4400
S.'iCL
G.
C O I i E X , SHU-HSI
HSI.W,EUGENE SAKL.ID .\SD
CIlI HV.1 \i'.\NG
lrol. i ! )
triazole in 300 mi. of concd. hydrochloric acid and 150 nil. tion of the ethereal si~~lutioti gave 8.8 g. ((io of concd. nitric acid was heated for one week under reflux. product. Fractionation gave an analytical The solution was cooled and the crystalline product collected 117' ( 1 2 t n ~ n . ) ;A,,, 276(s)(4.12),281(4.14),' on a filter, washed and dried t o give 1.2 g. ( 6 2 ' L ) of crude 11izaZ. Calcd. for C8H9S3:S ,28.55. Found: S ,28.72. product. Recrystallization from nitronietliane gave the &l'-(Benzotriazolyl)-butyramide.-To 1 .O g. (O.llOA i n o l e ) pure product, m.p. 25(i-260°. On admixture this material does not depress the m.p. Of an authentic sample o f 1,,5,6,7- o f p-1'-(benzotriazoly1)-butyric acid was added 4.0 ml. rif thionyl chloride. .kfter solution was cnmpIete, tht' tetrachlorobenzotriazole. \vas added dropmise with stirring t o lt5 rnl. of cril[l 2-Methyl-4,5,6,7-tetrachlorobenzotriazole from 2,s- mixture Dimethylbenzotriazole.--I solutioii of 1 .d g. ( 0.01 mole) concd. ammonium hydroxide. The product was collectrtl of 2,j-dimethylbenzotriazole in 80 r n l . of coticd. h>-dro- on a filter, washed with water and dried to give (l.:3 g . which was 30',;; of t h e theoretical amount. Sr chloric acid and 80 nil. of concd. nitric acid w:ts heated under reflux for 10 hr. The solution was cooled a n d the crystallizations from mater gave an analytical sample, 111.p. ln4-10bo; Am, 256(3.80),262(3.80), 280(3.61). crystalline product collected 011 a filter, iv:ihed :~nddried. .-lna/. Calcd. for ClcHI2S4O:S , 27.14. Found: 5 . Three recrystallizations of this solid from inethanol ga\-e 27.42. the pure product, m.p. 181-183". On adniixturt' this product does not depress t h e rn.p. of an autlictitic s:irnple Ultraviolet Absorption Data.-Ultraviolet absi!rpti( J t l o f 2--tneth~l-4,5,fi,i-tetrachlorobe1izotriaz1~lc. ~iie:isureiiietitswere macle with a Beckrnan D U photoclectric: 2,5-Dimethylbenzotriazole.--.\ solution of diazoniethanc spectrophotometer with 1.00-cnl. silica cells and a li>~clrogcit in ether was added slowly to 13.3 g. (0.1 mole) of 5-tnethyl- discharge lamp as the light source. T h e measurement\ were made in methanol solution. T h e data are recorded i l l benzotriazole dissolved in ethcr until L: qlight y c ~ l l i ~color ~v persisted. T h e resulting solution was refluxed until the the preceding Experimental sections as rvave lengths itt slight excess of diazoniethane xviis removed a n d dried over which maxima or shoulders( s) occur with the corresponding anhydrous sodium sulfate. Dry li>-drogen chltrrirle v z i s log e in parenthese.. then bubbled through the ethereal solution. Tlie precipitated hydrochlorides were r e t n ~ ~ v eti!d filtration. I?vapor:iTAX-ISYIILE, KEST~CKY
[CCJSTRlI3VTIOS O F THE SCHOOL O F SZIEUCE,
BRAYDEIS VSIVERSITY]
Preparation and Decomposition of a Cyclic Azo Compound. 3,6-Diphenyl-3,4,5,6-Te trahydropyridazine BY SAUL G. COIIEN,SHT-HSIHsI.\o,'~ ECGEXE S.XKLAD AXD CHI Hc.1 ~ I - . I N G ' ~ RECEIVED MARCH26, 1937 The azo compound I w a s prepare:l by addition of diethyl azndicarbouylate t o l,~-diphenyll~utadiene-l,~'~, hydrogeuatiotl. hydrolysis, decarboxvlatioti and autosidation ; :3Y7mp, log 6 2.89, displaced from 345 mp r j f trans-aliphatic azo comsol\-ents, including solutions containing styrene, with essentially quailpounds. Compound I decompose. in h~-drocarl~on titative yield of nitrogen, a n d :ilx,:it If)()times a s fast a t 8 : ) " as acJ-clic analogs. Solid I , heated a t about 125", Icd i i i part t o styrene and in part tlJrearraugement t o the hyrir:tzone txutomer. :Ittempts t o obtain products of addition of the biradiii cal 1,1-diphenyl-l,4-butadiyl t o stilbene nnd quinone failed T h e mode ( J f decomposition of I and its possible activity polymerization initiator 3re ciiycuswi.
be formed, would be of interest both for a study of its chemistry as such and because it is identical with the product of "tail-to-tail" reaction of two molecules of styrene which had once been proposed ,CH? cIr7 \ :is the active intermediate in the initiation of th.e CsE C H CH CsH thermal polymerization of styrene, ' but which is \ 'S-IS 110 longer supported.,5 I Preparation of Compound I.- the preparation of position, the biradical 1,4-diphenyl-l,4-butadiylthe azo compound I has been reported6 by (1) (IJ), CsH5CHCH2CH2CHC6Hj. Compound I, condensation of two molecules of a-chloroacetobecause of its cyclohexene type structure would be phenone semicarbazone to a compound which apa cis-azo compound, while acyclic aliphatic azo pears to be 2-carbamyl-:~,l,.5-trihydro-.3,r,-diphenylcompound are normally tuiins, and it seemed of in- pyridazine (a1 followed by ( 2 ) treatment with soterest t o compare its physical properties, its ease dium ethoxide a t l (ioo. The product was converted of decomposition and its products of decomposition to ,'~,T,-diphen~lp!-rid~~~i~ie by treatment with browith those of the closely related timzs-acyclic com- mine water and was assigned structure I. l y e repounds, 1-azo-bis-1-phenylethane or 1-azo-bis-1- peated this preparation and found that the comR K pound had an absorption maximum a t 291, my, log I I t 4.19, which has been characteristic of the hydraphenylpropane, CsH6-CH--N=N--CHC6H6(111), zones tautomeric with the acyclic azo compounds R = CH80rCnH5. The 1,4-biradicalII,whichmight in th.is a n d end absorption in the near (1) (a) T h i s paper is derived in p a r t from a thesii s u b m i t t e d b y ultraviolet but no maximum in the range of 300-Shu-hsi Hsiao in partial fulfillment of the degree of I I a s t e r of Art, i n 400 nip which would be characteristic of the azo Chemistry, Brandeis Univerqity. ( b ) F o r preliminary reiiort see compound. This. coupled with the strongly C . H . W a n g , S . Hsiao, E: Saklar! and S C . C'rihen, THISJor R S A I . , 79,
As part of our study of the chemistry of azo compounds" we undertook to prepare 3,G-diphenyl3,4,5,O-tetrahydropyridazine (I) and by its deconi-
, IJ 1: R l I a y , , i h r ~ i ,6 5 , 2824 (1913). a>-u,i h i c i , 75. ($133 (19.53). H o o w v e e n arid C. V. v a n Hoopstraten, h'rr l j ' o ? ,
2lil>l fI9r,T
i'crhen , i t i d c'
I T \\'xn,c, i f , i / , 77, I'lii .inr1
n. R
>,'"''I",
(10
;!'>d
7 2 , :3017
hug. 20, 1957
4401
3,6-DIPHENYL-3,4,5,6-TETRAHYDROPYRIDAZINE CHART1
ionizing conditions of preparation, which would favor tautomerism, and the high thermal stability of the material, lead us to assign t o it the tautomeric structure IV, m.p. 157-159’. CONHr
“\ i
//SCsH6-c
1
C02CzHj
CH
//
CH
/ \
A/ -
+
I
100
2-
CO?C,Hj
I
\
CH
SC02CzHi
CH
SCO?CzH:,
-0’Ij
I1
\C H
CH
‘CH’ CI ~ HVI~(95% yield)
C6Hs
(4 CcHjCH \XH-&
I
CH
CH-CaHi \CH~-CH? / /CH,-CH?
c 613:,
CsHb
I 1 CC&
IV
Compounds of type I11 have been prepared by conversion of the relevant ketone CeH&OR to the azine, hydrogenation to the hydrazine and oxidation to the azo c ~ m p o u n d . ~However, the reactions of y-diketones necessary for the formation of cyclic azo compounds related to I do not proceed this simply. The reactions of l,%-dibenzoylethanes and a c e t o n y l a c e t ~ n ewith ~ ~ ~ hydrazine ~ do not lead to isolation of the pure azine, ;.e., the 4,S-dihydropyridazine, but to a mixture from which the disproportionation products, the pyridazine and the tetrahydropyridazine, each substituted a t the 3and 6-positions, may be obtained. Again the conditions of formation of the tetrahydro compound would indicate t h a t the one from dibenzoylethane is probably the more stable tautomer IV. In our work treatment of 1,2-dibenzoylethane with hydrazine led to a mixture V which was apparently not readily separated into its components. Xttempted hydrogenation t o the hexah.ydropyridazine over platinum oxide in ethanol containing hydrogen chloride led to th.e hydrazone IV in about 50y0yield, while when the reaction was attempted in acetic acid, 3,6-diphenylpyridazine was obtained, also in about 50% yield. While we cannot rule out t h a t these products were formed by disproportionation of the dihydro compound in the presence of the hydrogenation catalyst, they may well have comprised the crude reaction product V. Attempted reduction of the hydrazone I V or the mixture V with lithium aluminum hydride was not successful, although some of th.e azo compound I may have been present in the product from V. I t seemed likely t h a t more vigorous reduction, as with zinc and hydrochloric acid, would lead to cleavage of the nitrogen-nitrogen bond.ll The azo compound I was prepared b y : (a) Diels-Alder addition of diethyl azo-dicarboxylate to 1,4-diphenylbutadiene, forming th.e adduct12 VI, (b) hydrogenation l 2 of the carbon-carbon double bond in VI, leading to VII, followed by (c) saponification of the hydrogenated adduct, decarboxylation and, apparently, autoxidation in ether solution to form I (Chart 1). Saponification of the adduct VI in methanol led, as reported,I2 to the tautomeric product IV instead of to the A4s5( 8 ) C. Paal and E. Dencks, THISJOURNAL, 36, 491 (1903). (9) E. E. Blake, Compt. rend., 170, 1324 (1920). (10) C. G. Overberger, N. R . Byrd and R . R. Mesrobian, THIS J O U R N A L , 7 8 , 1961 (19%). (11) 0 . Diels and K. Alder, A n n . , 460, 237 (1926). ( 1 2 ) K . Alder and H. Kiklas. ibid.. 685, 81 (1954)
I
CH
C
/ \
CH2 S I
/
kH
CH,
CH2 CH
CH I
I
C6H5 VI1 (Tomo yield)
CgH5 IY (65% yield)
CsHj
I
CH CH?
I
CH2
I ’
C&
CeHj
I
1
CH
CH
/ \
/ \
N (0,) CH?
NC02-K+
A ether
SC02-KC
l1-
C ‘H’ C& I(20-457, yield)
NCO:C?H,
\ /
\ /
t,
CH \CH’
I
C&
- 1
CH2
CH2
-
SH I SH
\CH’
1
CsHj
-
compound. LVhile hydrogenation of VI did not, in our experiment, lead to a product of quite as sharp a melting point as reported, elementary analysis was satisfactory. Attempted acid hydrolysis of both the adduct VI and the hydrogenated adduct VI1 led t o recovery of the respective starting materials. Alkaline hydrolysis of the hydrogenated adduct, compound VII, in glycol in the presence of air was reported12 to lead to the tautomeric product of oxidation IV, while saponification in the absence of air led to impure hexahydrodiphenylpyridazine.12 In our work, alkaline hydrolysis of VI1 in glycol under nitrogen followed by attempted precipitation of the hydrochloride of the hexahydro compound from the ether extract of the saponification product led to the hydrazone IV. Observation of some crystals, which decomposed a t 110’ with gas evolution, in a portion of the product which had not been treated with hydrogen chloride led to successful synthesis of 1. The hydrolysis of VI1 was carried out by treatment with. potassium hydroxide in refluxing methanol under nitrogen, decarboxylation apparently occurring concomitantly. The solution was diluted with water and extracted with ether, either with or without prior neutralization with hydrochloric acid. Concentration of the dried ether solution led to the azo compound I, autoxidation of the hydrazo compound apparently taking place a t this stage, since autoxidation during
4402
SAULG. COHEN,SHU-HSIHSIAO,EUGEXE SAKLAD AND CHI H U AI%-;AKG
the hydrolysis would lead t o the hydrazone tautomer.'* The compound melted with gas evolution when placed in a bath a t 110-120'; when heated slowly as in a normal melting point determination it sintered at 120°, discolored and melted a t 147154', apparently tautomerizing t o IV. The facile rearrangement makes isolation and characterization of I difficult. Preparation of a solution of I in acetic acid, followed immediately by concentration in vacuum, led t o isomerization to IT'. Preparation of a solution of I in benzene, followed by concentration in vacuum, did not lead t o rearrangement, I being recovered, dec. 120'. The ultraviolet absorption spectrum of I in cyclohexane showed maxima a t 287 mp, log e 3.49, and a t 387 m p , log e 2.89, the latter apparently to be attributed t o the 34.7 mp> azo linkage and being displaced from A,, characteristic of the aliphatic azo linkage, because of its cas character. Decomposition of 1.-Because of the relatively slow rate of decomposition of the acylic analogs of I (compound 111, R = CH?, half-life, 1.2.7 hr., l l O o ) , and the ready isomerization of I to IV, it seemed advisable a t first t o examine the nitrogen evolution from decomposition of I a t 133", wetted with a small amount of redistilled decalin. A high (cn. 90%) yield of nitrogen, obtained rapidly, indicated that thermal decomposition could be attained essentially completely without serious interference from rearrangement. The yield of nitrogen appeared somewhat less (cu. 80yc)when the decomposition was repeated a t 90'. I t was then found t h a t the decomposition could take place cleanly, in dilute solution (< 1%) in hydrocarbon solvents. Decomposition in decalin a t 133' and a t 100' led to about %yo yield of nitrogen. Decomposition in ethylbenzene that had not been freshly distilled led t o low, nonreproducible yields, rearrangement presumably taking place; distillation of the ethylbenzene led to high yields of nitrogen a t 100'. Since we would wish to examine compound I as a n initiator of polymerization and as a source of the biradical11, a possible intermediate in the thermal polymerization of styrene, the decomposition of compound I in 3.46 moles/l. styrene in ethylbenzene was examined briefly. Xitrogen evolution was rapid and essentially quantitative both a t 100 and a t 80'. The data on evolution of nitrogen are summarized in Table I. Observations made during the measurements of the evolution of nitrogen indicate t h a t decomposition was essentially complete in about 20 minutes a t 100' and t h a t the half-life at 80' was about 20 minutes. I n contrast, the half-life for decomposition of the acyclic analog C6H5CH(CH3)N= NCH(CH3)C6H6(111) is about 4 hr.3 a t 100'. I t may be estimated t h a t the first-order rate constant for decomposition of I a t 80' is about 6 X 10W4 set.-', while t h a t for I11 is about two orders of magnitude less, 4.5 X Apparently the cis-azo structure of I (possibly aided b y another factor to be discussed below) leads t o increased ease of decomposition, in addition to the shift in absorption maximum noted above. I t will be of interest t o evamine the kinetics of decomposition of cyclic azo compounds of this type. Extreme instability
Yo]. 79
had been reportedI3 for a seven-membered cyclic azo compound, but subsequent assigned a different structure t o the material. The sixmembered cyclic analog of azo-bis-isobutyronitrile was apparently too unstable t o be isolated."' B 24-memberedlj cyclic azo compound analogous t o I decomposed a t the same rate as the acyclic analog I11 (R = C P H ~ )and , had a n absorption niasimum a t 3.55 nip, characteristic of the acyclic cornpounds; the large ring presumably allowed the azo linkages to assume their normally preferred t r u r ~ s configurations. I t was of course desirable to ascertain, if possible, the nature of the hydrocarbon products of deconiposition. A sample of the azo compound I (0.03:< g.) was decomposed in the solid state under nitrogen, and the residue was worked up. The rearranged product IV was obtained in 3Oy0 yield, and it appears likely and not unreasonable that the isomerization occurs t o a greater extent under these conditions than in dilute solution in hydrocarboii solvents. The odor of styrene was detected readily immediately after the decomposition, and treatment of the filtrate, after remoiral of IV, with bromine in acetic acid led to styrene dibromide in F& yield (based on non-rearranged I ) . Since this product was isolated in only 17yoyield in a control experiment carried out under similar conditions, it may be t h a t half of the azo compound which decomposes is converted to styrene. The styrene may be formed (a) in a second reaction from the biradical I1 or (b) directly from decomposition of the azo compound into three fragments C J - I ~ C H C H ~ C H ~ C I ~--+ C ~ H 2C6HjCH==CI%? S (:L) CGHh
CeHa
C €I
CH
I
I
c
&5
CsHj
T h e latter course, leading directly t o three molecules and no radicals, might well contribute to the observed enhanced ease of decomposition of I . The rupture of the three bonds in process b need not be completely symmetrical, the two carbonnitrogen bonds being more completely broken in the transition state than the carbon-carbon bond and the transition state possibly having characteristics of the transition state of both processes a and b. This would contribute to increased ease of decomposition and allow both styrene and products of the biradical to be observed. Attempts were made t o find evidence for the formation of the biradical I1 by carrying out the decomposition of I in the presence of unsaturated material that might react with 11. In the presence of stilbene we failed to isolate the possible six-membered cyclic adduct, recovering part of the (13) C. G. Overberger, P. T. Huang and T. R Gihb, THISJor'RN.41 , 7 5 , 2082 (1R.53). 11 1) C C,. Orerberaer and R. S. Marks, ibid., 77, ?OR7 (lP.*,5> (13) C .G . Overberger and hl. Lapkin, i b i d . . 7 7 , 4b31 (1RJ3).
Aug. 20, 1957
TABLE I THERMAL DECOMPOSITION OF COMPOUND I EVOLUTION OF SITROGEN C m p d . I, Expt.
g.
Solvent, g.
T,''2 135 136 110
Mi.
Na
Yield,
TABLE I1 THERMALDECOMPOSITION OF COMPOUND 1 IN 3.46 M./L. STYRENE IN ETHYLBESZESE. POLYMER CONTEXT
0.0331 ,0422 .0194 .0203 ,0228 .0170 ,0199 ,0165 .0148 .0298
stilbene. In the presence of quinone the possible derivative of naphthohydroquinone was not found. I n addition to recovered quinone and quinhydrone, a small amount of the rearrangement product IV and a considerable quantity (47% yield) of the product of dehydrogenation of I or IV, 3,G-diphenylpyridazine, were obtained. I n order to obtain preliminary information about the efficacy of this potential biradical source as a polymerization initiator, the styrene-ethylbenzene solutions in which the azo compound had been decomposed in the nitrogen evolution experiments were examined for polymer contents and compared with blank solutions treated in the same way in the absence of compound I. The data are summarized in Table 11. In experiments carried out a t 100' (expts. 23, 24, 25, 26), the polymer was precipitated in methanol; an undesirably high yield of polymer was found in the blank run in the absence of azo compound I. After correction for this, i t appeared t h a t about 4 molecules of styrene had been polymerized per molecule of I originally present. I n experiments carried out a t 80' (expts. 34, 35, 36, 37), the volatile components were removed in vacuum until the residue was brought to constant weight; satisfactory low yields were obtained in the absence of I and the small corrections were made. It appeared t h a t about 8 molecules of styrene were rendered non-volatile per molecule of I originally present. Such a number has significance for comparison with other initiators only if (a) the rate of decomposition of the azo compound and (b) the fraction which is converted to radicals (as distinguished from styrene molecules) are known. Using the approximate rate constant, given before, and making the necessary corrections for concentration and temperature, we estimateI6 t h a t benzoyl peroxide would polymerize about 70 molecules of styrene per molecule of peroxide under similar (16) S. G Cohen, THISJOURIAL, 67, 17 (1916).
Polymer
%
90 0.050" 3.10 .060" 4.32 99 90 1.80 ,0505 ,040" 1.60 90 80 2.60 2.78" 135 108 2.37" 135 1.70 95 96 2.16" 2.00 100 17 1.70 96 1.90" 100 1.74b 1.29 82 100 20 2.76' 16 21 0.50 100 1.65' .0173 100 1.60 22 89 2 . 52c 2.85 27 ,0264 100 103 2 . 0gc 100 2.20 33 ,0215 99 1.S i d 1.40 23 ,0140 100 96 2.21d 100 2.13 24 ,0210 97 2.58 29 ,0253 1.97d 100 98 2.07d 100 2.20 31 ,0211 100 ,0207 34 2 . 23d 80 2.22 103 2.25 36 ,0223 2.12d 97 80 Decalin. Ethylbenzene (not distilled). Ethylbenzene (distilled). 3.46 moles/. styrene in ethylbenzene. 1 2 10 11 12 15 16
440.1
3,6-DIPHENYL-3,4,5,6-TETRAHYDROPYRID.%ZINE
Exp. Cmpd. I, T, no. m./L OC.
Time, min.
Sample, g.
Mole polymd. per mole cmpd. I
g. 70 23" 0.033 100 30 1 . 4 6 1 0.0361 5.8 4.3 24" ,035 100 30 2.112 ,0127 4 . 9 3 1 25O . , , 100 30 2.658 ,0199 1 . 8 26" . , . 100 30 2.089 ,0145 1 . 7 34' ,034 80 150 2.128 ,0842 8.7c 8 . 6 36' ,039 80 150 2.015 ,0897 9 . Y 8,s 3Sb . . . 80 150 2.115 ,0026 0 . 3 37' ... 80 150 1.952 ,0011 0 . 1 Sample was diluted with methanol and insoluble portion was weighed. Sample was evaporated to constant weight in vacuum, room temperature. Correction applied, assunling half the hydrocarbon part of the azo compound remains in the residue.
conditions. It is not clear, however, whether this larger number is due to the peroxide leading to long chains, while the azo compound through its biradical leads to smaller cyclic product^,^.'^,^^ or arises from a comparatively low yield of effective biradical from the azo compound, the larger part of it decomposing to styrene-the reverse of a possible initiating step in the thermal polymerization. Study of the kinetics of decomposition of I and of the properties of the polymer that may be formed in low yield are required to give indication as t o whether the biradical I1 may lead to high polymer and be involved in the thermal polymerization of styrene.
Experimentalxg 3,6-Diphenyl-2,3,4,5-tetrahydropyridazine(IV). A.--aChloroacetophenone, 15.5 g. (0.1 mole), in 125 ml. of ethanol was treated with 11 g. (0.1 mole) of semicarbazide hydrochloride in 12.5 ml. of water at 40" with gradual addition of 8.5 g. (0.1 mole) of sodium bicarbonate. The mixture was boiled and cooled, and the product was collected, washed with ethanol and dried; a-chloroacetophenone semicarbazone 12.5 g. (0.059 mole), 59% yield, m.p. 151-152", reported20 156'. The semjcarbazone, 12.5 g., was heated under reflux for 1.2 hr. with 11 g. (0.13 mole) of sodium bicarbonate in 200 ml. of 1 : 1 ethanol-water. The product was collected and dried; i . 3 g. (0.026 mole), 447; yield, m.p. 213-216", 218.5-220' after two crystallizations from benzene, reported6 221'. Anal. Calcd. for C17H~7Oh-3:C , 3 . 1 0 ; H, 6.13; N, 15.04. Found: C, i2.87; H, 5.85; K, 14.78. T h e product above, 2 g. (0.0072 mole), was heated for 6 hr. at 160" in a solution of 6 g. of sodium in 120 ml. of ethylene glycol and cooled. The product I V was collected and crystalli7erl frani ethanol, 1.6 g. (0.0068 mole), 947, yield, m.p. 157-159 , reported6 159'. S o gas was evolved when it was heated t o 300". The absorption spectrum was determined in chloroform in a Beckman DU spectrophotometer and showed a small minimum at 245 mp, log B 3.68, a maximum a t 292 mM, log E 4.19, which fell off rapidly t o log c 1.20 at 365 mp and more slowly to lop B 0.45 a t 400 mp. B.-Succinyl chloride, 20 g. (0.13 mole), in 56 ml. of thiophene-free benzene was added a t room temperature over a period of 2 hr. with stirring t o 25 g. (0.19 mole) of aluminum chloride in 200 ml. of benzene. The mixture was treated with ice and 20 ml. of concentrated hydrochloric (17) D. H. Johnson a n d A . V. Tobolsky, i b i d . , 7 4 , 938 (1952); K.E . Russell a n d A. V. Tobolsky, ibid., 76. 505'2 (1953). (18) B H. Zimm a n d J. K. Bragg, J. Polymev Sci., 9, 476 (1952). (19) Melting points are uncorrected. Elementary microanalyses were performed b y Dr. S. M. Nagy, Massachusetts I n s t i t u t e of Technology. (20) G. Knopfer. Monatsh., $1, 108 (1910).
4404
SAULG.COHEN,SHU-HSI HSIAO,EUGEKE S A K L AAND D CHI Hu.2 1 V . m ~
w i d . The benzene solution was concentrated and the precipitate was washed and crystallized from ethanol, 1,Ztiibenzoylethane, 5.0 g. (0.021 mole), 16% yield, m.p. 144115", reportedz1 144-145'. 1,2-Dibenzoylethane, 5 g. (0.021 mole), was dissolved in 30 ml. of ethanol and treateti with 2 g. of hydrazine hydrate. A white solid V was obtained, 4.8 g . , 96% yield, m.p. 140-210". -4ttempted crystallization from ethanol did not lead t o pure compounds. -1solution of 3 g. of the mixture V in 200 ml. of ethanol was treated with 5 ml. of ethanol saturated with hydrogen chloride, then with hydrogen over platinum oxide at 50" for 2.5 hr., filtered and cooled. Compound I\' crystallized out, 0.650 g., 1n.p. 144-152', 155-157', after recrystallization from alcohol, alone and when mixed with the product from procedure A , above. T h e original filtrate was made alkaline, leading t o an additional 1.1 g. of crude IV, m.p. 140155', 155-157' after several recrystallizations. T h e ultraviolet absorption spectrum was identical with t h a t described in A, above. C.-The adduct of diethyl azo-dicarboxylate and 1,4diphenylbutadiene, compound VI below, 1 g. (0.0026 mole), was boiled in 3 ml. of 40% potassium hydroxide in methanol for 1 hr. under nitrogen. T h e solution was cooled, diluted with 2 ml. of water and acidified with concentrated hydrochloric acid. A solid separated, \vas collected, washed with water and crystallized from methanol; 0.4 g., 64'3 yield, m.p. 156-158", mixed m.p. with I\', 157-159'. 3,6-Diphenylpyridazine. A,--.% solution of 1.0 g. of mixture V in 10 ml. of acetic acid was treated with hydrogen over platinum oxide a t 30 p.s.i. for 2 hr., filtered and concentrated in vacuum, leading t o 3,6-diplienylpyridazine, 0.50 g., 50% yield, m.p. 207-219", crystallized from ethanol, m.p. 219-220", reported'? m.p. 222". B.--A solution of IV, 0.384 g . (1.82 mmoles), iii 30 nil. of acetone was treated with 6 drops of 30Yc hydrogen peroxide at room temperature for 16 hr. and concentrated, The residue was crystallized from ethanol, leading to 3,6diphenylpyridazine, 0.155 g., 40% yield, m.p. and mixed m.p. 218-220". Attempted Reductions with Lithium Aluminum Hydride. --A: Treatment of the mixture V, 2 g., with 1.1g. of LiAIH4 in 50 ml. of ether under reflux for 6 hr. led t o material melting 15&180", 1.6 g. B: Treatment of 4.8 g. of mixture 1. with 1 g. of LiAlHa in di-n-butyl ether a t 80" for 13 h r . led t o 2.5 g. of material melting at 95-110°, 116-120' dec. after crystallization from methanol-water in Dry Ice. C: Treatment of the hydrazone IV, 0.5 g., with 0.1 g. of Li.41Ha in 50 ml. of di-n-butyl ether a t 80"for 13 hr. led t o recovered IV, 0.3 g. D: Treatment of the hydrazone IV, 0.350 g., with 0.150 g. of LiAlH4 in 30 ml. of di-n-butyl ether under reflux for 5 hr. led to recovered IV, 0.120 g.
1'01. 79
134--136°, reportedI2 13%'. A n d . C;tlcti. for C:.I-TI:SIO,: C,69.14; H,6.36. Found: C,69.13; H,6.-42. 3,4,5,6-Tetrahydro-3,6-diphenylpyridazine( I ) . A . 'l'he adduct V I , 5 g. (0.013 mole), was hydrogenated i n 300 nil. of acetic acid over platinum oxide a t 30 p.s.i. The solutioii was filtered and concentrated and t h e residue was crystLillized from ethanol, 3.5 g., 70% yield, m.p. 85-87', solid persisting t o R5', reported12 8 7 " . Recrystallization from ethanol did not affect the melting range. ilnal. Calcd. for C L ~ H ~ ~ KC,~ O ~ : H, 6.85. Found: C , 69.22; 69.06; H , 6.96. Treatment of the hydrogenated adduct \'I1 above with Concentrated hydrochloric acid in inetlianol under reflux for 1 hr. led to recovery of V I I . The adduct l?I was also unaffected under these conditions. .i solution of 1.Og. (2.6 mmoles) of VI1 and 1.5 g . ium hydroxide in 5 ml. of ethylene glycol w a \ boiled under nitrogen for 2 hr., cooled, diluted with 25 nil. of water and extracted with peroxide-free ether. The solution was dried over magnesium sulfate and treated with dry hydrogen chloride. *in oil precipitated, a t first white, then turning orange, crystallization of which from ethanol and water and from ethyl acetate led to the hydrazone IV, 111.1). 156-158". Some crystals were observed in the magnesiuin sulfate; the latter was dissolved in water, the crystals \rere collected and dried, dec. 110" with gas evolution when heated rapidly, sintered 98",melting over a range t o 1 6 ' when heated slowly. ( 2 ) . .i second saponification was carried out in the same way. The dried ether extrsct was Concentrated and cooled leading to long flat crystals, 0.284 g. (1.25 mmoles), 387, yield, decomposing with gas e\wlution a t 110". ( 3 ) : Saponification of 1.0 g. of VI1 by 2 g. of PCJtassium hydroxide in 5 nil. of boiling methanol was carried out similarly. The dried ether extract was conceutrated and crystals were obtained and dried in a desiccator; 0.15 g . (0.64 mmole), 25c1, yield, dec. 110'. (4): The hydrogenated adduct VII, 1.0 g. (2.6 mmoles), was boiled for 1 hr. under nitrogen in a sclution of 2.0 g. of potassium hydroxide in 5 ml. of methanol, cooled in ice, diluted with I O nil. of water, brought to PH 8 with 6 i V hydrochloric acid and extracted with ether. The ether solution was dried over magnesium sulfate, concentrated and refrigerated. Elongated plate-like crystals formed, 0.135 g., 22c70yield, decomposing with gas evolution n-hen placed in a bath a t 120'. A n d . Calcd. for ClsHl&?: C, 81.30; H , 6.82; S, 11.85. Found: C, 81.48; H , 6.92; N, 11.76. I n other runs yields varied from 20 to 457,. The ultraviolet absorption spectrum in cyclohexane showed maxima a t 287 mp, log E 3.49, and a t 387 m p , log E 2.89. Rearrangement of I.-:\ small quantity of the azo compound I was dissolved in acetic acid and the solution was immediately evaporated t o dryness in vacuum a t room tcniperature, leading t o the hydrazone IV, m . p . and mixed m . p . 1,2-Dicarboethoxy-3,6-diphenyl-l,2,3,6-tetrahydropyrida- 1n5- 158O . Decomposition of I. A. Nitrogen Evolution.-The azo zine (VI).-A%: 1,4-Diphenylbutadiene2* was prepared by compound I was dissolved in a small quantity of redistilled condensation of phenylacetic acid (150 g., 1.10 moles) and cinnamaldehyde (169 g., 1.28 moles) in acetic anhydride (155 solvent in a test-tube connected t o a thermostated gas buret, ml.) in the presence of lead oxide (122 g.) a t 145'; 50 g., the system (including the solution) was w e p t with oxygen22y, yield, m.p. 152-153', from benzene-ethanol, reported2* free nitrogen and leveled, the test-tube was heated a t 135" 152.5-153.5'. B: Diethyl 1,2-hydrazinedicarbox~.late~3or 110" for 0.5 hr. or at 100 or 90' for 1 hr. or a t 80" for 2.6 Iir. and brought back t o the thermostat temperature ( 3 0 ' ) was prepared from reaction of hydrazine hydrate (78.2 g.) anti the evolved gas n a s measured. The interim readings with ethyl chlorocarbonate (108 g., 1.00 mole) in ethanol at irere observed a t the reaction temperature. The volumes 0"; 47.5 g. (0.27 mole), yield, m.p. 132-133' from water, reportedz3 130". C: Diethyl azo-dicarhoxy1atez4 measured were sinall and the accuracy was probably about was prepared by treatment of a solution of 20 g. (0.11 mole) +5yG. T h e data are sunimarized in Table I . of diethyl 1,2-hydrazinedicarbosylate in 24 ml. of conB. Products of Decomposition.--( 1): Compound I , centrated nitric acid with 4.8 ml. of fuming nitric acid a t 0.033 g. (0.225 inmole), in a tared centrifuge-tube under O 3 for 1.5 hr. The mixture x a s poured into ice-water, es- nitrogen, was heated at 110' for a few minutes, then placed tracted with ether, washed with sodium bicarbonate, dried in a n oil-bath at 125' for 5 minutes, strong nitrogen evolution and distilled; 8.3 g. (0.048 mole), 427, yield, b.p. 106-108" and droplets condensing on the walls of the tube. (13 mm.), reportedz4 106" (13 mm.). D: 1,Z-Dicarbo- ensuing ethoxy-3,6-diphenyl-1,2,3,6-tetrah~-dropyridazine ( V I ) \vas The tube was opened and the odor of styrene was detected; prepared by reaction of 9.0 g. (0.03 mole) of diethyl azo- the tube xr-as swept again v i t h nitrogen, stoppered mid redicarboxylate with 9 g. (0.044 mole) of 1,4-diphenvlbutadi- weighed, loss of 0.008 g. being observed. The residue ene in 10 ml. of toluene on the steam-bath for 3 hr. The (solidified) was treated with 3 ml. of 9575 ethanol, leading toluene was removed in vacuum and the adduct \'I was t o compound IP, 0.016 g., 307, yield, m.p. 156-158', crystallized from ethyl acetate; 18.8 g., 9,5'3 yield, m . p . mixed m.p. 157-158". T h e filtrate was treated with 4%; ._~____ bromine in acetic acid until a pale yellow color persisted, diluted with 1 ml. of water and cooled, leading to styrene (21) S Kapf a n d C. Paal, Ber., 21, 3066 (1888). dibtoniide, m.p. and mixed m.p. 68-70", 0.006 g . (0.023 1 2 2 ) B. B. Corson, "Organic Syntheses," Coll. Vol. 11, J o h n TViley inmole), iy, yield. Styrene, 0.100 g. (1 mmole), w:ts disa n d Sons, Inc., Y e w York, N. Y . , 1948, p p 229-230. i i i l r e d in 3 ml. of ethanol and brominated as deccribetl 123) U. Sachsse, Rer., 27, 773 (1894) : i l i i i v r , Iv:\ding t o s t ~ r e n edilxoinidc, 11i.p. fi8-70°, 0.044 ( 2 4 ) 0. niels and P.F r i t z s r h r , i h i d . , 44, 3018 (191 I J .
QUINAZOLINES FROM AROMATIC AMINESAND CARBON DIOXIDE
Aug. 20, 193;
The ing. (0.17 mmole), 17y0 yield, reportedzs 72-73'. frared spectra of the two samples were identical, showing a strong carbon-bromine bond at 695 cm.-l. (2) -4 solution of compound I, 0.050 g. (0.212 mmole), and stilbene, 0.036 g. (0.212 mmole), in 1 ml. of ethylbenzene (b.p. 134-134.5") was heated in vacuum at 100' for 50 minutes, concentrated to dryness in vacuum and treated with methanol. Stilbene was recovered; 0.014 g., 3970 yield, m.p. and mixed m . p . 123-125'. The residue was an oil. ( 3 ) 1solution of I,O.O61 g. (0.26 mmole), and freshly sublimed quinone, m.p. 114-115', 0.221 g . (2.0mmoles),in6ml. of benzene wis heated under nitrogen at 90" (bath tempera( 2 7 ) R . Fittig and E E r d m a n n , A m , 216, 194 (1883).
[COYTRIRUTION So. 403 FROM
THE
4405
ture) for 42 hr. T h e solution was concentrated and sublimed in vacuum leading t o recovery of quinone and separation of some black solid, 0.020 g. melting unsharply above 160", presumably quinhydrone. T h e black residue, 0.145 g., was heated with a little ethanol, leading t o compound I V , 0.003 g., 5% yield, m.p. and mixed m.p. 155-157". The residue was chromatographed on alumina, leading t o 3,6-diphenylpyridazine, 0.028 g., 47Y0 yield, m.p. and mixed m.p. 219-220"
Acknowledgment.-IVe are pleased to acknowledge generous support of this work bv the National Science Foundation. ~ V A L T H A M MASS ,
CHEMICAL DEPARTMENT, EXPERIMENTAL STATION, E. I . DU POXTDE SEMOURS A'VD Co.]
Quinazolinediones from Aromatic Amines and Carbon Dioxide B Y T. L. CA41RPiS,D. D. COFFMAN AND
\v. \v. GILBERT
RECEIVED FEBRUARY 12. 1957 The reaction of carbon dioxide with certain primary aromatic amines a t 8500 atm. and 200-250' has given high conversions to 3-aryl-2,4(1H,3H)-quinazolinediones (I). A sharp pressure threshold for the reaction was found a t about 3300 atm.; the quinazolinediones were not formed at lower pressures, while conversions increased to 65-70'% a t the highest temperatures and pressures investigated.
Previous communications1 from this Laboratory have described investigations of the effects of pressures of 6000 to 8500 atm. on chemical reactions. This paper reports a new reaction, the high pressure synthesis of 3-aryl-2,4(1H,3H)-quinazolinediones (I) from certain primary aromatic amines and carbon dioxide according to the equation2
2 R2
H .-
11
I This unusual transformation has been examined in terms of the effects of temperature, pressure, solvents, catalysts and substituents. Conversions of aniline to 3-phenyl-2,4( 1H,3H)-quinazolinedione (I, R1 = R2 = H) as high as 70% were obtained a t temperatures above 200" a t 8500 atm., but the conversion fell to zero a t 130". A sharp pressure threshold for the reaction was found a t about 3300 atm. The quinazolinedione was not formed a t lower pressures, and the conversion increased rapidly with increased pressures above the threshold value. The reaction occurred in the presence of either alkaline or acidic catalysts, but with acidic catalysts the yield of quinazolinedione was de0
(1) (a) T. L. Cairns, G. L. Evans, A. W. Larchar a n d B. C. McKusick, THISJ O U R N A L , 74, 3982 (1952); (b) T. L. Cairns, A. W. Larchar and B. C. McKusick, ibid.. 74, 5633 (1952); (c) J . O V E .Chem., 17, 1497 (1952); (d) 18, 748 (1953); (e) T . L. Cairns, D. D. Coffman, Richard Cramer, A. a '. Larchar and B. C. McKusick, THISJOURNAL, 7 6 , 3024 (1954). (2) W. W. Gilbert, U. S. P a t e n t 2,680,741, June 8, 1954.
creased by formation of unidentified by-products. In the uncatalyzed reaction, formation of the corresponding sym-diarylurea was the chief competing reaction. Quinazolinediones were also obtained from otoluidine (15% conversion, R1 = CH3, R1 = H) and from $-toluidine (5OY0 conversion, RI = H, R2 = CH3), Quinazolinediones were not identified among the reaction products when the aromatic amine contained nitro, halogen or hydroxyl substituents or when the amine was a- or P-naphthylamine. Primary aromatic diamines have given complex intractable products with carbon dioxide under these conditions. These products may have been low molecular weight polymeric quinazolinediones or polymeric ureas. Experimental Aniline and CO2.--Aniline
(4.08 9.) and carbon dioxide (2.39 g.) were charged into a stainless steel cylinder fitted with a movable p i ~ t o n . ~ I n some runs a small quantity of nitrogen (ca. 0.3 g.) was used to ensure return of the piston t o its original position when the external pressure on it was released a t the end of the experiment. The c)-linder was placed in a Bridgman-type pressure a p p a r a t ~ sand , ~ its contents were subjected t o a n initial pressure of 8500 a t m . a t room temperature. T h e entire high-pressure system was then heated to 200". .After 14 hr. the apparatus was cooled t o room temperature. The final pressure was about 7900 atm. The pressure was released and the cylinder removed and vented. The reaction product was washed from the vessel with ether and collected on a filter t o give 3.37 g. of crude solid, m.p. 267-268". It was purified by recrystallization from a mixture of ethanol and benzene or by sublimation under reduced pressure t o give white crystals, m.p. 275280". Anal. Calcd. for ClaHloX20p: C, 70.57; H, 4.23; N , 11.76. Found: C, 70.76; H , 4 . 4 3 ; X, 11.60, 11.65. T h e product was identified as 3-phenyl-2,4-( 1H,3H)quinazolinedione by hydrolysis t o aniline and anthranilic (3) Cf.reference l a , p. 8986; I d , p. 749. (4) P. R'. Bridgman, "The Physics of High Pressure," C.. Bell a n d Sons, London, 1949, pp. 30-59.
