The synthesis and study of some of the physical properties of diphenylated fatty derivatives and their chromium tricarbonyl complexes

Chemistry and Physics of Lipids, 47 (1988) 209--216 Elsevier Scientific Publishers Ireland Ltd.

209

The synthesis and study of some of the physical properties of diphenylated fatty derivatives and their chromium tricarbonyl complexes Marcel S.F. Lie Ken Jie and Wilson L.K. Lam Department of Chemistry, University of Hong Kong, Pokfulam Road (Hong Kong) (Received October 8th, 1987; revised and accepted January 15th, 1988)

A series of 1,1-diphenyl-l-alkanols were synthesised by the reaction of phenyl magnesium bromide (PhMgBr) with nalkanoates. The infrared spectral analysis showed a medium sharp absorption band at 3400 cm -~ for the tertiary OH stretching vibration. The ~H-NMR analysis gave signals at 7.1--7.5 tf for the aromatic protons, and the protons of the remaining carbons of the short chain diphenylated alkanols were readily distinguished by their chemical shifts and splitting pattern. The ~3C-NMR results permitted the aromatic carbon nuclei to be differentiated, and the /3- and ),-effect exerted by the hydroxy and phenyl groups on the adjacent methylene carbon atoms allowed facile assignments of these nuclei in the short chain homologues. The mass spectral analysis confirmed the quaternary carbon position of the derivatives. The LH- and t3C-NMR spectral analyses of the chromium tricarbonyl complexes of some of these derivatives showed strong upfield shifts for the aromatic and neighbouring protons or carbon nuclei, due to the electron withdrawing behaviour of the chromium tricarbonyl ligand.

Keywords: synthesis; spectroscopic properties; l,l-diphenyl-l-alkanols; chromiumtricarbonyl complex.

Introduction Long chain fatty acids containing a phenyl group are not commonly found in seed oils or animal fats. Three closely related aromatic fatty acids were isolated from the lipid fraction of a marine bacterium and were shown to possess bronchodilating activities [1]. In the chemical transformation of long chain fatty acids, phenylstearic acid was prepared from oleic acid by the Friedel-Craft alkylation reaction [2]. The acid catalyzed reaction of phenol with oleic acid was described by Roe et al. [3]; and the use of methanesulfonic acid in the addition of aromatic compounds to oleic acid was reported by Ault et al. [4,5] and Foglia et al. [6,7]. Small quantities of aromatic derivatives were shown to be produced from polyunsaturated fatty acids, when such fatty acids were heated or hydrogenated in the presence of catalysts [8,9]. We have Correspondence to: Dr. M.S.F. Lie Ken Jie.

recently reported the synthesis and a study of the physical behaviour of l-phenyl-l-alkanols, and have also described the facile amide formation when the chromium tricarbonyl complex of these compounds were treated with nitriles in the presence of mineral acid [10]. This work was undertaken to examine further the physical behaviour of diphenylated fatty derivatives and to study the effect of the chromium tricarbonyl ligand on the phenyl and alkyl system of such fatty organometallic complexes. Arene chromium tricarbonyl complexes are well known for their stability. The chromium tricarbonyl ligand is readily complexed to a phenyl ring by refluxing the aromatic substrate with chromium hexacarbonyl. The chromium tricarbonyl ligand activates the phenyl ring and carbon atoms attached to the aromatic system, allowing chemical transformations to be conducted. The removal of the chromium tricarbonyl ligand from the reaction product is facile [11]. Hence, for these purposes a homologous

0009-3084/88/$03.50 © Elsevier Scientific Publishers Ireland Ltd. Published and Printed in Ireland

210

series of 1,1-diphenyl-l-alkanols were prepared from methyl n-alkanoates and the aromatic rings complexed to chromium tricarbonyl ligands (Scheme 1).

Results and discussion

Synthes& of 1, l-diphenyl-l-alkanols (Scheme 1) 1,1-Diphenyl-l-alkanols were readily obtained by reacting PhMgBr with n-alkanoates. A modified procedure was introduced to produce PhMgBr from bromobenzene and magnesium [12]. Instead of using iodine to activate the magnesium during the reaction, a mixture of bromobenzene, magnesium and tetrahydrofuran was placed in an ultrasonic cleaning bath and irradiated. The modification allowed the reaction to proceed smoothly and without any danger of overheating during the exothermal formation of the Grignard reagent. The derivatives (la-lh) were isolated from diethyl ether after acidification of the reaction product and purified by silicic acid column chromatography. Solid derivatives were further purified by recrystallization from light petroleum.

Physical properties of 1,l-diphenyl-l-alkanols (la-lh) The analytical and spectral data are presented in Tables I and II. With the exception of homologues le, ld and le, the remaining derivatives were all solids at room temperature with high melting points being recorded for the two shortest chain derivatives (la, lh). The thin-layer chromatographic analysis of these homologues

showed the possibility of sub-fractionation, with the shortest chain homologue (la) exhibiting the strongest affinity towards silicic acid, while the mobility of the other derivatives increased as the number of methylene groups in the alkyl chain increased. The gas-liquid chromatographic analysis gave increasing equivalent chain length (ECL) values from 13.27 for l a to 26.70 for lh on SE-30 stationary phase. From the infrared spectral analysis, the O - - H stretching vibration of the tertiary hydroxy group absorbed between 3400 and 3600 cm -t as a medium sharp peak. The aromatic C - - H and C = C stretching vibrations appeared at 3050 and between 1450 and 1600 cm -l, respectively. The mono-substituted nature o f the aromatic system was reflected by bands appearing at the 700--750 and 1050--1150 cm -l regions. The signal for the aromatic protons in the 1HNMR spectra (Table II) of these derivatives were shifted to 7.1--7.5 d and appeared as a singlet. The proton of the hydroxy group was normally found between 1.8 and 2.4 6, and could be verified by D20 exchange. Compound la showed a distinct singlet at 1.9 ~J for its methyl protons. In the next homologue of the series (lb), the methylene protons were shifted to 2.3 cl (quartet), while the methyl protons appeared as a distorted triplet at 0.9 6. A distinct signal at !.2 d (sextet) was the characteristic feature of compound lc, due to the protons of the methylene adjacent to the methyl group. For the remaining members of the series, the methylene protons located alpha to the quaternary carbon appeared as a triplet at 2.1--2.2 6, while the other methylene protons were shifted to 1.2--1.25 ~J, and with the methyl protons appearing at 0.87--0.90 6.

OH OH (n4]u)20/THFCrlCO)6 RCOOCH~ PhMgBr/THF ~ R C~l- ~/N)-x~ ~ R ~ ~/~/

- -

Cr(CO)~

Cr(CO),

R = CH~,CH~(CH~)nwhere n = 1,2,3,4,12,14of 16 Scheme I. Synthesis of l,l-diphenyl l-alkanols and |heir chromium tricarbonylcomplexes.

56--57

'PE25 = Petroleum ether/diethyl ether (3 : 1, v/v).

0.61

26.70

(3.7) (I .5) (0, 1) (0. I) (0.0) (0.0)

422 (0.07

394 (0.0)

(lh) CH3(CH2)~

24.99

47--48

(lg) CH~(CH2)~,

0.59

198 212 226 240 254 366

13.27 13.64 14.82 15.70 16.56 N.A.

79--80 92--93 liq. liq. liq. 39--40

0.34 0.44 0.47 0.51 0.54 0.56

184 (66.4)

183 (100)

(16.0) (15.1) (15.9) (19.6) (19.5) (85.7)

184 (89.6)

184 184 184 184 184 184

183 183 183 183 183 183 183 (100)

a+l

a (100) (100) (100) (100) (100) (100)

GLC (SE-30) Mass spectral analysis ECL

(la) CH~ (Ib) C H 3 C H 2 (IC) CH3(CH2) 2 (ld) CH~(CH2) ~ (le) CH~(CH2) , (If) CH~(CH2),2

R:

TLC (SiOJPE25)"

M"

m.p. (°C)

R

Compound RC(OH)Ph:

Melting points, TLC, GLC and mass spectral properties of l,l-diphenyl-l-alkanols.

TABLE I

(19.4) (4.4) (3.1) (2.9) (3.2) (2.7)

345 (2.3)

317 (3.6)

121 135 149 163 177 289

b (84.5) (85.7) (85.0) (81.2) (98.9) (29.8)

105 (90.5)

105 (40.1)

I05 105 105 105 105 105

PhC_--O ÷ (49.0) (40.3) (50.2) (42.9) (50.4) (1.2)

77 (26.7)

77 (I.7)

77 77 77 77 77 77

(18.6) (61.7) (54.7) (20.1) (M-18, 6.8), 193

(43.4), 18o (30.0)

376 (M-18, 9.7), 193 (20.7), 180 (16.0) 404 (M-18, 13.8), 193

(13.9)

107 107 154 107 348

Others

I,o

a

b

0.90 (t)

0.92 (t)

0.87 (t)

0.88 (t)

0.87 (t)

le

ld

le

If

lg

lh

1.22 (m) (n = 2) 1.24 (m) (n = 3) 1.24 (m) (n = l l ) 1.25 (m) (n = 13) 1.25 (m) (n = 15)

1)

-1.2 (sext)

(n =

--

1 . 9 (s)

0.9 (t) 0.84 (t)

lb

b

la

a

c

2.2(s)

2.2 (s)

2.1 (t)

2.2(t)

2.2 (s)

2.3 (s)

2.3 (s)

2.2 (s) 1.8 (s) 2.4 (s)

d

2.1 (t)

2.2 (t)

2.2 (t)

-2.3 (q) 2.2 (t)

c

e

?H d CH3(CH2)° CH2C(C6H5)2

C h e m i c a l shifts (d)

~H-NMR (6):

7 . 1 4 - - 7 . 5 (m)

7 . 1 7 - - 7 . 5 (m)

7 . 1 5 - - 7 . 5 (m)

7 . 0 6 - - 7 . 5 (m)

7 . 1 - - 7 . 5 (m)

7 . 1 - - 7 . 5 (m) 7 . 0 5 - - 7 . 5 (m) 7 . 0 2 - - 7 . 5 (m)

e

tH- and t3C-NMR analysis o f 1 , 1 - d i p h e n y l - l - a l k a n o l s .

T A B L E II

14.18

14.09

14.03

13.98

14.02

30.82 8.125 14.41

C-I 1

23.06

22.69

22.64

22.54

23.18

--17.06

C-10

~3C-NMR (ppm):

32.32

31.96

31.91

32.29

26.05

----

C-9

29.31--30.01 (m = 8) 29.36--30.07 (m = I0) 29.73--30.34 (m = 12)

--

--

----

C-8

24.12

23.78

23.73

23.46

--

m

C-7

42.25

42.09

42.04

42.04

41.87

-34.5 44.26

C-6

H CH3CH2CH2(CH2)~CH2CH2C~ C-ll 109 8 7 6 15 Ph

3

78.44

78.44

78.39

78.33

78.33

75.62 78.49 78.17

C-5

2' 3'

12 4

147.85

147.30

147.24

147.30

147.40

148.05 147.03 147.30

C-1

126.23

126.06

126.06

126.71

126.12

125.84 126.17 126.06

C-2/ C-2'

128.36

128.07

128.07

128.07

128.12

125.84 128.06 127.96

C-3/ C-Y

126.92

126.71

126.66

127.19

126.76

126.87 126.71 126.55

C-4

213 The results from the 13C-NMR analysis (Table II) of the derivatives provided much more structural information than data observed from the ~H-NMR studies. The shifts involving the carbon atoms of the aromatic nucleus resulted in four signals. The substituted aromatic carbon (C-I) was shifted to approx. 147 ppm, being influenced by the hydroxy group and the other phenyl group, both at the/J-position. The orthocarbon nuclei (C-2 and C-2') were assigned the lowest shift (126 ppm) as these nuclei were affected by the y-positioned hydroxy group, which caused an upfield shift. The signals due to the meta- and ortho-carbon shifts OH

y

--CH2--CH2--C---~ Ph were recognized by their two-fold intensity over the para and the substituted carbon atom signals in the spectra. Thus the lower intensity signal at approx. 126 ppm was assigned to the para-carbon nucleus of the aromatic ring. The quarternary carbon (to which the OH and phenyl systems are attached) was shifted to approx. 78 ppm. An interesting effect was the shifts of the carbon nuclei of the methylene groups at the/3and y-position from the hydroxy and the phenyl groups. Assignment of the shift signals for these two adjacent methylene carbon nuclei followed the same pattern exhibited by an OH group in other compounds [13]. Compound l a became unique in that the methyl carbon atom was shifted very much downfield to 30.82 ppm, as a result of the/3-effect exerted by the hydroxy and phenyl groups. The y-effect by these same groups caused the methyl carbon in compound lb to be shifted to the low value of 8.125 ppm. In compound le the methylene adjacent to the methyl group was shifted to 17.06 ppm due to the y-effect, while the signal for the remaining methylene carbon nucleus appeared at 44.26 ppm as a result of the/3-effects of the hydroxy and phenyl groups. The remaining longer chain derivatives (lf, lg, lh) gave signals between 29.0 and 30.0 ppm for the methylene carbons in the middle section of the alkyl chain.

The mass spectral analyses of these derivatives provided a characteristic base peak (a, 100o70) at m / z = 183, which was common to all derivatives (Table I). This fragment arose from the fragmentation of the bond between the quaternary carbon and the neighbouring methylene carbon. The intensity of the molecular ion (M ÷) was insignificant and in most cases non-observable. However, ion fragment m / z = 184 (a + 1) seemed to increase in intensity with increase in molecular weight of the homologue. Fragmentation between a phenyl ring and the quaternary carbon gave a fragment (M-77) of low intensity (<5o70), except in the case of compound l a where this fragment accounted for 19.4°70. In all spectra the appearance of an ion fragment m / z = 77 demonstrated the presence of the phenyl nucleus. There was also a fragment m / z = 105 which corresponded to P h C - O ÷ and was found in all spectra in high intensities (from 29.8 to 98.9%).

Bis-(chromium tricarbonyl) complexes o f 1,1diphenyl-l-alkanols The complexation of 1,l-diphenyl-l-alkanols with chromium hexacarbonyl was accomplished by refluxing a mixture of the reactants in ndibutyl ether and tetrahydrofuran under moisture-free nitrogen atmosphere for 4 days according to the method described by Pauson [14]. The isolated crude complex was purified by crystallization from diethyl ether and stored in the neat form at low temperature (0--5°C) under nitrogen. The yellow complexes decomposed (by turning greenish in colour) when allowed to remain in contact with air for more than 15 min. The yield of these complexation reactions averaged about 45°7o. The infrared spectral analysis of the bis(chromium tricarbonyl) complexes showed a very strong absorption band for the carbonyl groups of the chromium tricarbonyl ligand at 1900 cm-'. The frequencies of the absorption bands for the OH and the aromatic C = C stretching vibrations in these complexes were not much different from those observed for the non-complexed substrates.

1.88 (S) 0.87 (t) 0.94 (t)

0.88 (t)

lk

a

--1.40 (sext.) (n = 1) 1.2--1.5 (m) (n = 15)

b

Chemical shift (d)

2,3 (m)

-2.26 (g) 2.0 (m)

c

Cr(CO)3

OHd/.•/Cr(CO)3

CHflCH).CH2C-(,

|It lb lc

Complex of compound

~H-NMR (6):

2.0 (s)

2.16 (S) 2.10 (s) 2.05 (s)

d

5.1--5.98 (m)

5.1--5.85 (m) 5.08--5.94 (m) 5.1--5.9 (m)

e

14.09

30.99 7.80 14.11

C-II

C-9

22.70

. .

31.96

. . . . 16.46 --

C-IO

t3C-NMR (CDCI~, ppm):

'H- and ~C-NMR analysis of c h r o m i u m tricarbonyl complexes o f four 1, I-diphenyl-l-alkanols.

TABLE ili

29.69---30.40 (m = 12)

--

. .

C-8

23.01

C-7

42.80

-34.40 44.99

C-6

C-11 10 9

74.49

72.65 76.47 74.42

C-5

8

7

117.01

117.23 116.92 116.83

C-I

6~2'

88.19

89.22 88.57 88.15

C-2/ C-2'

93.29

92.42 93.19 93.38

C-3/ C-3'

Cr(CO)3 12

3'

93.50

94.53 93.77 93.23

C-4

OH 2 3 CH [ 1 /~.~.... Cr(COIz 3CH2CH=(CH~).CH2CH2C. j ¢ ~ 4

233.0

232.19 232.87 232.44

C-12

4~

215 The ~H-NMR spectra (Table III) of the complexed derivatives showed an upfield shift for the aromatic protons to the region between 5 and 6 d. With the chromium being relatively electron deficient due to the electron withdrawing property of the CO ligands, the complexation of the chromium tricarbonyl ligand to the aromatic nucleus appeared to affect the aromatic protons most, causing a deshielding effect to take place. However, the effect of the chromium tricarbonyl ligand on the remaining protons in the alkyl chain of the complex was insignificant and their chemical shifts appeared at about the same position as for those of the non-complexed substrates. In the ~3C-NMR spectral analysis, the aromatic carbon atoms were shifted to a much more upfield region. The signal for the substituted carbon (C-l) appeared at approx. 117 ppm (an upfield shift of approx. 30 ppm), and those of the ortho-, meta- and para-carbons were all shifted to the 88--95 ppm region. The effect of the ligand on the quaternary carbon was quite significant, as this carbon nucleus was shifted by 4 ppm upfield; while the remaining adjacent carbon nuclei of the methylene groups were only marginally affected (upfield shift of approx. 0.5 ppm). The carbonyl carbons of the chromium tricarbonyl ligand gave a signal at approx. 232 ppm.

Materials and methods Thin-layer chromatography (TLC) analysis was performed on microscope glass plates coated with silicic acid (about 0.1 mm thickness) and a mixture of petroleum ether/diethyl ether (1:3, v/v) used as developer. Column chromatographic purifications were carried out on silicic acid using mixture of petroleum ether/diethyl ether as eluent by gradient elution. Gas-liquid chromatographic analysis was carried out on a Varian 1400 gas chromatograph fitted with a packed column (2.0 mm diameter, 2 m, 5°7o SE30 or 5% OV-101 on Chromosorb W) using nitrogen (40 ml/min) as the carrier gas at an isothermal column temperature of 190°C with a flame ionization detector. External standards of

methyl myristate, palmitate and stearate were used as reference compounds and the ECL values calculated accordingly for each component. Infrared spectra were obtained on a Perkin Elmer model 577 spectrophotometer and NMR spectra on a JEOL FX90Q (90 MHz) instrument. Derivatives were dissolved in deuterated chloroform for ~3C-NMR analyses and chemical shifts reported in ppm relative to TMS. A Bransonic (model 321) ultrasonic bath was used in the preparation of the Grignard reagent. Mass spectral analyses were conducted on a VG 7070F mass spectrometer (4 kV, 70 eV, 200°C source) by direct insertion. Chromium hexacarbonyl was purchased from Strem Inc., Newbury Port, MA 01950, U.S.A. All solvents were dried and distilled before use.

Experimental

General procedure for the preparation of 1,1diphenyl- l-alkanols (la-lh) A mixture of bromobenzene (5.0 g, 0.032 mol), magnesium turning (0.8 g, 0.033 mol) and tetrahydrofuran (20 ml) was placed in a 100-ml round-bottom flask fitted with a water cooled condenser. The reaction vessel was partially submersed in an ultrasonic cleaning bath (20°C, 150 W, 55 kHz) filled with water and sonicated for 15 min. Methyl alkanoate (0.016 mol) in tetrahydrofuran (10 ml) was added and the reaction irradiated for a further 2 h. The reaction mixture was refluxed for a further 30 min. The cooled mixture was poured into water (100 ml), acidified with conc. HCI and extracted with diethyl ether (3 x 50 ml). The ethereal extract was washed with water (2 x 50 ml) and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the crude product purified by flash column chromatography [15] using silica (75 g, Merck no. 7734, 0.063--0.200 nm mesh size) and a mixture of petroleum ether/diethyl ether (4:1, v/v) as the eluent. Fractions of 50 ml each were collected and analysed by TLC. Fractions with components of similar R: values (R: = 0.4, using the same mixture of solvent as developer) were

216

pooled to give the pure 1,1-diphenyl-l-alkanols (average yield 780/0).

References 1

General procedure for the preparation of bis(chromium tricarbonyi) complexes of 1,1diphen y l- l-alkanols

2

3

A mixture of 1,1-diphenyl-l-alkanol (2.4 mmol), chromium hexacarbonyl (1.05 g, 4.8 mmol), n-dibutyl ether (10 ml) and tetrahydrofuran (5 ml) was refluxed under dry nitrogen for 4 days. The reaction mixture was cooled and suction filtered through a bed of preheated (ll0°C) silicic acid (5 g, 0.063--0.2 mm Kieselgel 60) placed in a sintered glass funnel. The silicic acid layer was washed with ndibutyl ether (5 ml). The solvent of the filtrate was evaporated under reduced pressure (1--2 mmHg pressure) at 60°C. Petroleum ether (b.p. 40--60°C, 20--50 ml) was added to the deep yellow oily residue to precipitate the crude product. The product was recrystallized from diethyl ether to given yellow crystals (average yield 45°7o).

4 5 6 7 8 9 10 11

12 13

Acknowledgements We thank the Lipid Research Fund and the Research Grants Committee of the University of Hong Kong for financial assistance.

14 15

G.S. Holland, D.D. Jamieson, J.L. Reichelt, G. Viset and R.J. Wells (1984) Chem. Ind. (London) 850--851. A.J. Stirton, B.B. Schaeffer, A.A. Stawitzke, J.K. Weil and W.C. Ault (1948) J. Am. Oil Chem. Soc. 25, 365-368. E.T. Roe, W.E. Parker and D. Swern (1959) J. Am. Oil Chem. Soc. 36, 656--659. W.C. Ault and A. Eisner (1962) J. Am. Oil Chem. Soc. 39, 132--133. A. Eisner, T. Perlstein and W.C. Ault (1962) J. Am. Oil Chem. Soc. 39, 290--292. Y. Nakano and T.A. Foglia (1984) J. Am. Oil Chem. Soc. 61,569--573. H. Kohashi and T.A. Foglia (1984) J. Am. Oil Chem. Soc. 61, 1048--1051. A.N. Sagredos and J.D. yon Mikusch (1970) Tetrahedron 26, 5587--5591. J.W.E. Coenen, Th. Wieske, R.S. Cross and H. Rinke (1967) J. Am. Oil Chem. Soc. 44, 344--349. M.S.F. Lie Ken Jie, W.L.K. Lam and H.B. Lao, J. Chem. Soc. Perkin Trans. I, in press. S.G. Davies (1982) Organotransition Metal Chemistry: Application to Organic Synthesis, Pergamon Press, New York, p. 70---74. J.D. Sprich and G.S. Lewandos (1983) Inorg. Chim. Acta, 76, L241--L242. J.B. Stothers (1972) Carbon-13 NMR Spectroscopy, Academic Press, New York, p. 140. C.A.L. Mahaffy and P.L. Pauson (1979) Inorg. Synth. 19, 154--158. W.C. Still, M. Khan and A. Mitral (1978) J. Org. Chem. 43, 2923--2925.