Nov. 20, 1854
CONDENSATION OF
prepared by conventional means and recrystallized from petroleum ether, had m.p. 60-62" (lit.376Cb620). 3,5-Dibromobenzoic acid (from 1,3-dibromo-4-nitrobenzene): m.p. 219-220" (lit.a8 219-220"); the amide, prepared by conventional means, had m.p. 184-186" (lit.3g 187'). 2,4-Dibromobenzoic acid (from 1,3-dibromo-5-nitrobenzene) : m.p. 163-167' (lit.J7168-169'); the amide, prepared by conventional means, had m.p. 195-196' (lit.3g 195"). 2,5-Dibromobenzoic acid (from 1,4-dibromo-2-nitrobenzene): m.p. 151-153' (lit.'o 157'); the mixed m.p. with an authentic sample (from permanganate oxidation of Eastman Kodak 2,5-dibromotoluene) of m.p. 156" was 152-155'. m-Bromobenzoic acid (from 1-bromo-2-nitrobenzene) : m.p. 151-163'; mixed m.p. with an authentic sample (Eastman Kodak) was 152-155'. Products from Reactions of Nitrosobenzene.-The reaction of nitrosobenzene with 2.6 g. of potassium cyanide in 25 cc. of 48y0 ethanol for one hour a t 155' furnished a small crop of red needles which, after crystallization from ethanol, weighed 0.3 g. and had m.p. 65-66'. These were recognized as azobenzene (m.p. 68") by reduction (tin and hydrochloric acid) to benzidine (m.p. 117-120') which did not depress the mixed m.p. with a n authentic sample. The run in 75% dyielded a yellowish neutral material of m.p. 29-31 ; the mixed m.p. with an authentic sample of azoxybenzene (m.p. 31.5-32.2') was 30-31.5". Experiments with Deuterium-labeled Compounds.-A tube was charged with 5.0 g. of nitrobenzene, 5.0 g. of anhydrous potassium cyanide, 5 cc. of the ethanol-0-d preparation described above, and 5 cc. of heavy water. It was ~
~~
(38) M. T. Bogert a n d W.F. H a n d , THISJOURNAL,^^, 042 (1903). (39) J. J. Slidborough, J. Ckem. Soc., 67, 591 (1895). (40) S . A . 1Crmp:il. Rec. t r o o . chim.,34, 148 (1915).
[CONTRIRUTION FROM
THE
57G1
A4-TETR.ZHYDROPHTIIAL.4LDEIIYDE
sealed, heated one hour at 150-lGO", and cooled. By our usual procedure, about 3 g. of nitrobenzene were recovered, and 0.380 g. of benzoic acid was obtained. After crystallization from common distilled w a t y , and then sublimation, the acid showed m.p. 120.5-121 . It was quantitatively diluted with repurified reagent grade benzoic acid, and the mixture was sublimed to give the analytical sample. A t Reed, a tube containing 2.2 g. of deuterium-labeled I-chloro-4-nitrobenzene, 5 g . of potassium cyanide and 30 cc. of 48% ethanol was sealed and heated at 160-170" for 75 minutes. The tube exploded as it was being opened, but a good deal of the product could be isolated from the lower part of the tube which did not statter. The m-chlorobenzoic acid product, m.p. 151-152 , was isolated in the usual way and purified by crystallization from water. It was quantitatively diluted with repurified Eastman Kodak m-chlorobenzoic acid, and the mixture was recrystallized from water to give the analytical sample. At North Carolina, essentially the same procedure was followed except that a lower ratio of cyanide t o nitro compound was employed. The deuterium analyses were done in the Division of Steroid Biochemistry, Sloan-Kettering Institute for Cancer Research, by Josephine Leong under the supervision of Dr. David K . Fukushima and Dr. Thomas F. Gallagher.
Acknowledgments.-We thank the Research Corporation for support of this research during its early stages, and the Office of Ordnance Research, U. S. Army, for financial assistance more recently. We are also grateful to Dr. David K. Fukushiiiia for his interest and advice. CHAPELHILL, N. C.
DEPARTMENT O F CHEMISTRY O F
THE
UNIVERSITY
OF
ROCHESTER]
A Rearrangement Involving Aromatization. The Condensation of a4-Tetrahydrophthalaldehyde with Diethyl Acetonedicarboxylatel BY D. S. TARBELL AND BERNARD WARGOTZ~ RECEIVEDJUXE 2, 1951 The condensation of A4-tctrahrdrophthalaldehydewith diethyl acetonedicarboxylate in the presence of piperidine acetate vields, by a rearrangement involving aromati7ation, 5,8-dihydro-2-hydroxy-3-carbethoxy-l-naphthaleneacetic acid ethyl ester ( I X ) The structure of this product has been established by converting it t o the following compounds, which have bcen synthesized : the lactone of 2-hydroxy-1-naphthaleneacetic acid (XI11), 2-hydroxy-3-carbethoxy-I-naphthaleneacetic acid ethyl ester and 5,B,7,8-tetr:~hydro-2-hydroxy-3-carbethoxy-l-naphthaleneacetic acid ethyl ester. The ultraviolet and infrared spectra of the compounds are in agreement with the assigned structures, and the mechanism of the aromatization is discussed. An improved procedure for preparing A4-tetrahydrophthalaldehydeis described, which involves the lithium aluminum hydride reducticn of ~ , ~ , T \ " , ~ ' - t e t r a ~ e t h y l t e t r a h r d r o r h t h a l a m j cIlteis fcund 11 a t a basic icn-cxchar gc resin is a good catalyst for the condensation of phthalaldehyde and diethyl acetonedicarboxylate.
The condensation of phthalaldehyde with diethyl acetonedicarboxylate leads to the dicarbethoxybenzocycloheptadieneone3I, and a similar reaction between phthalaldehyde and hydroxy- or methoxyor its methyl acetone yields /3, y-benzotr~polone~ ether.5 The use of A4-tetrahydrophthalaldehpde in similar condensation reactions might be expected to lead to compounds offering interesting possibilities for further synthetic operations in the tropolone and colchicine fields. The present paper reports a study of the condensation product from tetrahydrophthalaldehyde and diethyl acetonedicarboxylate; it is shown that the product does not contain a
seven-membered ring, as expected, but is actually a dihydronaphthalene derivative. The condensation reaction therefore involves a molecular rearrangement with the formation of a benzenoid instead of a seven-membered ring.
(1) This research was aided by a grant from t h e National Cancer Institute of t h e National Institutes of Health, Public Health Service. (2) Abbott Laboratories Fellow, 1953-1954. (3) J. Thiele and J . Schneider, Anw , 369, 287 (1909). (4) D. S. Tarbell, G. P. Scott and A . D. Kemp, THISJ O U R N A L , l a , 379 (1960). (5) (a) D. S. Tarbell and J. C. Bill, ibid., 74, 1234 (1952); (b) G. A. Nicholls and D. S. Tarbell, ibid., 74, 4935 (1952).
The preparation of A4-tetrahydrophthalaldehyde by addition of butadiene to maleic or fumaric dialdehyde was described previously.6 A more convenient method has been found to be the lithium
COOR
COOR
/
/
COOR
I
COOR
VI1
(6) D. L. Hufford, D. S. Tarbell and T. R. Koszalka, ibid., 74,3014 (1952).
D. S.TARBELL AND BERNARD l
5702
aluminum hydride reduction of N,N,N',N'-tetramethyl-A4-tetrahydrophthalamide(II), which is readily prepared from Ad-tetrahydrophthalyl chloride.',* 'The reduction leads to the formation of
0
I
T
~
~
~
~
~ Vel. T~( i
carbethoxy-1-naphthaleneaceticacid ethyl ester (IX), by a combination of degradative, synthetic CH*COOC?H,
lR11, R ,\R
= CON(CH3)2 111, R = CHO IV, R = CHtX(CH3)t
appreciable amounts of the diamine IV, if the lithium aluminum hydride is added rapidly to the diamide. The configurations of 11, I11 and IV are regarded as trans, because the tetrahydrophthalyl chloride (precursor of 11) is prepared7 from butadiene and fumaryl chloride ; furthermore, reduction of 111to hexahydrophthalaldehyde, and oxidation of this with silver oxide, yields trans-hexahydrophthalic acidg The condensation of 111 with diethyl acetonedicarboxylate yielded in the presence of piperidine acetatel0 a product, m.p. 126-127", of the composition expected for V, along with a by-product, probably 1'1. The behavior of the main product did not,
(yCH0 +
CH:COOR C=O 1
v'
CHO
Xb
Y
CHnC=O
+
CHtC=O
CHtCOOH
CHlCOOR COOR
pv\=/ /===
I
xe
!
/COOR
\=o+
c'
CH=CCOCH?COOR
&
I
XI11
XIV
and spectral evidence. I X showed infrared absorption bands in carbon disulfide a t 3090 (strongly asCOOR sociated hydroxyl), 1739 (normal ester carbonyl) T: VI, R = CzH6 and 1670 cm.-l (chelated ester carbonyl).14 I t however, correspond to that expected for structure gave a green ferric chloride color, was acetylated by V; thus, dehydrogenation with chloranil in xy- acetic anhydride, and was converted by saponificalene6,l1did not lead to Thiele's product I , and re- tion to a dibasic acid Xa. The saponification of duction with hydrogen and platinum in acetic acid the diester IX was accompanied by isomerization gave an uptake of only one mole of hydrogen in- of the double bond into conjugation with the benstead of three. I t was shown that under the same zenoid ring in Xa; re-esterification of X a did not conditions, Thiele's compound absorbed two moles regenerate IX, but gave instead an isomer Xb, This compound was also formed of hydrogen in the seven-membered ring, forming m.p. 113-114'. VII. Xn alternative structure VI11 for the con- from the lactone X I by treatment with thionyl densation product was ruled out by showing that chloride and alcohol. The ultraviolet spectra (see the material did not yield a carboxylic acid when below) of I X and X a and X b confirm the shift of treated with silver oxide12 or with chromic acid in the double bond into a position of conjugation in X a and derived compounds. The double bond acetic acid.13 may be in the 5,6- instead of the 7,S-position as A , -CHO -yCHCOOR shown. I The dibasic acid Xa was converted by heating to ' ,' VIIT, R CpHj 230" to a lactone X I , which melted with decompoW Y \ C O O R sition a t about 285'. The lactonic nature of X I was The structure of the condensation product was indicated by its composition and its behavior 011 titration; it consumed one mole of alkali in the eventually shown to be 5,8-dihydro-2-hydroxy-3cold, and a second one when heated. It showed in(71 K. Alder and R I . Schumacher, An%., 664, 107 (1949). frared bands a t 1797 (y-lactone carbonyl) and 1667 (8) T h e reduction of N,S,N'N'- tetr amethylphthalamide t o phthalaldehyde is reported b y F. \Veygand and D. Tietien, Chem. B e y . , 64, cm.-' (carboxy carbonyl). 62.5 (1951). The decarboxylation of X a with quinoline and 1 9 ) Lithium aluminum hydride does not invert carbon atoms a d copper powder yielded the neutral lactone XII, Il'oyce and D. B. Denney, jacent to t h e group being reduced ( D m.p. 12i0, which was converted by palladium-onT H I S J O U R K A L , 72, 5743 (1950). (IO) (a) R . K u h n , W. Badstiibner and C. Grundmann, Bey., 69, 98 charcoal in boiling biphenyl to the completely aro(1936); ( b ) A, C. Cope, el al., THISJOURNAL, 63, 3452, 3460 (1941). matic lactone X I I I , m.p. 103-104°. This product
\COOR
\CH=CCOCH,COOR
I
8 1
(11) R,T. Arnold and C. Collins, ibid., 61, 1407 (1939). (12) K . Bernhauer and R . Forster, J . p r a k l . Chem., 147, 199 (1937). (13) €1. Koechlin and T. Reichstein, Helz,. Chim. Acta, 30, 1673
(1947).
(14) (a) E. D. Bergmann, Y. Hirschberg and S. Pinchas, J . Chem. Soc., 2331 (1950); (b) I. M. Hunsherger, THISJ O U R N A I . , 72, 5026 (1950).
Nov. 20, 1954
CONDENSATION
O F A4-TETR411YDROPIITIIALALnRIIYD~
57G3
The tetrawith Raney nickel and hydro compound X X I I was converted to the chloromethyl derivative X X I I I with chloromethyl ether and zinc chloride in petroleum ether, and the latter was converted to the nitrile ester XXIV; some of the corresponding acid XXV was obtained also. Treatment of the nitrile ester XXIV with alcoholic hydrogen chloride gave a crude sample of the diethyl ester XX, which was purified by saponification and re-esterification. The diester X X thus obtained was identical with the product formed by catalytic reduction of IX. The main features of the ultraviolet spectra of the key compounds described, which were very useful in the structural work, are listed in Table I. The evidence for the position assigned to the double bond in IX, and in the diacid X a and its CH2COOR derivatives, is as follows. (1) The ultraviolet XV, R = C L " spectrum of I X is identical with that of its dihydro XVI, R = H compound X X , indicating that the double bond in IX + I X is not conjugated with the benzene ring. ( 2 ) Re-esterification of the diacid Xa yielded the diester Xb with an absorption band a t 340 mp, which is not shownz0by IX. XVIT, R = H XVIIT, R = CH2Cl The mechanism of the rearrangement involved &OH X I X , R = CHzCN in the formation of the aromatic ring in I X appears to present some novel features, and must involve '\COOCHI some such process as the following, in which bond a methyl l-chloromethyl-2-hydroxy-3-naphthoate17 (XVIII), the conversion of this to the nitrile XIX, is broken and bond b is formed, in structure XXVI hydrolysis of the nitrile to the acid XVI, and esterification of the latter to form the diester XV. The synthetic product XV was shown to be identical with the sample obtained by chloranil dehydrogenation by mixed m.p. and comparison of spectra; the two acetates were also identical. COOR Compound I X was dehydrogenated and acetylated by selenium dioxide in boiling acetic anhydride or its equivalent.21 The structure of IX is incomto form 2-acetoxy-3-carbethoxy-1-naphthaleneace-patible with the symmetrical cyclopropanone type tic acid ethyl ester, which was identical with the of intermediate, which has been demonstrated in the acetylation product from synthetic XV. alkaline rearrangement of a-haloketones,2 2 because The evidence given so far has established the the carbonyl group in XXVI is not converted to a structures of products obtained from IX by fairly carboxyl. The aromatization reactions of tropodrastic procedures, which might have involved mo- lones, in which a seven-membered ring is aromatized lecular rearrangement of the original structure. A under basic conditions,2 3 present some points of more conclusive proof of the structure was therefore similarity to the present reaction. provided by the synthesis of the dihydro compound X reasonably satisfactory picture of the rearXX, obtained from I X by catalytic reduction at rangement indicated in XXVI is the following, in room temperature.
was shown to be identical with the known lactone of 2-naphthol-1-acetic acid (XIV) by comparison with synthetic samples'" of both the lactone XI11 and the naphtholacetic acid XIV, through mixed m.p. and comparison of spectra. h further confirmation of structure I X for the condensation product was obtained by dehydrogenating i t in xylene with chloranil; the product XV melted a t 119-120°, and although it gave only EI slight depression on mixed m.p. with the starting material IX, its ultraviolet spectrum was definitely different and indicated the presence of a naphthalene nucleus. The structure of XV was established by its synthesis from methyl 2-hydroxy-3-naphthoate ; the steps involved were chloromethylation with chlorornethyl ether in acetic acidI6 to yield
,/)/$/,'"
CHzCOOR
R XXII, XXIII, XXIV, XXV,
R = H, R' = CHI R = CHaC1, R ' = CHa R = CHzCN, R' = CH3 R = CHzCN, R ' = H
Methyl 2-hydroxy-3-naphthoate (XVII) was reduced to the 5,6,7,8-tetrahydro compound X X I I (15) (a) M. Julia, Bull. SOC. chim. France, 20, 640 (1953); (b) A. H . Cook, J. Downor and B. Hornung, J . Chem. Soc., 502 (1941). (16) Cf. G. Vavon, J. Bolle and J. Calin, Bull. SOC. chim. France, 6, 1025 (1939); 0. Gawron, THISJ O U R N A L , 71, 744 (1949). (17) W. A. Jacobs end M. Heidelberger, J . B i d . Chem., 20, 682 (1915).
(18) R. T. Arnold, H . E . Zaugg and J . Sprung, THISJOURNAL, 63, 1314 (1941). (19) T h e method of Papa, Schwenk and Breiger, J . Org. Chem., 1 4 , 366 (1949), tor t h e reduction of 2-hydroxy-3-naphtboic acid t o t h e 5,6,7,8-tetrahydro compound with Raney alloy and alkali was unsatisfactory i n our hands, giving mixtures and poor yields. ( 2 0 ) T h e effect of t h e conjugated double bond on t h e zpectrum of the benzenoid ring is analogous t o t h a t of t h e double bond in 3,4-dihydronaphthalene on t h e spectrum of tetralin (R.A . Friedel and M. Orchin, "Ultraviolet Spectra of Aromatic Compounds," John Wiley and Sons Inc., 1951; figs. 10 and 29). T h e ultraviolet spectrum of 3,4-dihydro-6-methoxynaphthalene is given by R . B. Woodward and R . H. Eastman, THISJ O U R N A L , 66, 674 (1944). (21) It is possible t h a t t h e rearrangement indicated in X X V I m a y t a k e place before t h e seven-membered ring has been closed by t h e aldol condensation with t h e second aldehyde group of 111; however, t h e driving force in t h e rearrangement is undoubtedly t h e stability of t h e aromatic ring, and hence t h e ring closure is probably a t least simultaneous with t h e shift in t h e carbon skeleton. (22) R. B. Loftfield, THISJOURNAL,73, 4707 (1951); this article contains a n excellent summary of t h e earlier work. (23) Cf. t h e illuminating discussion b y W. E. Doering and L. H. Knox, i b i d . , 73, 832 (1951).
576 1
I). S.TARBELL AND BERNARD WARGOTZ TABLE I ULTRAVIO1,ET SPECTRA I N
9570
Maxima (mp)
ETHANOL
log
t
Uicarhcthosyhenzocye1~)hcpta~ienone (I) 235 4.4 273 4.6 310 (shoulder) 3.99
Bis-condensation product TrI from tetrahydrophth3laldeliytlc 252 4.23 1:;s-contleiisntior~protluct from phth:~lnltlchydci X3 4 13 ,j,S-I>iliydro-3-liy(lroxy-3cnrhethosyl-iinj)hlh:iletic:i[.t.lil. :i&I e t h y l c,stcr ( I S ) 31(i 4 ,35 2.7'7 3,N 390 .>. 3 ,
--
c)
Methyl 5,6,7,8-tetrahydro-2-hydrouy-3-naphthoate (XXII) 4 10 220 3 07 249 315 3 54 5,6,7,8-Tetrahj dro-2-hytlroxy-3-naphthoic acid" 4.33 219 240 4 15 375 3 57 The ester X S I I absorbs at longer wave lengths than the corresponding acid in alcohol solution, as found by Bcrgmann, et al. (ref. 14a), for salicylic acid, 2-11ytlrox~~-3-1iaphthoic acid and the corresponding citcrs.
which the anion XXVII, derived froni XXVI by action of base, gives a nucleophilic displacement of the hydroxyl group by migration of the carbonyl carlon with its electron pair. This process, followed by shift of a hydride ion, leads t o XXVIII, which gives I X by proton shifts. H C.-COOR
5,6-Dihydro-2-hydroxy-3-cnrbetliox~1 -11npht11nlenencetic:xid ethyl ester (SI)) 210 4.38 284 4.10 340 0.fi(i
3,6-Dihptlro-2-hydrox~--3-c:trl~or~I -nn~~htlinlenencetic acid (Sa) 284 3.85 326 3.48 5,~-Uihyclro-2-li~--tlrosJ.-3-carl~ns~-1 -:iaphthnletincetic acid lactonr ( X I ) 226 -1.31 280 4.19 31s 3.6'7
Vol. 76
COOR XXVII
SXVIII
An alternative scheme for the formation of IX, involving a series of cleavages and acylations, with the by-product VI as an intermediate, was shown to be improbable; VI did not yield IX when treated under the conditions of the original condensation.
Experimenta124
N,N.N',Nr-a4-Tetramethyltetrahydrophtha1amide (11).-
Crude A4-tetrahydrophthalyl chloride' (96 g.) in 1 1. of dry ether was chilled in a Dry Ice-acetone-bath, and 118 g. of anhydrous dimethylamine was added with vigorous stirring over a period of 20 niin., through a tube extending below 995 4 17 the surface of the solution. After addition was complete, 255 3.79 the solution waq stirred for 1 hr., the dimethylamine hydro262 3,%5 chloride was removed by filtration and the filter cake wai washed with dry ether. The combined filtrate5 werc 272 8.73 dried and concentrated in uacuo, giving 100 g. of crude mi 3,15 product; recrystallization of this material from hexane gave 93 g. of 11, m.p. 53-56', which was raised t o 55 50" 2-Hydrosy-3-carbethosyby further crystallization from hexane. 1 -11~~pht11nle11encetic acid ethyl ester (SV) Anal. Calcd. for C I Z H ~ O N ~ O C,Z :64.25; 13, 8.99; S, 213 4.69 12.49. Found: C , 64.30; H, 9.20; N, 12.30. 276 3.81 The corresponding N,N,N',N'-tetraethylamide wa1 pre?8S :: S!) pared in a similar manner. The analytical sample was pre300 .'j 7G.: pared by three distilllations through a short path still and did not crystallize; it had n Z o D1.4975. 07) 3 4x Anal. Calcd. for C I ~ H ~ ~ N ZC, O Z68.53; : H, 10.07; N, Diacid of SV (ST1) 9.99. Found: C, 68.66; H, 10.12; N, 0.84. ~~-Tetrahydrophthalaldehyde (111) .-To a cold ( 0 ' ) solu..in 4 . 11 q q tion of 38.0 g. of tetramethyltetrahydrophthalamidc (11) in 277 .>.,>4 :t niiyture of 700 cc. of ether and 200 cc. of tetrahydrofuran, 2% 3 , SO 9 0 g. of finely powdered lithium aluminum hydride w
