tivcly. These curves intersect a t the enantiotropic transition point T . I n the mestastable region, the solubility of the a'-form is represented by points on the curve CT'. This curve intersects the inchstable solubility curve of th(L 0-modification (shown by points on D T ' T ) a t the nietnstable enatitiotropic, transition p i n t T'. The locations of the intersections of the solubility curves of dodecylammonium chloride with refcrence to ternperaturc and concentration have been inserted in Table I. These data establish the trarisition temperature T quite definitely a t 57.3 =tO.l-, which is the value obtained by microscopic ohservations.l,-' The change of slope in the nietastablc region a t 1''occurs consistently a t 5-1.7 f 0.1'. Re-exaniinatioti or the (lata1 for the soluhility in %7"; ethmol shrm-.i.4:t slight h i n t of a siini1:ir iunre-
(1) C
\V IIiierr
and X
\\'
R i l i t o n . THISJ C I I J R ~ A I 64, 2824
(1'11.2)
ClITCAGO, ILLTYOI?
LABORATORIES Or' TIIf
[ C O V T R I P VTIO\ rROM TIIF R r S E A R C l I
GLlnnFN
COMPAVY-NAVAL STORES
nIVTSloV
1
111. Thermal Isomerization in the Liquid Phase
Nopol. BY
ported) intersection in the metastable region of this region of this system in the neighborhood of .i4.3', but too few experimental points have been recorded to demonstrate.the point conclusively. The changes in slope of the solubility curves4 of dodecylammoniuni bromide and iodide in benzene and 95% etha riol suggest that these substances may possess transitions similar to those of dodecylanlmoniuln chloride. The (lata for the anhydrous ethanol show no "break" in the solubility curve above the transition icinperature. The system of dodecylammonium chloride with carbon tctrabrornitle, with a eutectic a t G9.So, involves only the higher-temperature form, beta.
JOSEPI1
P.
n.ZIN, A L B E R T
El.
REST AND
R F C E I V m JA\TTARY
ROBERT L. 'IT'EBR
31, 1932
Upon heing heated in the liquid phase, nopol s h o ~ l racemizes y and undergoes loss of formaldehyde t o form a partly racemic 8-pinene through reversal of the 8-pinene-formaldehyde condensation. Simultaneously, the isomeric alcohols, dipentene-7carbinol and alloocimetiecarhinol are formed. Infrarrd a n d ultmviolct absorption y m t r a l d'lta are presented in support of t h e suggested course of the reaction
/?-Pinene (I) and formaldehyde condense to form nopol' (11) (G,G-dimethylbicyclo[3,1,1Ihept-2-ene2-ethanol), a structural derivative of a-pinene (111). Infrared spectra are shown in Fig. 1 for the two pinenes and for nopol. The products of pyrolysis of a-pinene ordinarily' recovered arc dipentene and the triene alloijcimene although it was recently shown3 that ocimetir can CTT, I
cTi. -cmorr I
CII I
Cl f -CHnO J T 1
I
be recovered from the pyrolysis products when a suitable method is employed to avoid its isomerization. Ocimene is so readily isomerized to alloocimene that the latter is usually the sole acyclic product isolated. Two geometric isomers of alloociimne have been described.4 Alloocimene may be re(1) J. P. Bain, THISJOURNAL, 68, 638 (1946). (2) B. Arbuzov, J . Gen. Chcm. (U.S.S.R.), 9, 21 (1933); Bcr., 6 7 B , 663 (1934). (3) J. E. Hawkins a n d H. G. I-Iunt, THIS JOURNAL, 79, 5379 (1951). (4) 5 J Hnpfielrl, S A . € T a l l and L A. Golrlhlatt, ibid , 66, 11.5 ( J 9441.
cyclized' in the vapor phase to a complex mixture consisting chiefly of alkyl cyclohexadienes in which a- antl P-pyronene and 1,3-dimethyl-l-ethyl-3,5cyclohexacliene predominate. At lower temperatures and in the liquid phase, alloocimene may be converted7 in high yields to a dimer or mixture of dimers. Nopol behaves similarly in the vapor phase since there were isolated products described as menthadiene-7-carbitioI' and alloocimenecarbinolRfrom nopol pyrolysis mixtures, but structures were not proved nor were secondary products of pyrolysis described. I t is the purpose of this paper to report that thermal isomerization of nopol is analogous to that of a-pinene and to show that the products of pyrolysis are dipentene-7-carbinol (IV), the alloocirnenecarbinol (V) antl partly racemized nopol. Simultaneously, a partly racemic 0-pinene is formed by loss of fortnaldehyde from the partly racemized nopol. Secondary products of pyrolysis will be referred to, but ill be more fully dcscrihed in a iortlicoming paper. Initial experiments showed that as nopol was heated a t reflux a t atmospheric pressure, the boiling point gradually rose, small amounts of paraformaldehyde appeared in the condenser and, as shown in Fig. 2 , absorptions in the ultraviolet region of the spectrum developed a t about A,, 278 inp. After about 3.5 hours of refluxing, the absorption rnaxi( 5 ) L A Goldblatt and S Palkm, rbrd , 66, 655 (1944) (6) E B Parker and L A Goldblatt. rbid , 72, 2151 (1950) (7) R E r u g i i i t t .inti J B Hawkins, rbid , 67, 242 (1945), 69, 319 (1947) ( 8 ) J P Ti-rn and A F1 R w t , U S P t t e n t 2,451,110 (November 0, (lW8)
Sept. 5 , 1952
THERMAL ISOMERIZATION IN THE LJQWID PHASE OF NOPOL
mum began to decrease and shift 5000 toward shorter wave lengths. Finally, after 13 hours of heating, a new 100 Xmax a t about 240 mp had appeared. 80 Alloocimene has been found to 60 possess A,,, about 275 mp, maximum extinction coefficient ( a = ~ g1. cm.) 1'. 40 about 3209 whereas the alkyl cyclo20 hexadiene9 formed by cyclization of 0 alloocimene show Am,, 265 mp, cy about 40. Alloocimene polymerlo ex100 hibits Amax 242 mp and a 95. Ultra80 violet spectra for alloocimene, allo60 ocimene polymer and alloocimenecarbinol (V) are shown in Fig. 4. The 40 series of ultraviolet spectra shown in 20 Fig. 2 are interpreted as indicating the formation of alloiicimenecarbinol 0 (V) then conversion of this product on continued heating to alloocimenecarbinol polymer. That there is also 80 present a mixture of alkyl cyclohexa60 diene carbinols in all heat treated samples of nopol is more evident from 40 examination of the ultraviolet spectra 20 of the fractionated pyrolysis products boiling close to nopol. These 100 fractions of crude recovered nopol possess Amax 265 mp and are free of 80 alloocimene carbinol and its polymer 8 which dominate the spectra of crude 9 pyrolysis mixtures shown in Fig. 2. .$ 40 There is no evidence that the pres2o ence of a carbinol group appreciably affects Amax of the particular chromo0 phore groups present. 100 A sample of nopol heated a t reflux (225 to 240') for 2.5 hours was fracgo tionated carefully to separate the 60 pyrolysis products. The data are shown in Fig. 3. The lowest boiling 40 product was @-pinene, a2% -15.9' 20 (10-cm. tube), while natural @0 pinenell is - 18.61'. a-Pinene racem i ~ e s l * 'a*t ~as ~ low temperatures as 100 175-200', but @-pinene does not 80 racemize even a t the somewhat higher temperature of refluxing no6o pol, about 225 to 240'. The next 40 higher boiling fraction was nopol, 20 a% -26.3' (10-cm. tube), although 0 the starting material was -35.86'. It is evident that, like a-pinene, 100 nopol slowly racemizes and that the partly racemic @-pinene recovered was derived from the partly race60 mized nopol through a reversal of 40 the P-pinene-formaldehyde condensation. 20 Fractions on both sides of the 0
Wave numbers in ern-'. 300025001500 1300 1100
4293
700
900
8
(9) Personal communication from Dr. L
A.
3
5
7
9
11
13
15
Goldblatt. Wave length in microns. (10) R. D. Walker, Jr , Thesis, University of Florida, Feb., 1961. Fig. 1.-Absorption spectra of: A, a-pinene; B, @-pinene; C, nopol; D, (11) R. E. Fuguitt, W. D. Stallcup and J. E allo&irnene; E, allo6cirnenecarbinol; F, limonene; G,dipentene-7-carbinol. Hawkins, THIS JOURNAL, 64, 2978 (1942). purest recovered nopal fractions ehswed (12) T. R.Snvich and L.A. Goldblatt, ibid , 67, 9027 (1948).
Am.
265
JOSEPII
Vol. 74
P.BAIN,ALEERT H. BEST .ZND ROBERTL. LYmrj
2.20 260 280 300 320 n'ave length in millimicronz. Fig. 2.--Sopol refluxed :it 235-245" for: 1, 10 minutes; 2, two hours; 3, three hours; 4, 13 hours; 5 , 20 hours
240 260 280 300 320 15'ave length in millimicroiis Fig 4 --Ultraviolet absorption spectra of: A, nlloocimene; B, nlloocimcne polymer, C, alloocirrienecarbinol
nip characteristic of alkyl cyclohexadienes having both double bonds in the ring. That the conipounds responsible for these absorptions are alkyl cyclohexadienecarbinols is suggested by the fact that as the alloocimenecarbinol (V)is formed and passes from a maxiinum to a minimum concentration, the total amount of materials possessing absorptions in the 260-270 nip region of the crude nopol recovered by fractionation of the incompletely pyrolyzed niatcrial increases as would tic cvpected if I' cyclizes as does alloociinene.
m'hen recovered, partly racemized nopol of a2% -20.3° (1O-cni. tube) was again refluxed for 2.5 hours and the pyrolysis mixture fractionated, the &pinene recovered showed CY*% - 12.GG" and the nopol recovered was -19.28°. The nopol recovered from this experiment contained about (5 to 8%, alkyl cyclohexadiene carbinols, which, as derivatives of optically inactive V, are themselves optically inactive. Therefore, the true rotation of the recoverecl unreacted nopol was about - 21 .so. The niajor pyrolysis product, boiling about IS" above nopol, is dipentene-i-carbinol (IV) as shown by comparison of its infrared spectrum with that of linionene (Fig. I) and the fact that the infrared spectrum of IV is identical with that of the product produced by dehydrochlorination of 1,S-dichloro-pinenthane-i-carbi~iol.~The structure of IV was further confirmed by its partial hydrogenation to carvoinenthene-i-carbinol (VI) and its complete hydrogenation to pinenthane-7-carbinol (VII) which was oxidized to the known'? p-menthane-icarboxylic acid. The allooeinienecarbinol (V) boiling about 6" above 11' showed A, 278 mq, CY 2-21 as compared to the values obtained in the course of this investigation for nlloocirnene, A, 277 mq, a 313. I n Fig. 1 is shown the infrared spectrum of mixed X and B alloocimcne isomers as ordinarily recovered from the fractionation of an a-pinene pyrolysis mixture ant1 thc spcctruiri of thc :~lloociincnec~rbinol (V).
220
1 .i800
1-11)
- -10 120
1 r,OOO
1,
r
i
220
D AI o i i i r o l C i 71, 7407 i 1 ~ ; o i
( 1 3) \AI
t:
iI lrlllr I n 4 I
A (:o~r~~,i.ltt
'it114 rr,lllr
Sept. 5 , 1952
THERMAL ISOMERIZATION IN THE LIQUIDPHASEOF NOPOL
The presence of three double bonds in V was confirmed by its hydrogenation to the corresponding saturated acyclic alcohol. Esters of nopol isomerize readily to esters of IV and V accompanied by cyclization products and polymer of esters of V, but do not yield ppinene or other hydrocarbons a t 235 to 245' as does nopol itself,
Experimental Spectra.-Ultraviolet spectra were obtained with a Beckman DU spectrophotometer. Isooctane was employed as the solvent except where otherwise noted. Infrared spectra presented in Fig. 1 were determined on the homogeneous liquid samples by Samuel Sadtler & Son who employed a Baird spectrophotometer equipped with a sodium chloride prism. Other infrared data were obtained in this Laboratory using a Perkin-Elmer 12-C instrument. Isomerization of Nopol .-Commercial grade nopol was fractionated t o obtain a constant boilingproduct, b.p. 110.5' (10-cm. tube). This material (10 mm.), a Z 3 D -35.86' , ,A above 220 m p in the ultraviolet region. showed no The purified product was refluxed a t 760 mm. pressure and 225 to 240'. Samples were taken a t intervals for infrared and ultraviolet analysis. Some typical results of the latter are shown in Fig. 2. A strong absorption appeared,, , ,A 278 mp and the extinction coefficient increased for 2.5 hours then began to decrease. At the end of 13 hours of heating, in this region was very weak and had shifted from the, , ,A 278 t o about 274 mp and a second and now much stronger Amax had appeared a t about 241 mp. After 20 hours of refluxing, there remained only a barely discernible inflection in the region 265 t o 275 mp, probably due t o the presence of alkyl cyclohexadienecarbinols. This last sample also a t about 240 mp and a new , , ,A a t about 230 mp showed, , ,A had developed. During the course of the isomerization, the boiling point gradually rose from about 225 t o 240". Examination of the infrared spectrum of the material a t the end of the 20-hour heating period showed that nopol was absent. Since neither nopol, 8-pinene nor dipentene-7carbinol shows an absorption maximum in the ultraviolet region above 220 mfi, their presence in the reaction mixture had little or no effect on the ultraviolet spectra of pyrolysis mixtures or on distilled fractions. A large batch of nopol was heated a t reflux a t 230-240" for 2.5 hours in order t o secure a maximum concentration of the material absorbing a t 278 mp then fractionated through a 100 cm. by 50 mm. Stedman column a t 10 mm. pressure and a t 10: 1 reflux ratio with the results shown in Fig. 3. Formaldehyde was recovered in appreciable quantities as paraformaldehyde from the reflux condenser employed in the isomerization step and from the fractions boiling a t about 48". I t was identified by mixed m.p. with an authentic sample, but no attempt was made t o estimate it quantitatively. @-Pinene (I) was the chief constituent of the fractions boiling below 110', mainly a t 48O, and was obtained on re~ fractionation of these fractions in high purity; n Z 51.4769, a Z 5-15.9" ~ (10-cm. tube). The infrared spectrum was identical with that of high purity P-pinene isolated from ~ C-~*~D -18.6' (IO-cm. tube). gum turpentine, n z 5 1.4769, Neither a-pinene nor other terpenes could be detected. Nopol (11) was identified by infrared analysis as the chief component of fractions boiling in the range 110-113° but traces of impurities were present in even the purest samples. These impurities exhibited absorptions in the ultraviolet 265 mp, of the same type as is shown by aregion,, , ,A terpinene and other alkyl cyclohexadienes having both double bonds in the ring. Their amount was estimated from infrared and ultraviolet absorption data not t o exceed about 3% of any recover&i nopol fraction and it is believed that they consist of two or more alkyl cyclohexadiene carbinols resulting from cyclization of alloocimenecarbinol (V). The purest nopol cuts showed -26.3" (10-cm. tube). Since the quantity of impurities present was too small t o affect the rotation appreciably, there was no doubt that the nopol had racemized. Dipentene-7-carbinol (IV) was recovered almost pure as fractions boiling in the range 128-129' though slight absorptions in the region 270-278 mp showed the presence of traces of alloncimenecnrbinol, The infrared spectra of the
4295
fractions showed a strong resemblance t o that of limonene and comparison with spectra of "menthadiene-7-carbinol"l~8 produced by vapor phase pyrolysis of nopol showed that the two carbinols were identical. As further proof of the suggested structure (IV) for this carbinol, 1,8-dichloro-7-pmenthane-carbinol1 was dehydrochlorinated by hot dilute sodium hydroxide and the product was shown t o have all characteristic bands of IV, but this dehydrochlorination product was not further purified and was obviously crude. The best sample of IV obtained by liquid phase pyrolysis ~ (10-cm. tube), dZ54 showed n'% 1.4981 and a Z 5+6.2" 0,958. Alloijcimenecarbinol ( V ) was most concentrated in fractions boiling a t about 132 t o 134' which were refractionated to yield constant boiling material, b.p. 134.7' a t 10 mm. The recovery of pure V by fractionation is not quantitative because of its tendency t o polymerize. The purest fractions ~ t o 1.5590; dZ5z5 showed a Z 60~(10-cm. tube); n Z 51.5580 0.9079; MDcalcd. 52.02, found 58.7. The character of the ultraviolet absorption spectrum is practically identical with , , ,A 277 mp, but that of alloocimene, showing the same somewhat smaller extinction coefficient, a 241. The infrared spectrum of V also shows strong similarities t o that of alloocimene. KO attempt was made t o separate 5' into the cis-trans forms probably present. A sample of 5' of 84.5% purity, the remainder IV, was hydrogenated a t 30-60 pounds pressure using platinum oxide catalyst. Allowing for absorption of hydrogen by the I V present t o form carvomenthene-7-carbinol, the V absorbed 97% of the hydrogen required for three double bonds1 The 7-methyl-3-ethyloctanol produced was fractionated t o yield the pure material, b.p. 114.5' a t 10 mm., nZ5D1.4398, d254 0.8354. Anal. Calcd. for C ~ ~ H Z C, ~ O76.67; : H , 14.04. Found: C, 76.49; H, 14.31. Pyrolysis of Partly Racemized Nopol.-The purest frac; tions of recovered, partly racemized nopol, a Z 5 D -26.3 (10-cm. tube), were combined and heated a t reflux a t 760 mm. pressure for 2.5 hours. Results of fractionation were similar t o those shown in Fig. 3. The 8-pinene was recovered in a t least 98% purity but now showed az5D -12.66' (10-cm. tube). The purest nopol recovered showed n % D 1.4920 and a Z 5 -19.3" ~ (10-cm. tube). It contained 265 mp, probably about 6 t o 8% impurities possessing,,,,A, alkyl cyclohexadienecarbinols, but this quantity of impurity is not sufficient t o affect the conclusion that the nopol had suffered further racemization during this second heating period. The dipentene-7-carbinol fractions contained about 2 to 4% of V b t t were otherwise pure and showed nZ5D 1.4980, a 2 5 ~f 4 , indicating that as might be expected, partly racemized nopol yields IV of lower rotation. @Pinene was shown t o undergo no racemization a t the temperatures employed here for decomposition of nopol t o formaldehyde and 8-pinene. Pure @-pinene, XZ5D 1.4771, a Z 3-18.61' ~ was heated in a sealed tube immersed in boiling nopol a t 225-240' for 3 hours. The contents of the tube became cloudy when cooled and possessed n% 1.4774 and a Z 3-19.88'. ~ Infrared analysis showed the presence of about 1% limonene and about 98% 8-pinene. When this and ~ product was fractionated, pure &pinene, n Z 61.4770, a z 3 D -18.58' was recovered. I n a second experiment conducted under approximately the same conditions but a t a slightly higher average temperature, &pinene yielded a cloudy mixture which was filtered t o remove myrcene polymer. T h e filtrate contained 8% limonene, a trace of myrcene and about 91% 8-pinene. After purification by fractionation, the 8-pinene showed nZ5D1.4769 and a Z 3 D -18.54'. It is evident from these experiments that the partly racemic p-pinene recovered from pyrolysis of nopol does not indicate racemization of &pinene but does indicate the partial racemization of nopol prior t o its decomposition t o formaldehyde and partly racemic 8-pinene. Carvomenthene-7-carbinol (VI) was produced by hydrogenation of 1 x 7 a t 30 t o 60 pounds pressure using platinum oxide catalyst. Only one mole of hydrogen could be added readily under these conditims. The product was frac~ d2540.9289. tionated a t 10 mm., b.p. 126"; n Z 51.4826; The presence of approximately one double bond was shown by bromine titration. Evidence of the structure of the product was apparent from comparison of its infrared spectrum with that of rarvomenthene produced by partial hydrogenation of
C. M. SUTER
Vol. 74
d-limonene. The two compounds show the same strong polymerized V contained approximately 31% unreacted V and 69% polymerized V, and t h a t the polymerized V infrared absorption band a t 11.03 p and the same medium possessed a n extinction coefficient, CY, of about 79. The strength bands a t 8.05 and 8.18 p . .4na/. Calcd. for CllHZ,,C):C , 78.51; H, 11.98. Found: infrared spectrum of this crude mixture of V and its polymer showed with certainty only one absorption band which apC , 78.11; 13, 12.07. peared t o be common with that of alloocimene dimer, a band p-Menthane-7-carbinol (VII) was produced by hydrogenaat 1 0 . 1 5 ~ . tion of a mixture of about 75% I V and 25% V using Raney Isomerization of Nopyl Acetate.-Nopyl acetate was nickel a t 1500-2000 pounds pressure. After removal of heated at 240" for 5 . 5 hours. The isomerized product con7-methyl-3-ethyloctanol resulting from the hyclrogenation tained free acetic :tcid equivalent to decomposition of about of V a t 110-116' at 10 nini., VI1 distilled at 126' a t 10 mm., fl.S70 of the nopyl acetate. The product was fractionated n% lA700, d*54 0.9117. I t was identified by oxidation a t 10 mm. and the fractions wcrc analyzed by ultraviolet with chromic acid-acetic acid to a mixture which partly and infrared methods. solidified. The solid acid nfter several recrystallizations Thcrc was formed no @-pinene or other low boiling t&rD from pentane melted at 77-78" and its infrared spectrum penes. The first fractions boiling over the range 109-132..5 x w s identical with that of a k 1 1 o w n sample ~~ of p-menthancwere rich in acetates showing , ,A 2G3 mp and believed to ;-carboxylic acid kindly furnishcd by Dr. L. -4.Goltiblatt. bc alkyl cyclohcxadicne carbinol acetates resulting from The liquid acids are thought t o be 3 mixture of the c i s - t r a n ~ cyclization of alloijcimenecarbinol acetate. The quantity isomers of this acid which indicates thnt thc 1-11 is a rnixtrirc of these conjugated cyclic acetates was estimated to be 10% of the two possible cis-trans alcohols. of the original nopyl acetate. There was also present in Alloocimene dimer? is readily produced by heating 3110these fractions nopyl acetate amounting t o 5% of the startocimeue at about 200' and its ultraviolet spectrum has been ing material. This work W:LS repe:lted. Alloiicimenc was Dipentene-7-carbinol acetate was obtained in about 55% heated at 20.5" for 10 hours and 40 minutes a t which time yield, b.p. 134' at 10 mm., n 2 6 1.4775. ~ I t s identity was the product contained about 17yo unchanged alloijcimene npparcnt from comparison of its infrared spectrum with that by ultraviolet absorption analysis. This result was in good of limonene and dipentene-7-carbino1, all of whose major agreement with Fuguitt14 who reported 19% unchanged absorption bands are common exccpt, of course, for the accdloiicimcne after heating alloBcimcne under the same con- txtc or hydroxyl absorptions. ditions of time and temperature, The partly polymerized Alloiicimenecarbinol acetate was obtained in about la% product was distilled at about 5 mrn. pressure through a yicltl; b.p. 130' at 10 mm., v . 2 5 ~ 1.526; extinction coefliqhort column ancl fractions of dirncr, h.p. 15,5-156', were cicrit for tlic purest fraction, DI 173, XmRa 279 mp. The collccted antl examined. ,411 fractions showed Amax 211m:ijor infrared absorption bands of the acetate coincide 212 nip antl the extinction coeflicient (a)of the fractions with those common to alloocimene and alloocimene carbinol. r:tngetl from 88 to 11O.G. The diiner is further character- I t was estimated from spectrophotometric data t h a t purity ized hy infrared nhsorption bnnds :It 10.15, 10.36, 11.5~&, of the best fraction was only about 85%, the remainder I 1.I3 a n d 11.87 h . chiefly dipentene-7-carbinol acetate. Alloocimenecarbinol (V) was polymerized by heating at The distillation residue amounted t o 1570 of the c h r g e for 10 hours and 40 minutes. The viscous product ancl was estimated t o contain 28% alloocimenecarbinol acehown b y infrared analysis to have retained the hydroxyl tate and 1.5% alloocirnenecarbinol polymer acetate, the group. I t s ultraviolet spectrum was determined in meth- latter showing,,,,A, 241. anol since thc product was partly insoluble in isoiictarie. Acknowledgment.-The authors wish to express The spectrum showed two absorption maxima, Am,, 242, N 05, a n d Am,, 276. Q 78. From thcse data and the known their appreciation to Dr. Philip Sadtler for providing crtirictiori coefficicnt for Z', it w i s calcu1:itecl that thr partlv the infrared absorption spectra shown in Fig. I . JxrrsnxvIr.LE,
[CONTRIBUTION FROM TIIE STERLISG-IYINTHROP
FLORIDA
RESEARCH ISSTITUTE 1
The Preparation of Some 1-Alkylamino-and Dialkylaminoalkylaminothiaxanthones' BY S. ARCHERAND C. 3f. SUTER RECEIVED M A R C H 8, 1952 The preparation of a n extensive series of 1-alkyl and dialkylaminoalkylaminothiaxanthoneswas undertaken as part of a study on the chemotherapy of schistosomiasis. T h e compounds were prepared by condensing a I-chlorothiaxanthone with a substituted alkylenediamine a t atmospheric pressure. The reqGrcd 1-chlorothiaxanthones were obtained by (a) condensing a thio- or dithiosalicylic acid with a 1-halo-4-methylbenzene; ( b ) treating a chlorothiophenol with a.n appropriately substituted o-chlorobenzoic acid followed by ring closure of the resulting o-arylmercaptobenzoic acid with sulfuric acid and (c) with a thiosalicyclic acid, followed by conversion of the resulting acid to the correcondensing 2,4-dichloronitrobenze~e sponding acid chloride and cyclizing with the aid of aluminum chloride. A modified mechanism for the condensation of dithiosalicylic acid with henzcne and its congeners is proposed.
Several years ago i t became of interest to prepare a sample of Miracil D (II), a new orally effective schistosoniicidal drug, which was developed in Germany during the recent war. The method of preparation2consisted of condensing diethylaminoethyl(1) T h e numbering system of t h e thiaxanthones used throughout this paper follows current Chrmical Abstracts usage. This differs from t h e system used b y t h e English a n d German workers in t h a t t h e sulfur a t o m is numbered 5 in one case a n d 10 in t h e other. T h e compound which M a u s (ref. 4) named 1,6-dichloro-4-methylthioxanthonecorresponds t o 1,7-dichlor0-4-methylthiaxanthone here. T h e minor differcnce in spelling should he noted. (2) Office of t h e Publication Board, Department of Commerce, Waqhingtoo, D. C . , Report Ns 881.
amine with 1-chloro-4methylthiaxanthone (I). The intermediate chlorothiaxanthone, I, was obtained mixed with the 4-chloro-1-methylthiaxanthone according to the proce$ure of Ullrnann and Glenck3who treated thiosalicylic acid with p-chlorotoluene in sulfuric acid. The 1-chloro isomer, I, is sufficiently reactive to condense with an amine a t elevated temperatures. When this work was repeated i t was found that in small scale runs it was possible to duplicate the results already reported ; however, on a larger scale (2) B. Ullmaan and 0,v. Olenck, Bcr., 49, 2487 (1816).
