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Conformation and tautomeric equilibria of 3-acyl-3,4-dihydrocoumarins: a 1H and 13C NMR study
dcumal of Molecular Structure. 127 (1985) Eisevier Science Publishers B.V., Andadam
127-133
-Printed
CONFORMATION .-i9-D TAUTOMERIC UMARINS: 3-ACYL3,4DlHYDROCO
M. F. SIMEONOV Institute
Department
EQUILIBRIA A ‘H AND %
OF NhtR STUDY
and S. L. SPASSOV
of Oganie
A_ BOJILOVA
in The Netherlands
Chemist.
of Sciences.
Bu&a.rianAcdemy
1113
Sofm
(Bulgmia)
and CI-IR_ IVANOV of Chemise,
University
of Sam
1 I26
Sofm
(Bulgark)
FL RADEGLIA Cent-t-o1 Institrzte of Physical Chemistry, 1199 Berlin-Adlershof (G.D.R.) (Received
22 August
The
Academy
of Sciences
of the GDR,
1984)
The steric and electronic effects of acyl substituents COR (R = Me, i-Pr, Ph and t-Bu) upon conformational and keto-enol equilibria in 3-acyl-3,4-dihydrocoumarins have been studied by ‘H and “C NMR spectroscopy_ With the increase of the effective size of R, preference for the equatorial position and the keto-form population increases considerably_ The “C substituent-induced chemical shifts are also discussed INTBODUCTION
Tautomeric equilibria in acyclic &licarbonyl compounds have been the subject of a number of studies bymeans of various chemical [l] and physical In [2] methods, including ‘H 131, DC 143 and “0 [5] NMR spectiscopy. most cases, only the keto (K) and cis-enol (CE) forms have been taken into consideration. Only for some ketoaldehydes has the trans-enol (TE) form been found [3] _
IKI
ITEI
f(;E-III
ICE-II
The c&en01 equilibrium, usually fast on the NMR timescale, has been also di;cussed in terms of unsymmetrical “classicaI” (CEI) or symmetrical (CEII) structures 13-51. The tautomeric phenomena in hetero-alicyclic &dicarbonyl compounds, however, have been much lesj studied [2] in connection with their conformation. Moreover, some of the data are rather controversial: the presence of trans-enolic species has been assumed for a number of a-acyllactones [lb] 0022-2860/85/$03.30
0
1985
Eisevier Science
Publishers
B-V.
128
and some 3-fonnylcamphors [6], but in the former case that was later rejected on the grounds of a W study 171. In the present paper, the infhrence of the acyl substituent COR (R = Me I, i-Pr II, Ph III, and t-Bu IV) on the conformational and tautomeric behaviour of 3-acyl-3,4xEhydrocoumarins was investigated by means of ‘Hand ‘% NMEspectroscopy. According ti a ‘H m study [S], compound HI exis& as z cifenol form, whereas for compound I the keto-enol ratio is -2:l. EXPEFUMENTALA
Compounds I-IV were synthesized by reduction of the corr=ponding 3-acylcoumarins with NaB& in pyridine solution, as described in ref. 8 for I and III. Compound II: (58% yield) m-p. 75-77°C; IR (CHCI,): 1725 (CO, IV: (54% yield) m-p. 141ketone), 1770 (CO, la&one) cm-‘. Compound 142°C; MS: m/z 232 (M’); IR (CHCI,): 1715 (CO, ketone), 1770 (CO, la&one) cm-‘. Analysis_ Cak. for C,HtiO,: C, 72.39; H, 6.94. Found: C, 72.45; H, 6.99. The starting 3-acylcoumtis were obtained as follows: compounds VII (R = i-Pr) and IX (R = t-Bu) by the method of Dean and Park [9], from salicylaldehyde and the corresponding Bketoacids and purified by column cbromatography on silica gel (ethylaeetate/hexane 3:7 and 1:4)_ Compound VII: (63% yield) m-p. 106108°C; IR (CHC13): 1690 (CO, ketone), 1735 (CO, la&one) cm-‘_ Analysis_ Ca!c. for CUHrzOs: C, 72.21; H, 5.59. Found: C, 72.16; H, 5.54. Compound IX: (59% yield) m-p_ 88-89°C (lit. [9] 8990°C). Compounds VI (R = Me) and VIII (R = Ph) were synthesized according to IlO] and [ll], respectively_ The ‘H and 13C NMR spectra were measured at 250-l and 62.89 MHz, respectively, on a Bruker WM-250 FT spectrometer. Some ‘H NMR spectra were obtained also at 80 MHz on a Tp_sl BS 487C spectrometer (CW mode). ‘% NMR spectra were run in -0.1 molar solutions with TMS as internal standard at, typically, 16K data points for FID and sweep-width -15000 Hz The chemical shifts were obtained with broad-band ‘H decoupling and for their assignment the single-tiequency off-resonance (SFORD) decoupling and J-modulated spin-echo methods were also used. The *H coupling constants of CH,CH went (ABX-type) were determined by second order analysis. IR spectra were measured in Ccl, solution and solid phase with a C. Zeiss UR-20 and Bruker IFS 113~ spectrometers, repectively. RESULTS AND DISCUSSION The keto-enol interconversion of compounds I-IV is slow on the NMR timescale, and so separate signals for the protons due to the different t-automerit spmies were observed and asigned on the basis of their position, multiplicity and intensity. The ‘H NMR data are given in Table 1.
129 TABLE
1
‘H NMR data for compounds FIV
(in CDCl,
solution)a
keto-form
I TI III TV
cisenol form
R
6Hx
&HA
kg
Me i-R Ph t-Bu
3.78 3.97 4.68 4.20
3.48 3.37 3-44 3-41
2.86 2.98 3.11 2.87
Whemical in R
6R
I’b-I
IJJj3xl
I’JABI
kEJAB)
k
2.36 1.20b
8.73 9.46 10.58 1202
6.49 6.34 5.45 6.54
16.16 15.57 16.23 15.70
3.56 3.75 3.75 -
2.10 l.lob 7.15 (mj -
7.25 (m)
1.25
shifts (6) in ppm (Th4!S = 0) and coupling constants (J) in Hz bFor CH, groups
A qualitative estimation of the equilibrium (Scheme 1) between two conformers of a halfchair type [12] can be made from experimental 3J13E and
3JBXvalues.
COR
Thus, taking into account the Karplus rule and the fact that 3JAx only reflects the changes of substituent, the following conclusions are drawn. First, with increase in the sutzstituent size the equatorial preference of the 3-acyl group increases_ Second, it is possible to make unequivocal assignment of protons Hx and Ha - the low-frequency shifted one (HA) is pseudoaxial in form a This is in accordance with the general conformational theory; moreover, a good linear correlation (r = 0.9957) for 3Ja with the conformational energy (-AGO) [13] of the substituent R was established, although R is not directly bonded to the ring. In the Same order (compolu;ds I + Iv), a tendency to deshielding for 6Hx was observed, in contrast tn negligible 6H, and &nB changes (an exception is compound III, where the phenyl anisotropic effect probably interferes). It seems that in this series practically the same conformer ratio is also retained in acetond6 solution, since insignificant changes in the ‘H NMR parameters were observed. -The quantitative estimation of tautomeric populations (Table 2) was achieved by comparing the integral intensity of the singlet CH2 signal in the cis-enol folm with that of the ketmform (AB part of ABX-multiplet), as well as Cram the proton signals of the acyl group in these two forms.
130 TABLE' Relativeabundanceofthe tauLomeric(K)*(CE)formsfor R
(CE)hd
(K>bmd
(CE)4=
Me
100 0 0 0
0 100 100 100
56 23 i 0
i-R Pb t-Bu
(KY'.= 44
compoundsFTV;L
(CE)=d
(KFd 35
65
(CE)==
(KF
24
76 100 100 100
i7
0
zoo
0
93 100
0 0
100 100
0 0
solution_ 'In % (55%); concen@ation 0.7 moiar. bin CDCI, solution =In CD,COCD, dImmeddteIy afterdirsolving. lAfter24 hours(thermodynamic equilibriumachieved). mC NlMR chemical shifts (SC) of compounds I-IV (Table 3) confirm the ‘H NMR analysis. Thus, initially, for compound I in CDCIB the signals for cis-enoh: species only were observed; after a few hours, these of the ketoform were also present In acetone-d, solution the signals of both keto and enol tautomers appear immediately after dissolving. Additionally, from 6c11 (in the case of COMe) the ciGeno1 equilibrium (Scheme 2) can be qualitatively evaluet& as a fast one: the observed value of 177.3 ppm is an approximate average lxween those experimentally observed in keto (201.2 ppm) and calculated (empirical additivity scheme [14]) for =C(OH)alkyl j?-agment (167-171 ppm). Thus, both cis-enol tautomers are TABLE3 '3CNMRchemicalshiftsforcompoun&I-Va R = CH KH3
0 r
1’ 2:x
I’ R=CH3
12
R: I'/
3’
\
4
n.
R&&3)3
Vd L
-
keto(K) C-2 c-3
enol(CE)
keto(K)
keto(K)
165.Bb 166_5= 168.8b 53.2 52-3 90-5
165i.gb 49.5 166_7= 165.9b 91.7= 46.9 50.2 26-l 26.9 26.4 26.6 26.6 25.9 C-4 25-i c-5 128.2* 129-l* 127.8" 12%8 128.2* 128.9 128.lf 124.7 125.4 124.5 129.6 128.3* 125.2 124-7 GC 124.8 129.4' 12&e* c-i .128.4* 129.2 128.4* 117.2 116-7 117.3 116.5 116.9 116.5 C-8 116-5 151.1 152.3 151.2 152.6 150.1 G9 151.0 121-l 123.0 119.9 121-i 121-4 1228 c-10 121.2 2023 177.3 c-11 201.2 20X4 208.7 193.9 19.2 19.1 C-l' 29.5 40.5 40.7 135.3 c-2 17.5 18-O 128-7 18.3 18.4 128.7 C-3' C4' 133.8
keto(K) 166.1b 45.3 28.1 128.02 124-6 128.4* 116-6 151.4 121.6 209.5 45.3 25.6
166.9= 45.8 129-O* 125.3 129.3* 117-l 1528 123.3 210.3 46.3 26.0
168.5b 29.1, 23.6: 128.1:; 124-e; 128.1: 116.8, 152.& 1228;
= 'In ppm (TMS = 0). bInCDCI,soluti~eCInCD,COCD,solution reL15a+Asignrnentunknown
dThedataarefrom
131
probably represented ;J1 comparable amounts. The 8c_2 cannot be used to discriminate between these two tautomers since it is expected to be in the range 160-165 for both (experimental value 168.8 ppm).
Qyf-J = QJ?Jo>
Scheme
2
It is interesting to consider the substituentcinduced UC chemical shifts (SCS) in compounds I-W in relation to the unsubstituted 3,4dihydrocoumarin V [15] (Table 4). Although the SCS effects in saturated molecules or ments are not as well understood as those in unsaturated systems [lS] , some conclusions can eventually be derived. Thus, similarly to 3Jxx, fl SCS (for C4) also correlate well with -AGo values (r = 0.9998). Dalling and Grant [17], and others [ 181, have observed a desbielding /3 SCS for equatorial CH3 and OH groups. Here, as R increases in size, a CGR equatorial preference and fi SCS (C-4) deshielding is also observed. CH24 proto_n.s in I-IV are also dghielded with respect to compound V [15b]. The fl’ SCS shielding on C-2 (carbonyl carbon) has zn approximately constant value (-2 ppm)_ Largest effects, however, w&e encountered in position C-3 (a SCS), where dghielding with respect to compound V subsides monotonously from I to IV, but linear correlation with Taft’s + inductive constants 1191 of R was not found. The latter indicates that other contributions besides the through-bond T-inductive transmission effect interfere (probably sr-polarization [ 161) A small y SCS shielding was observed for C-10, which decreases as R increases in size (an exception is compound III, R = Ph), which can be attrib uted to through-space (steric and electric effects), as well as through-bond polar interactions. The long-range SCS (G5 to C-8 atoms) is relatively small (-0.4 ppm) and obviously reflects some x-polarization transmission. TABLE
4
“C SCS effects
of COR
in compounds
I-IV
with
I C-2 (a’) c-3 (a) C-4 (0) c-5 G6 G7 C-8 G9 GlO
(7)
?I’he values represent
-2.7 123.2 + 2.1 +O.l + 0.4 +0.3 -0.3 -1-o -1.6 the difference
6grJ
I
respect
to 3,4-dihydrocoumarin
Va
II
III
Iv
-2.6 +20.5 +2.5 +O.l +0.3 -to_2 -0.3 -0.9 -1-4
-2.6 i-17-8 +3.3
-2.4 -16.2 -+4.5 4.1 +0.2 -PO.3 -0.2 -0.6 -i.2
-
6v_.
Cl
0 + 0.3 -l-o.3 -0.3 -0.8 -1-7
32
states s h o w i n t e r e s t i n g v a l u e s , dr, 5a and R6 c o n s t a n t s of the_~e t h r e e states are close to o n e another while the d ~ and d K constants exhibit large differences. I n p a r t i c , , I s r , t h e d a x c o n s t a n t o f t h e v24 (v = I ) s t a t e is p o s i t i v e , w h i l e those for the other states of the norms! species and for the ground states of all the isotopic species axe negative. However, on talcing averages of the values f o r t h e vz4 (o = 1 ) a n d v23 (v = 1) s t a t e s , t h e a v e r a g e s ( - - 8 . 6 1 3 a n d 4 6 . 6 0 1 k H z ) are close to those found for the ground state (--9.993 and 46.806 kHz). From the reported far-infrared spectra in the vapour phase, vibrational frequencies o f v-_4 a n d v-_3 [ 3 ] a r e a b o u t 2 1 6 a n d 2 2 8 c m - ' a n d s t r o n g F e r m i - r e s o n a n c e t y p e i n t e r a c t i o n is e x p e c t e d b e t w e e n t h e s e t w o state.s. T h e a b o v e e x p e r i m e n t a l facts may be related to thi~ L-,teraction in some way. F o r t h e s e c o n d e x c i t e d m e t h y l t o r s i o n a l s t a t e (v23 (v = 2 ) ) , C~hi]! e t al. reported only five b-type Q branch transitions. Although the spectra of this state were fairly wpslc, as expected, 12 b-type Q and R branch transitions could be observed_ On the other bsnd, no reasonable assignments to the observed spectra belonging to the second excited skeletal torsional state (v._~ (v = 2 ) ) c o u l d b e f o u n d t h o , , E h C a h i l l e t al. r e p o r t e d s i x b - t y p e Q b r a n c h transitions of this state. B_~RRIER T O T}LE M E T H Y L LNTERN_~L R O T A T I O N F r o m t h e A - - E s p l / t t i n g s o f t h e s p e c t r a b e l o n g i n g t o t h e v23 (v = 1) a n d (v = 2) states of the norton! species, the barrier to internal rotation of the methyl group was determined. The results are shown in Table 7. The moment o f i n e r t i a o f t h e m e t h y l g r o u p a r o u n d t h e i n t e r n a l r o t a t i o n a l nxi~ a n d t h e dLrectional cosine of the internal rotational ~xis in the molecule were comp u t e d f r o m t h e r~ c o o r d i n a t e v a l u e s o f t h r e e h y d r o g e n a t o m s l i s t e d i n T a b l e 4. T h e l e a s t - s q u a r e s c a l c u l a t i o n w a s c a r r i e d o u t in t h e s t a n d a r d f o r m o f PAM-bootstrap approximation B [ 1 1 ] i n c l u d i n g u p t o fOtLrth o r d e r t e r m s . T h e b a r r i e r s o b t a i n e d f r o m t h e s p l i t t i n g d a t a f o r t h e ~:3 (u = 1) a n d (o = 2 ) states are 3643 ± 75 and 3738 ± 60 cal tool-*, respectively. As a test, the directional cosines of the top axis were changed sliEhtly in the calculation and it was co~firmed thereby that the direction of the top zxi_~ c o m p u t e d f r o m t h e r s c o o r d i n a t e v a l u e s g i v e s t h e b e s t r e p r o d u c t i o n o f t h e p r e s e n t s p l i t t i n g d a t a . T h e v a l u e s r e p o r t e d b y C a h i l l e t al. a r e 3 7 5 0 a n d 3 8 3 0 c a l n~ol -~, r e s p e c t i v e l y _ T h e p r e s e n t v a l u e s a r e a b o u t 1 0 0 c a l m o l -* lower than theirs but the differences between the values obtained from the v = 1 a n d v = 2 s t a t e s a r e c l o s e in b o t h c a s e s . ACKNOWLEDGEMENT The authors express their sincere gratitude to Professor A. Im~rnura and Dr_ M . O h s a k u o f H i r o s h i r n a U n i v e r s i t y f o r t h e i r a s s i s ~ n c e a n d a d v i c e o n t h e MO calculations.
33 T_ABLE 7 I n t e r n a l r o t a t i o n analysis [ I . = 3 . 2 2 6 6 1 a i n u A2; (ka, Ab, k c ) = ( 0 . 5 4 2 9 3 , 0 . 8 3 9 7 8 , 0 . 0 ) ]
F (GHz) (=, Is, 7 ) a s V , (ca] t o o l - ' ) Transition
5Qs 6o~ 7,s 8,. 7,, 8,, 10:, -- 956 l l : , o - i0,,
= ]a~l-la.
v 2 , ( v = 2)
167.150 ( 0 _ 0 6 3 4 4 , 0 . 0 3 3 9 5 , 0.0) 101.58 3 6 4 3 -+ 7 5
167.135 ( 0 . 0 6 3 7 1 , 0.03367, 0.0) 104.24 3738 ± 60
A v ( A - - E )b ( M H z )
5,46,s ~ 7~_sS-_,82, -9:,-
SO:
",3 (v = I)
--0.25(7) ---0.52(8) ---0.24(0) --0.35(--2) 0.35(2) 0.42(1) 0.56(2) 0.72(--1)
,6 = l a A b / ] b ,
7
=
Transition
Au(A--E)b (MHz)
1,, 2,, 31: 4,s 5,, 6,5
2.10(18) 2.97(23) 4.08(16) 5.77(7) 8.01(--15) 10.94(--28) 2_19(--25) 2.27(1) 1.03(--21) 2.90(--16) 8.44(40)
~- Io, +- 202 ~ 30~ 4- 404 ~- 5o5 *- 606
1,, -- 00o
2,: 40, 4=. 8:6
*- lo, ~ 3,, ~ 4,, --- 8,,
laXelZc.
b F i g u r e s in pa_-entheses i n d i c a t e t h e d i f f e r e n c e s b e t w e e n t h e o b s e r v e d a n d c a l c u l a t e d splitting~. REFERENCES 1 (a) M. H a y a s h i a n d K. K u w a d a , J. M o l . S t r u c t . , 28 ( 1 9 7 5 ) 1 4 7 . ( b ) M . Haya~hi a n d K. K u w a d a , Bull. C h e m . S o c . J p n . , 47 ( 1 9 7 4 ) 3 0 0 6 . (c) H_ K a t o , J. N a k ~ g a w a a n d M_ H a y a s h i , J. M o l . S p e c t r o s c . , 8 0 ( 1 9 8 0 ) 272_ ( d ) Y. S h i k i , N_ Ib,,-.hi, M. O y a m a d a , J . N a k a g a w a a n d M. H a y a s h i , J_ M o l . S p e c t r o s c . , 87 ( 1 9 8 1 ) 357_ (e) M. H a y a s h i a n d M. A d a c h i , J. M o l . S t r u c t . , 7 8 ( 1 9 8 2 ) 53. (f') J. N a k a g a w a , M. I r n a c h i a n d M. H a y a s h i , J. M o l . S t r u c t . , 1 1 2 ( 1 9 8 4 ) 201. 2 (a) M. H a y ~ h i a n d H. K a t o , J . M o l . S p e c t r o s c . , 76 ( 1 9 7 9 ) 4 1 2 . ( b ) M. Haydn.h} a n d H. K a t o , J. M o l . S t r u c t . , 53 ( 1 9 7 9 ) 1 7 9 . (¢) M. H a y a s h i a n d H. K a t o , Bull. C h e m . S o c . Jpn_, 53 ( 1 9 8 0 ) 2 7 0 1 . ( d ) M. H a y a s h i , H. K a t o a n d M. O y a m a d a , J. Mol. S p e c t r o s c . , 83 ( 1 9 8 0 ) 4 0 8 . ( e) M. Hayz~hi, J. N a k a g a w a a n d H. K a t o , J. M o l . S p e c t r o s c . , 6 4 ( 1 9 8 0 ) 3 6 2 . (f ) J . N a k a g a w a , H. K a t o a n d M. H a y ~ h i , J. Mol. S p e c t r o s c . , 9 0 ( 1 9 8 1 ) 4 6 7 . 3 P. Cahill, L. P. G o l d a n d N. L. O w e n , J. C h e m . Phys., 48 ( 1 9 6 8 ) 1 6 2 0 . 4 S. K o n d o , E. H i r o t a a n d Y. l%Iorino, J. M o L S p e c t r o s c . , 28 ( 1 9 8 8 ) 4 7 1 . 5 D. R_ L i d e a n d D_ C h r i s t e n s e n , J . C h e m . P h y ~ , 35 ( 1 9 6 1 ) 1 3 7 4 . 6 D. d e K e r k h o v e V a r e n t , A n n . Soc_ Sci_ B r u x e l l e s , Ser. 1 , 8 4 ( 1 9 7 0 ) 2 7 7 ; R . E_ G o e d e r t i e r , J . P h y s . (Paris), 24 ( 1 9 6 3 ) 6 3 3 . 7 L. P a u l i n g , T h e N a t u r e oF t h e C h e m i c a l B o n d , C o r n e l l U n i v e r s i t y Press, Itn%ca, N Y , 1939, Ch. 5. 8 R . N e l s o n a n d L. P i e r c e , J. M o L S p e c t r o s c . , 18 ( 1 9 6 5 ) 3 4 4 . 9 J . S. M u e n t e r , J. C h e m . P h y ~ , 48 ( 1 9 5 8 ) 4 5 4 4 . 10 J. A . P o p l e , J. S. B i n k l e y , R. A . W h i t e s i d e , R. K r i s h n a n , R . S e e g e r , D. J. D e f r e e a , H . B . S c h / e g e l , S. T o p i o l a n d L. R . I ~ h n , Q.C.P.E-, 13 ( 1 9 8 1 ) 4 0 6 . 1 ! D. R . Hersr_hhach, J. C h e m . P h y s . , 3 1 ( 1 9 5 9 ) 9 1 .
127-133
-Printed
CONFORMATION .-i9-D TAUTOMERIC UMARINS: 3-ACYL3,4DlHYDROCO
M. F. SIMEONOV Institute
Department
EQUILIBRIA A ‘H AND %
OF NhtR STUDY
and S. L. SPASSOV
of Oganie
A_ BOJILOVA
in The Netherlands
Chemist.
of Sciences.
Bu&a.rianAcdemy
1113
Sofm
(Bulgmia)
and CI-IR_ IVANOV of Chemise,
University
of Sam
1 I26
Sofm
(Bulgark)
FL RADEGLIA Cent-t-o1 Institrzte of Physical Chemistry, 1199 Berlin-Adlershof (G.D.R.) (Received
22 August
The
Academy
of Sciences
of the GDR,
1984)
The steric and electronic effects of acyl substituents COR (R = Me, i-Pr, Ph and t-Bu) upon conformational and keto-enol equilibria in 3-acyl-3,4-dihydrocoumarins have been studied by ‘H and “C NMR spectroscopy_ With the increase of the effective size of R, preference for the equatorial position and the keto-form population increases considerably_ The “C substituent-induced chemical shifts are also discussed INTBODUCTION
Tautomeric equilibria in acyclic &licarbonyl compounds have been the subject of a number of studies bymeans of various chemical [l] and physical In [2] methods, including ‘H 131, DC 143 and “0 [5] NMR spectiscopy. most cases, only the keto (K) and cis-enol (CE) forms have been taken into consideration. Only for some ketoaldehydes has the trans-enol (TE) form been found [3] _
IKI
ITEI
f(;E-III
ICE-II
The c&en01 equilibrium, usually fast on the NMR timescale, has been also di;cussed in terms of unsymmetrical “classicaI” (CEI) or symmetrical (CEII) structures 13-51. The tautomeric phenomena in hetero-alicyclic &dicarbonyl compounds, however, have been much lesj studied [2] in connection with their conformation. Moreover, some of the data are rather controversial: the presence of trans-enolic species has been assumed for a number of a-acyllactones [lb] 0022-2860/85/$03.30
0
1985
Eisevier Science
Publishers
B-V.
128
and some 3-fonnylcamphors [6], but in the former case that was later rejected on the grounds of a W study 171. In the present paper, the infhrence of the acyl substituent COR (R = Me I, i-Pr II, Ph III, and t-Bu IV) on the conformational and tautomeric behaviour of 3-acyl-3,4xEhydrocoumarins was investigated by means of ‘Hand ‘% NMEspectroscopy. According ti a ‘H m study [S], compound HI exis& as z cifenol form, whereas for compound I the keto-enol ratio is -2:l. EXPEFUMENTALA
Compounds I-IV were synthesized by reduction of the corr=ponding 3-acylcoumarins with NaB& in pyridine solution, as described in ref. 8 for I and III. Compound II: (58% yield) m-p. 75-77°C; IR (CHCI,): 1725 (CO, IV: (54% yield) m-p. 141ketone), 1770 (CO, la&one) cm-‘. Compound 142°C; MS: m/z 232 (M’); IR (CHCI,): 1715 (CO, ketone), 1770 (CO, la&one) cm-‘. Analysis_ Cak. for C,HtiO,: C, 72.39; H, 6.94. Found: C, 72.45; H, 6.99. The starting 3-acylcoumtis were obtained as follows: compounds VII (R = i-Pr) and IX (R = t-Bu) by the method of Dean and Park [9], from salicylaldehyde and the corresponding Bketoacids and purified by column cbromatography on silica gel (ethylaeetate/hexane 3:7 and 1:4)_ Compound VII: (63% yield) m-p. 106108°C; IR (CHC13): 1690 (CO, ketone), 1735 (CO, la&one) cm-‘_ Analysis_ Ca!c. for CUHrzOs: C, 72.21; H, 5.59. Found: C, 72.16; H, 5.54. Compound IX: (59% yield) m-p_ 88-89°C (lit. [9] 8990°C). Compounds VI (R = Me) and VIII (R = Ph) were synthesized according to IlO] and [ll], respectively_ The ‘H and 13C NMR spectra were measured at 250-l and 62.89 MHz, respectively, on a Bruker WM-250 FT spectrometer. Some ‘H NMR spectra were obtained also at 80 MHz on a Tp_sl BS 487C spectrometer (CW mode). ‘% NMR spectra were run in -0.1 molar solutions with TMS as internal standard at, typically, 16K data points for FID and sweep-width -15000 Hz The chemical shifts were obtained with broad-band ‘H decoupling and for their assignment the single-tiequency off-resonance (SFORD) decoupling and J-modulated spin-echo methods were also used. The *H coupling constants of CH,CH went (ABX-type) were determined by second order analysis. IR spectra were measured in Ccl, solution and solid phase with a C. Zeiss UR-20 and Bruker IFS 113~ spectrometers, repectively. RESULTS AND DISCUSSION The keto-enol interconversion of compounds I-IV is slow on the NMR timescale, and so separate signals for the protons due to the different t-automerit spmies were observed and asigned on the basis of their position, multiplicity and intensity. The ‘H NMR data are given in Table 1.
129 TABLE
1
‘H NMR data for compounds FIV
(in CDCl,
solution)a
keto-form
I TI III TV
cisenol form
R
6Hx
&HA
kg
Me i-R Ph t-Bu
3.78 3.97 4.68 4.20
3.48 3.37 3-44 3-41
2.86 2.98 3.11 2.87
Whemical in R
6R
I’b-I
IJJj3xl
I’JABI
kEJAB)
k
2.36 1.20b
8.73 9.46 10.58 1202
6.49 6.34 5.45 6.54
16.16 15.57 16.23 15.70
3.56 3.75 3.75 -
2.10 l.lob 7.15 (mj -
7.25 (m)
1.25
shifts (6) in ppm (Th4!S = 0) and coupling constants (J) in Hz bFor CH, groups
A qualitative estimation of the equilibrium (Scheme 1) between two conformers of a halfchair type [12] can be made from experimental 3J13E and
3JBXvalues.
COR
Thus, taking into account the Karplus rule and the fact that 3JAx only reflects the changes of substituent, the following conclusions are drawn. First, with increase in the sutzstituent size the equatorial preference of the 3-acyl group increases_ Second, it is possible to make unequivocal assignment of protons Hx and Ha - the low-frequency shifted one (HA) is pseudoaxial in form a This is in accordance with the general conformational theory; moreover, a good linear correlation (r = 0.9957) for 3Ja with the conformational energy (-AGO) [13] of the substituent R was established, although R is not directly bonded to the ring. In the Same order (compolu;ds I + Iv), a tendency to deshielding for 6Hx was observed, in contrast tn negligible 6H, and &nB changes (an exception is compound III, where the phenyl anisotropic effect probably interferes). It seems that in this series practically the same conformer ratio is also retained in acetond6 solution, since insignificant changes in the ‘H NMR parameters were observed. -The quantitative estimation of tautomeric populations (Table 2) was achieved by comparing the integral intensity of the singlet CH2 signal in the cis-enol folm with that of the ketmform (AB part of ABX-multiplet), as well as Cram the proton signals of the acyl group in these two forms.
130 TABLE' Relativeabundanceofthe tauLomeric(K)*(CE)formsfor R
(CE)hd
(K>bmd
(CE)4=
Me
100 0 0 0
0 100 100 100
56 23 i 0
i-R Pb t-Bu
(KY'.= 44
compoundsFTV;L
(CE)=d
(KFd 35
65
(CE)==
(KF
24
76 100 100 100
i7
0
zoo
0
93 100
0 0
100 100
0 0
solution_ 'In % (55%); concen@ation 0.7 moiar. bin CDCI, solution =In CD,COCD, dImmeddteIy afterdirsolving. lAfter24 hours(thermodynamic equilibriumachieved). mC NlMR chemical shifts (SC) of compounds I-IV (Table 3) confirm the ‘H NMR analysis. Thus, initially, for compound I in CDCIB the signals for cis-enoh: species only were observed; after a few hours, these of the ketoform were also present In acetone-d, solution the signals of both keto and enol tautomers appear immediately after dissolving. Additionally, from 6c11 (in the case of COMe) the ciGeno1 equilibrium (Scheme 2) can be qualitatively evaluet& as a fast one: the observed value of 177.3 ppm is an approximate average lxween those experimentally observed in keto (201.2 ppm) and calculated (empirical additivity scheme [14]) for =C(OH)alkyl j?-agment (167-171 ppm). Thus, both cis-enol tautomers are TABLE3 '3CNMRchemicalshiftsforcompoun&I-Va R = CH KH3
0 r
1’ 2:x
I’ R=CH3
12
R: I'/
3’
\
4
n.
R&&3)3
Vd L
-
keto(K) C-2 c-3
enol(CE)
keto(K)
keto(K)
165.Bb 166_5= 168.8b 53.2 52-3 90-5
165i.gb 49.5 166_7= 165.9b 91.7= 46.9 50.2 26-l 26.9 26.4 26.6 26.6 25.9 C-4 25-i c-5 128.2* 129-l* 127.8" 12%8 128.2* 128.9 128.lf 124.7 125.4 124.5 129.6 128.3* 125.2 124-7 GC 124.8 129.4' 12&e* c-i .128.4* 129.2 128.4* 117.2 116-7 117.3 116.5 116.9 116.5 C-8 116-5 151.1 152.3 151.2 152.6 150.1 G9 151.0 121-l 123.0 119.9 121-i 121-4 1228 c-10 121.2 2023 177.3 c-11 201.2 20X4 208.7 193.9 19.2 19.1 C-l' 29.5 40.5 40.7 135.3 c-2 17.5 18-O 128-7 18.3 18.4 128.7 C-3' C4' 133.8
keto(K) 166.1b 45.3 28.1 128.02 124-6 128.4* 116-6 151.4 121.6 209.5 45.3 25.6
166.9= 45.8 129-O* 125.3 129.3* 117-l 1528 123.3 210.3 46.3 26.0
168.5b 29.1, 23.6: 128.1:; 124-e; 128.1: 116.8, 152.& 1228;
= 'In ppm (TMS = 0). bInCDCI,soluti~eCInCD,COCD,solution reL15a+Asignrnentunknown
dThedataarefrom
131
probably represented ;J1 comparable amounts. The 8c_2 cannot be used to discriminate between these two tautomers since it is expected to be in the range 160-165 for both (experimental value 168.8 ppm).
Qyf-J = QJ?Jo>
Scheme
2
It is interesting to consider the substituentcinduced UC chemical shifts (SCS) in compounds I-W in relation to the unsubstituted 3,4dihydrocoumarin V [15] (Table 4). Although the SCS effects in saturated molecules or ments are not as well understood as those in unsaturated systems [lS] , some conclusions can eventually be derived. Thus, similarly to 3Jxx, fl SCS (for C4) also correlate well with -AGo values (r = 0.9998). Dalling and Grant [17], and others [ 181, have observed a desbielding /3 SCS for equatorial CH3 and OH groups. Here, as R increases in size, a CGR equatorial preference and fi SCS (C-4) deshielding is also observed. CH24 proto_n.s in I-IV are also dghielded with respect to compound V [15b]. The fl’ SCS shielding on C-2 (carbonyl carbon) has zn approximately constant value (-2 ppm)_ Largest effects, however, w&e encountered in position C-3 (a SCS), where dghielding with respect to compound V subsides monotonously from I to IV, but linear correlation with Taft’s + inductive constants 1191 of R was not found. The latter indicates that other contributions besides the through-bond T-inductive transmission effect interfere (probably sr-polarization [ 161) A small y SCS shielding was observed for C-10, which decreases as R increases in size (an exception is compound III, R = Ph), which can be attrib uted to through-space (steric and electric effects), as well as through-bond polar interactions. The long-range SCS (G5 to C-8 atoms) is relatively small (-0.4 ppm) and obviously reflects some x-polarization transmission. TABLE
4
“C SCS effects
of COR
in compounds
I-IV
with
I C-2 (a’) c-3 (a) C-4 (0) c-5 G6 G7 C-8 G9 GlO
(7)
?I’he values represent
-2.7 123.2 + 2.1 +O.l + 0.4 +0.3 -0.3 -1-o -1.6 the difference
6grJ
I
respect
to 3,4-dihydrocoumarin
Va
II
III
Iv
-2.6 +20.5 +2.5 +O.l +0.3 -to_2 -0.3 -0.9 -1-4
-2.6 i-17-8 +3.3
-2.4 -16.2 -+4.5 4.1 +0.2 -PO.3 -0.2 -0.6 -i.2
-
6v_.
Cl
0 + 0.3 -l-o.3 -0.3 -0.8 -1-7
32
states s h o w i n t e r e s t i n g v a l u e s , dr, 5a and R6 c o n s t a n t s of the_~e t h r e e states are close to o n e another while the d ~ and d K constants exhibit large differences. I n p a r t i c , , I s r , t h e d a x c o n s t a n t o f t h e v24 (v = I ) s t a t e is p o s i t i v e , w h i l e those for the other states of the norms! species and for the ground states of all the isotopic species axe negative. However, on talcing averages of the values f o r t h e vz4 (o = 1 ) a n d v23 (v = 1) s t a t e s , t h e a v e r a g e s ( - - 8 . 6 1 3 a n d 4 6 . 6 0 1 k H z ) are close to those found for the ground state (--9.993 and 46.806 kHz). From the reported far-infrared spectra in the vapour phase, vibrational frequencies o f v-_4 a n d v-_3 [ 3 ] a r e a b o u t 2 1 6 a n d 2 2 8 c m - ' a n d s t r o n g F e r m i - r e s o n a n c e t y p e i n t e r a c t i o n is e x p e c t e d b e t w e e n t h e s e t w o state.s. T h e a b o v e e x p e r i m e n t a l facts may be related to thi~ L-,teraction in some way. F o r t h e s e c o n d e x c i t e d m e t h y l t o r s i o n a l s t a t e (v23 (v = 2 ) ) , C~hi]! e t al. reported only five b-type Q branch transitions. Although the spectra of this state were fairly wpslc, as expected, 12 b-type Q and R branch transitions could be observed_ On the other bsnd, no reasonable assignments to the observed spectra belonging to the second excited skeletal torsional state (v._~ (v = 2 ) ) c o u l d b e f o u n d t h o , , E h C a h i l l e t al. r e p o r t e d s i x b - t y p e Q b r a n c h transitions of this state. B_~RRIER T O T}LE M E T H Y L LNTERN_~L R O T A T I O N F r o m t h e A - - E s p l / t t i n g s o f t h e s p e c t r a b e l o n g i n g t o t h e v23 (v = 1) a n d (v = 2) states of the norton! species, the barrier to internal rotation of the methyl group was determined. The results are shown in Table 7. The moment o f i n e r t i a o f t h e m e t h y l g r o u p a r o u n d t h e i n t e r n a l r o t a t i o n a l nxi~ a n d t h e dLrectional cosine of the internal rotational ~xis in the molecule were comp u t e d f r o m t h e r~ c o o r d i n a t e v a l u e s o f t h r e e h y d r o g e n a t o m s l i s t e d i n T a b l e 4. T h e l e a s t - s q u a r e s c a l c u l a t i o n w a s c a r r i e d o u t in t h e s t a n d a r d f o r m o f PAM-bootstrap approximation B [ 1 1 ] i n c l u d i n g u p t o fOtLrth o r d e r t e r m s . T h e b a r r i e r s o b t a i n e d f r o m t h e s p l i t t i n g d a t a f o r t h e ~:3 (u = 1) a n d (o = 2 ) states are 3643 ± 75 and 3738 ± 60 cal tool-*, respectively. As a test, the directional cosines of the top axis were changed sliEhtly in the calculation and it was co~firmed thereby that the direction of the top zxi_~ c o m p u t e d f r o m t h e r s c o o r d i n a t e v a l u e s g i v e s t h e b e s t r e p r o d u c t i o n o f t h e p r e s e n t s p l i t t i n g d a t a . T h e v a l u e s r e p o r t e d b y C a h i l l e t al. a r e 3 7 5 0 a n d 3 8 3 0 c a l n~ol -~, r e s p e c t i v e l y _ T h e p r e s e n t v a l u e s a r e a b o u t 1 0 0 c a l m o l -* lower than theirs but the differences between the values obtained from the v = 1 a n d v = 2 s t a t e s a r e c l o s e in b o t h c a s e s . ACKNOWLEDGEMENT The authors express their sincere gratitude to Professor A. Im~rnura and Dr_ M . O h s a k u o f H i r o s h i r n a U n i v e r s i t y f o r t h e i r a s s i s ~ n c e a n d a d v i c e o n t h e MO calculations.
33 T_ABLE 7 I n t e r n a l r o t a t i o n analysis [ I . = 3 . 2 2 6 6 1 a i n u A2; (ka, Ab, k c ) = ( 0 . 5 4 2 9 3 , 0 . 8 3 9 7 8 , 0 . 0 ) ]
F (GHz) (=, Is, 7 ) a s V , (ca] t o o l - ' ) Transition
5Qs 6o~ 7,s 8,. 7,, 8,, 10:, -- 956 l l : , o - i0,,
= ]a~l-la.
v 2 , ( v = 2)
167.150 ( 0 _ 0 6 3 4 4 , 0 . 0 3 3 9 5 , 0.0) 101.58 3 6 4 3 -+ 7 5
167.135 ( 0 . 0 6 3 7 1 , 0.03367, 0.0) 104.24 3738 ± 60
A v ( A - - E )b ( M H z )
5,46,s ~ 7~_sS-_,82, -9:,-
SO:
",3 (v = I)
--0.25(7) ---0.52(8) ---0.24(0) --0.35(--2) 0.35(2) 0.42(1) 0.56(2) 0.72(--1)
,6 = l a A b / ] b ,
7
=
Transition
Au(A--E)b (MHz)
1,, 2,, 31: 4,s 5,, 6,5
2.10(18) 2.97(23) 4.08(16) 5.77(7) 8.01(--15) 10.94(--28) 2_19(--25) 2.27(1) 1.03(--21) 2.90(--16) 8.44(40)
~- Io, +- 202 ~ 30~ 4- 404 ~- 5o5 *- 606
1,, -- 00o
2,: 40, 4=. 8:6
*- lo, ~ 3,, ~ 4,, --- 8,,
laXelZc.
b F i g u r e s in pa_-entheses i n d i c a t e t h e d i f f e r e n c e s b e t w e e n t h e o b s e r v e d a n d c a l c u l a t e d splitting~. REFERENCES 1 (a) M. H a y a s h i a n d K. K u w a d a , J. M o l . S t r u c t . , 28 ( 1 9 7 5 ) 1 4 7 . ( b ) M . Haya~hi a n d K. K u w a d a , Bull. C h e m . S o c . J p n . , 47 ( 1 9 7 4 ) 3 0 0 6 . (c) H_ K a t o , J. N a k ~ g a w a a n d M_ H a y a s h i , J. M o l . S p e c t r o s c . , 8 0 ( 1 9 8 0 ) 272_ ( d ) Y. S h i k i , N_ Ib,,-.hi, M. O y a m a d a , J . N a k a g a w a a n d M. H a y a s h i , J_ M o l . S p e c t r o s c . , 87 ( 1 9 8 1 ) 357_ (e) M. H a y a s h i a n d M. A d a c h i , J. M o l . S t r u c t . , 7 8 ( 1 9 8 2 ) 53. (f') J. N a k a g a w a , M. I r n a c h i a n d M. H a y a s h i , J. M o l . S t r u c t . , 1 1 2 ( 1 9 8 4 ) 201. 2 (a) M. H a y ~ h i a n d H. K a t o , J . M o l . S p e c t r o s c . , 76 ( 1 9 7 9 ) 4 1 2 . ( b ) M. Haydn.h} a n d H. K a t o , J. M o l . S t r u c t . , 53 ( 1 9 7 9 ) 1 7 9 . (¢) M. H a y a s h i a n d H. K a t o , Bull. C h e m . S o c . Jpn_, 53 ( 1 9 8 0 ) 2 7 0 1 . ( d ) M. H a y a s h i , H. K a t o a n d M. O y a m a d a , J. Mol. S p e c t r o s c . , 83 ( 1 9 8 0 ) 4 0 8 . ( e) M. Hayz~hi, J. N a k a g a w a a n d H. K a t o , J. M o l . S p e c t r o s c . , 6 4 ( 1 9 8 0 ) 3 6 2 . (f ) J . N a k a g a w a , H. K a t o a n d M. H a y ~ h i , J. Mol. S p e c t r o s c . , 9 0 ( 1 9 8 1 ) 4 6 7 . 3 P. Cahill, L. P. G o l d a n d N. L. O w e n , J. C h e m . Phys., 48 ( 1 9 6 8 ) 1 6 2 0 . 4 S. K o n d o , E. H i r o t a a n d Y. l%Iorino, J. M o L S p e c t r o s c . , 28 ( 1 9 8 8 ) 4 7 1 . 5 D. R_ L i d e a n d D_ C h r i s t e n s e n , J . C h e m . P h y ~ , 35 ( 1 9 6 1 ) 1 3 7 4 . 6 D. d e K e r k h o v e V a r e n t , A n n . Soc_ Sci_ B r u x e l l e s , Ser. 1 , 8 4 ( 1 9 7 0 ) 2 7 7 ; R . E_ G o e d e r t i e r , J . P h y s . (Paris), 24 ( 1 9 6 3 ) 6 3 3 . 7 L. P a u l i n g , T h e N a t u r e oF t h e C h e m i c a l B o n d , C o r n e l l U n i v e r s i t y Press, Itn%ca, N Y , 1939, Ch. 5. 8 R . N e l s o n a n d L. P i e r c e , J. M o L S p e c t r o s c . , 18 ( 1 9 6 5 ) 3 4 4 . 9 J . S. M u e n t e r , J. C h e m . P h y ~ , 48 ( 1 9 5 8 ) 4 5 4 4 . 10 J. A . P o p l e , J. S. B i n k l e y , R. A . W h i t e s i d e , R. K r i s h n a n , R . S e e g e r , D. J. D e f r e e a , H . B . S c h / e g e l , S. T o p i o l a n d L. R . I ~ h n , Q.C.P.E-, 13 ( 1 9 8 1 ) 4 0 6 . 1 ! D. R . Hersr_hhach, J. C h e m . P h y s . , 3 1 ( 1 9 5 9 ) 9 1 .