Superacid-Catalyzed Reductive Friedel-Crafts Reaction of Arenes Using Arenecarbaldehyde Acetals

Article abstract of DOI:10.1021/jo961897e

Reaction of 2-aryl-1,3-dioxane with arenes in the presence of a catalytic amount of trifluoromethane-sulfonic acid gave the corresponding diarylmethanes in good to excellent yields. The acid-catalyzed Friedel-Crafts benzylation of arenes could altenatively be carried out using arenecarbaldehyde and 1,3-propanediol. The reaction was assumed to proceed through a redox process involving hydride shift from the cyclic acetal moiety to the benzylic carbon. The hydride shift was confirmed by the reaction with 5-ethyl-2-phenyl-4,4,6,6-tetradeuterio-1,3-dioxane, wherein more than 90% deuterium was incorporated into the benzylic carbon of the diphenylmethane. Diphenylmethyl ether Ph₂CHOCH₂CH₂CH₂OH also reacted with benzene to afford diphenylmethane under the same reaction conditions, suggesting that the ether should be the plausible intermediate that underwent the hydride shift.

Full text of DOI:10.1021/jo961897e

J . Org. Chem. 1997, 62, 151-156
151
Su p er a cid -Ca ta lyzed Red u ctive F r ied el-Cr a fts Rea ction of Ar en es
Usin g Ar en eca r ba ld eh yd e Aceta ls
Shin-ichi Fukuzawa,*,† Teruhisa Tsuchimoto,‡ and Tamejiro Hiyama‡
Department of Applied Chemistry, Chuo University, Kasuga, Bunkyo-ku, Tokyo 112, J apan,
and Research Laboratory of Resources Utilization, Tokyo Institute of Technology, 4259 Nagatsuda,
Midori-ku, Yokohama 226, J apan
Received October 8, 1996X
Reaction of 2-aryl-1,3-dioxane with arenes in the presence of a catalytic amount of trifluoromethane-
sulfonic acid gave the corresponding diarylmethanes in good to excellent yields. The acid-catalyzed
Friedel-Crafts benzylation of arenes could altenatively be carried out using arenecarbaldehyde
and 1,3-propanediol. The reaction was assumed to proceed through a redox process involving
hydride shift from the cyclic acetal moiety to the benzylic carbon. The hydride shift was confirmed
by the reaction with 5-ethyl-2-phenyl-4,4,6,6-tetradeuterio-1,3-dioxane, wherein more than 90%
deuterium was incorporated into the benzylic carbon of the diphenylmethane. Diphenylmethyl
ether Ph2CHOCH2CH2CH2OH also reacted with benzene to afford diphenylmethane under the same
reaction conditions, suggesting that the ether should be the plausible intermediate that underwent
the hydride shift.
In tr od u ction
Resu lts a n d Discu ssion
Rea ction of Ben za ld eh yd e Aceta ls w ith Ben zen e
in th e P r esen ce of TF SA. When a solution of 2-phenyl-
1,3-dioxane in benzene was heated to reflux for 10 h in
the presence of a catalytic amount of TFSA (5 mol % to
the acetal), diphenylmethane was isolated in good yields
(Scheme 1, R ) H, n ) 1).7 It is worth noting that the
benzylation reaction took place with a redox process, and
no triphenylmethane, triphenylmethanol, or anthracene
was produced in sharp contrast to the FC reaction of
benzaldehyde with benzene. Lewis acids like AlCl3,
TiCl4, ZnCl2, and BF3‚Et2O were totally inactive except
It has been reported that the Friedel-Crafts (FC)
reaction of arenecarbaldehydes with arenes under highly
acidic conditions gives a complex mixture of products like
triarylmethane, triarylmethanol, diarylmethane, and an-
thracene derivatives.1 The mechanism of this reaction
has recently been studied independently by Shudo2 and
Olah,3 and the product distribution was found to depend
on the reaction conditions: triphenylmethane was ex-
clusively produced when a large excess amount of tri-
fluoromethanesulfonic acid (TFSA)4 (100 equiv to ben-
zaldehyde) was employed as the acid catalyst.3 However,
this type of FC reaction has eluded synthetic interest
because of the need for a large excess amount of TFSA
and the production of a complex mixture of products.
8
for Sc(OTf)3 and SnCl4. The use of such Brønsted acids
as CF3COOH and H2SO4 resulted in the production of a
trace amount of diphenylmethane. We applied the above
reaction conditions to 2-phenyl-1,3-dioxolane, 2-phenyl-
1,3-dioxepane, and 2-phenyl-4,6-dimethyl-1,3-dioxane.
The results are summarized in Table 1. 2-Phenyl-4,6-
dimethyl-1,3-dioxane similarly reacted with benzene to
give diphenylmethane in 51% yield (Table 1, run 2), but
the reaction with 4,4,6,6-tetramethyl-1,3-dioxane (Table
1, run 3) did not produce diphenylmethane. Starting
with 2-phenyl-1,3-dioxolane (Table 1, run 4), diphenyl-
methane was again obtained in 48% yield, but 2-phenyl-
1,3-dioxepane (Table 1, run 5) afforded only a trace
amount of the product. With dimethyl acetal, diisopropyl
acetal, or dibutyl acetal of benzaldehyde, no or a small
amount of the product formed, benzaldehyde being the
main product (Table 1, runs 6-8).
To the best of our knowledge, the synthetically useful
FC reaction using an acetal as an electrophile has never
been reported except for the gallium(II) dichloride-
promoted reactions to give diarylmethane derivatives.5
During the study of the activation of acetals by lanthani-
de(III) triflate,6 we have coincidentally found that TFSA
also effectively catalyzed the reductive FC reaction of
arenecarbaldehyde cyclic acetals with arenes to produce
diarylmethanes as the sole products. We report here the
details of the acid-catalyzed reductive FC reaction using
an acetal as the electrophile. We also discuss the
mechanism of the reaction.
Rea ction of 2-Ar yl-1,3-d ioxa n es w ith Ar en es. As
described above, 1,3-dioxane derivatives were found to
be a suitable electrophile for the reductive FC reaction.
Table 2 shows the results of the TFSA-catalyzed reduc-
tive FC reaction of various 2-aryl-1,3-dioxanes with
representative arenes. The reaction was carried out in
arene as a solvent when its boiling point was relatively
† Chuo University.
‡ Tokyo Institute of Technology.
X Abstract published in Advance ACS Abstracts, December 15, 1996.
(1) Roberts, R. M.; El-Khawaga, A. M.; Sweeney, K. M.; El-Zohry,
M. F. J . Org. Chem. 1987, 52, 1591.
(2) Saito, S.; Ohwada, T.; Shudo, K. J . Am. Chem. Soc. 1995, 117,
11081.
(3) Olah, G. A.; Rasul, G.; York, C.; Prakash, G. K. J . Am. Chem.
Soc. 1995, 117, 11211.
(4) TFSA is defined as the superacid by Olah et al. See: Olah, G.
A.; Prakash, G. K. S.; Sommer, J . Science 1979, 206, 13.
(5) Hashimoto, Y.; Hirata, K.; Kagoshima, H.; Kihara, N.; Hasegwa,
M, Saigo, K. Tetrahedron 1993, 27, 5969; Tetrahedron Lett. 1992, 42,
6351.
(6) Fukuzawa, S.; Tsuchimoto, T.; Hotaka, T.; Hiyama, T. Synlett
1995, 1077.
(7) When the reaction was performed under Olah’s conditions, i.e.,
adding 100 equiv of TFSA to the acetal, the reaction product was a
complex mixture of compounds including diphenylmethane, triphenyl-
methanol, triphenylmethane, anthracene, etc.
(8) Tsuchimoto, T.; Hiyama, T.; Fukuzawa, S. J . Chem. Soc., Chem.
Commun. 1996, 2345.
S0022-3263(96)01897-X CCC: $14.00 © 1997 American Chemical Society

152 J . Org. Chem., Vol. 62, No. 1, 1997
Fukuzawa et al.
Sch em e 1
deactivated arenecarbaldehyde acetals as 4-chloro-, 4-flu-
oro-, or 4-nitrophenyl acetals.10 Figure 1 illustrates time-
dependent formation of diarylmethanes in the reaction
of 2-(4-methylphenyl)-, 2-phenyl-, and 2-(4-chlorophenyl)-
1,3-dioxane with benzene. The reactivity order is con-
sistent with the mechanism involving a benzylic cationic
intermediate. When 2-cyclohexyl-1,3-dioxane was em-
ployed instead of 2-aryl-1,3-dioxane for the reaction with
p-xylene, the desired cyclohexyldimethylbenzene was not
obtained and polymeric material formed. With 2-phenyl-
2-methyl-1,3-dioxane, only trace amounts of alkylated
products were detected along with several unidentified
products.11
Ta ble 1. TF SA-Ca ta lyzed Rea ction s of Ben za ld eh yd e
Aceta ls w ith Ben zen ea
Rea ction of Ar en eca r ba ld eh yd es w ith Ar en es in
th e P r esen ce of 1,3-P r op a n ed iol. Since acetalization
takes place under acidic conditions, we considered that
the reductive FC benzylation reaction should be possible
starting with arenecarbaldehyde and 1,3-propanediol.
Actually, the acid-catalyzed benzylation of benzene using
benzaldehyde and 1,3-propanediol cleanly proceeded to
give diphenylmethane in accord with the reaction of
2-phenyl-1,3-dioxane. Thus, the reaction should involve
the acid-catalyzed acetalization of benzaldehyde for the
first step. The acetal formation was confirmed by the
reaction of benzaldehyde with 1,3-propanediol in dichlo-
romethane. In the absence of 1,3-propanediol, no reac-
tion took place. Table 3 summarizes the reaction of
various arenecarbaldehydes with some arenes in the
presence of 1,3-propanediol. As readily seen, each reac-
tion gave the corresponding diarylmethane(s) in good to
excellent yields. The reaction has an advantage that
preparation of acetals is not needed. The isomer ratios
were virtually the same as those observed for the reaction
with the acetals.
Rea ction Mech a n ism . The reductive FC reaction
with acetals should involve a redox process. Without a
redox process, the expected products would be triphenyl-
methane and/or diphenylmethyl ether.12 Thus, the ques-
tion arises of where the hydride comes from. Since no
triarylmethanol or triarylmethane could be isolated and
a redox process should not occur between triarylmethane
and diarylmethyl cation,13 involvement of diarylmethyl
cation is not likely. We attribute that to the hydride
source to the cyclic acetal moiety and propose a reaction
mechanism as presented in Scheme 2. The oxygen atom
of the acetal ring is first protonated and then undergoes
the acetal ring opening to form a benzyl cationic inter-
mediate (3) stabilized by phenyl and the 3-hydroxypro-
poxy substituent. The cationic intermediate is electro-
philically attacked by benzene to form diphenylmethyl
ether 5. The hydrogen atom on the alkoxy carbon then
migrates to the benzylic carbon and eliminates
3-hydroxypropanal (7) or its equivalent.14,15
a
A mixture of acetal (1.0 mmol), benzene (5.0 mL), and TFSA
b
(0.05 mmol) was heated to reflux for 10 h. GC yield.
low. With arenes of higher boiling point, 1,2-dichloro-
ethane or nitromethane was used as the solvent. The
reaction in dichloromethane, chloroform, or carbon dis-
ulfide resulted in no reaction. In every case, arene was
employed in excess. The benzylation reaction proceeded
smoothly with arenes substituted by electron-donating
group(s) to give the corresponding diarylmethanes in
good to excellent yields without contamination of byprod-
ucts. The reaction with anisole was an exception, giving
a low yield of the desired benzylanisole albeit complete
consumption of the starting acetal (Table 2, run 5). This
is probably because the reactive benzylanisole might have
undergone further benzylation to give complex polymeric
products. The isomer ratio of o-:m-:p-products of the
reaction with toluene or anisole was similar to that
observed in the usual Lewis acid catalyzed FC reaction
using benzyl chloride or benzyl alcohol.9 Benzaldehyde
acetals having an electron-donating or -withdrawing
group at C(4) similarly reacted with arenes to give the
corresponding diarylmethanes in good to excellent yields.
The reaction was fast with such activated arenecarbal-
dehyde acetals as 4-methylphenyl and slow with such
(10) (a) DeHaan, F. P.; Delker, G. L.; Covey, W. D.; Ahn, J .;
Anksman, M. S.; Brehm, E. C.; Chang, J .; Chicz, R. M.; Cowan, R. L.;
Ferrara, D. M.; Fong, C. H.; Harper, J . D.; Irani, C. D.; Kim, J . Y.;
Meinhold, R. W.; Miller, K. D.; Roberts, M. P.; Stoler, E. M.; Suh, Y.
J .; Tang, M.; Williams, E. L. J . Am. Chem. Soc. 1984, 106, 7038. (b)
DeHaan, F. P.; Chan, W. H.; Chang, J .; Cheng, T. B.; Chiriboga, D.
A.; Irving, M. M.; Kaufman, C. R.; Kim, G. Y.; Kumar, A.; Na, J .;
Nguyen, T. T.; Nguyen, D. T.; Patel, B. R.; Sarin, N. P.; Tidwell, J . H.
J . Am. Chem. Soc. 1990, 112, 356.
(11) Styrene dimer was one of the main products.
(12) For a review, see: Olah, G. A. Friedel-Crafts and Related
Reactions; Wiley-Interscience: New York, 1964; Vol. 2, Part 1.
(13) In the acid-catalyzed Friedel-Crafts reaction with benzalde-
hyde, the methyne hydrogen of triphenylmethane transfers to the
benzyl cation to give diphenylmethane and the trityl cation, which is
attacked by water. See ref 2.
(9) (a) Olah, G. A.; Kobayashi, S.; Tashiro, M. J . Am. Chem. Soc.
1972, 94, 7448. (b) Olah, G. A.; Olah, J . A.; Ohyama, T. J . Am. Chem.
Soc. 1984, 106, 5284.

Reductive Friedel-Crafts Reaction of Arenes
J . Org. Chem., Vol. 62, No. 1, 1997 153
Ta ble 2. TF SA-Ca ta lyzed F C Ben zyla tion of 2-Ar yl-1,3-d ioxa n e w ith Ar en esa
a
b
d
2-Aryl-1,3-dioxane (1.0 mmol), arene (5.0 mL), TFSA (0.05 mmol). GC yield. c Determined by GC. The reaction was carried out in
1,2-dichloroethane.
The hydride shift was evidenced by the experiment
using 2-phenyl-4,4,6,6-tetradeuterio-5-ethyl-1,3-dioxane
(10); the reaction with benzene gave more than 90%
deuteriated diphenylmethane (11) (Scheme 3). That no
reaction took place with 2-phenyl-4,4,6,6-tetramethyl-1,3-
dioxane is also consistent with the hydride shift mech-
anism (Table 1, run 3).
When the reaction was performed using benzene-d6,
no deuterium incorporation was observed into the ben-
zylic carbon (Scheme 4). This fact strongly suggests that
the hydrogen source is not benzene and the redox process
should proceed via the hydride shift from the acetal
moiety.
Diphenylmethyl ether (5) was separately prepared and
(14) Hydride ion transfer from the alkoxy carbon of tetrahydrofuran,
1,3-dioxolane, and 1,3-dioxepan to a trityl cation has been reported.
Din, K-u.; Plesch, P. H. J . Chem. Soc., Perkin Trans. 2 1987, 937.
(15) The oxidation product of the alkyl group was not detected
because it may undergo a condensation reaction to form polymeric
products.

154 J . Org. Chem., Vol. 62, No. 1, 1997
Fukuzawa et al.
Sch em e 3
Sch em e 4
Sch em e 5
F igu r e 1. Reaction rate plot of the reaction of benzene with
2-(4-methylphenyl)- (9), 2-phenyl- (b), and 2-(4-chlorophenyl)-
1,3-dioxane (2).
Sch em e 2
process (Scheme 5).16 The driving force of the hydride
shift must be protonation of the etheral oxygen because
diphenylmethyl ether 5 was recovered in the absence of
TFSA. Thus, it may safely be concluded that the hydride
source is the alkoxy group of the acetal group and that
diphenylmethyl ether 5 is the most likely intermediate.
For the 1,3-hydride shift, two ways are possible as shown
in Scheme 2. At present, no evidence is available to
determine which is a probable pathway.
Exp er im en ta l Section
Gen er a l Meth od s. 1H and 13C NMR spectra were recorded
in CDCl3 solutions. The chemical shifts are reported in δ units
downfield from the internal reference, Me4Si. Infrared spectra
were measured in CHCl3 solutions or as KBr pellets. GC and
GC/MS analyses were carried out on a capillary column (DB-
5-30N-STD, J &W Scientific, 0.25 mm, 30 m) (helium as the
carrier gas). High-resolution mass spectral analyses were
carried out at Sagami Chemical Research Center, Kanagawa,
J apan. Elemental analyses were carried out in the microana-
lytical laboratory of Chuo University. Column chromatogra-
phy on SiO2 was performed using Merck silica gel 60.
Ma ter ia ls. TFSA was kindly supplied from Central Glass
Co., Ltd (J apan). Benzene, toluene, mesitylene, p-xylene, and
anisole were distilled from CaH2 and kept over molecular
sieves 4A under nitrogen. All of the aldehydes are com-
mercially available and were purified by distillation under
reduced pressure before use. Authentic samples of substituted
diarylmethanes for the GC/MS analyses were prepared by the
Lewis acid-catalyzed Friedel-Crafts benzylation of the sub-
stituted benzyl chloride with arenes.9
Benzaldehyde diisopropyl acetal was prepared according to
the literature procedure.17 Benzaldehyde dibutyl acetal was
prepared by acid-catalyzed transacetalization of benzaldehyde
dimethyl acetal with 1-butanol.
P r ep a r a tion of Ar en eca r ba ld eh yd e Aceta ls. Cyclic
acetals of arenecarbaldehydes were prepared by the acid-
catalyzed acetalization with the corresponding diol.18 A typical
experimental procedure for the acetalization reaction follows.
A two-neck, round-bottom flask, equipped with a Dean-Stark
trap, was charged with a mixture of p-tolualdehyde (2.4 g, 20
(16) Because treatment of diphenylmethyl ether Ph2CHOCH2CH2-
CH3 with a catalytic amount of TFSA similarly afforded diphenyl-
methane under the FC conditions, the terminal hydroxy group is not
essential for the hydride shift process.
(17) Roelofsen, D. P.; van Bekkum, H. Synthesis 1972, 419.
(18) Napolitano, E.; Fiaschi, R.; Mastrorilli, E. Synthesis 1986, 122.
subjected to the reaction with benzene under the FC
conditions. Here again, diphenylmethane was produced
in 40-50% yield, suggesting that the diphenylmethyl
ether was a likely intermediate for the hydride shift

Reductive Friedel-Crafts Reaction of Arenes
J . Org. Chem., Vol. 62, No. 1, 1997 155
Ta ble 3. TF SA-Ca ta lyzed F C Ben zyla tion of Ald eh yd es w ith Ar en es in th e P r esen ce of 1,3-P r op a n ed iola
a
b
Aldehyde (1.0 mmol), arene (5.0 mL), 1,3-propanediol (1.1 mmol), TFSA (0.05 mmol). GC yield. c Determined by GC.
2
3
mmol), 1,3-propanediol (1.9 g, 25 mmol), p-toluenesulfonic acid
(40 mg), and benzene (100 mL). The solution was heated at
reflux with stirring until no further water separated. The
solution was then cooled to room temperature. Triethylamine
(1.0 mL) was added to the reaction mixture, which was then
partitioned between diethyl ether and water. The organic
phase was washed with 10% sodium hydroxide (20 mL) and
then with brine and dried over K2CO3. Evaporation of the
solvent gave almost pure 2-(4-methylphenyl)-1,3-dioxane,
which was purified by recrystallization from pentane (3.5 g,
19.7 mmol, 98% yield). Spectral and analytical data of the
arenecarbaldehyde acetals of the substituted benzaldehydes
are as follows.
67.3, 100.8, 115.0 (d, J CF ) 44 Hz), 127.8 (d, J CF ) 18 Hz),
4 1
134.7 (d, J CF ) 6 Hz), 162.9 (d, J CF ) 490 Hz). Anal. Calcd
for C10H11FO2: C, 65.92; H, 6.09. Found: C, 65.86; H, 6.20.
2-(4-Nitr op h en yl)-1,3-d ioxa n e (833-64-7): mp 108-109
°C; IR (CHCl3) 1105, 1349, 1525, 2860 cm-1 1H NMR (400
;
MHz, CDCl3) δ 1.5 (m, 1H), 2.1-2.3 (m, 1H), 4.03 (m, 2H),
4.29 (m, 2H), 5.57 (s, 1H), 7.66 (d, 2H, J ) 8.8 Hz), 8.21 (d,
2H, J ) 8.8 Hz); 13C NMR (CDCl3) δ 25.5, 67.2, 99.7, 123.2,
127.0, 145.1, 147.9. Anal. Calcd for C10H11NO4: C, 57.41; H,
5.30; N, 6.70. Found: C, 57.57; H, 5.40; N, 6.69.
2-(Bip h en yl-4-yl)-1,3-d ioxa n e: mp 56-59 °C; IR (KBr)
700, 768, 826, 849, 970, 992, 1015, 1103, 1148, 1235, 1379,
1389, 1487, 2872 cm-1; H NMR (400 MHz, CDCl3) δ 1.4 (m,
1
2-(4-Meth ylp h en yl)-1,3-d ioxa n e (5563-40-1): mp 30-33
°C; IR (CHCl3) 813, 988, 1103, 1152, 1237, 1379, 2858, 3014
1H), 2.1-2.2 (m, 1H), 3.99 (dt, 2H, J ) 11.9, 2.2 Hz), 4.26 (dd,
2H, J ) 10.7, 5.0 Hz), 5.50 (s, 1H), 7.2-7.3 (m, 5H); 13C NMR
(CDCl3) δ 25.7, 67.3, 101.3, 126.3, 126.9, 127.1, 127.3, 128.6,
137.7, 140.8, 141.5. Anal. Calcd for C16H16O2: C, 79.97; H,
6.71. Found: C, 80.08; H, 6.74.
1
cm-1; H NMR (400 MHz, CDCl3) δ 1.4 (m, 1H), 2.0-2.1 (m,
1H), 2.19 (s, 3H), 3.98 (dt, 2H, J ) 11.9, 2.2 Hz), 4.25 (dd, 2H,
J ) 10.7, 4.9 Hz), 5.47 (s, 1H), 7.16 (d, 2H, J ) 8.1 Hz), 7.36
(d, 2H, J ) 8.1 Hz); 13C NMR (CDCl3) δ 21.1, 25.7, 67.3, 101.6,
125.8, 128.8, 135.9, 138.4. Anal. Calcd for C11H14O2: C, 74.13;
H, 7.92. Found: C, 74.10; H, 7.82.
2-(1-Na p h th yl)-1,3-d ioxa n e (66671-26-9): mp 64-66 °C;
IR (CHCl3) 998, 1081, 1113, 1151, 1209, 1238, 2856, 3013 cm-1
;
1H NMR (400 MHz, CDCl3) δ 1.40 (m, 1H), 2.2-2.4 (m, 1H),
4.0 (m, 2H), 4.3 (m, 2H), 6.01 (s, 1H), 7.4-8.2 (m, 7H); 13C
NMR (CDCl3) δ 25.7, 67.5, 100.8, 124.1, 124.2, 125.0, 125.5,
126.0, 128.4, 129.3, 130.4, 133.7, 133.8. Anal. Calcd for
C14H14O2: C, 78.48; H, 6.59. Found: C, 78.09; H, 6.62.
2-(4-Meth oxyp h en yl)-1,3-d ioxa n e (5689-71-4): mp 42-
45 °C; IR (CHCl3) 829, 988, 1036, 1103, 1149, 1173, 1210, 1251,
1379, 1519, 1615, 2857, 2960, 3014 cm-1; 1H NMR (200 MHz,
CDCl3) δ 1.33-1.47 (m, 1H), 2.05-2.34 (m, 1H), 3.95 (dt, 2H,
J ) 12.1, 2.4 Hz), 4.23 (dd, 2H, 10.6, 5.1 Hz), 5.44 (s, 1H),
6.87 (m, 2H), 7.40 (m, 2H); 13C NMR (CDCl3) δ 25.7, 55.2, 67.2,
101.5, 113.5, 127.2, 131.3, 159.8. Anal. Calcd for C11H14O3:
C, 68.02; H, 7.27. Found: C, 67.68; H, 7.20.
2-(4-Ch lor op h en yl)-1,3-d ioxa n e (6413-52-1): mp 59-60
°C; IR (CHCl3) 821, 1017, 1107, 1149, 1222, 1237, 1378, 2859
1
cm-1; H NMR (400 MHz, CDCl3) δ 1.2 (m, 1H), 2.0-2.1 (m,
1H), 3.80 (dt, 2H, J ) 11.9, 2.2 Hz), 4.10 (dd, 2H, J ) 10.7, 4.9
Hz), 5.31 (s, 1H), 7.20 (d, 2H, J ) 8.8 Hz), 7.30 (d, 2H, J ) 8.8
Hz); 13C NMR (CDCl3) δ 25.4, 67.1, 100.3, 127.3, 128.4, 134.1,
137.1. Anal. Calcd for C10H11ClO2: C, 60.46; H, 5.58.
Found: C, 60,47; H, 5.52.
2-(4-F lu or op h en yl)-1,3-d ioxa n e: bp 90 °C/0.6 mmHg
(Kugelrohr distillation); IR (neat) 833, 992, 1017, 1105, 1154,
1225, 1280, 1381, 1514, 1605, 1612, 2857, 2969 cm-1; 1H NMR
(200 MHz, CDCl3) δ 1.3-1.5 (m, 1H), 2.05-2.33 (m, 1H), 3.96
(dt, 2H, J ) 17.4, 2.4 Hz), 4.21 (dd, 2H, J ) 5.1, 1.2 Hz), 5.46
(s, 1H), 7.03 (m, 2H), 7.45 (m, 2H); 13C NMR (CDCl3) δ 25.6,
2-P h en yl-4,4,6,6-tetr a d eu ter io-5-eth yl-1,3-d ioxa n e (10).
This compound was obtained as a ca. 7:3 diastereomeric

156 J . Org. Chem., Vol. 62, No. 1, 1997
Fukuzawa et al.
mixture by the reaction of benzaldehyde with 1,1,3,3-tetra-
deuterio-2-ethyl-1,3-propanediol (vide infra), which was ob-
tained by the reduction of diethyl ethylmalonate with LiAlD4:
IR (neat) 698, 744, 1032, 1069, 1103, 1167, 1385, 1456, 2087,
6.85-7.53 (m, 8H), 7.67-8.05 (m, 3H); 13C NMR (CDCl3) δ
21.0, 38.6, 124-139 (additional several peaks). Anal. Calcd
for C18H16: C, 93.06; H, 6.94. Found: C, 93.29; H, 6.93.
Acid -Ca ta lyzed Rea ction of Ar en eca r ba ld eh yd es w ith
Ar en es in th e P r esen ce of 1,3-P r op a n ed iol. A Typ ica l
Exp er im en ta l P r oced u r e. TFSA (8.0 mg, 0.05 mmol) was
added to a solution of 4-chlorobenzaldehyde (141 mg, 1.0 mmol)
and 1,3-propanediol (84 mg, 1.1 mmol) in toluene (5.0 mL) at
room temperature with stirring. The mixture was stirred at
reflux temperature for 18 h. The reaction mixture was cooled
and poured into aqueous NaHCO3. The organic phase was
separated, and the aqueous phase was extracted with diethyl
ether. The combined organic extracts were washed with brine
and dried over MgSO4. GC/MS analysis revealed the presence
of an isomeric mixture of ditolylmethanes, each amount being
determined with naphthalene as the internal standard. The
isomer ratio of the o-, m-, and p-substituted diarylmethane
was determined by GC, and retention times were compared
with those of the authentic samples.9
1
2213 2963 cm-1; H NMR (400 MHz, CDCl3) (major diastere-
omer) δ 0.91 (t, 3H, J ) 7.9 Hz), 1.13 (quint, 2H, J ) 7.2Hz),
2.02 (br t, 1H, J ) 6.6Hz), 5.40 (s, 1H), 7.25-7.54 (m, 5H); 13
C
NMR (CDCl3) δ 10.9, 21.1, 35.4, 71.6 (quint, J ) 84 Hz), 101.4,
126.0, 128.2, 128.7, 138.5; 1H NMR (400 MHz, CDCl3) (minor
diastereomer) δ 1.00 (t, 3H, J ) 7.5 Hz), 1.27 (t, 1H, J )
7.3Hz), 1.84 (quint, 2H, J ) 7.3 Hz), 5.49 (s, 1H), 7.25-7.54
(m, 5H); 13C NMR (CDCl3) δ 12.0, 22.2, 35.7, 69.5 (quint, J )
84 Hz), 101.7, 126.0, 128.2, 128.7, 138.8; HRMS calcd for
C12H12D4O2 m/ z 196.1397, found 196.1376.
1,1,3,3-Tetr adeu ter io-2-eth yl-1,3-pr opan ediol. This com-
pound was prepared by the following procedure. A 50-mL two-
neck round-bottom flask, fitted with a dropping funnel and a
reflux condenser connected with a argon line, was charged with
lithium aluminum deuteride (949 mg, 25 mmol) and diethyl
ether (20 mL). The mixture was heated to reflux for 30 min
and then cooled to room temperature. A solution of diethyl
ethylmalonate (3.8 g, 20 mmol) dissolved in diethyl ether (20
mL) was added slowly with stirring at such a rate that the
solvent continued to reflux gently. After the addtion was
completed, the mixture was stirred at the reflux temperature
for an additional 3 h. The mixture was cooled to room
temperature, and the excess deuteride was decomposed by the
addition of saturated sodium sulfate solution. The insoluble
material was filtered and washed fully with chloroform. The
combined filtrate was dried over MgSO4 and concentrated to
give a crude product. Purification by flash chromatography,
using hexane/ether (1/1), afforded the diol (984 mg, 46%) as
an oil. IR (neat) 943, 1071, 1092, 1105, 1156, 1171, 1381, 1464,
2093, 2207, 2878, 2936, 2964, 3345 cm-1; 1H NMR (200 MHz,
CDCl3) δ 0.94 (t, 3H, J ) 7.8 Hz), 1.29 (quint, 2H, J ) 7.5
Hz), 1.60 (br t, 1H, J ) 6.3 Hz), 4.00 (br, 2H); 13C NMR (CDCl3)
δ 11.5, 11.5, 20.4, 43.3, 63.9 (quint, J ) 83 Hz).
Acid -Ca ta lyzed Rea ction of Ar en eca r ba ld eh yd e Ac-
eta ls w ith Ar en es. A Typ ica l Exp er im en ta l P r oced u r e.
TFSA (8 mg, 0.05 mmol) was added to a solution of 2-(4-
chlorophenyl)-1,3-dioxane (199 mg, 1.0 mmol) in toluene (5.0
mL) at room temperature with stirring. The mixture was
stirred at reflux temperature for 17 h, cooled, and poured into
aqueous NaHCO3. The organic phase was separated, and the
aqueous phase was extracted with diethyl ether. The com-
bined organic extracts were washed with brine and dried over
MgSO4. GC/MS analysis revealed that the crude product
contained (4-chlorophenyl)-p-tolylmethane, (4-chlorophenyl)-
o-tolylmethane, and (4-chlorophenyl)-m-tolylmethane; each
amount and the isomer ratio were determined using naph-
thalene as the standard and compared with each authentic
sample.9 Most of the products are known compounds and were
characterized by a comparison of their spectral data with those
of authentic samples unless otherwise noted.9
3-Hydr oxypr opyl Diph en ylm eth yl Eth er (5). This ether
was prepared by the reduction of 2,2-diphenyl-1,3-dioxane with
LiAlH4-AlCl3:19 mp 41-42 °C; IR (KBr) 698, 739, 1022, 1082,
1100, 3359, 3432 cm-1 1H NMR (200 MHz, CDCl3) δ 1.89
;
(quint, 2H, J ) 5.7 Hz), 2.23 (br s 1H), 3.64 (t, 2H, J ) 5.7
Hz), 3.80 (t, 2H, J ) 5.7 Hz), 5.35 (s, 1H), 7.18-7.38 (m, 10
H); 13C NMR (CDCl3) δ 32.2, 61.8, 68.0, 84.2, 126.8, 127.5,
128.4, 142. Anal. Calcd for C16H18O2: C, 79.31; H, 7.49.
Found: C, 78.98; H, 7.56.
Registr y n os. p r ovid ed by th e a u th or : benzaldehyde
dimethyl acetal, 1125-88-8; benzaldehyde dibutyl acetal, 5395-
08-4; benzaldehyde diisopropyl acetal, 38115-81-0; 2-phenyl-
1,3-dioxolane, 936-51-5; 2-phenyl-1,3-dioxane, 772-01-0; 2-phen-
yl-4,6-dimethyl-1,3-dioxane, 4233-09-4; 2-phenyl-4,4,6,6,-
tetramethyl-1,3-dioxane, 62977-15-5; 2-phenyl-1,3-dioxepane,
2749-68-0; 2-(4-methylphenyl)-1,3-dioxane, 5663-40-1; 2-(4-
chlorophenyl)-1,3-dioxane, 6413-52-1; 2-(4-methoxyphenyl)-1,3-
dioxane, 5689-71-4; 2-(4-nitrophenyl)-1,3-dioxane, 833-64-7;
2-(1-naphthalenyl)-1,3-dioxane, 66671-26-9; 1,1′-methylenebi-
sbenzene, 101-81-5; 1,1′-(methylene-d)bisbenzene, 20389-18-
8; phenylmethylbenzene-d5, 103730-93-4; 1-methyl-2-(phenyl-
methyl)benzene, 713-36-0; 1-methyl-3-(phenylmethyl)benzene,
620-47-3; 1-methyl-4-(phenylmethyl)benzene, 620-83-7; 1,4-
dimethyl-2-(phenylmethyl)benzene, 13540-50-6; 1,3,5-tri-
methyl-2-(phenylmethyl)benzene, 4453-79-6; 1-methoxy-2-
(phenylmethyl)benzene, 883-90-9; 1-methoxy-3-(phenylmeth-
yl)benzene, 23450-27-3; 1-methoxy-4-(phenylmethyl)benzene,
834-14-0; 1-methyl-2-(4-methylphenyl)methylbenzene, 21895-
17-0; 1-methyl-3-(4-methylphenyl)methylbenzene, 21895-16-
9; 1,1′-ethylenebis(4-methylbenzene), 4957-14-6; 1,4-dimethyl-
2-(4-methylphenyl)methylbenzene, 721-45-9; 1-chloro-4-(phenyl-
methyl)benzene, 831-81-2; 1-fluoro-4-(phenylmethyl)benzene,
587-79-1; 1-[(4-chlorophenyl)methyl]-2-methylbenzene, 55676-
88-5; 1-chloro-4-[(3-methylphenyl)methyl]benzene, 91410-28-
5; 1-chloro-4-[(4-methylphenyl)methyl]benzene, 30203-87-3;
2-[(4-chlorophenyl)methyl]-1,4-dimethylbenzene, 85716-72-9;
1-[(4-methoxyphenyl) methyl]-2-methylbenzene, 53039-52-4;
1-[(4-methoxyphenyl)methyl]-3-methylbenzene, 53039-51-3;
1-methoxy-4-[(4-methylphenyl)methyl]benzene, 22865-60-7; 4-(p-
methylbenzyl)biphenyl, 30203-93-1; 1-[(2-methylphenyl)meth-
yl]naphthalene, 20204-73-3; 1-[(4-methylphenyl)methyl]naph-
thalene, 20204-71-1; 1,1′-(propoxymethylene)bisbenzene, 13594-
71-3.
Spectral and analytical data of new compounds prepared
follow.
(Bip h en yl-4-yl)tolylm eth a n e. This compound was ob-
tained by the reaction of toluene with (2-biphenyl-4-yl)-
1,3-dioxane: mp 55-60 °C; IR (KBr) 689, 696, 727, 745, 756,
772, 797, 816, 1406, 1487, 1512 cm-1 1H NMR (200 MHz,
;
CDCl3) (o-isomer) δ 2.26 (s, 3H), 4.00 (s, 2H), 7.00-7.60 (m,
13H); 13C NMR (CDCl3) δ 19.7, 39.1, 124-141 (additional
1
several peaks); H NMR (200 MHz, CDCl3) (p-isomer) δ 2.30
(s, 3H), 3.96 (s, 2H), 7.00-7.60 (m, 13H); 13C NMR (CDCl3) δ
21.0, 41.5, 124-141 (additional several peaks). Anal. Calcd
for C20H18: C, 92.98; H, 7.02. Found: C, 92.92; H, 7.15.
(1-Na p h th yl)tolylm eth a n e. This compound was obtained
by the reaction of toluene with 2-(1-naphthyl)-1,3-dioxane: bp
165 °C/0.6 mmHg (Kugelrohr distillation); IR (neat) 779, 791,
1397, 1512 cm-1; 1H NMR (200 MHz, CDCl3) (o-isomer) δ 2.30
(s, 3H), 4.39 (s, 2H), 6.85-7.53 (m, 8H), 7.67-8.05 (m, 3H);
13C NMR (CDCl3) δ 19.6, 36.2, 124-139 (additional several
peaks); 1H NMR (200 MHz, CDCl3) (m-isomer) δ 2.27 (s, 3H),
4.39 (s, 2H), 6.85-7.53 (m, 8H), 7.67-8.05 (m, 3H); 13C NMR
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra of all benzaldehyde and 4-substituted benzaldehyde
acetals and diarylmethanes prepared in the present study (33
pages). This material is contained in libraries on microfiche,
immediately follows this article in the microfilm version of the
journal, and can be ordered from the ACS; see any current
masthead page for ordering information.
J O961897E
(19) The general experimental protocols followed in this study
parallel those described in the literature: Eliel, E. L.; Badding, V. D.;
Rerick, M. N. J . Am. Chem. Soc. 1962, 84, 2371.
1
(CDCl3) δ 21.0, 41.5, 124-139 (additional several peaks); H
NMR (200 MHz, CDCl3) (p-isomer) δ 2.28 (s, 3H), 4.39 (s, 2H),