Table I. Five Samples from Each of Five Pools of CSF from Different Sources Were Analyzed for Their Content of 5-HIAA Mean 5-HIAA in Std dev in Pool ng/ml CSF i std dev of mean Range 1 8.2 i 0 . 5 6.1 7.6-8.8 2 17.2 =t1 . 1 6.4 16.3-19 .O 3 26.4 i 0 . 5 1.9 26 .&26.9 4 28.7 i 0.3 1.o 28.2-29.0 5 32.0 i 0.5 1.6 31.3-32.5
fragmentogram (Figure 2B) of the 5-HIAA-d2 derivative, The standard curve was linear over the range studied. The precision of this analytical method for 5-HIAA was determined by analyzing five pools of human CSF from different sources five times each. The pools contained between 8 and 32 ng 5-HIAA/ml and the standard deviation was less than 7% below 20 ng/ml and 1-2Z above this level (Table I). The CSF pool 3 was analyzed for its content of 5-HIAA after having been stored frozen at -15 “C for two months. The loss of 5-HIAA during this period was less than 5 %. ACKNOWLEDGMERTT
lower spectrum. The compound contains not only 5-HIAAd2, but also mono- and nondeuterated 5-HIAA (62 and 19 %, respectively, of the dideuterated). The mass spectrometer could be focused exactly on mle 538 and 540 on channels 1 and 2, respectively, without contributions from ions of adjacent m / e , when mass fragmentography was used. This is shown by the agreement between the relative proportion of the fragments in the mass fragmentograms (Figures 2A and B ) and the mass spectra (Figure 1). The standard curves for the quantitative determination of 5-HIAA in CSF (Figure 3) were prepared using 5-HIAA-d2as the internal standard. The intercept of the ordinate at 0.20 is in agreement with the ratio between m / e 538 and 540 in the mass spectrum (Figure 1, lower spectrum) and in the mass
We appreciate the help of Birgitta Sjoqvist in performing the radio-gas chromatographic studies and for the skillful technical assistance we are indebted to Eva Dufva. D. Efron, NIMH, kindly supplied the 5-HIPA. The project has been cleared by the ethical committee at the Karolinska Institute. RECEIVED for review November 15,1971. Accepted February 8, 1972. This project was supported by grants from the Tri-Centennial Fund of the Bank of Sweden to B. Holmstedt (68153) and to B. Cronholm and F. Sjoqvist (68/90), the National Institutes of Health, Bethesda, Md., (GM 13 978), the National Institute of Mental Health, Chevy Chase, Md., (Grant MH 12007), the Wallenberg Foundation, Swedish Medical Research Council B 72-40 Y-2375-05, and by funds from the Karolinska Institute.
Hexafluoroacetone Ketals as Derivatives for Positional and Geometrical Characterization of Double Bonds Bruce M. Johnson and James W . Taylor1 Department of Chemistry, University of Wisconsin, Madison, Wis. 53706
The characterization of double bond position and geometry has been improved through conversion of n-al kenes to hexafluoroacetone ketals. Derivatives are synthesized by stereospecifically forming bromohydrins from the alkenes and converting them to ketals via base-promoted reaction with hexafluoroacetone in sealed glass reaction tubes. The addition of hexafluoroacetone proceeds with at least 97% trans specificity. Mass spectral fragmentations which indicate the original double bond position are discussed as are the stereochemical effects. The uses of GLC, NMR, and IR for derivative characterization are also examined. The combination of GC and MS on the derivative provides complete characterization of the original olefin.
MASS SPECTROMETRIC ANALYSIS of long chain unsaturated compounds is complicated by geometrical and positional isomerization which may occur before fragmentation of the molecular ion (1-3). Since olefin isomerization is a facile process, the mass spectra of a series of positional and geometrical isomers are generally very similar and extremely Author to whom correspondence should be directed. (1) J. H. Beynon, “Mass Spectrometry and its Applications to Organic Chemistry,” Elsevier, Amsterdam, 1960, p 262. (2) D. S.Weinberg and C. Djerassi,J. Org. Chem., 31,115 (1966). (3) B. J. Millard and D. F. Shaw, J. Chem. SOC.B, 1966,664. 1438
ANALYTICAL CHEMISTRY, VOL. 44, NO. 8,JULY 1972
difficult to use for structural assignments. The most successful approach to this problem has been to form a derivative of the double bond which has a fragmentation pattern reflecting the original configuration of the unsaturated molecules. The first such alkene derivative was produced by reduction of the double bond with deuteriohydrazine ( 4 ) . Use of this derivative, however, was complicated by partial H-D exchange (5, 6). Other approaches have included oxidation of the double bond to an epoxide used directly (7) or followed by conversion to ketones (6) or N,N-dimethylamino alcohols (8). Methoxymercuric adducts have been de-mercurated to a pair of isomeric methoxy compounds (9). Double bonds have also been oxidized to 1,2-diols and converted to dimethyl
(4) N. Dinh-Nguyen, R. Ryhage, and S. Stallberg-Stenhagen, Ark. Kemi, 15,433 (1960). (5) N. Dinh-Nguyen, R. Ryhage, S. Stallberg-Stenhagen, and E. Stenhagen, ibid., 18,393 (1961). (6) G. W. Kenner and E. Stenhagen, Acta Chem. Scand., 18, 1551 (1964). (7) R. T. Aplin and L. Coles, Chem. Commun., 1967,858. (8) H. Audier, S. Bory, M. Fetizon, P. Longevialle, and R. Toubiana, Bull. Soc. Chim. Fr., 1964,3034. (9) P. Abley, F. J. McQuillin, D. E. Minnikin, K. Kusamran, K. Maskens, and N. Polgar, Chem. Commun.,1970,348.
ethers (10) or bis(trimethylsily1) ethers (11). These derivatives have met with varying success for locating the position of the double bond; however, none is applicable for providing information on the geometry. Cyclic boronate esters which preserve the stereochemistry as well as bond position have been prepaied from 1,2- and 1,3-diols (12) but have not been applied to long chain olefins or unsaturated fatty esters, In contrast, the cyclic acetone ketal I has been shown to be useful for both olefins (13) and unsaturated fatty esters (14). This derivative is prepared by oxidation of the double bond with OsOl followed by conversion of the resulting 1,2-diol to the cyclic acetone ketal, also a stereospecific reaction. In this reaction sequence, for example, a cis olefin is converted to a cis dioxolane. Electron impact induced fragmentation gives products which can be related to both geometry and position of the original double bond. Geometric isomers can be separated by GLC; however, positional isomers cannot if the original double bond is near the center of a long chain. Furthermore, this derivative is quite easily hydrolyzed so all handling procedures must rigorously exclude moisture. The success of the acetone ketal I suggested that the hexafluoroacetone derived analog I1 might provide a more easily RICH-
I
CHR,
I
O\,/O
/ \
CH,
CH,
I
P
interpreted mass spectrum. The a-cleavage fragments, which indicate the position of the original double bond, are increased by 108 mass units. All a-cleavage fragments, therefore, appear above mass 208 where the spectrum is relatively free of interfering peaks and their identification is simplified. Fluorine would also aid in distinguishing fragments which originate in the ring as opposed to those from the hydrocarbon moiety. In addition, the fluoro derivative would be expected to be thermally and hydrolytically stable without a large change in volatility. In this study we wish to concentrate on the synthesis and properties of the fluoro derivative I1 and present mass spectrometric evidence of its usefulness for positional identification of olefins. Extensions to other systems containing carbon double bonds should be possible from the data discussed here. The application of other techniques for characterization will also be discussed briefly. EXPERIMENTAL
All reagents were used as received. 1-Octene, cis- and truns-2-octene, N-bromosuccinimide, dimethyl sulfoxide, and tri-n-butylamine were supplied by Aldrich Chemical Co:, Milwaukee, Wis., and hexafluoroacetone by Columbia Organic Chemicals, Columbia, S.C. The cis and trans isomers of 2-, 3-, 4-, 5-decenes, 3-, 4-octenes, and 3-dodecene and trans-3-nonene were obtained from Chemical Samples Co., Columbus, Ohio. All olefins were specified as 95% pure or (10) W. G. Niehaus, Jr., and R. Ryhage, ANAL.CHEM.,40, 1840 (1968). (11) P. Capella and C. M. Zorzut, ibid., p 1458. (12) C. J. W. Brooks and J. Watson, Chem. Commun.. 1967.952. (13) R. E. Wolff, G. Wolff, and J. A. McCloskey, Tefrahedron,22, 3093 (1966). (14) J. A. McCloskey and M. J. McClelland, J. Amer. Chem. SOC., 87, 5090 (1965).
better. Microanalyses were performed by Spang Microanalytical Laboratory, Ann Arbor, Mich. Preparative gas chromatography was carried out with a Varian-Aerograph Model 705 using a 3/8-in. X 20-ft aluminum column packed with 15 Carbowax 20M on 60/80 mesh Chromosorb P (HMDS). Normal operating conditions were: injector, 198 "C; flame ionization detector, 200 "C; detector split ratio, 10; column, 110-40 "C as required for separation, Flow rates were: air, 400 ml/min; hydrogen, 22 ml/min; helium (carrier), 200 ml/min. Injections of 50100 p1 were made and heart cut material was collected at room temperature. Preparatively collected compounds were analyzed on the same column at 130 "C using 1-pl samples. No compound had greater than 0.3% impurities, Le., isomers of the desired compound which were most difficult to separate. Instrumental conditions were unchanged for all runs and the uncorrected retention times were used for the plot of log R us. carbon number. Mass spectra were obtained using a modified Finnegan Model 1015 quadrupole instrument. Modifications include an all glass and Teflon inlet system, a Keithley Model 602 electrometer for measurement of ion currents, and a main vacuum system employing a Welch Model 3102B turbomolecular pump. An interface system was built to provide three channels of output data with relative sensitivities of 1, 10, and 100 from a single input to increase dynamic range. The spectral data from the interface were recorded on magnetic tape using a Sangamo Model 3500 FM tape recorder allowing playback to either a strip chart recorder or an analog-todigital converter for computer processing. In order to minimize the effects of instrumental instabilities, the mass spectrometer was tuned to give unit resolution over the mass range of 40-500 just prior to use, and the spectra of all compounds were recorded in a short period over which no change in performance was noted. Samples were run at source pressures of 1.0-2.5 X 10-5 Torr with the inlet at 90110 "C. The mass range 25-370 was scanned in 360 sec during which sample pressure variations were less than 0.1 X 10-6 Torr. Spectra were recorded in triplicate at electron impact energies of 70 eV and 250 pA emission current. Mass spectral data were reduced using Raytheon 706 and Univac 1108 computers. Peak intensities for each spectrum were calculated as % ; Z ~ S and triplicate runs averaged. Individual deviations from the average for some peaks reached a maximum of 5 (relative) but most were within 2 %. High resolution mass spectral data were obtained with a n AEI MS-902C. Infrared spectra were recorded using a Perkin-Elmer Model 421 grating spectrophotometer. Samples were run neat between NaCl plates. NMR spectra were run on a Varian Associates XL-100 spectrometer at 100 MHz for protons and 94.1 MHz for fluorine. Samples were prepared as 20% v/v in CDC13 with 1 TMS for proton work and in actone-ds with 5 % CFCll for fluorine work. The hexafluoroacetone ketals are synthesized in two steps. First an alkene is converted to a bromohydrin using a procedure adapted from the literature (15). The bromohydrin is then condensed with hexafluoroacetone to give the desired product. The most successful procedure is illustrated below using cis-3-octene. Variations in the ketal synthesis will be discussed in a later section. Cis-3-Octene Bromohydrin. Cis-3-octene, 3.51 grams (0.0313 mole), was added to a 250-ml flask from a syringe weighed before and after delivery. About 50 ml of dry DMSO and 5.0 ml of "wet" DMSO (0.0127 mole H20/ml) was added and the mixture stirred vigorously while 11.1 grams (0.0626 mole) of N-bromosuccinimide was added. in small portions over a period of 30 min. During this addition (15) D. R. Dalton, V. P. Dutta, and D. C. Jones, J. Amer. Chem. Soc., 90, 5498 (1968). ANALYTICAL CHEMISTRY, VOL. 44, NO. 8, JULY 1972
1439
the mixfiure initially turned orange and then returned to colorless until about half of the N-bromosuccinimide was added, after this the mixture retained the orange color. Following an additional 2 hr of stirring, the reaction mixture was poured into a 500-ml separatory funnel containing 100 ml of pentane and 200 ml of water. The aqueous layer was extracted once more with 100 ml of pentane and discarded. The combined pentane layers were washed with four 100-ml portions of water, dried over anhydrous magnesium sulfate, filtered, and the pentane removed in ljacuo to give 6.7 grams of a sweet smelling colorless liquid. Gas chromatographic analysis suggested a mixture of threo-3-bromo-4-octanol and threo-4-bromo-3-octanol with small amounts (less than 5 %) of unidentified impurities. This crude product was used without further purification in the next step. Cis-Z,Z-Bis(trifluoromethyl)-4-butyl-5-ethyl-1,3-dioxolane. The crude bromohydrin mixture was put in a heavy walled borosilicate glass reaction tube (25-mm 0.d. and 20 cm long fitted with a 14/35 joint for connection to a vacuum line) containing 10 ml of pentane, Tri-n-butylamine, 7.45 ml (0.0313 mole) was added and the vessel connected to a vacuum line, the contents were frozen with liquid nitrogen, the air was pumped out, and excess hexafluoroacetone (0.0394 mole) condensed into the reaction tube. Hexafluoroacetone, a gas at room temperature, had been previously expanded into a vacuum line of known volume and the quantity transferred calculated from the pressure before and after condensation. The tube was then sealed while under vacuum, placed in a safety enclosure, and placed in an oven for 2 days at 75 "C. At the end of the reaction period, the vessel was allowed to cool to room temperature during which time crystals formed; the mixture was frozen with liquid nitrogen; the reaction vessel was opened; and the contents were warmed to room temperature slowly in a hood to allow unreacted hexafluoroacetone to escape. The mixture was washed into a 500-ml separatory funnel using 250 ml of water and 100 ml of pentane. The aqueous layer was extracted twice more with 100-ml portions of pentane and discarded. The combined pentane layers were washed twice with 100-ml portions of 1N sulfuric acid and twice with 100-ml portions of water, dried over anhydrous magnesium sulfate, filtered, and the excess pentane removed in ljucuo to give 9.82 grams of light yellow liquid. Gas chromatographic analysis of the crude product indicated 4.2 % unreacted bromohydrin, 14% residual solvent, and 81 % desired product. The small remainder consisted of three unidentified compounds. The overall yield, based on starting olefin, was estimated at 85%. The crude product was vacuum distilled and heart cut material, bp 72-3 "C at 9.8 mm, exceeding 97% pure product, was collected. This was then purified by preparative gas chromatography. Two representative samples were submitted for elemental analysis. Cis-2,2-bis(trifluoromethyl)-4-methyl-5-pentyl-1,3dioxolane. Anal. Calcd for CllHI6F6O2: C, 44.88; H, 5.48; F, 38.76. Found: C, 44.93; H, 5.37; F, 38.65. Exact mass : calcd, 294.105435 ; found (mass spectrometry), 294.101 (low intensity). Trans-2,2-bis(trifluoromethyl)-4-ethyl-5-hexyl1,3-dioxolane. Anal. Calcd for C13H20F602:C, 48.43; H, 6.25; F,35.39. Found: C,48.18;H,6.11;F,35.22. Exactmass: calcd, 322.136733; found (mass spectrometry), 322.1357.
RESULTS AND DISCUSSION
Derivative Preparation. Synthesis of the new derivative I1 requires a different approach than that used for the acetone ketal I. The unusual stability of hexafluoroacetone adducts prevents synthesis directly from a diol as was used for the acetonide. The fact that fluoroketones form stable, isolable adducts with water, aliphatic alcohols, and ammonia indicates that the ketone-hemiketal equilibrium heavily favors hemi1440
ANALYTICAL CHEMISTRY, VOL. 44, NO. 8, JULY 1972
ketal (16). Further reaction of the hemiketal with an alcohol does not occur. The hydroxyl group of the hemiketal is acidic, however, and capable of alkylation. Reaction of haloacetones with ethylene chlorohydrin has been studied by Simmons and Wiley (17). They have shown that basepromoted ketal formation proceeds via hydration of the haloacetone by the hydroxyl followed by intramolecular alkylation to form the cyclic ethylene ketal. The stepwise nature of this reaction has been demonstrated by reacting a haloketone with ethanol and methyl sulfate to give only the unsymmetrical methyl ethyl ketal. One equivalent of added base is required for the hemiketal to ketal step. The dioxolanes formed by reaction of hexafluoroacetone with ethylene chlorohydrin are extremely stable. Treatment with concentrated H2S04 at 150 and 170 "C or 20% methanolic HC1, 6N "Os, 6N HzS04,or 2N NaOH at steam bath temperatures for several hours resulted in only minor decomposition. In order to synthesize the fluorodioxolanes described above, a reaction which converts olefins stereospecifically to halohydrins is required. Dalton, Dutta, and Jones have reported that the elements of HOBr can be added stereospecifically across the carbon-carbon double bond by reaction of an alkene with N-bromosuccinimide in wet dimethyl sulfoxide (15). The bromohydrin is formed in high yields with at least 97% trans specific addition. This reaction provides the necessary intermediate for a successful derivatization scheme. Consider the example of a cis-alkene I11 which has been converted to the threo-bromohydrin IV:
m
IIL
This reaction in the linear alkene system gives two positionally isomeric products when R1 # R2 (Le,, the OH and Br groups may be interchanged). The isomer distribution is expected to show no particular preference, except in the 1-alkene case, since R1 and R2exert similar directive influence. However, the ketal formed from each of these isomers is the same so that isomer distribution is unimportant here. The procedure used for synthesizing the bromohydrins was essentially that of Dalton, Dutta, and Jones (15) with the deletion of nitrogen atmosphere and cooling. The additions of N-bromosuccinimide were made in small portions rather than as a single portion. Generation of side products was found to be unimportant so the crude bromohydrin was used directly for the ketal synthesis after washing with water to remove dimethyl sulfoxide and drying. The fact that bromohydrin purification is unnecessary becomes an advantage when analyzing mixtures of olefins of different molecular weight because there is no chance of fractionation of the bromohydrin. The stereochemistry of the reaction between hexafluoroacetone and the bromohydrin has recently been established as trans addition (18) by fluorine NMR. From the example above, the bromohydrin reacts with hexafluoroacetone to form hemiketal V followed by base-promoted backside attack (16) C. G. Krespan and W. J. Middleton, Fluorine Chem. Reo., 1, 145 (1967). (17) H. E. Simmons and D. W. Wiley, J . Amer. Chem. SOC.,82, 2288 (1959). (18) B. M. Johnson and J. W. Taylor, Chem. Commun., 1972,296.
on the bromine containing carbon, inverting the configuration, yielding the cis-ketal, VI. This reaction proceeds with
2.30
c-3.
/
2.20 t-3.
2.10 Ip
P
m
near quantitative stereospecific addition. The evidence for this is that the resulting dioxolane is contaminated with the isomeric impurity to an extent less than expected if the starting olefin is of minimum stated purity. The assignment of the geometrical configuration of the dioxolanes has been made on the basis of the fluorine and proton NMR spectra and by analogy with the physical properties of some 2,2-dimethyl-
4,5-disubstituted-l,3-dioxolanes. From an examination of molecular models one would predict that the 19F NMR spectra of the trifluoromethyl groups should differ because of the shielding differences of the methine and methylene protons. In the trans-dioxolane, the environment of the CF3 groups should be similar for a conformationally mobile ring system. A near singlet representing an A6 pattern was observed, as expected, for the ketal derived from trans-4-octene (1-80.62 ppm from CFC13) indicating trans-olefin + erythro-bromohydrin + transdioxolane reaction stereospecificity. Examination of this peak at higher resolution revealed it to be a triplet caused by H-F coupling with the two ring protons (JH-F= 0.6 Hz). The spectrum of the cis isomer exhibited the CF3 nonequivalence predicted. A complex symmetrical multiplet (centered +79.88 ppm from CFC13) was observed confirming the prediction for the cis geometry of the dioxolane derived from cis-4-octene. The proton NMR spectra have the expected methyl and methylene multiplets. The trans-methine protons (6 = 3.97 ppm from TMS) are shifted less than the cis-methine protons (6 = 4.49 ppm from TMS), a trend also observed for some 4,5-dialkyl dioxolanes (19) and 4,5-dialkenyl dioxolanes (20). Further substantiation of the geometrical assignments comes from a comparison of the trends in refractive index and boiling point (Table I) with trends reported for series of other nonfluorinated 1,3-dioxolanes. The table lists the boiling ranges over which product of about 9 5 Z purity was obtained when distilling crude product. Lower refractive indices and boiling points for the trans isomers are similar to trends noted in the previously mentioned 4,5-substituted-1,3-dioxolanes (20, 21). Gas chromatographic retentions (Figure 1) also follow the trend of trans < cis as reported for the cyclic acetone ketals (13, 14). Thus, a highly stereospecific reaction scheme is presented which can be used to prepare derivatives of carboncarbon double bonds with known stereochemistry. Improvements in synthesis techniques have made it possible to obtain overall yields, olefin to ketal, of at least 85 %. Instead of bubbling hexafluoroacetone (bp, -24 "C) into a pentane solution of bromohydrin at atmospheric pressure, a vacuum manifold of known volume equipped with a mercury manometer was used to transfer it to a reaction vessel by freezing with liquid nitrogen. This eliminates the uncertainty involved in other methods of transfer. Addition of one equivalent of base catalyzes the reaction and neu(19) Sa-Le-Thi-Thuan and J. Wiemann, Bull. Soc. Chim.Fr., 1968, 4550. (20) J. Chuche, G. Dana, and M.-R. Monot, ibid.,1967,3300. (21) R.Epsztein, S . Holand, and I. Marszak, ibid.,1968,4175.
2.00 1.90
c-3
1.80 m 0 0
7:
t -2 c-4
c-5
1 .
1.70 1.60
E-2
/
.
.
/
::: :
1.50
1.40
1-3 1-4
1.30
. I
9
8
10
ORIGINAL OLEFIN
12
11
CARBON NUMBER
Figure 1. Gas chromatographic retentions of the derivatives referred to the original olefin c = cis, t =
frans, number
= position of original
double bond
tralizes the HBr formed. Use of anhydrous potassium carbonate for the base as suggested by Simmons and Wiley (1 7) gave poor yields and caused experimental difficulties in the sealed tube reactions. Tertiary amines were superior in this respect. Tri-n-butylamine gave higher yields than quinoline and was more easily extracted. The combination of sealed reaction vessels and aliphatic tertiary amines increased yields by at least a factor of two. Addition of an inert solvent helped to prevent polymer formation and aided the removal of solid amine hydrobromide from the reaction tube. The unusual stability of these compounds allows workup with water and dilute acid to remove amine hydrobromide and free amine. This also permits the derivatization of mixtures which can be separated after reaction. Mass Spectrometry. Preliminary studies of the mass spectrometric fragmentation reveal that the ketal derivatives are very useful. The principal high mass fragment results from loss of CF3from the molecular ion a to give a stabilized carbonium ion b (22). The intensity of the molecular ion is
+.
RICH
I
-CHR, I
-
RICH-CHR,
I + (
OkpQ
I CFl
a
b very low and it may not be observed under normal conditions. However, ion b may be used instead for obtaining (22) F. W. McLafferty, "Interpretation of Mass Spectra," W. A.
Benjamin, New York, N.Y., 1966,p 110. ANALYTICAL CHEMISTRY, VOL. 44, NO. 8, JULY 1972
1441
m/’
Figure 2. Mass spectrum of trans-2,2-bis(trifluoromethyl)-4-butyl-5-ethyl-1,3-dioxolane(trans-3-octenederivative) the identity of the original species. This ion is at least twice as intense as any other ion above mass 150 as shown in Figures 2,3, and 4. The ions resulting from a-cleavage, c and d, are used to locate the position of the double bond in the original olefin. A series M-CnH2n+lis observed with the intensity of peaks c and d greatest. In Figures 2, 3, and 4, peaks of less than R,FH-
CH
the intensity of f increases faster than d as Rz becomes larger. The presence of ions e and f 29 mass units below ions c and d helps to confirm the assignment of the a-cleavage peaks and permit unequivocal determination of the bond position in the original olefin. In the low mass region, peaks characteristic of the hydrocarbon series are abundant. In addition, ions of formula CnH2n+10are found which correspond to cleavage similar to that just described with rearrangement of a proton to form the protonated aldehyde ions g and h. The rearranged
+
d
C
0.05% 235are not shown. The importance of 0- and ycleavage is found to be less than 10% of a-cleavage. There is a significant discrimination effect causing the fragment c to be less intense than d where R1is the smaller alkyl group. The trend toward a favored loss of the larger group is well known for electron impact induced fragmentation reactions (23) so that for loss of R1 = CHI, the intensity of c is indeed low. In cases where R1 is larger than methyl, the intensity of c is great enough to prevent any possible confusion in the assignment of a-cleavage. Another reaction which shows the same trend in the intensity is the loss of RCHO from the ring by cleavage and rearrangement giving the suggested cyclic structures e and f.
c F, I
+
CF,-C-
a
RICH0
a
RICHO f
This reaction is even more susceptible to mass discrimination since ion e remains small until RIis greater than propyl and (23) H. Budzikiewicz, C. Djerassi, and D. H. Williams, “Interpretation of Mass Spectra of Organic Compounds,” Holden-Day, San Francisco, Calif., 1964, p 29. 1442
ANALYTICAL CHEMISTRY, VOL. 44, NO. 8,JULY 1972
+
R, CH=OH
HO=CHR,
0
h
proton probably comes from the a-carbon instead of the ring since the 1-octene derivative has no peak for ion h (R1= H) whereas the trans-2-octene and trans-2-decene derivatives give intensities for ion h of 2.78 and 1.35% Z36,respectively. These peaks give further support to the assignment of double bond position. The stereochemical influence on ion fragmentation reactions, as might be expected (13, 1 4 , results primarily in ion intensity differences. At any given mass the intensity ratio for a cis-trans pair of positional isomers generally lies between 0.5 and 2. The &:trans intensity ratios can vary considerably along a series of positional isomers since the relative size of the alkyl groups changes rapidly for the compounds studied here. For the fragmentations previously described, the a-cleavage gives a cis :trans ratio less than one. The loss of aldehyde and formation of protonated aldehyde reactions give cis :trans ratios less than one. These observations suggest that complete characterization by mass spectrometry would be possible only if standard compounds are available for sorting the intensity ratios. In contrast to the acetone ketals, these fluorinated ketals give no fragmentation involving the formation of a protonated epoxide ion where the greatest cis-trans ratio was observed (13). In the absence of a complete set of standard compounds, however, the mass spectrometric data would need to be combined with information from other techniques. Gas Chromatography. Gas chromatographic retentions provide a powerful auxilliary technique for characterizing isomeric compounds, As can be seen in Figure 1, all cistrans isomers are well separated for a particular position of the
-
14.0
12.0
-
50
Figure 3. Mass spectrum of truns-2,2-bis(trifluoromethyl)-4-ethyl-5-hexyl-1,3-dioxolane (trans-3-decene derivative)
I
100-
o, /c\
0,
CF,
CF.
6.0
4.0
2.0
50
Figure 4. Mass spectrum of truns-2,2-bis(trifluoromethyl)-4-ethyl-5-octyl-ly3-dioxolane(trans-3-dodecene derivative)
original double bond. However, as the alkyl groups become larger, with the dioxolane ring moving to the center of the chain, the separation of positional isomers rapidly diminishes. Separation is further complicated by overlap of compounds with different chain length so that complete identification by gas chromatography becomes impossible. Combined gas chromatography-mass spectrometry could be used very effectively to solve this problem. The mass spectra uniquely identify the carbon number and bond position of the original olefin and the chromatographic retention can be used to establish the geometry. With modification of the synthesis procedure, this approach should prove to be extremely useful for micro samples. Infrared and Nuclear Magnetic Resonance Spectrometry. Other types of spectrometry also prove useful for determining the geometry of the derivative but require larger samples. If sufficient quantities of sample are available, NMR and IR can give definite information about geometric isomers but relatively little about positional isomers. As cited earlier, NMR chemical shifts of the ring protons are greater for the
cis isomers. Further interpretation of the methylene and methyl regions becomes extremely difficult, especially for internal isomers of the longer chain compounds. The infrared spectra between 1200 and 1050 crn-l, tabulated in Table I, can provide positional information if a complete set of comparison standards is available. A clear distinction can be made between cis-trans isomers. In the trans isomer spectra, a doublet, both peaks having nearly equal intensity, is observed at 1154 and 1126 crn-'. Ketals derived from trans-2-alkenes also have an absorption at 1166 cm-' which is slightly stronger than the doublet. In the cis isomers, a single strong absorption is noted at 1143 cm-I with shoulders showing trends which appear to be related to the lengths of R1and RP. The spectrum of 1-octene derivative in this region indicates that terminal and cis-alkenes give derivatives with similar spectra. Thus for sample sizes above the micro scale, a combination of mass spectrometry and IR or NMR may be useful for complete characterization of the original olefin. A more detailed study of the positional and geometrical influences on ANALYTICAL CHEMISTRY, VOL. 44, NO. 8 , JULY 1972
1443
Table I. Properties of 2,2Bis(trifiuoromethy1)-4,5-dialkyl-1,3-dioxolanes IR 1200-1050 cm-l ng Maximae Shoulders6 bp P (mm) 78-82 (8.7). 1143 1.3640d 1164 1110 1196 57-63 (
