STUDIES ON THE NATURE OF THE RACEM.ICMODIFICATIONS OF OPTICALLY ACTIVE

COMPOUNDS IN THE SOLID STATE

Part VI. The Nature of the Racemic Modifications of 3-Nitro-p­toluidino-, 5-Iodo-o-toluidino-, 4-Nitro-o-toluidino-,

Oxy-, 2-N;tro-p-toluidino-, 3-Nitro-4-chloroanilino-, 2 : 5-Dichloroanilino.and 4.Chloro-o-toluidino-methylenecamphors

By BAWA KARTAR SINGH, F.A.Se., AND RAM KUMAll TEWAlU(From the Panjab Umvunty 11131Uute 01 Chemistry, Lahore, and tM ChemiJtry

Department. Unherlity 0/ Allahabad)

Received February 24, 1947

IN this paper we have described our investigation of the nature of theracemic modifications of o~methylenecamphor and its condensation productswith 3-nitro-p-toluidine. 5-iodo-o-toluidine, 4-nitro-o-toluidine, 2-nitro-p­toluidine,3-aitro-4-chloroariiline,2: 5-dichloroanilineand4-chloro-o-toluidine.

A racemic modification may exist in the solid state in one of thefollowing three forms: (1) a mechanical mixture (conglomerate) of thed- and I-forms; (2) a true racemic compound of the d- and I-forms; and(3) a solid solution (mixedcrystal) of the optically active and opposite forms.

Three methods have been devised for determining the nature of theracemic modification. Two of these methods based on measurements offreezing-point and solubility of the racemic modification and its mixtureswith its d- or I-form are due to Roozeboom and Bruni," The third Bioche­mical Method, which depends upon the different actions of the opticallyactive and opposite forms on micro- and higher-organisms, has been devisedby one of us.2

We have employed Roozeboom's freezing-point (melting-point) methodin this investigation. A melting-point-composition-diagram for mixtures ofthe racemic modification and its d- or I-form is prepared: a racemicmixture of the d- and I-forms gives a diagram consisting of two curveswith a minimum of temperature, the eutectic point (Type I); the racemiccompound gives a diagram consisting of three curves with two minima(eutectic points) and a maximum of temperature lType II); and the solidsolution (mixed crystal) of the d- and I-isomers will give a single continuouscurve joining the melting-points of the optically active and opposite forms

At 389

390 Bawa Kartar Singh and Raro Kumar Tewari

(l"yp: I[I). In the present investigation we have not come across an example of Type III.

The nature of the middle branch (Type II) often indicates the dr of stability of the compound; ii" the compound is sufficiently stable, t~,e middle branch forros the greater part of the whole curve and rises a~d falls abruptly. When the compound is extremely unstable, t•e middle branch of the curve is smaUer and is much ttatter in appearance. We have applir these considerations in indicating the degree of stability of the racemic f o T m s .

The dextro-, l~vo- and racemic-forms of the substances were prepared by methods already described, s The melting-point determit~ations were carried out by preparing ah Ÿ mixture of accurately weighed quanti- ties of the racemic modification and its d- or l-forro and determining the melting-point of the mixturo by the capillary-tube method. The melting- points (in ~ C.) are given in Tables I-VIII.

D~usSrON

3-Nitro-p-toluidz'nomethflenecamphor.--The melting-point determinations are given in Table I. The melting-point-composition-diagram 0Fig. 1) con- sists of two symmetrical curves with a eutectic point. This shows that the racemic modification is a true d/-mixture and confortas to Type I mentioned above.

~99 m

"o n~" Q .

lS]'

o d i 20 lood 8o

FIO. I.

�9 ,.o~. ,,,.,~~ .,,o~ . . ,o~ ~ ' ' ' ~ ' ' ' ' m ~ ~

6o 8o tood[ 80 60 4 o 6O 40 20 o d ~ 20 40 60

Pcrcents~e ComposJ| |on

199 ~

1,37"

195 ~

19) ~

t89" ZO od! 8 0 Iooi

3-Nitro-p-toluidinomethylenecamphors

5-Iodo-o-toluidinomethylenecamphor.--The melting-point dr237 axe given in Table II. The melting-point-composition-diagram (Fig. 2) consists of three curves with two eutectic points. Therefore, the racemic modification is a true d/-compound and confortas to Type II mentioned abow. It is very stable, and the range of stability is very large as the middle branch is very steep and occupies almost the whole of the diagram.

Rac, mie Modii~r ons of O~/itallj, Active Comlbounds--'- V l

t64"

162"

/ \ , ~

o / \ 50 )

I~ ) 46" / \

391

od| 20 4o 8o so tood/ 8o 60 40 2o o d l tood 60 60 40 20 od.o] 20 40 60 80 100|

Pe rcen/el~e CnmDosition F[G. 2. 5-lodo-o-toluidinomethylenr162

4-N'itro-o.toluiditwmethylenecamphor.~The melting-point determinations are given in Table III. The melting-point-composition-diagram (Fig. 3) shows that the raccmic modification is a true d/-compound Cl'ype II). The shape of the middle branch indicates that it is faJrly stable and that the range of stability is fairly large.

~~~~

~ ,,,

t~f u~d 20 l o

/ \

F~o. 3.

/ \ J

/

40 60 80 IG 80 6O ,tO �9 0 40 2O Odp| 2o ,to 60 8 0

~,'cc.ta~o Compo~ifion 4-Ni~o*o-toluidino~ylaaecamphors

143"

I")i"

;55"

i :b l *

i$$4

f)3 ~

392 Bawa Kartar Singh and Ram Kumar Tewari

Oxymethylenecamphor.-The melting-point determinations are given inTable IV. The melting-point-composition-diagram (Fig. 4) shows that theracemic modification is a true dl-compound (Type lI). It is stable bu t therange of stability is small.

so"

82~

.

.1\ J

"r-, V '\ ./

l"""- V ~ ,.-

"od! 20 40 60 80 loodl 80 60 40 20 od

82°

84

~

.s 80oQ"

~ 11fII:

~ 16

~ 7~t

ilood eo 60 40 20 od,oI 20 40 60 eo IDolPercenta,ge CDmposition

FIo. 4. Oxymethylenecamphors•2-Nitro-p-toluidinomethylenecamphor.-The melting-point determinations

are givenin Table V. The melting-point-composition-diagram (Fig. S) showsthat the racemic modification is a true dl-compound (Type II). It is stablebut the range of stability is small as is clear from the shape of the middlebranch of the diagram..

1S'

16"

oe'

92'

100d 80 60 "0 20 odpl 20 40 60 80 1001'Percenf4ge Composition

FlO. S. 2-Nitro+to1uidinomcthylenecamphors·

," 1

94 1

92 1

90" \ I,

\ I I 1sa\ V

86 1

84" \ / 1

\ I82 1

i\. / <, I.aII

~ i'-"t-' 1

176od! 20 40 60 eo lOQdI 80 60 40 20 odl

",ICit.c:.o.: I-Qj

i:l

t9

Racemic Modi/icagions of Ogbtically Active ComŸ 393

3-Nitro-4-chloroanilinomethyIenecamphor.~The melting-point determina- tions ate given in Table VI. The melting-point-composition-diagram (Fig. 6) shows that the racemic modi¡ is a true d/-compound (Type II). Ir is much less stable as the middle curve is flatter in appearance.

~ i�91 ~ �91 ~

216' ' 216"

;,o8' 2os ~

. \ / Y' 2og , 2or

~o,' ~ ~"~ ~"='~ ~ 2o4"

, o , ' / ~ ,oz" ~00 e! 00"

odl 2o 4o 60 80 loodl Bo 60 4o 20 odi ~ood eo �91 4o 20 odpl 20 4o co 80 I00!

Percentd~e CompositJon

Fzo. 6. 3-Nitro-4-cldoroŸ

2: 5-Dichloroanilbmmethylenecamphor.--The melting-point determinations ate given in Table YII. The melting-point-composition-diagram (Fig. 7) shows that the racemic modiflcation is a true d/-ccmpcund (Type II) of low stability and that the range of stability is small.

LA" t,tl ~

. [ 1~lg,~ ~ ,a |39o f

13 '5' L53" Od )0 4O ~ SO wodL eSO 6O 40 XO od! t o o d e m eo ~o 2o odpl ~o ,to Go so mol

r~e rcenf4~[e Corn~3~ion

F ~ . 7. 2 : 5 - D i c h l o r o a n i i i n o m e t h y l e n e c a m p h o r s

4-Chloro-o-toluidinomethfle~ecamphor.~The melting-point dete~z0iva~- tions are given in Table VIII. The meltingopoint-composition-diagram (Fig. 8) shows that the racemic moditication is a true d/-compcu~d (Tylc�91 II)

394 Bawa Kartar Singh and Ram Kumar Tewari

of little stability. The range of stability is very small as indicated by theflat nature of the middle curve•

lS0

U6'

110'

14"

1:/"I

&0 40 20 od,ol 20 40 60 80 1001~rcentage Com"position

4-Cb!ofo-o-toluidinomethylenecamphors

.

.~ J

\ /1

" /.r--- ....-

0-- 1° 1odl 20 40 fiO 80 toodl 80 60 40 20 od

w\ClOd 80

FIG. 8.

o:t

TABLE I

3-Nitro-p-toluidinomethylene­camphors

Mixed meJtina-poiots of 1he racemic modificationwith its d- or I-fonn.

TABLB II

S-Iodo-o-toluidinome/hylene­camphors

Mixed melting.points of the racemicmodification with its d· Of I·ronn.

Wt. " o! the Wt "of the Melti..... pointf:ICemlC' -modification t/- or I'{orm o{ the mixture

10011088'10eoeo40102G10o

1108070108040SOJG10o

Od10203040aoeo'1080110

10010120SO~

ao80'108080

108

193.4°193·8l.·S1",0194':194·a194·e194·7191·0195·0IN·:191·8191'S194·0194·1194'4194·5194'8194·S191501UNI·:

Wt. " of the Wt. % of the Melting-pointracemicmodification t/. or I·{orm of the mixture

100 OJ 181·4"80 10 181·080 20 180·170 SO 111·980 'I) 157'4lIG so 1151'540 80 1113·4ao 70 110'8Jl) 80 147·810 110 143·2II 911 140·80 100 141·11

90 101 181·080 20 110·0'10 30 lllS·880 ~ 117'880 110 1151·840 80 113·830 70 180·820 80 If.7·210 110 141·8I 911 140·80 100 141'11

Raceraic Modil~cations of OŸ Active Comt~ounds--VI 395

TABLe I ] I TABLE I V

4-Nitro-o-toluich'nomethylenecamphors Oxymethylenecamphors Mixed mdting-points of the racemie modification Mixed nwlting-points of the rexr

with its d- or / - forro .

Wt. % of the racemic Wt. % of the

modifir ! d - o r l-forro

100 90 80 70 6 0 50 40 30 20 10 0

90 80 70 60 50 40 30 20 10

0

Od I0 20 30 40 50 60 70 80 90 I00 I01 20 30 40 50 60 70 80 90 I00

modification with its d- or /-forro.

Mehing-point Wt. q£ of the of the mixture racemic

modification

139.40 lOO 138- 6 90 136.6 80 134.5 7O 133-4 60 133.0 50 133.4 40 134.0 30 138.2 20 I36-2 I0 137"8 0 138 -6 90 136-8 80 134-6 70 133-5 60 133-0 50 133"4 40 134-1 30 135-0 20 136.3 10 137-8 0

Wt. 9Ÿ of the d- or l-form

Od 10 20 30 40 50 60 70 80 90

100 10l 20 30 40 50 60 70 80 90

150

M el ting-point of the mixture

78.2* 77-3 76-3 75.6 75.3 75.6 75 -9 76.4 77.3 78.2 80 "2 77.3 76.3 75-5 75-3 75 "5 75.9 76-5 77"5 78 "3 80.2

TAeLE V TABLE VI 2.Nitro-p-toluidotomethylenecamphors 3-Nitro-4-chloroanilinomethyIenecamphors

Mixed melting.points of the recemic modification Mixed melting-points of the racemic with its d- or i-forro.

Wt. % Of t h e [ w t of the I Melting-point z~cemic i ~" %

raodi¡ ] a" or 14orto l of the mixture

19O 90 80 70 60 50 40 30 20 I0 o

90 80 70 60 50 40 30 2 0 l0

0

Od lO 20 30 40 50 60 70 80 90

105 10l 20 30 40 50 60 70 80 90

100

modification with its d- or l-forro.

Wt. ~ of the r a c e m i c

modiflc ation

181-3" 1~0 180-6 90 179.7 80 179 -2 70 179.7 60 180-6 50 181-8 40 183.7 30 185-8 2O 189.2 10 193.4 0 180 "6 90 179-9 80 179-2 70 179 "6 60 180.6 50 182.0 40 183.4 20 186.0 20 189-0 l0 193.4 0

Wt. ~ of the d- or/-forro

Od 10 20 30 40 50 60 7O 8O 9O

100 lOt 2O 3O 40 5O 6O 70 8O 9O

100

Melting-point of the u~xture

~ 0 4 . 5 s 204.4 204.2 204-0 203-4 202.7 202.0 205.6 208.0 211.8 215-2 204.4 204-2 203.9 203.6 202-9 202-0 205.2 208.4 212.0 ~5 .2

396 Bawa Kartar Singh and Ram Kumar Tewari

TABLE VII TABLE VIII2: 5-Dichloroanilinomethylene- 4-Chloro-o-toluidinomethylene-

camphors camphorsMixed melting-poiDts of the racemic modificatiOll Mixed melting-points of the racemic

with its d- or I-form. modification with its d- or I-form.

Wt.~e:~cthe Wt. % of the Melting-pointmodification d- or I-form of the mixture

Wt. % of the Wt. % of the Melting-pointracemicmodification d- or I-form of the mixture

100 Od I36·S·90 10 136·680 20 136·470 30 136·260 40 136·450 50 136·740 60 137·030 70 137·520 80 138·110 10 138·70 100 139·4

90 101 136·680 20 136·370 30 136·:80 40 138·450 50 136·640 60 137·130 70 137·510 80 138·010 90 138·70 100 131·4

100908070605040302010o

9080'7060SO40302010o

Od102030405060708090

10010/20304050607080gO

100

116·2·116·0115·7115·5115·7115'9116'4117·0118·1119·2121'2118·0115·8115'511"7116·1118·5117·1118·0us-e121·2

1. Roozeboom, H. W. B.BruDi, G.Singh, B. K., and Perti, O. N.

--and Nayar. B. K. K.-- and Perti, O. N.

2. Bhatia, H. B., and Singh, B. K.3. Sinah. B. K., alld Tewari, R. K.

SUMMARY

The racemic modification of 3-nitro-p-toluidinomethylenecamphor is atrue dl-miJIture whereas the racemic modifications of S-iodo~-toluidino-_

4-nitro-o-toluidino-_ oxy-_ 2-nitro-p-toluidino-_ 3-nitro-4-chloroanilino-_ 2: Sodlchloroanilinc- and 4-chloro-o-toluidino-methylenecamphors are all truedl-compounds.

The stability of the racemic forms is also discussed.

We wish to thank the University of Allahabad. where this work \\!asdone. for the provision of research facilities.

R.EFERBNCES

Z. physikal. CJIem., 1899, 28, 494... Gcru. chim. 11m., 1900, 30, 35.. • hoc. Nat. Acad. Sci., India. 1943, 13, 59; 1944,

14 A, 79.•• Proc.1Nl. Acad. Sci., 1945, 22 A, 46.

Ibid., 1945, 22 A, 170..• P1'OC. Nat. Aetld. Sci., IlIdia, 1944, 14, 171..• Prot:. IntI. Acad. Sci.. 1945, 22 A, 20; 1946,

23A, 218.