Reaction of Resorcinol With Acetone

Full text of DOI:10.1021/jo961647y

J . Org. Chem. 1997, 62, 737-742
737
Rea ction of Resor cin ol With Aceton e
P. Livant,* T. R. Webb, and Weizheng Xu
Department of Chemistry, Auburn University,
Auburn, Alabama 36849-5312
Received August 26, 1996
Resorcinol is a solid having a reported mp of 109-110
1
°
C. Therefore, it was surprising to obtain by recrystal-
lizing a sample of impure resorcinol from a mixture of
chloroform and acetone a solid of mp 182-203 °C.
Since acetone and resorcinol are both venerable organic
compounds, rich with history, it is reasonable to suspect
that the reaction of resorcinol with acetone had been
studied previously. Indeed, to the best of our knowledge,
this reaction was reported for the first time in 1892 by
Causse.2 He obtained a solid, mp 212-213 °C, analyzing
as C15
16 4
H O and forming a diacetate and a dibenzoate,
synthesized but none explain how 6 was excluded from
consideration. One lone report9 contended 6 was ob-
tained in the reaction of resorcinol with mesityl oxide,
for which he proposed structure 1. This was questioned
in 1910 by Schmidlin and Lang who reported following
Causse’s procedure and obtaining a product (mp 230-
but it was not clear why 5 was not the product. A few
2
40 °C) whose elemental analysis was consistent with
10
patents reported that spirobichroman 7 was formed in
the formula C12 , i.e. a compound formed by con-
14 2
H O
the reaction of acetone with resorcinol. In sum, more
than a century after its first report, the structure of the
product of the reaction of resorcinol with acetone had not
been established.
densation of one resorcinol with two acetones with loss
of two waters.3 No structure was proposed, however.
4
Sen and co-workers reported in 1930 that the reaction
of acetone with resorcinol gave either 2 (mp 153 °C) or 3
(mp 165 °C) depending on the mole ratio of the reactants,
Resu lts a n d Discu ssion
Our curiosity was thus piqued, and we purified the
aberrant resorcinol obtained from our “recrystallization”.
The analytically pure material had mp 231-2 °C. El-
emental analysis and HRMS established the formula
C
18
H
20
O
4
.
The compound formed a trimethyl ether
1
3
derivative (8) and a triacetate derivative (9). The C-
NMR and DEPT-135 spectra showed six quaternary
aromatic carbons, four of which were near 158 ppm and
therefore bearing oxygen, six methine aromatic carbons,
three methyl carbons, one methylene carbon and two
the nature of the acid catalyst, and the temperature and
duration of the reaction. The assertion that 3 was
orange-red in color was vigorously disputed by Weiss-
berger and Thiele,5 who, however, did not offer an
alternative structure for the product. Malhotra and
Banerjee in 1990 studied the kinetics of reaction of
acetone with resorcinol and asserted that the product had
the structure 4.6
1
quaternary aliphatic carbons. The H-NMR and COSY
showed two separate aromatic spin systems of three
protons each, three methyl singlets, and a methylene AB
quartet. These data, taken together, are consistent with
both 5 and 6, but without further data, distinguishing
11
between the two is impossible.
(
8) (a) Bruin, P.; Klootwijk, A. U.S. Patent 2 947 760, 1960; Chem
Abstr. 1960, 55, 13450b. (b) Sumitomo Chem. Co. Ltd. J pn Patent
0 139 375, 1980; Chem Abstr. 1981, 94, 103168f. (c) Mitsui Petrochem.
This reaction has appeared more often in the patent
literature than in scholarly journals. A 1959 British
8
Ind. Ltd. J pn Patent J P 81 05 476, 1981; Chem Abstr. 1981, 95, 97590q
d) Mitsui Petrochem. Ind. Ltd. J pn Patent J P 82 16 877, 1982; Chem
Abstr. 1982, 97, 6153b. (e) Mitsui Petrochem. Ind. Ltd. J pn Patent J P
7
patent, with admirable candor, properly assigned the
product structure ambiguously as either 5 or 6 (mp 225
8
2 114 585, 1982; Chem Abstr. 1982, 97, 216003d. (f) Mitsui Petrochem.
Ind. Ltd. J pn Patent J P 59 88 479, 1984; Chem Abstr. 1984, 101,
71099. (g) Mitsui Petrochem. Ind. Ltd. J pn Patent J P 59 157 113,
°
C). Since 1959, a plenitude of procedures for synthesiz-
ing from acetone and resorcinol a solid with mp ca. 225
C has been patented8 and all these patent abstracts
baldly assert 5 to be the structure of the material
1
°
1984; Chem Abstr. 1985, 102, 46742w. (h) Matsunaga, F.; Kondo, M.
J pn Patent J P 61 27 979, 1986; Chem Abstr. 1986, 105, 42540t. (i)
Matsunaga, F.; Kondo, M. J pn Patent J P 61 27 980, 1986; Chem Abstr.
1
986, 105, 42541u. (j) Matsunaga, F.; Kondo, M. J pn Patent J P
(
1) Robertson, J . M.; Ubbelohde, A. R. Proc. R. Soc. A 1938, 167,
61 69 770, 1986; Chem Abstr. 1986, 105, 97315d.
(9) Kondrat’eva, G. G.; Volkotrub, M. N. Sin. Issled. Eff. Khim-
Dobavok., Polim. Mater. 1969, No. 2, 373-376.; Chem. Abstr.1972, 76,
59369z.
1
22-135.
(
(
(
2) Causse, M. H. Bull. Soc. Chim. Paris, Ser. 3 1892, 7, 563-566.
3) Schmidlin, J .; Lang, R. Chem. Ber. 1910, 43, 2806-2820.
4) (a) Sen, R. N.; Quadrat-I-Khuda, M. J . Indian Chem. Soc. 1930,
(10) (a) Sumitomo Chem. Co. Ltd., J pn. Patent 80,139,383, 1980;
1
7
1
, 167-175. (b) Sen, R. N.; Chattopadhya, N. C.; Sen-Gupta, S. C. Ibid.
930, 7, 997-1006.
(
Chem. Abstr. 1981, 94, 121358x. The abstract contains a misprint: R
and R are interchanged. (b) Harada, H.; Usui, M. J pn. Patent J P 62,-
103,085, 1987; Chem. Abstr. 1988, 109, 92832t. (c) Harada, H.; Usui,
M. J pn. Patent 62,111,988, 1987; Chem. Abstr. 1988, 109, 149374b.
2
5) Weissberger, A.; Thiele, J . J . Chem. Soc. 1934, 148-151.
6) Malhotra, H. C.; Banerjee, S. J . Indian Chem. Soc. 1990, 67,
(
1
1
17-119.
3 3
(11) A referee has proposed that reaction with (CH ) SiI would
distinguish 5 and 6. We thank the referee for this thoughtful sugges-
tion.
(
7) N. V. deBataafsche Petroleum Maatschappij Br. Patent 822 659,
959; Chem. Abstr. 1960, 54, 7740b.
S0022-3263(96)01647-7 CCC: $14.00 © 1997 American Chemical Society

7
38 J . Org. Chem., Vol. 62, No. 3, 1997
Notes
Ta ble 1. Ca lcu la tion s of Con for m a tion a l En er gies
∆E (kcal/mol)
MM2
MM3
AM1
PM3
0.25
-0.55
1.41
3-21G(*)
1
1
1
1
0e a 10a
1e a 11a
2e a 12a
3e a 13a
-2.90
-3.31
-1.70
-2.14a
-3.01
-3.16a
-1.86
-2.40a
-0.14
-0.76
0.35
-2.04
-2.52
-1.12
-1.34
-0.36
7.31
a
Missing torsional parameters set to zero.
2
,4-diacetoxyphenyl ring when hydrogen-bond-mediated
dimer formation is precluded by the presence of the acetyl
groups?
Modeling the methylated ring of 5 or 9 as 10a or 10e
(
where a and e refer to the phenyl), in 10a one finds a
CH
/Ph 1,3-diaxial interaction (3.4 kcal/mol)14 and in 10e
both a CH
F igu r e 1. The structure of the product of the reaction of
resorcinol with acetone, 5. The figure was constructed from
X-ray crystallographic data. Spheres are of arbitrary radius.
Plain spheres represent carbon and the stippled spheres
represent oxygen. For clarity, all hydrogens were omitted, save
OH hydrogens and two hydrogens on the nonaromatic ring,
which are indicated by small spheres. An ether of crystalliza-
tion (see Figure 2) is not shown.
3
1
5
3
3
/CH 1,3-diaxial interaction (3.7 kcal/mol)
and a CH
Taking these into account, 10e a 10a is predicted to have
G ) -1.2 kcal/mol. The experimental ∆G is -1.23 (
.01 kcal/mol at 173 K.14 Better models for 5 (or 9)
include oxygen in the ring (11), a double bond in the ring
12), or, best, both (13). The empirical approach which
was successful for 10 cannot be applied to 11-13 because
not all the required energies of interaction have been
measured. We therefore turned to molecular mech-
anics, semiempirical, and low-level ab initio calculations
(Table 1).
/Ph geminal interaction (1.45 kcal/mol).16
3
∆
0
F igu r e 2. The H-bonded dimer formed by 5 in the solid state.
Numbering follows the flavan convention. Average O4′-O7
distance is 2.77 Å, with an average O-H‚‚‚O angle of 156°.
The phenolic OH at 2′ hydrogen-bonds an ether of crystalliza-
tion.
(
We were fortunate to be able to grow single crystals of
both the “new” material and its triacetate derivative and
obtained X-ray structures of the two. On the basis of the
X-ray crystal structure of the product (Figure 1) it now
may be stated with certainty that the acid-catalyzed
reaction of resorcinol with acetone gives 5. Although the
crystal used in the X-ray work came from our serendipi-
tous synthesis, we could also prepare the identical
material more conventionally by reaction of acetone with
With regard to 10, the present MM2 and MM3 results
were not too different from ∆E ) -3.26 kcal/mol found
over two decades ago.17 The ab initio calculation for 10
appears “best” in the senses that (i) the sign is right, and
(ii) if one takes ∆E to be ∆H for the sake of discussion, a
∆
S of -4.7 eu would be required to produce the experi-
mental ∆G. This ∆S seems reasonable. By contrast,
PM3 gives the wrong sign and would demand ∆S ) +8.6
eu, which seems rather large.18
2 2
excess resorcinol in ether-CH Cl solvent containing 10%
aqueous HCl.
It is interesting that all calculations predict the axial
phenyl invertomer to be more prevalent in 11, with ring
oxygen, than in 10. Also, all calculations (save PM3)
predict more “a” invertomer in 13, with ring oxygen, than
in 12. The standard explanation of the 1.45 kcal/mol
CH /Ph geminal interaction is predicated on the interac-
3
tions of equatorial H’s at the 2 and 6 positions of
cyclohexane with the ortho H’s of equatorial Ph, as in i,
The crystal structure of 5 was not without a small
surprise, viz. that the 2,4-dihydroxyphenyl substituent
was pseudoaxial, as was the corresponding ring of
triacetate 9. On the basis of the A-values of phenyl and
methyl (2.87 and 1.74 kcal/mol, respectively),12 one might
have crudely predicted a 1.13 kcal/mol advantage for the
opposite invertomer. However, in the crystal, 5 is a
hydrogen-bonded dimer, as shown in Figure 2, and bears
a resemblance to Rebek’s “capsule” dimers.13 However,
why does the triacetate derivative, 9, also sport an axial
(14) Manoharan, M.; Eliel, E. L. J . Am. Chem. Soc. 1984, 106, 367-
372.
(15) Allinger, N. L.; Miller, M. A. J . Am. Chem. Soc. 1961, 83, 2145-
2146.
(
16) Eliel, E. L.; Manoharan, M. J . Org. Chem. 1981, 46, 1959-
1
962.
(
12) Bushweller, C. H. In Conformational Behavior of Six-Membered
(17) Allinger, N. L.; Tribble, M. T. Tetrahedron Lett. 1971, 3259-
3262.
(18) (a) Gundertofte, K.; Palm, J .; Pettersson, I.; Stamvik, A. J .
Rings. Analysis, Dynamics, and Stereoelectronic Effects; J uaristi, E.,
Ed.; VCH: New York, 1995; Chapter 2.
(
13) Vald e´ s, C.; Spitz, U. P.; Toledo, L. M.; Kubik, S. W.; Rebek, J .,
Comput. Chem. 1991, 12, 200-208 (b) Ferguson, D. M.; Glauser, W.
A.; Raber, D. J . J . Comput. Chem. 1989, 10, 903-910.
J r. J . Am. Chem. Soc. 1995, 117, 12733-12745.

Notes
entry
J . Org. Chem., Vol. 62, No. 3, 1997 739
sample of 7 was prepared following a literature method.21
Using concd HCl instead of 10% HCl gives a clean
reaction in only one case (entry 9). As one goes from
entry 10 to entry 15, “other” products, which we have
not attempted to identify, increase in number and
eventually predominate. A particularly striking example
of the effect of water concentration in the aqueous HCl
used is provided by entries 3 and 10. In the former case,
Ta ble 2. P r od u ct Distr ibu tion s
% of mixturea
initial conditions
A:R:HClb
HClc
5
7
Rb
others
1
2
3
4
5
6
7
8
9
1:6:2
1:6:1
1:3:1
1:2:1
1:1:1
2:1:1
3:1:1
6:1:1
1:6:1
1:3:1
1:2:1
1:1:1
2:1:1
3:1:1
6:1:1
2.2:1:1.6
3.8:1:1.1
d
d
d
d
d
d
d
d
c
c
c
c
c
c
c
e
f
93.0
99.8
99.0
99.4
49.8
6.9
17.4
22.5
99.6
9.1
28.3
14.8
20.9
18
11
23
3.9
-
3.1
0.2
0.2
0.6
10.8
26.2
21.2
3.8
0.4
4.5
-
21.1
7.9
3
1
2
-
-
0.7
-
-
-
29.5
58.7
48.6
13.5
-
72.7
53.7
47.3
17.8
10
9.9
7.3
12.8
60.2
-
5
is formed almost quantitatively, while in the latter, 7
is the major product. Entries 16 and 17 reproduced
4
a
literature reaction conditions reported to lead to 2 and
1
1
1
1
1
1
1
1
0
1
2
3
4
5
6
7
13.7
18.0
16.8
53.4
69
79
60
80
2
1
, respectively. These reactions in fact led to very
complex product mixtures. NMR spectra of the latter
product mixture strongly suggested oligomer or polymer
formation.
d
d
d
d
9
15
17
While we have not made any rigorous attempt to
determine the mechanism of the reaction of acetone with
excess resorcinol, we did find that mesityl oxide produces
3
-
a
From HPLC. b A ) acetone, R ) resorcinol. c c ) 36% HCl, d
5
when heated with HCl and excess resorcinol, correcting
)
10% HCl, e ) 5% HCl; reaction solvent water, f ) 36% HCl; no
reaction solvent. A multitude of peaks made integration less
trustworthy.
d
9
the earlier report that the product is 6. Therefore, a
mechanism for the acetone plus resorcinol reaction which
involves the intermediacy of mesityl oxide is not ruled
out. Interestingly, phorone and an excess of resorcinol
give 7, and in much better yield than the literature
procedure.21 It is tempting to speculate that yields of 5
and 7 in Table 2 are a reflection of how much mesityl
oxide vs phorone is formed by self-condensation of acetone
under the particular conditions of the reaction.
below.19 One might have thought replacing CH
with O,
2
as in ii, would relieve one of the interactions and thus
favor the “e” invertomer. However, ii has two C-O bonds
2
0
(
typically 1.441 Å) where i had two C-C bonds (typi-
20
cally 1.535 Å). This contraction of the ring dimensions,
we believe, magnifies the difference between CH /CH
,3-diaxial interaction and CH /Ph 1,3-diaxial interaction
with CH /CH worse) and accounts for the calculated
results. Introduction of the double bond (10 becoming
2, or 11 becoming 13) also contracts the ring dimensions
3
3
1
(
3
3
3
1
As might be expected, ketones other than acetone react
slightly and causes the ring to adopt a half-chair. The
proportion of “a” invertomer is always calculated to
decrease, which suggests the difference in 1,3-diaxial
interactions is diminished, probably as a result of the
adoption of the half-chair form.
with resorcinol to give products analogous to 5. Two
22
simple examples are cyclopentanone and cyclohexanone,
which give 14 and 15, respectively. The sole aliphatic
methine proton in each of these compounds is easy to
locate unambiguously using DEPT and C-H correlation
techniques, and each is free of overlap with adjacent
signals. The coupling constants are 7.9 and 11.2 Hz in
the case of the triacetate derivative of 14, and 4.2 and
2.1 Hz in the case of the triacetate derivative of 15. This
means the proton in question is axial or pseudoaxial,
which narrows the choice of the stereochemistry of the
We have examined the 13C-NMR spectrum of 9 at
temperatures down to -118 °C but were unable to “freeze
out” the invertomer equilibrium (although differential
broadening was observed). Taking 13 as the best ap-
proximation to 9, it is heartening to note that all methods
of calculation (except PM3) predict 13a to be favored,
which is consistent with the X-ray result.
1
The outcome of the reaction of acetone with resorcinol
depends on the mole ratio of reactants (see Table 2), and
even on whether 10% HCl or 36% HCl is used. Using
(
21) Liska, K. J . J . Med. Chem. 1972, 15, 1177-1179. The structure
is assigned incorrectly; however, the present spectroscopic evidence
leaves little doubt that the material is 7. Of critical importance is the
C chemical shift of the spiro carbon, 99.95 ppm, which may be
compared with the reported chemical shift of C2 of 2,2-dimethyl-1,3-
dioxane, 99.2 ppm (Riddell, F. G. J . Chem. Soc. B 1970, 331-333).
(
1991, Chem. Abstr. 1992 116, 204535b. (b) Nunomura, M.; Hashimoto,
M.; Kasuya, K.; Kato, K. J pn. patent J P 04,177,353, 1992, Chem. Abstr.
993, 118, 70166n. (c) Uetani, Y.; Nakanishi, H.; Doi, Y. PCT Int. Appl.
WO 92 12,205, 1992, Chem. Abstr. 1993, 118, 222901p. (d) Moritomo,
T.; Sugyama, Y.; Shiomi, H.; Saito, N.; Kanekawa, S. J pn. Patent J P
6,157,717, 1994, Chem. Abstr. 1994, 121, 207371j. (e) Hozumi, S.;
Kitayama, S.; Nakagawa, H. J pn patent J P 06,279,431, 1994, Chem.
Abstr. 1995, 122, 105673n. (f) Tomioka, A.; Kamyu, Y.; Nakanishi, H.;
Kuwana, K. J pn. Patent J P 06,236,030, 1994, Chem. Abstr. 1995, 122,
174432v. (g) Kamya, Y.; Tomioka, A.; Kuwana, K.; Nakanishi, H.;
Ueda, J . J pn. Patent J P 06,250,386, 1994, Chem. Abstr. 1995, 122,
174434x.
1
3
1
0% HCl, 5 is produced exclusively, provided there is an
excess of resorcinol (entries 1-4). At equimolar acetone
and resorcinol (entry 5) or with acetone in excess (entries
22) (a) Uetani, Y.; Nakanishi, H. PCT Int. Appl. WO 91 09,346,
6
-8), complex product mixtures are obtained. In certain
cases (entries 6 and 7), spirobichroman 7 is clearly the
major product, but in other cases (entry 8) at least eleven
other peaks aside from 5, 7, and resorcinol, roughly
comparable in area, could be discerned. An authentic
1
0
(
19) Eliel, E. L.; Wilen, S. H. Stereochemistry of Organic Compounds;
Wiley: New York, 1994; pp 705-706.
20) Allen, F. H.; Kennard, O.; Watson, D. G.; Brammer, L.; Orpen,
A. G.; Taylor, R. J . Chem. Soc., Perkin Trans 2 1987, S1-S19.
(

7
40 J . Org. Chem., Vol. 62, No. 3, 1997
Notes
in the freezer for 3 days. The precipitated solid, mp 182-203
°
C, was recrystallized twice from ether/hexane, mp 231-232 °C.
Anal. Calcd for C18
H, 6.71. HRMS: m/ z Calcd for C18
00.1367. MS (EI): m/ z (rel intens) 300(M ,13), 175(21), 163-
13), 151(100), 150(34), 137(15), 135(36), 123(27), 107(19), 91-
10), 79(12), 77(21), 69(12). 1H-NMR (CD
OD, 400 MHz): 8.248
H
20
O
4
: C, 71.98; H, 6.71. Found: C, 72.04;
20 4
H O
: 300.1362. Found:
+
3
(
(
(
(
3
s, 1H), 7.913 (s, 1H), 7.904 (s, 1H), 6.965 (d, J ) 8.5, 1H), 6.901
d, J ) 8.4, 1H), 6.297 (d, J ) 2.5, 1H), 6.225 (dd, J ) 8.4, 2.5,
1
H), 6.111 (d, J ) 2.4, 1H), 6.032 (dd, J ) 8.5, 2.4, 1H), 2.962
(d, J ) 13.8, 1H), 1.796 (d, J ) 13.8, 1H), 1.612 (s, 3H), 1.174 (s,
3
1
1
H), 0.748 (s, 3H). 13C-NMR (CD
3
CN, 62.9 MHz): 157.94 (quat),
57.05 (quat), 155.74 (quat), 154.24 (quat), 128.79 (CH, 2 C’s),
24.31 (quat), 123.90 (quat), 109.64 (CH), 107.48 (CH), 104.38
(
(
(
(
(
CH), 104.25 (CH), 79.37 (quat), 46.51 (CH
2 3
), 33.29 (CH ), 31.07
quat), 30.67 (CH ), 30.04 (CH ). IR (KBr): 3262(br,s), 2978-
3
3
m), 2899(m), 1622(s), 1592(m), 1518(m), 1503(s), 1443(s), 1383-
m), 1296(s), 1271(m), 1250(m), 1154(s), 1132(s), 1100(s), 1073-
-
1
m), 997(m), 980(s), 843(s), 804(m) cm
b) From Acetone and Resorcinol. A mixture of 2.063 g (18.74
mmol) of resorcinol, 0.362 g (6.23 mmol) of acetone, 2.0 mL of
0% aqueous HCl, 30 mL of ether, and 30 mL of CH Cl was
.
(
1
2
2
stirred and refluxed 12 h. After removal of solvents, addition
of water afforded a precipitate, which was collected and washed
repeatedly with water. After oven-drying, 0.826 g of 5 was
obtained (88% yield), 97% pure by HPLC, and spectroscopically
identical to the material described above.
ring junction. As shown, molecular mechanics calcula-
tions23 suggest the cis ring junction for both 14 and 15.
(
c) From Mesityl Oxide and Resorcinol. A mixture of 2.940 g
26.70 mmol) of resorcinol, 0.436 g (4.45 mmol) of mesityl oxide,
.5 mL of 10% aqueous HCl, 35 mL of ether, and 35 mL of CH
Cl was stirred and refluxed 12 h. Workup was as in part (b),
(
1
2
-
2
giving 1.215 g (91%) of 5, spectroscopically identical to the
material described above.
Cr ysta l Str u ctu r e of 5.24 A clear plate, 0.60 × 0.55 × 0.25
mm, was mounted on a Siemens R3m/V diffractometer, using
Mo KR radiation (λ ) 0.71073 Å). Twenty-four reflections in
the range 7.3 < θ < 14.5° were used for determination of lattice
parameters. Triclinic, a ) 7.9250(10) Å, b ) 11.585(2) Å, c )
1
1.963(2) Å, R ) 81.760(10)°, â ) 78.940(10)°, γ ) 86.410(10)°,
3
V ) 1066.1(3) Å , Z ) 2. Space group P 1h . 4073 reflections (3782
independent reflections) were collected in the range 3.5 < 2θ <
5
0.0; 0 e h e 9, -13 e k e 13, -13 e l e 14, of which 2733
were considered (F > 4.0σ(F)) observed. Two standard reflec-
tions were measured every 100 reflections. An empirical
absorption correction based on ψ scans was applied; transmission
varied between 0.940 and 0.906.
The structure was solved via direct methods using SHELXTL
PLUS. Full matrix least squares refinement on F led to R )
4
.74%, wR ) 7.11% (observed data), R ) 6.66%, wR ) 7.73%
Finally, we have found that the reaction of resorcinol
with mesityl oxide is not an isolated instance: other R,â-
unsaturated ketones undergo the analogous reaction with
resorcinol. For example, 2-cyclohexenone reacts with
resorcinol to give 16. Investigation of the reaction of
resorcinol with other R,â-unsaturated ketones is in
progress and will be reported shortly.
-1
2
2
(
all data), w ) σ (F) + 0.0017F . Goodness of fit 1.38. A riding,
isotropic H model was used. Data-to-parameter ratio 11.2.
Largest ∆/σ 0.003; mean ∆/σ 0.001. Largest peak/hole in final
difference map: 0.22/-0.28 e Å
-
3
.
2
,2′-Sp ir obi(7-h yd r oxy-4,4-d im eth ylch r om a n ), 7. (a) Pre-
2
0
pared by the method of Liska with a few minor modifications:
the reaction was refluxed 12 h instead of 5 h, the benzene phase
was dried over Na
ethanol, the black residue was partitioned between water and
CH Cl twice, the combined CH Cl phase was washed twice
with water, dried over Na SO , and filtered, and CH Cl was
removed to afford additional crude product. Yield after two
2 4
SO rather than dried azeotropically with
2
2
2
2
2
4
2
2
2
0
recrystallizations from CHCl
00 °C). Anal. Calcd for C21
C, 73.96; H, 7.17. HRMS: m/ z Calcd for C21
Found: 340.16748. MS (EI): m/ z (rel intens) 340(M , 4), 325-
3
55%, mp 200-201 °C (lit. 199-
: C, 74.09; H, 7.11. Found:
: 340.16746.
2
24 4
H O
24 4
H O
+
(
6), 176(9), 175(75), 155(17), 152(10), 151(100), 123(14), 77(12).
1
H-NMR (CD
3 3
COCD , 250 MHz): 7.169 (d, J ) 8.5, 1H), 6.437
(
1
dd, J ) 8.5, 2.5, 1H), 6.094 (d, J ) 2.5, 1H), 2.078 (d, J ) 14.1,
1
3
H), 1.938 (d, J ) 14.1, 1H), 1.534 (s, 3H), 1.295 (s, 3H). C-
COCD , 63 MHz): 157.20 (quat), 152.18 (quat), 127.98
Exp er im en ta l Section
NMR (CD
3
3
4
-(3,4-Dih yd r o-7-h yd r oxy-2,4,4-tr im eth yl-2H-1-ben zop y-
(CH), 123.47 (quat), 110.19 (CH), 104.55 (CH), 99.95 (quat), 47.38
(CH ), 32.96 (CH ), 32.73 (CH ), 30.93 (quat).
r a n -2-yl)-1,3-ben zen ed iol, 5. (a) Serendipitous. A mixture of
impure resorcinol and acetone was heated to boiling and
chloroform added to the cloud point. The mixture was stored
2
3
3
(24) The author has deposited atomic coordinates for this structure
have been deposited with the Cambridge Crystallographic Data Centre.
The coordinates can be obtained, on request, from the Director,
Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge,
CB2 1EZ, UK.
(
23) PCMODEL for Windows, Serena Software, 1993. Coupling
constants predicted by this software for 14 are J ) 7.8, 9.9 Hz and for
5 are J ) 3.9, 12.3 Hz.
1

Notes
J . Org. Chem., Vol. 62, No. 3, 1997 741
(
b) From Phorone and Resorcinol. A mixture of 0.675 g (4.88
Cr ysta l Str u ctu r e of 9.24 A clear truncated plate 0.26 ×
0.40 × 0.55 mm was selected. Twenty-four reflections in the
range 7.0 < θ < 15.0° gave a monoclinic cell, a ) 9.563(5) Å, b
mmol) of 2,6-dimethyl-2,5-heptadien-4-one, 3.226 g of resorcinol
(
2
29.30 mmol), 1.8 mL of 10% aqueous HCl, 20 mL of ether, and
0 mL of CH Cl was stirred and refluxed 24 h. After removal
of solvent, the mixture was poured into 100 mL of water,
extracted twice with 60 mL CH Cl
, washed with 3 × 60 mL
water, and dried over Na SO . Filtration and removal of solvent
gave 1.372 g (85%) of 7, mp 199-200 °C. Using the method
employed for preparing 9 (see below), the diacetate derivative
of 7 was prepared, 95% yield, recrystallized from EtOAc/hexanes,
3
2
2
) 15.014(8) Å, c ) 16.458(7) Å, â ) 105.84(4)°, V ) 2273(2) Å ,
P2 /n, Z ) 4 using a Siemens R3m/V diffractometer and Mo KR
1
2
2
radiation (λ ) 0.71073 Å). An amount of 4465 reflections (4029
independent reflections) were collected, 3.5 e 2θ e 50.0°, 0 e h
e 11, 0 e k e 17, -19 e l e 18, of which 2176 were considered
observed (F > 4.0σ(F)). Two standard reflections were measured
every 100 reflections. An empirical absorption correction based
on ψ scans was applied; transmission varied between 0.936 and
0.890. Structure solution and refinement were carried out as
2
4
mp 194-195 °C. Anal. Calcd for C25
Found: C, 70.65; H, 6.69. HRMS: m/ z Calcd for C25
24.1886. Found: 424.1881. MS (EI): m/ z (rel intens) 424-
28 6
H O : C, 70.74; H, 6.65.
28 6
H O :
-
1
2
2
4
(
(
7
2
1
(
1
3
for 5; however w ) σ (F) + 0.0008F , and data-to-parameter
ratio was 7.8. Final R ) 5.14%, wR ) 6.23% (observed data), R
) 10.24%, wR ) 7.29% (all data), goodness of fit 1.42. Largest
∆/σ 0.002; mean ∆/σ 0.000. Largest peak/hole in final difference
+
M , 6), 409(33), 382(10), 367(17), 217(43), 193(25), 190(12), 175-
1
45), 151(72), 77(10), 43(100). H-NMR (CD
3
CN, 250 MHz):
.404 (d, J ) 8.5, 1H), 6.697 (dd, J ) 2.2, 8.5, 1H), 6.382 (d, J )
.2, 1H), 2.155 (s, 3H), 2.150 and 2.055 (AB quartet, J ) 14.3),
.582 (s, 3H), 1.343 (s, 3H). 13C-NMR (CD
CN, 63 MHz): 170.84
-
3
map: 0.21/-0.17 e Å
.
3
2′,4′,7-Tr ih yd r oxy-2,3-p r op a n ofla va n -4-sp ir ocyclop en -
ta n e, 14. A mixture of 1.011 g (12.02 mmol) of cyclopentanone,
3.965 g (36.01 mmol) of resorcinol, 4.4 mL of 10% aqueous HCl,
35 mL of ether, and 35 mL of CH Cl was stirred and refluxed
CdO), 152.05 (quat), 151.07 (quat), 130.76 (quat), 128.90 (CH),
16.67 (CH), 111.87 (CH), 99.92 (quat), 46.92 (CH
2.86 (CH ), 31.68 (quat), 21.55 (CH ).
,3-Dim eth oxy-4-(3,4-dih ydr o-7-m eth oxy-2,4,4-tr im eth yl-
H-1-ben zop yr a n -2-yl)ben zen e, 8. A mixture of 0.510 g (1.70
2 3
), 33.04 (CH ),
3
3
2
2
1
24 h. Solvents were removed, and the mixture was poured into
100 mL of water and taken up into 3 × 50 mL of CH Cl . The
organic phase was washed with water 3 × 50 mL, dried over
Na SO , and filtered and solvent removed to afford 1.423 g of
crude 14. HRMS: m/ z Calcd for C22 : 352.1675. Found:
2
2
2
mmol) of 5, 0.790 g (5.57 mmol) of methyl iodide, 2.0 g (14 mmol)
of K CO , and 20 mL of acetone was stirred and refluxed 12 h.
2
3
2
4
Acetone and excess methyl iodide were removed on the rotary
evaporator, 70 mL of water was added, and the mixture was
extracted with 3 × 40 mL of ether. The ether extracts were dried
24 4
H O
+
352.1681. MS (EI): m/ z (rel intens) 352(M ,8), 190(11), 177-
(100), 176(71), 175(27), 161(24), 159(11), 149(21), 147(32), 123-
(51), 115(10), 107(10), 91(17), 84(15), 77(17), 69(15), 67(10),
65(10), 56(13), 55(44), 43(15). Since 14 was difficult to purify
satisfactorily, its triacetate derivative was prepared using the
procedure to make 9, mp 162-163.5 °C, after recrystallization
from EtOAc/hexanes and drying under vacuum, 92% yield.
2 4
over Na SO and filtered, and the solvent was removed. The
solid residue was recrystallized from ether/hexane to afford 0.540
g of 8 (93%), mp 102-103 °C. Anal. Calcd for C21 : C,
3.66; H, 7.65. Found: C, 73.56; H, 7.68. HRMS: m/ z Calcd
for C21 : 342.1831. Found: 342.1835. MS (EI): m/ z (rel
intens) 342(M ,18), 189(18), 178(49), 165(52), 164(15), 163(100),
26 4
H O
7
26 4
H O
+
HRMS: m/ z Calcd for C28
MS (EI): m/ z (rel intens) 478(M ,5), 436(11), 219(37), 218(49),
30 7
H O : 478.19915. Found: 478.19919.
+
1
4
49(24), 135(35), 121(15), 91(18), 77(20), 59(20), 57(25), 56(20),
3(52), 41(32), 29(19), 27(17), 15(34). H-NMR (CD
1
3
CN, 250
201(15), 178(10), 177(82), 176(100), 175(21), 161(15), 149(11),
1
MHz): 7.13 (d, J ) 8.6, 1H), 7.07 (d, J ) 8.5, 1H), 6.51 (d, J )
.6, 1H), 6.49 (d, J ) 2.5, 1H), 6.45 (dd, J ) 8.5, 2.6, 1H), 6.32
dd, J ) 8.6, 2.5, 1H), 3.83 (s, 3H), 3.77 (s, 3H), 3.71 (s, 3H),
.95 (d, J ) 14.0, 1H), 1.87 (d, J ) 14.0, 1H), 1.61 (s, 3H), 1.19
s, 3H), 0.63 (s, 3H). C-NMR (CD
60.10 (quat), 158.68 (quat), 154.72 (quat), 128.64 (CH), 128.31
CH), 126.63 (quat), 124.85 (quat), 108.32 (CH), 104.94 (CH),
02.77 (CH), 100.25 (CH), 78.79 (quat), 55.96 (CH , 3 C’s), 46.61
CH ), 33.31 (CH ), 31.12 (quat), 30.42 (CH ), 30.06 (CH ). IR:
147(21), 123(36), 43(79) H-NMR (CDCl
3
, 400 MHz): 7.547 (d,
2
(
2
(
1
(
1
(
J ) 8.7, 1H), 7.051 (d, J ) 8.5, 1H), 6.940 (d, J ) 2.3, 1H), 6.882
(dd, J ) 2.3, 8.7, 1H), 6.730 (d, J ) 2.3, 1H), 6.623 (dd, J ) 2.4,
8.5, 1H), 2.765 (dd, J ) 7.9, 11.2, 1H), 2.346 (s, 3H), 2.298 (s,
3H), 2.254 (s, 3H), 2.309 (m, 1H), 2.125 (m, 1H), 2.00-1.46 (m,
1
3
3
CN, 63 MHz): 161.18 (quat),
10H), 1.15-0.98 (m, 2H) 13C-NMR (CDCl
, 63 MHz, proton
3
correlations from C-H correlation spectrum): 169.41 (CdO),
168.81 (CdO), 168.28 (C)O), 152.74 (quat), 149.62 (quat), 149.54
(quat), 146.79 (quat), 132.96 (quat), 128.56 (CH, 7.55), 127.69
(CH, 7.05), 127.14 (quat), 118.66 (CH, 6.88), 116.88 (CH, 6.94),
113.66 (CH, 6.62), 109.44 (CH, 6.73), 87.17 (quat), 51.04 (CH,
3
2
3
3
3
1
1
8
617(s), 1582(s), 1505(s), 1466(m), 1443(m), 1414(m), 1256(s),
204(s), 1165(s), 1132(m), 1113(m), 1065(m), 1032(m), 988(m),
-
1
37(m) cm
,3-Dia cetoxy-4-(3,4-d ih yd r o-7-a cetoxy-2,4,4-tr im eth yl-
H-1-ben zop yr a n -2-yl)ben zen e, 9. A 0.603 g (2.01 mmol)
.
2.77), 44.74 (quat), 41.53 (two CH
2
s, 0.98, 1.11, 2.12, 2.31), 38.84
, 1.50, 1.93), 24.48 (CH , 1.54), 24.34
, 1.72, 1.85), 21.36 (CH ), 21.16 (CH ),
1
(CH
(CH
2
, 1.56, 1.94), 28.81 (CH
, 1.73), 21.75 (CH
).
2
2
2
2
2
3
3
amount of 5 and 10 mL of dry pyridine were placed in a 25 mL
three-necked round-bottom flask fitted with a thermometer,
condenser, addition funnel, and magnetic stir bar. Acetic
anhydride (3.246 g, 31.8 mmol) was added dropwise to the stirred
solution, and the reaction mixture was stirred at 40-50 °C for
21.09 (CH
3
2,3-Bu t a n o-2′,4′,7-t r ih yd r oxyfla va n -4-sp ir ocycloh e x-
a n e, 15. The procedure used to prepare 14 was used. A 0.620
g (6.32 mmol) amount of cyclohexanone, 2.085 g (18.94 mmol)
of resorcinol, 2.3 mL of 10% aqueous HCl, 20 mL each of ether
1
.5 h. After allowing to cool to room temperature, the mixture
and CH
mp 219-221 °C, after vacuum drying. HRMS: m/ z Calcd for
380.1988. Found: 380.1987. MS (EI): m/ z (rel
2 2
Cl , reflux 24 h. A 1.182 g amount of crude product,
was poured onto 60 mL ice-water whereupon a precipitate
formed. This was collected by filtration, recrystallized from ethyl
acetate/hexane, and dried in vacuo, giving 0.710 g of 9, mp 127-
30 °C (83%). One further recrystallization provided an analyti-
cally pure sample, mp 129-130 °C. Anal. Calcd for C24
C, 67.59; H, 6.15. Found: C, 67.59; H, 6.12. HRMS: m/ z Calcd
for C24 : 426.1679. Found: 426.1686. MS (EI): m/ z (rel
intens) 426(M ,5), 384(4), 193(12), 192(11), 175(13), 163(26), 151-
49), 150(88) 137(21), 135(22), 123(12), 107(12), 77(11), 43(100),
24 28 4
C H O :
+
intens) 380(M ,10), 309(10), 191(65), 190(81), 175(20), 162(26),
161(51), 147(44), 123(100), 115(12), 91(15), 81(11), 69(14), 55-
(14). Since 15 was difficult to purify satisfactorily, its triacetate
derivative was prepared using the procedure to make 9, mp 200-
201 °C, after recrystallization from EtOAc/hexanes, 91% yield.
1
26 7
H O :
26 7
H O
+
Anal. Calcd for C30
H, 6.81. HRMS: m/ z Calcd for C30
506.229. MS (EI): m/ z (rel intens) 507(12), 506(M ,12), 464-
H
34
O
7
: C, 71.13; H, 6.77. Found: C, 71.03;
: 506.230. Found:
(
34 7
H O
1
+
1
1
3
2
5(33). H-NMR (CD
3
CN, 250 MHz): 0.76 (s, 3H), 1.30 (s, 3H),
.61 (s, 3H), 2.10 (d, J ) 14.4), 2.20 (s, 3H), 2.24 (s, 3H), 2.34 (s,
H), 2.67 (d, J ) 14.4), 6.65 (dd, J ) 8.5, 2.4, 1H), 6.72 (d, J )
.4, 1H), 6.86 (dd, J ) 8.6, 2.4, 1H), 6.92 (d, J ) 2.3, 1H), 7.25
d, J ) 8.5, 1H), 7.41 (d, J ) 8.6, 1H). C-NMR (CD
MHz): 170.55 (quat), 170.22 (quat), 169.94 (quat), 153.69 (quat),
51.07 (quat, 2 Cs), 148.76 (quat), 135.43 (quat), 129.97 (quat),
28.57 (CH, 2 Cs), 120.13 (CH), 118.76 (CH), 115.71 (CH), 111.53
CH), 78.51 (quat), 46.89 (CH
(11), 274(11), 233(69), 232(67), 191(100), 189(79), 187(11), 175-
(20), 173(13), 165(10), 162(21), 161(45), 149(10), 147(31), 123(65),
1
91(10), 44(22), 43(75) H-NMR (CDCl
3
, 400 MHz): 7.294 (d, J
1
3
(
3
CN, 63
) 8.8, 1H), 7.159 (d, J ) 8.6, 1H), 6.949 (d, J ) 2.3, 1H), 6.789
(dd, J ) 2.3, 8.8, 1H), 6.770 (d, J ) 2.5, 1H), 6.631 (dd, J ) 2.5,
8.6, 1H), 3.134 (dd, J ) 4.2, 12.1, 1H), 2.413 (s, 3H), 2.298 (s,
3H), 2.224 (s, 3H), 1.90-1.52 (m, 11H), 1.48-1.15 (m, 5H), 0.99-
1
1
(
1
3
2
), 32.70 (CH
3
), 31.47 (quat), 30.91
), 21.27 (CH ). IR:
0.75 (m, 2H).
3
C-NMR (CDCl , 63 MHz, proton correlations
(
CH
3
), 31.30 (CH
3
), 21.85 (CH
3
), 21.34 (CH
3
3
from C-H correlation spectrum): 169.36 (CdO), 168.63 (CdO),
168.03 (CdO), 152.83 (quat), 149.45 (quat), 149.28 (quat), 146.85
(quat), 135.86 (quat), 128.00 (quat), 127.74 (CH, 7.16), 127.44
(CH, 7.29), 118.92 (CH, 6.78), 116.90 (CH, 6.95), 113.95 (CH,
1
1
9
763(vs), 1611(s), 1590(s), 1497(s), 1422(s), 1372(s), 1312(m),
215(br, s), 1148(s), 1129(s), 1103(s), 1059(s), 1017(s), 974(m),
03(s), 856(w), 814(w) cm-1
.

7
42 J . Org. Chem., Vol. 62, No. 3, 1997
Notes
6
.63), 109.44 (CH, 6.77), 79.42 (quat), 39.56 (CH
2
, 0.84), 39.38
(CH), 105.05 (CH), 102.64 (CH), 81.84 (quat; C2), 39.44 (CH
2
;
(
CH
2
, 1.84), 38.24 (quat), 35.65 (CH
6.27 (CH , 1.30, 1.86), 26.13 (CH , 1.21, 1.69), 24.76 (CH
.80), 22.25 (CH , 1.40, 1.62), 21.81 (CH , 1.20, 1.58), 21.74 (CH
.40), 21.42 (CH , 1.60), 21.18 (CH , 2.30), 21.07 (CH , 2.20).
′,4′,7-Tr ih yd r oxy-2,4-p r op a n ofla va n , 16. A mixture of
.272 g (2.83 mmol) of 2-cyclohexenone, 1.825 g (16.57 mmol) of
2
, 1.75), 35.42 (CH, 3.13),
C9), 34.81 (CH ; C3), 33.29 (CH ; C11), 32.81 (CH; C4), 19.30
2
2
2
1
2
2
2
2
, 1.17,
(CH ; C10). The triacetate derivative of 16 was prepared as
2
2
2
3
,
before, mp 145-146 °C, 91% yield. Anal. Calcd for C24H24O7:
C, 67.91; H, 5.70. Found: C, 67.89; H, 5.71. HRMS: m/ z Calcd
2
3
3
2
for C24
H
24
O
7
: 424.1522. Found: 424.1524. MS (EI): m/ z (rel
0
+
intens) 424(M ,8), 382(11), 381(14), 365(15), 340(12), 339(15),
resorcinol, 1 mL of 10% aq HCl, 15 mL of ether, and 15 mL of
CH Cl was stirred and refluxed 12 h. After removing solvent
at the rotary evaporator, the residue was taken up in 80 mL of
water and extracted with 3 × 30 mL of CH Cl . The combined
CH Cl
extracts were washed with 2 × 40 mL water, dried over
Na SO , and filtered, and the solvent was removed to afford
.711 g (87%) of a colorless solid. This was subjected to silica
3
23(12),297(15), 255(16), 188(16), 187(11), 176(13), 175(14), 162-
2
2
1
(
14), 161(20), 149(20), 147(22), 136(44), 123(51), 43(100). H-
NMR (CD CN, 250 MHz): 7.589 (d, J ) 8.6, 1H), 7.099 (d, J )
.1, 1H), 7.023 (dd, J ) 2.4, 8.6, 1H), 6.881 (d, J ) 2.4, 1H),
.579 (dd, J ) 2.3, 8.1, 1H), 6.463 (d, J ) 2.3, 1H), 3.19 (m, 1H),
3
2
2
8
6
2
2
2
2
4
1
3
.4-1.4 (m), 2.244 (s, 3H), 2.215 (s, 3H), 2.026 (s, 3H). C-NMR
CN, 63 MHz): 170.61 (CdO), 170.36 (CdO), 170.17 (CdO),
57.45 (quat), 151.53 (quat), 151.38 (quat), 150.32 (quat), 135.72
0
(CD
3
gel chromatography (ethyl acetate:hexanes 30:70) followed by
drying at 110 °C under vacuum to give 608 mg (72%) analytically
1
(quat), 129.72 (CH), 128.34 (CH), 125.27 (quat), 120.12 (CH),
pure 16, mp 190-191 °C. Anal. Calcd for C18
H, 6.08. Found: C, 72.40; H, 6.13. HRMS: m/ z Calcd for
298.1205. Found: 298.1202. MS (EI): m/ z (rel
18 4
H O : C, 72.47;
1
3
19.53 (CH), 114.16 (CH), 109.50 (CH), 78.80 (quat), 38.25 (CH
2
),
),
4.44 (CH
2
), 33.42 (CH), 21.56 (CH
)
3 3
), 21.34 (CH ), 21.31 (CH
3
18 18 4
C H O :
+
19.25 (CH
2
intens) 298(M ,45), 255(66), 188(36), 176(41), 175(35), 162(30),
1
1
61(58), 160(25), 149(43), 148(23), 147(63), 136(99), 123(100),
Ta ble 2. Resorcinol, acetone, and HCl (10% or 36%) were
stirred and refluxed in a mixture of 2 mL of ether and 2 mL of
1
15(22), 107(26), 91(29), 77(47), 69(34), 65(23). H-NMR (CD
3
-
OD, 400 MHz; assignments from COSY and C-H correlation
2 2
CH Cl for 12 h. The reaction mixture was poured into 50 mL
spectra): 1.510 (m, 2H; H10a and H10e), 1.658 (m, 1H; H11e),
of H O, and the precipitate thus formed was collected by
2
1
2
.792 (m, 1H; H11a), 1.858 (m, 1H; H3e), 2.008 (m, 1H; H9e),
.251 (m, 1H; H9a), 2.692 (dd J ) 13.0, 2.9, 1H; H3a), 3.011
filtration, washed thoroughly with water, and dried at 80 °C
overnight. The product mixtures were analyzed by HPLC on a
C18 column using acetonitrile:water 65:35, with UV detection
at 280 nm. Integration of the chromatogram of a weighed
mixture of 5 and 7 gave areas within 1% of the actual mole
fractions.
(
6
approximately quintet J ) 3.2, 1H; H4), 6.27-6.34 (m, 4H),
.820 (d J ) 8.1, 1H; H5 or H6′), 7.245 (d J ) 9.2, 1H; H6′ or
H5). The COSY revealed several long-range couplings: H3e/
H9e, H3e/H11e, H9e/H11e. C-NMR (CD
1
3
3
CN, 63 MHz): 158.42
(quat), 157.45 (quat), 157.00 (quat), 156.65 (quat), 129.91 (CH),
1
27.54 (CH), 123.62 (quat), 119.25 (quat), 108.84 (CH), 107.76
J O961647Y