July 20, 1962
~ O l t I l t l U N I C 4 T I O N STO THE EDITOR
2s33
Hydrogenation’O of (11) yielded the alkyl derivative (111). Anal. Calcd. for C35H4003hr4: C, 74.44; H, 7.14; N, 9.92. Found: C, 73.86; H, 7.17; N, 9.94. Oxidative degradation of (111) yielded only methylethylmaleimide in the neutral fraction. Oxidation of (I) by oxygen in alkaline dimethylformamide yielded a dicarbonyl derivative (IV) . IV Anal. Calcd. for C35H3806N4:C , 70.68; H, 6.44; plying that product formation is controlled by K, 9.42. Found: C, 70.31; H, 6.32; K, 9.46. other factors than the field effect of the remote Under the same conditions mesopyropheophorbide substituent. a (V) yielded the C9-Clo ring diketone.” (111) was likewise oxidized to its dicarbonyl derivative DEPARTMENT OF CHEMISTRY UNIVERSITYOF DELAWARE HAROLD KWART (VI). Further oxidation of (VI) by HzOz in alkaNEWARK, DELAWARE T. TAKESHITA line dimethylformamide yielded a tricarboxylic RECEIVED MAY24,1962 acid (VII). A portion was methylated and converted to its zinc complex. Anal. Calcd. for ZnC35H3cO3N4(OCH3),: OCH,, 13.0. Found: OCH,, STUDIES OF CHLOROBIUM CHLOROPHYLLS. V. 12.9. The remainder was dried a t 100’ to yield CHLOROBIUM CHLOROPHYLLS (660)’ a product (VIII) whose visible absorption spectrum Sir: resembled that of purpurin 18.12 It was methylThe evidence presented below suggests that ated and converted to its zinc complex. Anal. Chlorobium chlorophylls (660) are derivatives of Calcd. for ZnCa5Ha504N4(0CH3) : OCH3, 4.62. 6 - methyl - 2 - desvinyl - 2 - cz - hydroxyethyl- Found: OCH3, 3.03. Dilute methanolic KOH pyropheophorbide converted (VIII) back to (VII). Treatment of Hydrolysis of crude “pheophytin” (660) in dilute the trimethyl ester of (VII) with methanolic KOH hot methanolic KOH and partition chromatography in pyridine did not generate the Molisch phase between aqueous HC1 and ether on Celite columns4 test intermediate as i t does when chlorinee-trigave seven fractions which were designated 1-7. methyl ester is treated 1 i k e ~ i s e . l This ~ result All fractions possessed a conjugated carbonyl excluded the possibility of a cyclohexanone ring group5; all possessed a hydroxyalkyl group which in (I). could be oxidized to a conjugated carbonyl group6 HI in acetic acid converted (I) into a porphyrin or dehydrated t o an alkenyl group?; all gave a containing a conjugated carbonyl group and an negative hlolisch phase test.8 Comparison of ethyl in place of a hydroxyethyl group., .4nal. their visible absorption spectra revealed no sig- Calcd. for C35H3803N4: C, 73.70; H, 6.81; N, nificant differences among them. 9.96. Found: C, 74.32; H, 7.03; X, 10.02. The The neutral imides obtained from the fractions visible absorption spectrum was of the “etio’’ by oxidative degradation were exanlined by gas- type.12 (VII) was heated in HCl (lY0) in a sealed liquid partition c h r o m a t ~ g r a p h y . ~Fractions .~ 1 tube at 185’ for three hours. The wave lengths and 2 yielded an unidentified product; fractions 3 of the absorption maxima of the resulting porphyrin and 4 yielded methyl-n-propylmaleimide; and frac- and of phyll~porphyrin’~ were identical. However, tions 5, 6 and 7 yielded methylethylmaleimide. bands I1 and 111 of the Chlorobium product ab-4fter conversion of the hydroxyalkyl group to an sorbed with equal intensities. alkyl group, fractions 3 and 4 yielded niethylethylThe above result suggested that (I) possessed inaleirnide in addition to tiiethyl-n-propylmaleim- an a l b l group attached to one of the methine ide. Dihydroheinatinic acid imide was shown bridge carbon atonis. I t was shown to be a t earlier to occur iii thc a c i d fractioii l’roni partially Ca by the iollowiIig: (IT)exposed to soinewhat .5,g purified pheophorbidc ((KO) These results in- aged, ctliaiiol-frcc. dry chloroiorii~was converted tlicate ilie nature o f tlic substituents 011 Riitgs I , to a chlorine-containing product (IX) whose visible 1 I and 11.. absorption spectrum was almost superposable F’ractioii 5 ( I ) (..I m I . Calcd. for C:laM40C)4N4: iipon that of (I).’5 . 1 no/. Calcd. for CeaH&C , i 2 . 3 9 ; H, ti.94; N, 9.65. Found: C. 72.45; N I C ~ : C , ti9.40; 13, (i.18: N, 9.81; C1, 6.20. H, 7.43; K,!1.89) was used for the following studies: Foulltl: ‘2, 69.14; 1-1, t-).9i; S , 9.75; C1, 6.10. Dehydration of (1) iii phosphoric acid (lOO:h, Ciso, The same product was obtained using the method 30 min.) yielded the alkenyl derivative (11). described by N’oodward and Skari6.‘6 The proton d n d . Calcd. for C35HaaO&4: C, 74.iO; H, 6.81; magnetic resonance spectra of (111), (V) and (IX) N, 9.96. Found: C, i5.09; H, 6.S3; N , 10.00. were measured in CDCl3. The signal assigned to the C8-protonl6 was absent from the spectra of (1) S . I L ,S>c..,83, IliTC, (10) ( 1I ) (12) (13) (14)
/io,. , I
2836
COMMUNICATIONS TO THE EDITOR
VOl. 84
addition, the spectra indicated that all contained position of the equilibrium mixture was determined the same number of methyl groups, but that (111) by gas phase chromatography on a column of ycontained an extra ethyl group. It remains t o methyl-y-nitropimelonitrile, and the A P for the be determined whether the Cg substituent is methyl isomerizationll trans cis-1,3-diisopropylcycloand the CSsubstituent is ethyl or vice versa. hexane was found to be -1.91 f 0.01 kcal./mole The authors wish to thank Drs. S.F. MacDonald a t 560'K. When the symmetry properties of the and H. J. Bernstein of the Division of Pure Chem- molecule are taken into account, from this value istry for generous assistance. Analyses were one calculates that for the reaction equatorial isocarried out by Mr. A. E. Castagne. propyl $ axial isopropyl, AFOzss = 2.10 kcal./ mole. (17) X , R . C. Postdoctoral Fellow, 1959-1961. (18) N,R . C. Postdoctoral Fellow, 1960-1961. An independent measurement of the free energy (19) N. R . C . Postdoctoral Fellow, 1961-1962. of an axial isopropyl group was also made by deterDIVISION OF APPLIED BIOLOGY A. S. HOLT mining the equilibrium point for the isomerization NATIONAL RESEARCH COUNCIL D. W. HUGHES~, H. J. KEXDE'~ of the cis and trans ethyl 4-isopropylcyclohexaneOTTAWA, CANADA J. w.Pr'RDIElg carboxylates. The free energy of an axial ethyl carboxylate group was determined in the present RECEIVED May 4, 1962 work (by equilibration of the ethyl 4-t-butylcyclohexanecarboxylates) as 1.24 kcal./mole a t 373'K., CONFORMATIONAL ANALYSIS. XXXI. THE in agreement with literature values.12 One can ISOPROPYL GROUP'~Zs' then calculate the free energy of the alkyl group Sir : from the measured equilibrium constant using the Conformational energies of simple alkyl groups equation A P a l k y l = RT In [ ( K i K c o o E t - 1)/ are the fundamental quantities on which conforma( K c o o E t - Ki) 1, where Ki is the observed constant tional analysis is based, and values for the methyl for the cis $ trans-isomerization and K c o o E t is the and ethyl groups are known4 to be about 1.8 kcal./ constant for an axial & equatorial carbethoxyl. mole. The numerical values previously reported In this work the equilibration was carried out for the isopropyl group range from 2.5 to 3.55 kcal./ a t temperatures in the range of 329-416'K. using with the value 3.3 being commonly ethanol as solvent with sodium ethoxide catalyst. quoted.4a Other evidence8 has been taken as sup- The analysis was done by gas chromatography on a port for a value for isopropyl which is considerably Tide column, and the observed equilibrium congreater than those of methyl and ethyl. A rough stants gave A P = 2.49 (at 416') and 2.22 (at statistical treatment of the problem suggests that 329O), which gives a value of AFO = 2.12 kcal./ while the axial isopropyl loses rotational freedom mole a t 298'. Similar studies were carried out to a greater extent than do the smaller groups, the with the 4-methyl and 4-ethyl carboxylates and the effect is small, and partially cancelled by a n oppos- data are summarized in Table I. These values ing enthalpy difference, and i t can be predicted lead to standard free energy changes as given in that a t ordinary temperatures the free energy of Table 11. a n axial isopropyl should be only slightly greater than those of methyl and ethyl. If this prediction TABLEI were to be correct, i t would mean that the a priori EQUILIBRIUM CONSTANTS FOR THE REACTION ETHYLcis-4assumption often made that an isopropyl group is ALKYLCYCLOHEXANECARBOXYLATE F! ETHYL trans-4almost as "big" as a t-butyl groupg and is sufficient ALKYLCYCLOHEXANECARBOXYLATE to establish a fair dcgree of conformational homoT,OK. Me Et i-Pr T. OK. L-Bu geneity in simple molecules would have to be 415.7 4.61 3.33 3.78 416.2 3.30 abandoned, except as a rough approximation. 376.7 4.01 4.44 5.26 3.97 375.1 The free energy of an axial isopropyl (relative to 352.4 5.83 4.85 4.20 352.9 4.34 an equatorial) has therefore been determined in 329.4 6.55 5.38 4.77 329.1 4.90 two independent ways. First, 1,3-diisopropylTABLE I1 cyclohexane has been equilibrated a t elevated temperatures with a palladium catalyst, lo the com- ITALUES' FOR 'rHERMODYNAhfIC QUANTITIES FOR T H E RE(1) Paper XXX, N . L. Allinger and W. Szkrybalo. J . O v g . Chem., in press (1962). (2) This resrarrh was supported hy a grant from the National Sricnre Foundation. ( 3 ) The new compounds used in thiF wnrk w e r e all obtained b y straight forward unequivocal methods and gave proper analytical data. (1) (a) W. G . Dauben and K . S. Pitzer in M. S . Newman's "Steric I.:ffects in Organic Chemistry," John Wiley and Sons, New York, 19.56, p. 1 ; (b) N. L. Allinger and S. IIu, J . A m . Chem. Soc.. 84, 370 (1962). ( 5 ) S. Winstein and N . J . Holness, J . A m . Chem. Soc., 7 7 , 5662 (1955). (ti) D. S . Noyce and L. J. Dolby, J . Org. Chem., 26, 3619 (1961). (7) H. van Bekkum, P . E. Verkade and B. M. Wepster, Konikl. A-ed. A k a d . Wetenschap. Proc. Ser. B , 6 4 , No. 1, 161 (1961). ( 8 ) (a) A. R . H. Cole and P. R . Jefferies, J . Chem. Sac., 4391 (19.56); (b) W. Tagaki and T. Mitsui, J . Org. Chem., 26, 1476 (1960). (9) For example, (a) W. Klyne, Erperientia, 12, 119 (1956); (b) B. C. Lawes, J . A m . Chem. Sac., 84, 239 (1962). (10) N. L. Allinger and J. L. Coke, J . A m . Chem. Soc., 81, 4080 (1959); 82, 2653 (1900).
ACTION
*
EQUATORIAL AXIAL ALKYLCYCLOHEXANE AT 298OK. Alkyl
AFO, kral./mole
Methyl 1.87 Ethyl 1.80 Isopropyl 2.11 0 Calculated from the experitneutal data in Table I. The probable error in AFO estimated to be 0.1 kcal./mole.
The qualitative conclusion is that the isopropyl group is essentially the same size (in the present (11) Values for AH0 and A S 0 were obtained but are anomalous, Presumably because of the presence of appreciable amounts of boat forms at the high temperatures used. Further discussion will be given in the full paper. (12) (a) E. L. Eliel, H. Haubenstock and R. V. Acharya, J . A m . Chem. Soc., 83, 2351 (1961); (b) N. L. Allinger and R. J. Curby, J . Oig. Chem., 26, 933 (1961); (c) E . L. Eliel and M. Gianni, Tet7ahedron Letters, 97 (1962).
