Some Unusual Reactions of 2-Tetralone - ACS Publications

Methoxide catalyzed condensation of dimethyl oxalate with 2-tetralone in non-polar media, results in substitution in the. 3-position accompanied by ...
0 downloads 0 Views 358KB Size
MILTONU. SOFFER, ROUERTA A. STEWAKT AND GKACE L. SMIITIJ

1556

IFol. 74

TABLEI LITHIUM

ALUMINUM HYDRIDE REDUCTION PRODUCTS OF W-CYCLOHEXYLALKYLKETENE DIMERS OF TYPE: [C&ll(CH2)n-CHCO]l

Moles reagent

%

No. OH

21 62 45 71

0.82 .77 .90 .XI

Yield,

n per mole dimer

Formula

0

1.8 CiJItsOn 1.7 ClbH& 2 1.8 GoHMOZ" 4 2.0 (&H& Refractive inclcx% 1.4771. 1

OC. B p .

M.P., OC.

hfm.

145-148 168-172 94-96

4 3 10

58.5-60 52.5-53.5

39.5-40

-

Analyses, % Carbon Hydrogen Calcd. Found Calcd. Found

76.2 77.1 77.9 79.1

76.6 76.9 78.3 78.8

11.1 11.4 11.8 12.1

11.4 11.8 12.2 12.0

TABLE I1 DERIVATIVES OF REDUCTION PRODUCTS OF TYPE(11) ,---

n

0

Formula

GsHmOrNz SSHI~O~NZ Cz;HsaOrNz

3,5-Dinitrobenzoate M.P., Nitrogen, % ' OC. Calcd. Found

104-104.4 6.28 58-58.5 5.91 55-56 5.58 CuHts07Nza 59 5.02 Attempts to isolate the pyrazoline were unsuccessful. 1 2 4

Pyrazoline

Formula

M.P., OC.

6.42 GIHJoN~O~ 64-65 6.01 C24HJ4NtOl 109 D 5.70 5.20 CaoHaNiOt 112-1 13 b Anal. Calcd.: C, 66.7; H,8.24. Found:

Preparation of Substituted Pyrazo1ines.-Treatment of samples of the reduction products with 2,44initrophenylhydrazine, in the usual manner, gave deep orange colored pyrazolines. Several modifications of this procedure failed to produce a suitable derivative of the reduction product

Nitrogen, % Calcd. Found

13.5 12.7

13.7 12.3

10.6 10.9 C, 67.2; H, 8.40.

where n = 2. Analytical data of thcsc derivativcs are describcd Table 11.

iii

KASHVILLE 8, TENNESSEE RECEIVED SEPTEMBER 25, 1951

[CONTRIBUTION FROM THE CHEMICAL LABORATORIES OF SMITH COLLEGE AND WELLESLEY COLLEGE, AND THE DYSON PERRINS LABORATORY OF OXFORD UNIVERSITY;

Some Unusual Reactions of 2-Tetralone BY MILTON D. SOFFER, ROBERTA A. STEWART AND GRACE L. SMITH Methoxide catalyzed condensation of dimethyl oxalate with 2-tetralone in non-polar media, results in substitution in the 3-position accompanied by dehydrogenation of the tetralone nucleus at the expense of the side chain. The structure of the product, methyl 3-hydroxy-2-naphthylglycolatt, is shown by dcgradation. 2-Tetralone is smoothly converted to 8-naphthol by the action of bromine.

Although the alkylation of 2-tetralone and its a unique course. -.Thecrystalline product had the monocyclic analog, phenylacetone, proceeds ex- expected enolic properties, but failed to undergo clusively1*2in the highly reactive position, CI, elimination of carbon monoxide when heated with ester condensation may take a different course. powdered soft g l a s s The isolation of methanol It has been shown recently that while formylation of phenyl acetone with ethyl formate occurs a t Ca in the presence of sodium alkoxide or sodamide in non-polar '~'OOXIC media (ether), the reaction in alcoliolic sodium methoxide or ethoxide proceeds exclusively a t C1.s On the other hand, the only product reported from the condensation of phenylacetone with ethyl oxalate in the presence of ethanolic sodium \Coon \CH?OH ethoxide is the C3-glyoxalate.4 I I u , R = CHz 111 IV In the present work it was shown III), 11 = 1 I tliat the glyoxalation of %tetralone, with methyl oxalate and dry sodium methox- from the latter treatment5 precluded an initial lacide in benzene, occurs in the 3-position and takes tone structure. for the '-glyoxalate Inspection Of the (1) M. D. Soffer, R. A . Stewart, J. C. Cavagnol, H. E. Gellerson (I) shows that i t may be regarded as the fully and E. A. Bowler, T H I SJOCKNAL. 72, 3704 (1950). (2) C. hl. Suter and A. \T, Weston, ibid., 64, 533 (1942). ketonoid form of the phenolic hydroxy ester, IIa, (3) M . Montagne, Bol. i m t . win. Univ. Aufon. M c x . , 2 , N O . 2, 57 which could from the glyoxalate by a series (19.16); C. A , , 44, 130 (1990). (4) 11. Keskin, RLO.fnculld .rei. u t l i u . I l f n n b u l , Scr. A, 11, KO.'4. 143 (1046).

( 5 ) I\'. E. Ihchnianii, \V. Cole and A. I.. \\'ilds,

824 (1040).

TiIIS JorrRNaL,

62,

1557

REACTIONS OF %TETRALONE

March 20, 1952

I

4.4 -

i

.,.....*

______

-.-._._

I I-

i

i!

of enolic tautomerizations. In line with this structure, IIa, the compound exhibited infrared absorption in the hydroxyl and ester carbonyl regions, but not in the ketone carbonyl region, and showed in the ultraviolet, absorption distinctly different from that of 2-tetralone but almost identical with that of /3-naphthol (Fig. 1). The corresponding acid (IIb) and the reduction product (111, vide infra) showed similar absorption in the ultraviolet and also the characteristic bands for the functional groups in the infrared. Each of these compounds formed a red precipitate with benzene diazonium chloride, indicating an unsubstituted 1-position. The structure shown, (IIa) was confirmed by reduction with lithium aluminum hydride to the crystalline triol, 111, and conversion of the latter, by periodate cleavage, to 3-hydroxy-2-naphthaldehyde(IV), m.p. 99-100' [oxime, m.p. 207.5-208' (dec.) The behavior of 2-tetralone on glyoxalation is in contrast with that of 1-tetralone, which gives the normal product.' In separate experiments* it was observed that 2-tetralone was smoothly converted to p-naphthols under conditions1°for the conversion of 1-tetralone to its 2-bromo derivative. We wish to express our appreciation to the Research Corporation for a Frederick Gardner Cottrell Special Grant-in-Aid supporting this work. Experimental * l Methyl 3-Hydroxy-2-naphthylglycolate(IIa).-The reaction was carried out according to the procedure of Bach(6) The recorded melting points for the aldehyde and oxime are 09 and 207' (dec.) [T.Boehm and E. Profit, Arch. Pharm., Z69, 25 (1931) 1; for 2-hydroxy-1-naphthaldehydethe corresponding melting points are 84' [P. Ruggli and E. Burckhardt, Helo. Chim. Acto, 23, 445 (1940)l. and 148-150' or 158-160° [H. A. Torrey and C. M. Brewster, THISJOURNAL, 36, 426 (191311. (7) W. E. Bachmann and D. G . Thomas, ibid., 63, 598 (1941). ( 8 ) We are indebted to Hilda E. Gdlerson for these experiments. (9) Dr. J. A. Barltrop of Oxford University has informed us that he has independently made the same observation. ( I O ) A I.. Wilds and J A J n h r i w n , Jr.. THISJOIrRNAr,, 68, 88 ( 1 !ldG), ( 1 1 ) All lurlliug poruts are corrected.

mann, Cole and Wilds,' using dry sodium methylate from 4.09 g. (0.178 mole) of sodium, 100 ml. of anhydrous benzene, 20.06 g. (0.170 mole) of purified dimethyl oxalate and 23.71 g. (0.162 mole) of freshly prepared 2-tetralone. During the addition of the ketone the colorless solution turned red and finally brown and a large amount of crystalline material separated. After 2.5 hours at room temperature the mixture was.retiuxed for ten minutes. Excess ice-cold 6 N hydrochloric acid was added and the resulting solid filtered. The benzene solution, after washing with water and aqueous sodium bicarbonate, gave, on evaporation of the solvent, an additional amount of the glycolic ester. The crude product was recrystallized by dissolving in methanol and displacing most of the solvent with benzene at: the boiling point, yielding 16.9 g. (45%) of material melting a t 150-155". An analytical sample melted a t 153-154"; ,':A; 2.91 I.I (hydroxyl), 5.77 fi (carboxylate).1* The white ester gave a green color with ferric chloride solution, reduced Tollens reagent, and formed a red precipitate with benzenediazonium chloride. \Vith concentrated sulfuric acid it underwent a series of color changes: red, to orange, to gray-green, to blue-green, to blue, to purple. Anal. Calcd. for CllH~02(COOCH3): OCHs, 13.4; sapon. equiv., 232; mol. wt., 232. Found: OCHI, 13.5; sapn. equiv., 231, 233; mol wt. (Rast), 235. 3-Hydroxy-2-naphthylglycolicAcid (IIb).-Two grams of the ester (IIa) was saponified by reaction with an excess of 2% sodium hydroxide a t 0" for one hour. The acid was isolated in the usual manner (1.52 g., 81%), and recrystallized from methanol-benzene as described previously, and by further recrystallization from water; m.p. 166166.5" (dec.), A,=': 2.97 p (hydroxyl), 5.77 p (carboxylate)." This compound was also isolated from the sodium bicarbonate washings from the isolation of the glycolate ester (IIa). The pure white solid readily reduced Tollens reagent and formed a green color with ferric chloride solution. A solution of the acid in concentrated sulfuric acid turned from gray-green, to blue-green, to inky blue, to violet, and bubbles of gas were evolved. Anal. Calcd. €or C~1HpO~(COOH):C, 66.05; H, 4.6; neut. equiv., 218. Found: C, 66.5, 66.6; H, 4.7, 4.8; neut. equiv., 221, 221. 3-Hydroxy-2-naphthylethyleneGlycol (III).-In a flamedried, three-necked flask, fitted with a dropping funnel, condenser and mercury-seal stirrer was placed 4.67 g. (0.123 mole) of lithium aluminum hydride and 150 ml. of dry (12) Randall, Fowler, Fuson and Dangl, "Infrared Determination of Organic Structures," D. Van Nostrand Co., Tnc , New York, 1949. We are iodebted to Mr. Philip Sndtler of Samuel P . Sadtlrr and Son, PLiladrlyhin. k'n , for the infrared determinations

1558

V. BOEKELHEIDE AND FRANK PENNINGTON

ether. Dry nitrogen was passed through the system, and the mixture was stirred for one-half hour. An ether solution of 9.45 g. (0.041 mole) of methyl 3-hydroxy-2-naphthylglycolate (IIa) was added dropwise t o the milky-white suspension, at a rate sufficient t o maintain reflux. The turbid reaction mixture was stirred overnight a t room temperature. The excess lithium aluminum hydride was decomposed by the slow, drop& addition of water. The yellow turbid solution wae a d i f i e d with 150 ml. of 10% hydrochloric rcid, and the enolic material isolated from the ether solution by the usual extraction procedure. The crude yellow crystalline triol, m.p. 14&149', was obtained in quantitative yiekl (8.4 g.). After recrystallization, as mentioned previously from methanol-benzene, it melted at 152-153';. =,I, 2.81 p (hydroxyl), no carbonyl absxption.l* The w h t e product formed a bright green color with ferric chloride solution, reduced Tollens reagent, and yielded a red precipitate upon treatment with benzenediazonium d o r i d e . The compound was unchanged by refluxhg for two hours with semicarbazide hydrochloride in ethanol-pyridine. Anal. Calcd. for C&luO,: C, 70.6; H I 5.9. Found: C, 70.3, 70.55; H, 6.0, 5.95. One milliliter of acetic anhydride was added, dropwise, to a cold solution of0.M g. ofthe compoandin 2 ml. of anhydrous pyridine, and the mixture was slowly brought ts room temperature and then heated at 35" for one-half hour. Ice shavings were added and the product mf&me!&d with ether and washed well with dilute kjdrochloric acid, aqueouosdam c@jcw@ apd finnlly with water. Tbe white crgstolliwtrufdds wti&d 086 g. (93%). RscrqstolliEatian frora bepuantaattoleum &ea- (b.p. 80-60') Qd not change tbe d t h g point, 87-87.6*, A s 1 , 5 . 7 8 ~(carboxylate), no hydroryl absorptian.1;

Vol.

74

Anal. Calcd. for C&oOs(CH&O)s: C, 65.45; H, 5.5; CHSCO, 39.1. Found: C, 65.8, 05.6; H, 5.4, 5.5; CHaCO, 38.65, 38.9. 3-Hydroxy-Z-naphthaldehyde .-A. solution of 268 mg. (O.ll6~nole)of potassium penodatc m 15 ml. of 1 N sulfuric.acid was added to a solution of 233 mg. (0.00114 mole) of the triol (111) in 12 ml. of 95% ethanol. After ten minutes the orange aldehyde was atered, washed well with water, and dried; yield 0.12 g. (60%). Recrystfiation from aqueous acetic acid gave pure yellow needles of the phenolic aldehyde, m.p. 99-100'.6 The compound gave a green color with aqueous ferric chloride and formed a red-orange precipitate with benzenedimnium chloride. The oxime was prepared quantitatively in pyridine absolute ethanol, and was recrystallized from aqueous ethanol; m.p. 207.6-208" (dec.).' The pale yellow needles gave a blue color with ferric chloride solution. Anal. Calcd. for CllHoO~N:N, 7.5. Found: N, 7.3. The Reaction between 2-Tetralone and Bromine.--An ether solution of 10.7 g. (0.073 mole) of %tetralone was treated with 11.66 g. (0.073 mole) of bromine according to the procedurelo for the bromination of 1-tetralone. Evaporation of the washed extract gave 11.18 g. (106%) of crude 2-naphthol, m.p. 10!2-108'. Treatment with Norite and alumina, and reaptallization from ether-petroleum ether am3 bmzene-petroleum ether gave t$e colorless halogen-free prsdnct, m.p. and m.m.p. 120-121 ; picrate, m.p. 156.5167.5' (recorded" m.p. 155.5').

(q)

(la)

0.L.Beuil and E.8. Hauber, Tam JOWXNAL,08, lOST (1981).

NOXTEIAMPTON, MASSACHUSETTS RECEIVED SEPT$MBEiR 26, 1961

[CONTRIBUTION FROM THE DEPARTMENT OF CHEWISTRY, UNIVERSITY OF ROCHESTER]

Cads as Intermediates in the Synthesis of Colchicine Analogs BYV. BOBKELHEIDE AND FRANK C.PENNINGTON' Exploratory work has been carried aut to determine the usefulness of the von Pechmann coumarin condensation as a

route to the synthesis of derivatives of colchicme. Althoagh it has been possible to prepare a tricyclic molecule (XVI) h a h g some of the stmctud festans present in colchicine, difficulties encountered in attempts to prepare compounds more dosely related to colchicine b v e not yet been resolved.

In a previous study of coumarius as synthetic intermediates2 the suggestion was made that cmmarins would be k@cd intermediates in the synthesis of rnuledes related to colchicine. ?*he basis for this suggestion lay in the fact that the synthesis of hydrogenated eolcbicine derivatives requires the linking together of an alicyclic ring and a methoxylated aromstk ring, amd the VOII Pechmann coamarin condensatim is an sdat method for accomprishing this type of union. It Is the purpose of this, communicatiari to report the resalts of eome expkm.bry work baaed on this idea, including the synthesis of a tricyclic compound having m e of the structural features present in colchicine. Since any scheme involving the use of coumarins in a synthesis af thb type mukl vquis-e a t some stage in the &heme tbat thelactone ring of the coumarins be cleaved, our first experiments were dhtcted toopard tbe syntfiesis aad ring-opening reactions d some mdel c o e . As slzown

yield, Methylation of 1 using potassium carbonate and methyl iodide readily gave I1 which, in turn,

was coaverted to V by reaction with dimethyl sulfate and strong aqueous base. Although the ring-opening of coumarins using dimethyl sulfate and aqueous base ca.n lead directly to the corresponding ester,2 it proved to be 8 better p r d u r e in this case to isolate the acid (V) and convert it to the ester (VI) by reaction with diazomethane. OH R

b e I o w , w @ 4 u n d e m e n t c ~ n ~ ~ with 2-carbethoxycyclohexanonet o give I m good (I) Prednctod Recqacch Fellow,Natiaaal Cancer Institute. Public Health Service. 1960-1961. (21 V. Boekelbeide and A. P. Michelr, THIS JOURNAL, 74, 266 (1952).

e

I, R 11, R 111, R IV, R

QCH3

V. VI, VII, VIII,

= -H, n = 2 = -CHa, n 3 2 = -H, n = 3

= -CHs, x

3

= -H, x = 2 R = -CHI, n = 2 R = -H. n = 3 R = -cH~, n = 3

R

In view of the fact that ring C of colchicine is now