Application of Laser-Excited Raman Spectroscopy to Organic Chemistry. III. A Skeletal Frequency Correlation for Cedrane-Type Molecules.':'

D. W. Mayo

Department of Chemistry, Bowdoin College, Brunswick, Maine 04011

Stanley K. Freeman

Research Center, International Flavors and Fragrances, Incorporated, Union Beach, New Jersey 07735

(Received 16 March 1970; revision received 1 June 1970)

The use of Raman spectroscopy in the determination of complex molecular structure is discussed. For 12 eedranes, five of the seven most intense bands observed between 900 and 500 cm -1 appear in a series of relatively narrow wavenumber ranges, and these are correlatable with the eedrane skeleton. A band of variable intensity at ca. 320 em -1, characterized by a p value of 0.2-0.4, may be included in the correlation pattern. IND~CX HEADINaS: Raman spectroscopy; Characterization of eedrane-type molecules; Frequency

correlations.

INTRODUCTION

With the development of the cw gas laser and the subsequent reduction in sample size limitations associ- ated with observing the Raman effect, it now has be- come possible to explore a number of applications to structural studies of complex organic molecules utilizing this scattering phenomenon which heretofore had remained inaccessible.

We wish to describe at this t ime our initial efforts in employing Raman spectroscopy as a probe for the identification of complex carbon skeletons. This s tudy was prompted in par t by the rapidly increasing num- ber of natural ly occurring substances isolated in limited quantities during the search for physio- logically active materials. Molecular s tructure deter- mination of such compounds, part icularly the high response substances, is of major interest. The direct skeletal elucidation of these natural products, which often contain polycarbocyclic systems, has been restricted almost exclusively to x-ray diffraction methods or chemical degradation.

I t has been pointed out by Jones 1 tha t skeletal vibrations involving carbon-carbon bonds dominate the Raman scattering of steroid spectra in the region between 1000 and 300 cm- ' . In addition, it was ob- served that the vibrational modes a t t r ibuted to polar functional groups contained in these molecules gener- ally scatter ra ther poorly in the Raman effect. If a representative number of vibrationMly coupled skeletal modes are relatively unaffected by structural variations of ring substituents and undergo mass and electronic perturbations in a correlatable fashion, then fingerprint band assignments would allow confident identification of the molecular backbone based solely on comparison of Raman spectral data of an unknown sample with reference compilations.

* Part II--S. K. Freeman, Appl. Spectrosc. 24, 42 (1970).

A sesquiterpene series, the cedranes, was chosen as the first skeleton for investigation. These molecules contain a closely knit tricyclic system (see Table I). The choice of the cedranes was based on several factors which would tend to make this system a favorable one for establishing a skeletal correlation. (1) The skeleton contains three ra ther rigid carbo- cyclic rings. Incorporat ion of carbon rings into a molecular backbone increases the scattering intensi ty of the system for low wavenumber line shifts when compared to the open chain analogs (see Fig. 1). The vibrational modes of cyclic atomic arrangements usually give rise to larger effective changes in polariza- bility. (2) Of the 12 examples reported here, nearly all have the functionali ty confined to a consistent and limited area of the molecule, mainly at carbon atoms eight and nine. This localization of the chemically reactive portions of the cedrane molecules would tend to minimize mass and electronic distortions on the coupled vibrations. (3) Most spectra could be ob- tained on liquid samples, thus avoiding the problems of solvent effects and polymorphism. (4) The deriva- tives chiefly involved systems possessing polar func- tional groups which would help to avoid the intro- duction of additional intense bands in the spectral region of interest. 1

I. EXPERIMENTAL

The spectra were obtained with an Applied Physics Corporation Raman spectrophotometer (Cary model 81) which had been converted for 6328 A excitation. A Spectra-Physics Corporat ion model 125 H e - N e laser was employed as the exciting source. The system averaged 30 mW at the sample. Coaxial 180 ° viewing of the samples contained in 0.7 mm i.d. Pyrex capil- laries was the s tandard sampling procedure. Approxi- mate intensity values were obtained by estimating

Volume 24, Number 6, 1970 APPLIED SPECTROSCOPY 591

Table I. Cedranes examined.

Trivial Chemical Abstracts name name Structure

c~-Cedrene Cedr-8-ene

B-Cedrene Cedr-8 (15)-ene

Andrane

Thujamber

8BH-Cedrane, 8,9-epoxy

8f~H-Cedrane, 8,13-epoxy

I

• 0

Cedrenylacetate 8f~H-Cedran-8-Olacetate : ~ o o c c H a

0

Cedrone 8~H-Cedran-9-one ~ /

/~-Isobiotol Cedi~8(15)-en-3-ol H H ~ O ~ J

~-Biotol Cedr-8 (15)-en-4-ol HO

Cedrol 8~H-Cedran-8-ol H L.~g~O H I

Cedrenone Cedr-8-en-10-one ~ /

I

Cedrenal Cedr-8-en-15-al • C H O

peak heights above background. All samples appeared to be at least 95~o pure by gas chromatographic analysis. Depolarization measurements were carried out with a Spex Industries, Incorporated laser-Raman system equipped with a ~ m Czerny-Turner double monochromator (1200 g/mm, blazed at 5000 A), and a Spex ER-1 (pieoammeter) electronic readout assembly. A Spectra-Physics model 125 He-Ne 6328 A laser was operated at approximately 75 mW, and an I T T Industries Company FW 130 photo- multiplier tube was maintained between 1600 and 1850 V (10-s-10 -9 A full scale). Band centers reported in this paper are accurate to ~ 3 cm -~ and the spec- trometer slits were set for 5 cm -~ average resolution. Area measurements for determining depolarization data were obtained by cutting out and weighing regions under band envelopes.

I , I i I f I i I i I i J 1 2 0 0 JO00 800 600 400

Wavenumbers

FFm. 1. Partial Raman spectra of cyclohexane (upper curve) and n-hexane (lower curve) contained in 0.07 mE i.d. Pyrex capillaries, recorded under identical instrumental conditions.

I I . RESULTS

I t was found that the cedranes exhibit a sequence of strong, sharp Raman bands in the 1000-100 cm -1 spectral region. Two representative spectra are shown in Fig. 2. The complex and unpredictable coupling shifts in the skeletal frequencies between compounds, although small, were somewhat larger than expected. Consequently, it was necessary to introduce a rough intensity constraint into the correlation. By limiting the empirical selection to the seven most intense bands between 900 and 500 cm -1, it was possible to identify five bands within a series of reasonably narrow wave- number ranges which appear to be associated primarily with displacements of skeletal atoms (see Table II) and which are moderately insensitive to the type and position of substitution on the ring system. As a result of the present investigation and similar studies soon to be reported, it would seem that this approach appears to be a useful extension of characterizing ring systems by means of a single Raman band. 2

Intensity variations within the five band sequence, although only estimates, show some dependence upon skeletal distortion. Thus, cedrenone, the derivative

Table II. Five-band correlation with intensity constraint."

812±10 cm -1 775±15 730±15 582 ±20 534 ::i: 15

B a n d mus t be one of seven most intense bands in: the '900 to 500:cmm~region.

592 Volume 24, Humber 6, 1970

T I--

Z

I--

Z

ALPHA-CEDRENE D7

~ 6

~ 5

%4

~3

~,, ~A / ~/'/ ,, o I jk_~V"~ ~

1500

~.8

~7

3.6

).4

33

)z

A

iooo

AI UVL,

V ~

A J~

MI

).7

Q,@

0,5

Q,4

0 3

, ~ , i I l r l ' / / V ' l , , IV ~o,

r)Q

5oo

!A A I~ A I v

V \ ' ~

o~9

] I - -

Z LiJ I - - Z

: / J ] 1500

BETA-CEDRENE

~,9

)r 4

3.3

u V

A

I ~lV lll , ,I " ' / ~ A I

I ~ , i Al l /

-t'o I

I LIi III L il , I I I ff .LLI I , | I I , I j L.,, ILl, I/

V

| ,

v V

./t N

V

I000 500 0 WAVENUMBERS

Fia. 2. Raman spectra of alpha-cedrene (upper curve) and beta-cedrene (lower curve).

which possesses one of the most significant structural deviations from eedrane, gives the poorest correlation of the 12 compounds studied. In fact, on strict grounds it would have failed the pa t te rn test because only four

of the five bands meet the intensi ty and wavenumber range limits. The fifth band does fall well within the defined wavenumber range, but ranks 10th with respect to intensity. In addition, three other com-

APPLIED SPECTROSCOPY 593

Table II I . Relative intensities of five band correlation arranged in decreasing order, a

Andrane ThuJamber Cedrenone ~ - C e d r e n e Cedrol Cedrane Cedrenyl A c e t a t e ~ - C e d r e n e Cedrenal ~ - I s o b i o t o l Cedrone ~ -B lo to l ,

547 530 715 ~ 745-- 725 - - 728 - -

751 740 506 570 -- 565 578 /

,2 /562 \6 0

582

648 / 811 /

770 - - 776 802 /

~ 8 9 0 / 730

/ 775

740 ~ __ 565 580 ~ / ~ / 7 7 5 / 562 585

, 8 0 / / .0 6.88\/86

aValue given in wevenumber shifts from the 6328 ~ exciting l£ne.

pounds in the series (fl-biotol, ¢~-isobiotol, and ee- drone), two of which were examined as solids, show appreciable intensi ty reversals (see Table I I I ) . I t would be difficult in this s i tuat ion to assess the possi- bility of fundamenta l mode crossover (assuming tha t the modes could be accurately defined) wi thout access to a much larger number of examples. However, it is interesting to note tha t these three derivat ives signifi- cant ly depar t f rom the localized subst i tut ion pat tern .

A fur ther correlation which seems to have promise has been developed in the case of the cedranes. A band below.400 e m - ' can be assigned a l imiting range of 315~25 em- ' . This band was not included in the five band correlation because of large variat ions in in- tensity. While measurement of the depolarizat ion ratios of several of the eedrane sesquiterpenes ex- peetedly revealed tha t nearly all the R a m a n lines showed significant depolarizat ion (p < 0.1) because of the low s y m m e t r y of the system, the band in the 315 e m - ' region consistently gave higher values (p = 0.2-0.4). The depolarizat ion ratio of the 315 e m - ' band, therefore, could be used to identify and t rack

Table iV. Correlation of 3 1 5 ± 2 5 cm -1 band with depolarization ratio, a

Compound ~, (em -1) p Value

Cedrane 320 0.15 o~-Cedrene 320 0.3 B-Cedrene 334 0.2 Andrane 300 0.4 Thujamber 292 0.2 Cedrenyl acetate . . . b . . . Cedrone 334 0.2 fl-Isobiotol c 334 - - - f l - B i o t o l ~ 330 • • • Cedrol c 330 • • • Cedrenone 312 0.3 Cedrenal 325 0.3

All bands except in the ease of cedrenM were bands between 1000 and 100 em -l.

b Obscured by background. c Solid at room temperature.

one of the 10 most intense

this skeletal mode (see Table IV). This type of informat ion proved useful in the case of cedrenM. Although there are several weak to med ium bands in the 315 c m - ' region, no strong bands are present. The question is raised, therefore: Does cedrenal fail to correlate with the 315 c m - ' band (which is one of the 10 most intense bands between 1000 and 100 cm - ' in all the other known examples) or has there occurred an unusual drop in in tensi ty? The location of a band of modera te intensi ty at 329 cm -1 possessing a p value of 0.3 permits assigning this line to the correlation mode.

Thus, in addit ion to the in tensi ty constra int placed on the five band correlation test, in some instances a sixth band may be included by utilizing a depolariza- t ion ratio constraint in the identification of the cedrane skeleton. The statist ical chance of a molecule passing the six band correlation and not possessing the cedrane skeleton is finite but fairly remote. A more likely risk accompanying this type of analysis could involve a cedrane- type skeleton suffering sufficient functional group distort ion to result in correlation failure (for example, the borderline case of cedrenone). I t is, of course, possible t ha t other sites on the cedrane skeleton not as yet invest igated m a y exhibit unusual sensit ivity to substi tution.

These correlations, which depend to a rough extent on relative intensi ty measurements , are subject to possible distort ion f rom a number of influences such as the resonance R a m a n effect and photomult ipl ier response characteristics. Pre l iminary da ta utilizing argon ion excitation, however, have not indicated t ha t any significant deviat ion is to be expected in shifting to this exciting line. M a n y monocyelie (e.g., limonene, humulene, carvone), bicyclic (e.g., pinane, borneol, caryophyllene, ~-cadinene), and tricyclic (e.g., a - a n d ~-patehuolene, longifolene, thujopsene) na tura l ly occurring substances were spectral ly examined to tes t the val idi ty of the eedrane skeletal f requency pat tern.

5 9 4 Volume 24, Number 6, 1970

None was encountered which successfully met the cedrane ring sys tem constraints.

ACKNOWLEDGMENTS

The authors gratefully acknowledge the interest and cooperation of Professor Ellis Lippincot t of the D e p a r t m e n t of Chemis t ry of the Univers i ty of Maryland. Init ial phases of this invest igat ion were carried out at College Pa rk and were suppor ted in par t

by a Public Hea l th Service Fellowship 1-F3-6M-11, 127-01 f rom the Nat ional Ins t i tu te of General Medical Sciences to D W M . We are indebted to Dr. B. Tomi ta of the Univers i ty of Tokyo for samples of ~-biotol and f~-isobiotol.

1. R. Norman Jones, Proe. Int. Sym. Mol. Struct. Spectrosc. Tokyo, Japan, September 1962, p. A-218-1.

2. K. L. Stevens and J. R. Scherer, J. Agr. Food Chem. 15, 673 (1968).

Application of Laser-Excited Raman Spectroscopy to Organic Chemistry. IV. A Skeletal Frequency Correlation for Pinane-Type Molecules

Stanley K. Freeman

Research Center, International Flavors and Fragrances, Incorporated, Union Beach, New Jersey 07735

D. W. Mayo

Department of Chemistry, Bowcloia College, Brunswick, Maine 04011

(Received 2 April 1970; revision received 29 June 1970)

An examination of 13 pinanes indicates that the pinane ring system can be characterized by a pattern of seven Raman bands in the spectral region between 1100 and 350 cm -~. INDEX HEADINGS: Raman spectroscopy; Pinanes.

INTRODUCTION

A skeletal f requency correlation pa t t e rn recently has been reported for the cedrane ring sy s t em) We now report the results of a similar invest igat ion on the pinane skeleton (I).

l 0

! 5

7 4

5

I

The number of bands observed in a vibrat ional spect rum generally increases with increasing molecular complexity. Consequently, pinanes would be expected to display simpler profiles than cedranes, pa tchuo- lanes, longifolanes, etc. in the R a m a n region between

ca. 1000 and 300 em -1. Comparison of the spectra generated on some pinanes and tricyclic sesquiterpenes confirms this expectat ion (e.g., Fig. 1).

I. EXPERIMENTAL

Spectra were recorded on a Spex Industries, In- corporated l a s e r - R a m a n sys tem equipped with a ~ m Cze rny -Turne r double monochromator (1200 g / ram, blazed at 5000 A), and a Spek ER-1 (picoammeter) electronic readout assembly. A Spectra-Physics H e - N e 6328 A laser was employed (ca. 50 m W at sample) and an I T T Industr ies Company F W 130 photomult ipl ier tube was mainta ined between 1600 and 1850V (10-8-10 -9 A full scale). Frequencies reported are accurate to ± 3 cm -1. The spect rometer slits were set for 5 cm -1 resolution at the exciting line and spectra recorded at 100 em-~/min with a period of 1.2 sec. Purit ies of materials examined exceeded 95% (GLC) and spectra were recorded on samples contained in 0.7 m m i.d. Pyrex capillary tubes. Depolar izat ion values ( ± 2 0 % precision on ca. 660 cm -I bands) were gained by changing the orientat ion of the analyzer.

Volume 24, Number 6, 1970 APPLIED SPECTROSCOPY 595