[CONTRIBUTION FROX THE
DANIEL SIEFF RESEARCH INSTITUTE]
SUBSTITUTED STILBENES AND 1,4-DIPHENYLBUTADIENES. PART 11. SYNTHESIS AND PROPERTIES O F MONOHALOGENO DERIVATIVES FELIX BERGMANN, JAEL WEIZMAN,
AND
DAVID SCIIAPIRQ
Received M a y 5 , 1944
The Perkin reaction is the method most commonly used for the synthesis of substituted stilbenes. However, its applicability is frequently restricted by the inaccessibility of the reactants. The Meerwein reaction, on the other hand, is based on the coupling of cinnamic acids with diazotized amines which are, in general, readily available. Despite this obvious advantage, the latter method has been applied in but a few cases since the original publication of Meerwein in 1939 (1). Fuson and Cooke (2) used the reaction for the preparation of 4-carbalkoxystilbenes from alkyl p-aminobensoates, and in this laboratory it has been used with substituted naphthylamines (3). Furthermore, the vinylog of cinnamic acid, cinnamalacetic acid, has been used as the second reactant. This extension of the Meerwein method permits the synthesis of unilaterally substituted 1,4-diphenylbutadienes and has since been used by Bachman and Hoaglin (4) for the preparation of l-(o-nitrophenyl)-4-phenyl-l,3-butadiene. Koelsch ( 5 ) found that, in contrast to all other a,&unsaturated acid derivatives, which add the aryl residue at the a-carbon atom, acrylonitrile or acrylic esters combine with the diazotized component through the &carbon atom. The theoretical significance of this observation nil1 be discussed below. I n recent years we have applied the Meerwein reaction in a large number of cases with the purpose of determining the limits of its applicability and of elucidating its mechanism. In the present paper we describe three isomeric monochloro- and monobromo-stilbenes and the chlorodiphenylbutadienes. Meerwein originally used only o- or p-substituted anilines in the reaction. We have found that meta-derivatives also react, the same observation having been made in the meantime by Koelsch ( 5 ) . Usually the yield decreases in the order para > meta > ortho, and the ortho-substituted products as a rule are so impure that the usual means of isolation, e.g., distillation or crystallization, are unsatisfactory. In these cases the easy conversion of the products into the di- or tetra-bromides, respectively, has been used to advantage. Two standard methods for the regeneration of the unsaturated compounds from the bromides were used: (a) boiling in quinoline solution [the original method of Pfeiffer (6), who used pyridine for the same purpose, did not succeed in a number of cases] and (b) treatment of the bromides with potassium iodide in acetone solution. With either method the tetrabromides lose all four bromine atoms at once Debromination with potassium iodide proceeded in all cases a t room temperature. Although no direct comparison of stereoisomeric pairs as to rate of reaction was possible, it is indicated by the work of Young, Pressmann, and Coryell (7), that the bromides of trans-stilbenes react over a hundred times as rapidly as those of 488
409
STILBENES AND DIPHENYLBUTADIENES
the cis-derivatives. The easy and complete removal of bromine, therefore, makes it, probable that the stilbenes and diphenylbutadienes which are formed in the Meerwein reaction possess the trans and trans ,trans configuration, respectively. This conclusion is in accord with other chemical evidence which has been brought forward previously (3, 4). TABLE I MONOHALOGENO STILBENES AND DERIVATIVES SUBSTITUENT
Sone .......................... o -C! hlor o . . . . . . . . . . . . . . . . . . . . . . . m-Chloro. . . . . . . . . . . . . . . . . . . . . . p-Chloro.. . . . . . . . . . . . . . . . . . . . . o-Rromo., . . . . . . . . . . . . . . . . . . . . m-13romo . . . . . . . . . . . . . . . . . . . . . p-nromo . . . . . . . . . . . . . . . . . . . . . . . (8
1) I :
li
I-
.I .I
1
M.P.,
"c
M.P. OF DIBROMIDE
124
"c
M.P. OF DIBENZYL
237 1s2u 166 1906 181 166 202b
4OQ
74 129**0 34 89 139
OC
52 liquid liquid 49 7 ?
32d
Wages and Terzner, Ber., 36,3965 (1902) report the m.p. 176' for the dibromide Anschutz, Ber., 60, 1320 (1927). v . Wztlther and Wetzlich, J . prakt. Chem., 61, 196 (1900). Speer and Hill, J . Org. Chem., 2, 139 (1937).
TABLE 11
SUBSTITUENT
1 I-
None.. . . . . . . . . . . o-Chloro . . . . . . . . . tn-Chloro . . . . . . . . p-Chloro . . . . . . . . .
1
1
MONOCHLORO-1 ,4-DIPHENYLBUTADIENES M.P.,
'c
152 110 112 161
~
FLUOXESCENCE
blue blue blue blue-violet
M.P. OF
M.P. O?
c o ~ ~ ~ ~ ~ B;TETRAP'O ~"I D E ,
none brown violet red-violet
C
236 220 202 221
~207 179 188 218
52 liquid liquid
35
I
In Tables I and 11, which summarize our results, several general features are recognizable. The melting points show a regular trend in nearly all cases. Since only one factor, the position of the substituent, is varied in all series, the substances are suitable for comparison. First may be noted the enormous differences between the saturated dibenzyls or diphenylbutanes and the conesponding di- or tetra-bromides. It is known that these bromides assume a more or less rigid structure due to the repulsive forces between the bromine atoms
410
BERGMANN, WEIZMAN, AND SCHAPIRO
themselves and between bromine atoms and the benzene ring (f9.l Similarly, in the adducts of the various diphenylbutadienes with maleic anhydride (I) two kinds of intramolecular movements are theoretically possible, free rotation of the benzene rings about the C-aryl bonds, and oscillative puckering of the central cyclohexene ring. Both are overcome by electronic interaction between the phenyl groups and the carbonyl groups in the anhydride ring. We may therefore conclude that the rigid structure of such molecules is associated with a comparatively high melting point, ic., with high intermolecular attractive forces, resulting in high lattice energy. On the other hand, the free intramolecular rotations or oscillations in the saturated hydrocarbons diminish the lattice energy. In the unsaturated compounds, in which conjugation of the olefinic links with the aromatic rings occurs, the free rotation of the phenyl ring is restricted by resonance, which imparts some double-bond character to the C-aryl bonds. The substituents then modify the degree of resonance. Halogen in the para position enhances resonance, as should also an ortho substituent. Here, horn-ever, the inverse effect is observed, partly due to steric hindrance-bromine has a more pronounced effect than chlorine-and partly due to direct electronic interaction with the adjacent double bond. A meta substituent can exert only an inductive effect, which in this case enhances free rotation. A striking difference between the chloro- and bromo-stilbenes is observed during catalytic hydrogenation. All three isomeric chlorostilbenes are reduced quantitatively to the chlorodibenxyls. On the other hand, the bronio compounds split off hydrogen bromide simultaneously with saturation of the olefinic bond, although the reaction stops after the absorption of about one mole of hydrogen. The product consists of a mixture of dibenxyl and bromodibenzyl which can not be separated satisfactorily. It is known that in catalytic hydrogenations halogencan be removed from aromatic rings in the order I > Br > Cl(l0). However, in all these cases, the halogen has to be activated by further substituents, c.g., nitro groups. No such activating influence has so far been recognized for a vinyl group as an additional substituent. The nature of this influence is not yet clear. In this connection it is of great interest that in the reaction of halogenated stilbenes with alkali metals, even chlorine is quantitatively removed from the benzene ring. This peculiar reaction will be described in a forthcoming paper. EXPERIMENTAL
All melting points are uncorrected. 1. o-Chlorostilbene. (a) Meerwein reaction. A solution of o-chloroaniline in water (lo0 cc.) and hydrochloric acid (80 cc.) was diazotized a t 0" with a solution of sodium nitrite (15 g.) in water (30 cc.). The clear diazo solutions was added to a cooled solution of cin1 T h a t not merely the mass or the size of the substituent is responsible for the high melting point, is indicated by comparison of trans-stilbene dibromide (227") with hexahydrostilbene dibromide (153"), in which one phenyl ring has been completely reduced (9). * For the successful accomplishment of Meerwein reactions the preparation of completely clear diazo solutions is the fundamental condition. A simple method, which permits quantitative diazotization in dilute acid of even the weakest aniline bases, will be published later.
STILBENES AND DIPHENYLBUTADIENES
41 1
naniic acid (30 g.) in acetone (250 cc.). After addition and solution of sodium acetate (44 9.) a solution of cupric chloride (8.5 g.) in water (20 cc.) was added. The temperature was allowed t o rise slowly to 20", when gas evolution began. Stirring was continued at 23-24' for 3 hrs. At the end of the coupling reaction two layers had formed in the mixture. The upper layer consisted of a dark green oil, and the lower layer of a bright green wateracetone mixture. After steam distillation the oil was dissolved in benzene, washed several tiines with 3 N ammonium hydroxide, and then with water. Distillation yielded 7 g. of a red oil boiling a t 150" a t 0.1 mm. The red color could not be removed by repeated distillation and the oil did not crystallize. For purification i t was converted into the dibromide by treatment with excess bromine in carbon tetrachloride. The dibromide crystallized in long rods from petroleum ether (130") and melted a t 181-182". The dibromide was dissolved in acetone and treated with 4 moles of potassium iodide. Reaction proceeded quickly a t room temperature and was completed by heating on the writer-bath for a n hour. Distillation gave a nearly colorless oil boiling a t 145' at 0.03 mm.; yield 4 g. or 9%. The substance crystallized on standing, and melted at 39-40'. ( h ) GTignard reaction. The reaction between benaylmagnesium chloride (0.15 mole) and o-chiorobenzaldehyde (0.1 mole) yielded an oil, from which by distillation a fraction boiling a t 145" a t 0.05 mm. was isolated. I t crystallized on trituration with methanol, and was recrystallized from the same solvent, melting at 75". The substance is the expected carbinol, benzyl-o-chlorophenylcarbinol;yield 30%. The same carbinol resulted in about 70% yield from the interaction of o-chloroiodobenzene and phenylacetaldehyde. A n a l . Calc'd for C14H&IO: C, 72.4; H , 5.6. Found: C, 72.2; H, 5.3. T e carbinol is remarkably resistant t o dehydration. Potassium bisulfate at 180' was ineffective. When the carbinol was acetylated with acetic anhydride and the acetate heated to 300" for one hour, deacylation occurred. The o-chlorostilbene distilled at 208210" at 30 mm.; yield 8 0 ~ o . Reduction of o-chlorostilbene with palladium-barium sulfate in ethanol gave an oil boiling at 138-139" a t 3.5 mm., n? 1.5850. Anal. Calc'd for C14H&l: C, 77.8; H, 6.0. Found: C, 77.4; H, 6.2. 1. m-Chlorostilbene. The hleerwein reaction was carried out as described above with the same quantities of material. Evolution of gas took place a t 16-20". The oily product was distilled i n V U C Z L O , and boiled at 175-180" at 0.2 mm. The yellow-red distillate crystallized immediately. It was triturated with ligroin and recrystallized from ethanol, m.p. 73-74"; yield 7 g. or 16%. Anal. Calc'd for ClrHllCl: C, 78.5; H, 5.1. Found: C, 78.3; H, 5.2. The dibromide crystallized from petroleum ether (130") in branched leaflets, m.p. 166". Anal. Calc'd for C14H11Br~Cl: C, 44.9; H, 2.9. Found: C, 45.0; H , 2.6. m-Chlorostilbene (1.3 9.) in ethanol (20 cc.), when reduced with Raney nickel absorbed 130 cc. of hydrogen in 5 minutes ( t , 13'; p , 762 mm.); calc'd 142 cc. Distillation of the product gave a yellow oil boiling at 148" a t 3 mm. which did not crystallize, n: 1.5790. .4nal. Calc'd for C14H&1: C, 77.8; H , 6.0. Found: C, 78.1; €I, 5.8. 3. p-Chlorostilbene. Reaction occurred a t 14-16'. The residue which remained after steam distillation u-as dissolved in benzene and washed as above. After removal of the solvent a crystalline residue was obtained directly, which crystallized as shiny leaflets from isopropyl alcohol, m.p. 129'; yield 40%. The dibromides formed prismatic plates from petroleum ether (130") and melted a t 189-190".
p-Chlorostilbene (5 g . ) in ethanol (75 cc.), when reduced in the presence of Raney nickel absorbed in one hour 525 cc. of hydrogen ( t , 16"; p , 762 mm.); calc'd 550 cc. The residue crystallized on trituration with a little methanol, and melted a t 49".
412
BERGMANN, WEIZMAN, AND SCHAPIRO
Anal. Calc'd for C14HI:Cl:C, 77.8; H, 6.0. Found: C, 77.6; H, 5.8. 4 . o-Bromostilbene. The Meerwein reaction was carried out as before. The reaction temperature was 23-27'. Distillation i n vacuo yielded a red-brown oil which was purified via the dibromide. The dibromide was recrystallized twice from petroleum ether (130") and melted at 181'. Anal. Calc'd for C14HllBrl:C, 40.1; H, 2.6. Found: C, 40.4; H , 2.9. Decomposition of the dibromide with potassium iodide in acetone yielded a yellowish oil which boiled a t 143-145' a t 0.15 mm.; yield 4 g. or So/,. After several days the oil crystallized in big plates melting at 34'. Anal. Calc'd for ClrHltBr: C, 64.9; H, 4.2. Found: C, 64.9; H, 4.0. o-Bromodibenzyl. (a) Catalytic reduction of o-bromostilbene in ethanol over Raney nickel gave an oily product boiling at 135-140' a t 3 mm., which according to analysis consisted of a mixture of hydrocarbon and brominated compounds. Anal. Calc'd for C I ~ H ~ C, ~B 64.4; ~ : H, 5.0. Found: C, 75.0; H, 5.8. (b) Sandmeyer reaction with o-aminodibenzyl ( 1 1 ) . o-Aminodibenzyl (11 g.) was converted into its sulfate n-ith 12 g. of sulfuric acid and 135 cc. of water. The sulfate was diazotized with 5 g. of sodium nitrite in 15 cc. of water at 0-5". The filtered diazo solution was added dropwise to a warm (40") solution of cuprous bromide (5 g.) and the reaction mixture was stirred for half an hour a t 45". The semi-solid precipitate was dissolved in ether, the solution filtered and washed with sodium hydroxide solution and dilute hydrochloric acid. Rectification gave 7.5 g. of a n oil which boiled a t 115" a t 0.3 mm. Further distillation gave s fraction boiling a t 160" a t 22 mm. which crystallized immediately, and melted at 51". It was halogen-free and gave no melting point depression in mixture with dibenzyl. Another fraction boiling at 180" at 22 mm., showed on analysis about 79% carbon. This fraction, therefore, again consisted of a mixture of dibenzyl and o-bromodibenzyl. Anal. Found: C , 79.4; H, 6.2. 6. m-Bromostilbene. The diazo compound reacted in this case a t 25". The reaction mixture, after standing overnight, deposited a dark oil which was taken up in benzene. On washing with ammonia a heavy emulsion was formed. Separation of the benzene and water layer was facilitated-by addition of concentrated sodium chloride solution. The benzene solution, after evaporation of the solvent, left a resinous residue which was extracted several times with boiling ethsnol. The ethanol solution was boiled with charcoal and the solvent partly distilled off, The residue crystallized on trituration with ethanol and acetone. Recrystallization from ethanol gave clusters of needles, and from petroleum ether (SO'), twinned plates melting a t S9-90"; yield 17%. Anal. Calc'd for CI4HIIBr: C, 64.9; H, 4.2. Found: C, 64.7; H , 4.3. The dibromide, which was prepared in chloroform solution, formed long lance!s from petroleum ether (130") and melted a t 166'. Anal. Calc'd for Cl4HtlBi-S: C, 40.1; H, 2.6. Found: C, 39.9; H, 2.9. m-Bromostilbene (0.8 9.) in ethanol (25 cc.) absorbed 75 cc. of hydrogen during about one hour in the presence of Raney nickel ( p , 760 mm.; t , 16"). Then absorption came to a standstill. Calc'd (for 1 mole of hydrogen) 73 cc. The oily product was distilled i n vacuo, b.p. 140-145' at 0.5 mm. Anal. Calc'd for CI4HlaBr;C, 64.4; H, 5.0. CI4HlsBr CI4HI4: C, 75.8; H, 6.1. Found: C, 77.3; 77.4; H , 6.5; 6.3. Analysis shows that the mixture is composed of about 50% bromodibenzyl and 50' c dibenzyl.
+
STILBENES AND DIPHENYLBUTADIENES
413
6. p-Bronwstilbene. Reaction occurred at 24". The benzene residue crystallized immediately from isopropanol, and melted a t 139". Seventeen grams of p-bromoaniline yielded 6 g. of p-bromostilbene, or 23%. The dibromide crystallizes from xylene-petroleum ether (130")in prismatic plates melting at 201-202". p-Bromostilbene (1.7 8.) in ethanol (30cc.) absorbed 145 cc. of hydrogen in the presence of Raney nickel (1, 16"; p , 760 mm.); calc'd 155 cc. The oily residue was distilled, boiling at 155-160' a t 0.5mm. Analysis shows that i t consists almost exactly of an equimolecular mixture of dibenzyl with bromodibenzyl. Anal. Calc'd for Cl4H11Br CIdH1,: C, 75.8; H, 6.1. Found: C, 75.2;H, 6.0. 7. o-Chlorodiphenylbutadiene. A solution of o-chloroaniline (6.4 g.) in concentrated hydrochloric acid (6 cc.) and water (20cc.) was diazotized with a solution of sodium nitrite (4.2g.) in water (8cc.). The clear diazo solution was added to a solution of cinnamalacetic acids (8.8 g.), in acetone (250 cc.). A cloudy precipitate was formed. After addition of sodium acetate (10g.) and cupric chloride (29.) the temperature was raised slowly. Reaction started a t 20" and the solution gradually became clear. After steam distillation, the residual oil was dissolved in chloroform and washed with sodium hydroxide. Distillation in a high vacuum gave about 2 g. of a main fraction boiling at 220' at 0.04 mm. This oil crystallized on trituration with methanol-acetone. Recrystallized twice from ethanol, formed clusters of leaflets melting at 110'; the l-(o-chlorophenyl)-4-phenyl-l,3-butadiene yield 1.2 g. or 10%. Anal. Calc'd for CldI&l: C, 80.0; H, 5.4. Found: C, 79.9; HI 5.6. Brominstion was carried out in chloroform solution. The oily residue wv&8triturated with ethanol and recrystallized from butyl acetate, forming plates which melted at 220'. Anal. Calc'd for C1&1,Br4C1: C, 34.3; H, 2.3. Found: C, 33.8;HI 2.2. Catalytic reduction in ethyl acetate over palladium-barium sulfate gave a greenish oil boiling at 180" at 0.05 mm. Anal. Calc'd for ClsH1rCl: C, 78.7;H, 7.0. Found: C, 78.3;H, 6.6. l-(o-chlorophenyl)-4-phenyl-l,3-butadiene (0.15 9.) and maleic anhydride (0.6 9.) were melted together a t 110" and the liquid mixture heated on a water-bath for one hour. The maw was dissolved in acetic acid and the reaction product (0.1 g.) precipitated b y water. It was recrystallized twice from butanol-acetic acid, forming twinned plates which melted at 178-179'. Anal. Calc'd for C&t&lOS: C, 71.0; H, 4.4. Found: C, 71.3;H, 4.1. 8. i-(rn-Chlorophenyl)-4-phenyl-l ,%butadiene. Reaction occurred at 35". After steam distillation, a semi-solid brown mass deposited on the bottom of the flask. The water was decanted m d the residue kneaded with acetic acid. From ethanol, 3.5g. or 29% of twinned leaflets were obtained melting a t 114". Anal. Calc'd fbr c , & € l ~ C lC, : 80.0; H, 5.4. Found: C, 80.0; H, 4.9. The tetrabromide crystallized from petroleum ether (130") in plates melting at 202'. Anal. Calc'd for CI&l,Br&l: C, 34.3;H, 2.3. Found: C, 34.7;H, 2.4. Catalytic reduction: 1 g. of l-(m-chlorophenyl)-4-phenyl-l'a-butadiene in glacial acetic acid (25 co.) absorbed the required amount of hydrogen in 20 minutes. Distillation gave a nearly colorless oil which boiled at 190" at 0.06 mm.
+
-__ * The method of
Plati, Strain, and Warren (12)proved much superior t o previous syntheses. In our experience, i t is essential to recrystallize the cinnamalacetone from ligroin before oxidation with sodium hypochlorite, in order t o secure an acid of good quality and in satisfactory yield.
414
BERGMANN, WEIZMAN, AND SCHAPIRO
Anal. Calc'd for C&,Cl: C, 78.7; H, 7.0. Found: C, 79.1; H, 7.1. The maleic anhydride adduct was formed by heating on a water-bath 1-(m-chloropheny1)4-phenyl-1,3-butadiene (0.35 9.) and maleic anhydride (1 9.) for 12 hours. The product was isolated by treatment with dilute acetic acid. S.ecrysta1lization from butyl acetatepetroleum ether (130') gave clusters of plates melting a t 188'; yield 0.3 g. Anal. Calc'd for C20H&lOj: C, 71.0; H, 4.4. Found: C, 70.9; H, 4.3. 9 . 1 - (p-Chlorophenyl)-.&phenyE-l,%butadiene. Reaction occurred a t 23". The residue from the steam distillation crystallized directly on trituration with acetic acid. The substance (11 9.) was first recrystallized from acetic acid, then from petroleum ether (130'), forming flat plates which melted a t 161'; yield of the pure product 4 g. or 33%. Anal. Calc'd for ClSH&l: C, 80.0; H, 5.4. Found: C, 80.3; H, 5.4. The tetrabromide crystallized in clusters of plates from petroleum ether (130") with addition of a few drops of xylene. It melted at 224'. Anal. Calc'd for CldHltBrrCl:C, 34.3; H, 2.3. Found: C, 34.1; H, 2.0. Catalytic reduction of l-(p-chlorophenyl)-4-phenyl-l, 3-butadiene (1 g.) over Raney nickel in warm acetic acid (25 cc.) proceeded during 10 minutes; 200 cc. of hydrogen was absorbed ( p , 759 mm.; t , 22"); calc'd 190 cc. The product was distilled i n vacuo, boiling at 175-180' at 0.6 mm., and crystallized spontaneously, melting a t 35". Anal. Calc'd for ClflHltCl: C, 78.7; H, 7.0. Found: C, 78.5; H, 7.4. The maleic anhydride adduct of l-(p-chlorophenyl)-4-phenyl-1,3-butadiene (0.4 g.) with maleic anhydride (1 9.) was formed on heating the mixture on a water-bath for five hours. The mass was dissolved in hot acetic acid. On cooling, the adduct precipitated. From glacial acetic acid, clusters of plates were formed melting a t 212'; yield 0.4 g. Anal. Calc'd for C20Hl&10t: C , 71.0; H, 4.4. Found: C, 71.4; H , 4.2. SUMMARY
By means of the Meerwein reaction, the three series of monochloro-, monobromo-stilbenes, and monochloro-1 ,4-diphenylbutadienes and certain derivatives were prepared. The regular variations in melting points, observed in all three series, are related to the different factors which influence the rigidity of molecular structure. On catalytic hydrogenation, all the chloro derivatives give the saturated chloro compounds, whereas the bromine is removed from the aromatic ring to about 50%. REHOVOTH, PALESTINE. REFERENCES (1) (2) (3) (4) (5) (6) (7) (8) (9) (10) (11) (12)
MEERWEIN,BUCHNER, AND EYSTER, J. prakt. Chem., 162,237 (1939). FUSON A N D COOKE, J . Am. Chem. Soc., 82, 1180 (1940). F. BERGMANN AND WEINBERG, J. OTg. Chem., 8, 134 (1941). AND HOAGLIN, J . Org. Chem., 8, 300 (1943). BACHMAN KOELSCH, J . Am. Chem. SOC.,86,57 (1943). PFEIFFER, Be?-., 46, 1810 (1912). YOUNG,PRESSMANN, AND CORYELL, J. Am. Chem. Soc., 61, 1640 (1939). IMCCULLOUGH, J. Am. Chem. Soc., 62, 480 (1940). TIFFENEAU A N D KURIAKI, Compt. rend., 209, 465 (1939). WINANS,J . Am. Chem. SOC.,81, 3564 (1939). RUGGLIAND STAUB,Helv. Chim. Acta, 20, 37 (1937). PLATI,STRAIN,AND WARREN, J . Am. Chem. SOC.,86, 1274 (1943).
