(11.1 g ) , which crystallised from petroleum in white glisten-ingneedles (10.3 g, 76y0), m.p.80" (Found: C, 76.1; H, 9.5.C14H,,O, requires C, 76.4; H, 9.1 %).3,4-0ihydro-5-isopro$yl-6-methylnaphthalen- 1 (2H)-one( X) .-(a) The foregoing butyric acid (3.3 g, 15 mmol), phos-phorus pentachloride (3.3 g, 16 mmol), and benzene (60 ml)were stirred a t room temperature for 45 min and thenwarmed a t 45 "C for 10 min. A solution of tin(1v) chloride(4.5 ml) in benzene (15 ml) was dropped into the cooledmixture during 15 min. Stirring was continued for 1 h a troom temperature and for 1 h a t 45 "C. The mixture wasdecomposed with cold dilute hydrochloric acid and theproduct extracted with benzene.The extract was washedwith dilute alkali and finally distilled to afford 3,4-dihydro-5-isopropyl-6-methylnaphthalen- 1 (2H) -0fie (X) (2.7 g, go%),b.p. 145" at 1 mmHg (Found: C, 83.0; H, 9.3. Cl,H180 re-quires C, 83.2; H, 8.9%) ; it solidified to a low-melting solid(30-35') ; Y,, 1 685 and 1 612 cm-l; T 2.30 (1 H, d, J 8 Hz,8-H), 3.03 (1 H, d, J 8 Hz, 7-H), 6.50 (1 H, m, J 7 Hz,CHMe,), 7.02 (2 H, t, J 5 Hz, 4-H,), 7.60 (3 H, s, 6-Me), 7.60(2 H, m, 2-H,), 7.92 (2 H, m, 3-H,), and 8.64 (6 H, d, J 7 Hz,CMe,) ; dinitrophenylhydrazone, m.p. 240" (from benzene-methanol) (Found: N, 14.7. C2,H,,N404 requires N,14.6%). The ketone showed a single peak on g.1.c.(b) The acid chloride from the acid (IX) (5.0 g) was treatedwith anhydrous aluminium chloride (4.0 g) in carbon disul-phide (25 ml) in the cold.The dark red product was de-composed with dilute hydrochloric acid and then distilled insteam. The ketonic material was extracted with benzeneand distilled to afford a sweet-smelling oil (3.6 g), b.p. 125-140" at 0.5 mmHg. G.1.c. showed it to be a ca. 2 : 5 : 3 mix-ture of three ketones (vmx 1 685 cm-l; retention times 11,20, and 25 min). The last peak corresponded to the tetra-lone (X). N.m.r. spectra of the mixture indicated partialloss of the isopropyl group. The first and the second com-ponents were thus possibly the tetralones (XI) and (XII).(c) Treatment of the acid (IX) with polyphosphoric acidat 100 "C for 1 h yielded a mixture very similar to that ob-tained in (b) (g.1.c.).In addition, there were two minorpeaks in the chromatogram.y-( 5-Iso$ropyl-6-methyl-l-naphthyl) butyric Acid (XIV) .-A mixture of 3,4-dihydro-5-isopropyl-6-methylnaphthalen-(VI) *1 (2H) -one (X) (3.62 g, 18 mmol), methyl y-bromocrotonate(6.5 g, 36 mmol), zinc amalgam wool (3.0 g), and dry benzene(20 ml) was heated under reflux for 1 h. More zinc amalgam(2 g), methyl y-bromocrotonate (4.4 g), and benzene (15 ml)were added and refluxing was continued for a further 3 h.The red mixture was decomposed with ice and hydrochloricacid, and the benzene layer was separated, washed, dried,and evaporated. The residue was distilled to yield methyly- (3,4-dihydro-5-isopropyl-6-methyl- 1-naphthyl) crotonate(XIII) (3.0 g, 58%) as a viscous gum. The methyl ester(4.5 g) was intimately mixed with palladium black (0.3 g) loand heated at 280-300 "C under carbon dioxide for 3 h.The melt was extracted with hot benzene and filtered.Theviscous residue left after removal of benzene was hydrolysedwith ethanolic 10% potassium hydroxide to afford y45-iso-propyl-6-methyl-l-naphthy1)butyric acid (XIV) (3.3 g), whichcrystallised from benzene-petroleum in white plates (1.5 g) ,m.p. 80" (Found: C, 80.0; H, 8.3. C1,H,,O, requires C,80.0; H, 8.1%); T 2.00 (1 H, 2d, J 9 and 3 Hz, 4-H), 2.30( l H , d, J 9 Hz, 8-H), 2.84 (3 H, m, ArH), 6.20 (1 H, m,J 7 Hz, CHMe,), 6.94 (2 H, t, J 7 Hz, ArCH,), 7.50 (3 H, s,6-Me), 7.52-8.26 (4 H, m, 2 x CH,), and 8.45 (6 H, d, J 7Hz, CMe,).3,4-Dihydro-8-isopropyl-7-methylphenanthren- 1 (2H) -one(XV) .-A mixture of the foregoing acid (1.62 g, 6 mmol) withphosphorus pentachloride (1.28 g, 6.1 mmol) in benzene(25 ml) was stirred at room temperature for 30 min, and thenwarmed at 50 "C for 5 min.A solution of tin(rv) chloride(1.8 ml) in benzene (10 ml) was added at 5-10 "C within 15min and stirring was continued for 1 h at room temperatureand for another 1 h at 45 "C. The product on conventionaIwork-up yielded a neutral material (1.26 g) which was passedthrough a column of activated alumina (benzene-petroleumas eluant). 3,4-Dihydro-8-iso~ropyL7-methyl~henanth~en-l(2H)-one (XV) wasobtained as a gum (1.2 g, 80%) (Found:C, 85.9; H, 8.1. C1,H,,O requires C, 85.7; H, 7.9%); itgave a single spot on t.1.c. and showed vmx.(CHC1,) 1 680cm-l; T 2.00 (2 H, ABq, 10- and 9-H), 2.55 (2 H, ABq,J 9 Hz, 5- and 6-H), 6.20 (1 H, rn, CHMe,), 6.75 (2 H,t, J 6 Hz, 4-H,), 7.48 (3 H, s, 7-Me), 7.30-8.14 (4 H,m, 2 x CH,), and 8.50 (6 H, d, J 7 Hz, CMe,) ; dinitrophenyl-hydrazone, m.p. 288' (from benzene-methanol) (Found :N, 13.1.l-Iso~ro~yl-2,8-dimethyl~henanthrene (XVI) .-A solutionof the preceding ketone (1.3 g) in benzene (40 ml) was heatedwith an excess of methylmagnesium iodide in ether. Theproduct after the usual work-up furnished an alcohol, m.p.130-135", which was heated with 10% palladium-charcoal(0.7 g) at 300 "C for 2 h. The hydrocarbon was taken up inpetroleum and passed through an alumina column to yield agum (700 mg) . This was directly converted into the picrate,m.p. 170-173", which in turn was eluted through an aluminacolumn with ether to afford l-iso~ro~yl-2,8-dimethylphenan-threne (XVI) as a crystalline solid (420 mg, 32y0), m.p. 75-80". It crystallised from benzene-petroleum or methanolto furnishshiningflakes, m.p. 80.5-81" (Found: C, 91.7; H,8.4. C1,H,, requires C, 91.9; and H, 8.1%); z 1.50-1.82(2 H, m, 4- and 5-H), 1.90-2.40 (2 H, m, 9- and 10-H), 2.50-2.85 (3 H, m, ArH), 6.20 (1 H, m, CHMe,), 7.30 (3 H, s,%Me), 7.46 (3 H, s, 2-Me), and 8.48 (6 H, d, J 7 Hz, CMe,);$&rate, m.p. 176" (from ethanol) (Found: 62.5; H, 5.0; N,8.9. C,,H,,N,O, requires C, 62.9; H, 4.8; N, 8.8%);C24H&404 requires N, 13.0%).10 D. Nasipuri and A. K. Mitra, J.C.S. Perkin I , 1973, 286;J. W. Cook and R. Schoental, J . Chem. SOG., 1946, 2881975trinitrobenzene derivative, m.p. 198" (from ethanol) (Found: We thank Dr. D. N. Roy, Faculty of Forestry, Shade TreeC, 64.9; H, 5.2; N, 9.0. C,,H,,N,O, requires C, 65.0; H, Research Laboratory, University of Toronto, Canada, and5.0; N, 9.1%). Short and Wang report 2 m.p.s 168.5- Dr. U. R. Ghatak, Indian Association for the Cultivation of170" and 177-179" for their hydrocarbon and trinitro- Science, Calcutta-32, for n.m.r. spectra.benzene derivative, respectively. [5/686 Received, 1 lth April, 1975

ISSN:1472-7781    

DOI:10.1039/P19750002052

出版商:RSC    

年代:1975

数据来源: RSC