DDQ oxidation of hydroxyisochromans and homologues

Article abstract of DOI:10.1080/14786410902975590

Some hydroxyisochromans and hydroxyphthalans are tested under oxidative conditions obtaining hydroxybenzophenone derivatives. All reactions were followed by 1H NMR spectroscopy. Some final main oxidation products were also isolated and characterised.

Full text of DOI:10.1080/14786410902975590

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Natural Product Research: Formerly
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DDQ oxidation of hydroxyisochromans
and homologues
Marcella Guiso a , Carolina Marra a & Francesco Piccioni a
a Dipartimento di Chimica , Università di Roma La Sapienza ,
Piazzale Aldo Moro 5, 00185 Roma, Italy
Published online: 10 Mar 2010.
To cite this article: Marcella Guiso , Carolina Marra & Francesco Piccioni (2010) DDQ oxidation of
hydroxyisochromans and homologues, Natural Product Research: Formerly Natural Product Letters,
24:4, 331-340, DOI: 10.1080/14786410902975590
To link to this article: http://dx.doi.org/10.1080/14786410902975590
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Natural Product Research
Vol. 24, No. 4, 10 March 2010, 331–340
DDQ oxidation of hydroxyisochromans and homologues
*
Marcella Guiso, Carolina Marra and Francesco Piccioni
`
Dipartimento di Chimica, Universita di Roma La Sapienza, Piazzale Aldo Moro 5,
00185 Roma, Italy
(Received 3 March 2009; final version received 10 April 2009)
Some hydroxyisochromans and hydroxyphthalans are tested under
oxidative conditions obtaining hydroxybenzophenone derivatives. All
reactions were followed by 1H NMR spectroscopy. Some final main
oxidation products were also isolated and characterised.
Keywords: hydroxyisochromans; hydroxyphthalans; hydroxy-1,3-dihydro-
isobenzofurans; hydroxybenzophenones; oxidation; DDQ
1. Introduction
Phenolic compounds are very important for their antioxidant activity (Bonfili et al.,
2008; Lien, Ren, Bui, & Wang, 1999), but the structures of their oxidation products
very often remain unknown.
Some years ago we synthesised many hydroxyisochroman and hydroxyphthalan
(hydroxy-1,3-dihydroisobenzofurans) derivatives (Guiso, Betrow, & Marra, 2008;
Guiso, Bianco, Marra, & Cavarischia, 2003; Guiso, Marra, & Cavarischia, 2001).
Two of these compounds, namely 1-phenyl-isochroman-6,7-diol (1) and 1-(4-
hydroxy-3-methoxy-phenyl)isochroman-6,7-diol (2), have been studied for their
interesting antioxidant activity (Lorenz et al., 2005; G. Togna, Franconi, A. Togna,
Marra, & Guiso, 2003).
We investigate the structures of the oxidation compounds of some hydro-
xyisochromans, mainly those obtained by oxidising the isochromans prepared from
2-(3,4-dihydroxy-phenyl)ethanol (3), and aliphatic or aromatic aldehydes prepared
by oxa-Pictet–Spengler reaction. Successively, we extended our investigations to the
oxidation of isochromans obtained from 2-(3-hydroxyphenyl)ethanol (4) as well as
to that of phthalan derivatives.
We tested many oxidation agents, but we chose DDQ because the course of the
reaction could easily be followed recording the 1H NMR spectra of the whole
reaction mixture at different times without any work up, which also allowed us to
investigate the structure of the initially formed oxidation products, even if a little
stable.
*Corresponding author. Email: carolina.marra@uniroma1.it
ISSN 1478–6419 print/ISSN 1029–2349 online
ß 2010 Taylor & Francis
DOI: 10.1080/14786410902975590
http://www.informaworld.com

332
M. Guiso et al.
2. Results and discussion
Here we report the behaviour towards the oxidation of isochromans and phthalans
derivatives.
We first performed, in the same reaction conditions, the oxidation of the parent
alcoholic compound 3 to investigate if the behaviour towards the oxidation of its
catechol function could change in the derived isochromans.
The first oxidation product of 3 was, as expected, the orthoquinone (5), which
appears quite stable in the reaction medium for almost 24 h (Figure 1). Its formation
was clearly demonstrated by the 1H NMR spectrum, registered in the same reaction
medium; in fact, the downfield shift of the H-6 double doublet and the contemporary
upfield shift of the H-5 doublet and the H-2 broad singlet are all in accordance with
the above transformation.
Successively we examined many isochroman-6,7-diols obtained by reacting 3 with
differently substituted aromatic aldehydes. In all occasions, immediately after DDQ
addition, the signals of the corresponding orthobenzoquinone appeared. During this
time, the orthoquinone structure slowly converted into the main oxidation
compound, a hydroxybenzophenone derivative arising from the oxidation of the
C1 dibenzylic carbon to a carbonyl group (Scheme 1; Table 1).
All these benzophenone derivatives were stable; therefore it was possible to
extract, purify and easily characterise these compounds.
We hypothesise that the orthoquinone may be in equilibrium with a quinone
methide form which undergoes addition of water at C1. The subsequent opening of
the hemiacetalic ring affords the hydroxybenzophenone derivative.
Also the isochroman-6,7-diols prepared by using aliphatic aldehydes first showed
the orthoquinone formation, but, successively, the main oxidation product was a
HO
HO
O
O
DDQ
OH
OH
3
5
Figure 1. Hydroxytyrosol oxidation.
HO
O
DDQ
O
O
HO
O
HO
R1
O
CH2OH
O
R
O
H
R
R1
:
O
H
R
R
HO
DDQ
O
R1 = H, OH
R
Scheme 1. Hydroxyisochroman derivatives’ oxidation.

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333
Table 1. Oxidation products of 1-aryl-hydroxyisochroman derivatives and their
1H NMR data.
5
4
5
8
4
3
HO
R1
OH
HO
R1
DDQ
3
6
6
O
O
7
1
1
7
8
′
1
′
2
′
′
6
5
R3
R3
′
3
′
4
R2
R2
Reagents
R1
Products
1H NMR data (ppm)
R2
R3
No.
OH
OH
OMe
7
2.79 (2 H, t, J ¼ 7.0 Hz, H-3); 3.67 (2 H, t,
J ¼ 7.0 Hz, H-4); 3.90 (3 H, s, OCH3); 6.6-
6.9 (3 H, H-5, H-8, H-50); 7.25 (1 H, dd,
J ¼ 8.4 Hz, J ¼ 1.8 Hz, H-60); 7.46 (1 H, d,
J ¼ 1.8 Hz, H-20)
OH
OH
OH
H
Cl
H
H
H
8
9
2.77 (2 H, t, H-3); 3.63 (2 H, t, J ¼ 6.6 Hz, H-4);
6.77 (1 H, H-5); 6.84 (1 H, H-8); 7.0-8.0 (5 H,
H-20, H-30, H-40, H-50, H-60)
2.76 (2 H, t, H-3); 3.59 (2 H, t, H-4); 6.76 (1 H,
H-5); 6.84 (1 H, H-8); 7.2-7.8 (4 H, H-20, H-
30, H-50, H-60)
OMe
10
2.47 (2 H, t, H-4); 3.75 (2 H, t, H-3); 3.90 (3 H,
s, OCH3); 6.24 (1 H, s, H-5); 6.37 (1 H, s,
H-8); 6.92 (2 H, d, J ¼ 7.8 Hz, H-30, H-50);
7.54 (2 H, d, J ¼ 7.8 Hz, H-20, H-60)
H
COOMe
H
H
11
2.90 (2 H, t, J ¼ 6.6 Hz, H-3); 3.68 (2 H, t,
J ¼ 6.Hz 6, H-4); 3.88 (3 H, s, OCH3); 6.66
(1 H, dd, J ¼ 8.4 Hz, J ¼ 2.4 Hz, H-7); 6.82
(1 H, d, J ¼ 2.4 Hz, H-5); 7.74 (2 H, d,
J ¼ 8.4 Hz, H-20, H-60); 7.90 (1 H, d,
J ¼ 8.4 Hz, H-8); 8.01 (2 H, d, J ¼ 8.4 Hz,
H-30, H-50)
H
H
Cl
12
13
2.86 (2 H, t, J ¼ 6.6 Hz, H-3); 3.66 (2 H, t,
J ¼ 6.6 Hz, H-4); 6.66 (1 H, dd, J ¼ 8.4 Hz,
J ¼ 2.4 Hz, H-7); 6.81 (1 H, d, J ¼ 2.4 Hz,
H-5); 7.16 (1 H, d, J ¼ 8.4 Hz, H-8); 7.45
(2 H, d, J ¼ 8.4 Hz, H-30, H50); 7.66 (2 H, d,
J ¼ 8.4 Hz, H-20, H-60)
OCH2O
2.87 (2 H, t, J ¼ 6.9 Hz, H-3); 3.71 (2 H, t,
J ¼ 6.9 Hz, H-4); 6.73 (1 H, dd, J ¼ 8.1 Hz,
J ¼ 2.4 Hz, H-7); 6.12 (2 H, s, O-CH2-O);
6.86-6.93 (2 H, H-5, H50); 7.18 (1 H, d,
J ¼ 8.1 Hz, H-8); 7.26 (1 H, H-20); 7.27 (1 H,
dd, J ¼ 6.3 Hz, J ¼ 1.5 Hz, H-60)

334
M. Guiso et al.
Table 2. Oxidation products of 1-alkyl-hydroxyisochroman derivatives and their
1H NMR data.
5
4
5
4
HO
R2
HO
R1
DDQ
3
3
6
6
O
O
7
7
1
8
8
O
R2
Reagents
R1
Products
1H NMR data (ppm)
R2
No.
OH
Octyl
14
2.86 (2 H, t, J ¼ 6.0 Hz, H-3); 4.40 (2 H, t, J ¼ 6.0 Hz, H-4);
6.67 (1 H, s, H-5); 7.43 (1 H, s, H-60)
H
Butyl
15
2.98 (2 H, t, J ¼ 6.3 Hz, H-3); 4.43 (2 H, t, J ¼ 6.3 Hz, H-4);
6.76 (1 H, J ¼ 2.4 Hz, H-5); 6.83 (1 H, dd, J ¼ 8.4 Hz,
J ¼ 2.4 Hz, H-7); 7.82 (1 H, d, J ¼ 8.4 Hz, H-8)
O
HO
O
DDQ
HO
O
H
O
O
H
:
O
R
R1
H
R1
R
R1
R
R1 = H, OH
Scheme 2. 5-Hydroxyphthalan and 5,7-dihydroxyphthalan derivatives’ oxidation.
lactone arising from the transformation of the benzylic C1 in a carboxylic function,
with the loss of the remaining aliphatic chain owing to a further oxidation of the
C20 of the aldehyde moiety (see Table 2).
1
The H NMR spectra recorded during the DDQ oxidation of the isochromans
obtained from the alcohol (4) and aromatic aldehydes showed a very quick
disappearance of the H-1 signal, while those of 2 H-3 and 2 H-4 turned into two
triplets (near 2.89 and 3.67 ppm, respectively), indicating the opening of the
heterocyclic ring. Also, in this case, a hydroxybenzoquinone derivative was formed,
perhaps via a quinone–methide intermediate, too unstable to allow the registration
of its spectrum, in our experimental conditions.
The oxidation performed on the isochroman prepared from alcohol (4) and an
aliphatic aldehyde, as pentanal, behaved similarly to that on 1-alkyl-isochroman-6,
7-diol; in fact, the final oxidation compound is the related lactone, as shown by the
triplet of the primary esterified alcoholic function at 4.43 ppm and the doublet of the
aromatic proton at C-8 at 7.82 ppm.
The DDQ oxidation performed on 1,3-dihydrophthalans prepared from
3-hydroxybenzyl alcohol (6) and aromatic aldehydes also afforded benzophenone

Natural Product Research
335
derivatives, but with an aldehydic group arising from the oxidation of the C-3
benzylic etheral function involved in the dihydrophthalan ring (Scheme 2). It has
been noted that the isolated benzophenones from isochroman oxidation gave clear
1H NMR spectra in deuterated acetone or ACN, while their spectra recorded in
deuterated methanol appear more complex, owing to the equilibrium between the
carbonylic and the cyclic hemiacetalic structures, as confirmed by the presence of
a hemiacetalic carbon signal in 13C NMR spectra (around 100 ppm).
The oxidation of the 1,3-dihydro-5-hydroxy-phthalan obtained from p-hydroxy-
benzaldehyde was very rapid. Ten minutes after the addition of DDQ it was almost
totally transformed into the related benzoquinone derivative (18), which remained
unchanged after 24 h in the reaction medium.
The oxidation of phthalan from 4-methoxybenzaldehyde also afforded a stable
benzophenone derivative (17) with aldehydic group, which was isolated and
characterised by 13C NMR spectrum.
The oxidation of the 1,3-dihydro-5,7-dihydroxy-phthalan prepared from
p-chlorobenzaldehyde afforded, initially, an unstable oxidation product. In fact
the related benzophenone derivative (20) reaches its maximum concentration after an
hour and a half. Successively, degradation products showing proton aldehydic
signals appeared (see Table 3).
The 1,3-dihydro-5,7-dihydroxy-phthalan obtained from benzaldehyde showed
a similar behaviour; in fact, after 10 reaction minutes the expected oxidation
product (19) appeared. Its 1H NMR spectrum was characterised from the
presence of an aldehydic proton singlet at 9.63 ppm, the deshielding of H-20 and
H-60 protons and the shift of the H-4 and H-6 protons signals to 6.91 and 6.65 ppm,
respectively. Its maximum concentration was reached after an hour and a half and
then it reduced.
3. Experimental
3.1. General remarks
1H and 13C NMR spectra were measured by a Varian Mercury 300 MHz
spectrometer, chemical shifts are expressed in ppm relative to TMS and values of J
are quoted in Hertz. NMR data marked with an asterisk (*) may be reversed. The
product’s purification was obtained by solid–liquid column chromatography on
Merck 0.063–0.20 nm silica gel treated with diluted HCl, then washed with hot
water to eliminate Clꢀ ions, dried and activated at 120ꢁC for 24 h. Silica gel was
treated with 10% of water before using. The ratio of silica gel : product is 100 : 1.
The eluting solutions were determined case by case. TLC: 5 ꢂ 20 Silica gel 60 F254
Merck. Plates were revealed by spraying with 2 N H2SO4, then heating at 120ꢁC.
Micro-analyses: CE Instruments. MS analyses were performed on a triple
quadrupole PE-SCIEX API 365 (Perkin–Elmer Sciex Instruments, Foster City,
CA, USA), equipped with Turboin Spray interface in negative ion mode. Reagents:
Fluka. Solvents: Carlo Erba. All hydroxyisochromans and hydroxyphthalans
used were prepared according to the procedure reported earlier (Guiso et al., 2008,
2003, 2001).

336
M. Guiso et al.
1
Table 3. Oxidation products of hydroxyphthalans derivatives and their H NMR data.
O
4
4
3
HO
HO
5
H
O
DDQ
R3
3
5
O
6
6
1
1
7
7
R1
R1
R3
R2
R2
Reagents
Products
1H NMR data (ppm)
R1
H
R2
R3
No.
OCH2O
16
6.06 (2 H, s, O–CH2–O); 6.86 (1 H, d, J ¼ 8.1 Hz, H-50);
7.09 (1 H, dd, J ¼ 8.4 Hz, J ¼ 2.7 Hz, H-6); 7.24 (1 H,
dd, J ¼ 8.1 Hz, J ¼ 1.8 Hz, H-60); 7.30 (1 H, d,
J ¼ 1.8 Hz, H-20); 7.33 (1 H, J ¼ 2.4 Hz, H-4); 7.40
(1 H, d, J ¼ 8.4 Hz, H-7); 9.89 (1 H, s, H-3)
H
H
OMe
OH
H
H
17
18
3.91 (3 H, s, OCH3); 7.04 (2 H, d, J ¼ 8.8 Hz, H-30,
H-50); 7.18 (1 H, dd, J ¼ 8.4 Hz, J ¼ 2.6 Hz, H-6);
7.44 (1 H, d, J ¼ 2.6 Hz, H-4); 7.50 (1 H, d,
J ¼ 8.4 Hz, H-7); 7.80 (2 H, d, J ¼ 8.8 Hz, H-20, H60);
10.01 (1 H, s, H-3)
6.87 (2 H, d, J ¼ 8.7 Hz, H-30, H-50); 7.09 (1 H, dd,
J ¼ 8.1 Hz, J ¼ 2.4 Hz, H-6); 7.33 (1 H, d, J ¼ 2.4 Hz,
H-4); 7.41 (1 H, d, J ¼ 8.1 Hz, H-7); 7.67 (2 H, d,
J ¼ 8.7 Hz, H-20, H60); 9.91 (1 H, s, H-3)
OH
OH
H
H
H
19
20
6.66 (1 H, d, J ¼ 2.4 Hz, H-6); 6.92 (1 H, d,
J ¼ 2.4 Hz, H-4); 7.2-7.8 (5 H, phenyl moiety); 9.62
(1 H, s, H-3)
Cl
6.65 (1 H, d, J ¼ 2.4 Hz, H-6); 6.92 (1 H, d, J ¼ 2.4 Hz,
H-4); 7.43 (2 H, d, J ¼ 8.4 Hz, H-30, H-50); 7.66
(2 H, d, J ¼ 8.4 Hz, H-20, H-60); 9.63 (1 H, s, H-3)
3.2. General oxidation procedure
Twenty milligrams of compound for oxidation was dissolved in CD3CN and the
1H NMR spectrum was recorded. Then, directly into the NMR tube, a 2 molar
1
amount of DDQ was added. Different controls were effectuated by recording H
NMR spectra at different times until complete disappearance of the substrate.
3.2.1. Compound 5
The quinone formation was complete after 10 reaction minutes and compound 5
remained unchanged until 10 h.
1H NMR (ppm): 7.06 (H, dd, J ¼ 9.9, 1.8 Hz, H-6); 6.29 (H, d, J ¼ 9.9 Hz, H-5); 6.20
(H, bs, J ¼ 1.8 Hz, H-2); 3.74 (2 H, t, J ¼ 6.0 Hz, H-20); 2.55 (2 H, t, J ¼ 6.0 Hz, H-10).

Natural Product Research
337
3.2.2. Compound 7
The quinone (21) formation was complete after 10 reaction minutes. The
disappearance of 21 was complete after 24 h. The main oxidation product (7,
20 mg, yield 95%) was obtained by chromatography on silica gel column eluted by
1
CHCl3 : MeOH ¼ 9 : 1. H NMR data are reported in Table 1. 13C NMR: 197.2
(R2C¼O); 151.0 (C-40); 147.0 (C-30); 146.0 (C-6); 141.8 (C-7); 133.6 (C-8a); 130.1
(C-10); 129.7 (C-4a); 125.5 (C-60); 119.0 (C-8); 116.9 (C-5); 115.9 (C-50); 111.8 (C-20);
62.9 (C-3); 54.5 (OCH3); 35.0 (C-4). IR 3300, 2950, 2850, 1690, 1650, 1590, 1560,
1460, 1390, 1300, 1240, 1130 and 1090 cmꢀ1. [M–H]ꢀ ¼ 303.3. Elemental analysis of
C16H16O6 (304.30): Calcd: C 63.15, H 5.30, Found: C 62.84, H 5.46.
1
Compound 21: H NMR (ppm): 2.77 (1H, m, H-4a); 2.91 (1H, m, H-4b); 3.75 (1H,
m, H-3a); 3.81 (3H, s, OCH3); 4.04 (1H, m, H-3b); 5.30 (1H, d, J ¼ 1.5 Hz, H-1); 5.63
(1H, s, H-5); 6.21 (1H, s, H-8); 6.65–6.92 (3H, m, H20, H50, H60).
3.2.3. Compound 8
The quinone (22) formation was complete after 10 reaction minutes. The
disappearance of 22 was complete after 48 h. The main product (8) remained
1
unchanged for a week. H NMR data are reported in Table 1.
1
Compound 22: H NMR (ppm): 2.80 (1H, m, H-3a); 2.90 (1H, m, H-3b); 3.79 (1H,
m, H-4a); 4.05 (1H, m, H-4b); 5.42 (1H, d, J ¼ 1.8 Hz, H-1); 5.58 (1H, d, J ¼ 1.8 Hz,
H-8); 6.23 (1H, s, H-5), 7.39 (5H, m, H-20, H-30, H-40, H-50, H-60).
3.2.4. Compound 9
The quinone (23) formation was complete after 7 reaction minutes. The disappear-
ance of 23 was complete after 24 h. The main product (9) remained unchanged for
1
two days. H NMR data are reported in Table 1.
1
Compound 23: H NMR (ppm): 2.79 (1H, m, H-3a); 2.89 (1H, m, H-3b); 3.78 (1H,
m, H-4a); 4.04 (1H, m, H-4b); 5.41 (1H, d, J ¼ 1.8 Hz, H-1); 5.59 (1H, s, H-8); 6.22
(1H, s, H-5); 7.25-7.45 (4H, m, H-20, H-30, H-50, H-60).
3.2.5. Compound 10
The quinone (24) formation was complete after 10 reaction minutes. The
disappearance of 24 was complete after 24 h. The main product (compound 10)
1
remained unchanged for two days. H NMR data are reported in Table 1.
1
Compound 24 (quinone): H NMR (ppm): 2.79 (1H, m, H-3a); 2.95 (1H, m, H-3b);
3.80 (1H, m, H-4a); 3.82 (3H, s, CH3O); 4.10 (1H, m, H-4b); 5.95 (1H, s, H-1); 6.39
(1H, s, H-5); 6.84 (2H, d, J ¼ 8.4 Hz, H-30, H-50); 7.19 (2H, d, J ¼ 8.4 Hz, H-20, H-60).
3.2.6. Compound 11
The disappearance of the substrate was quite complete after 45 min. The compound
11 became quite prevalent and remained unchanged for two days. 1H NMR data are
reported in Table 1.

338
M. Guiso et al.
3.2.7. Compound 12
The disappearance of the substrate was quite complete after 25 min. The compound
12 became quite prevalent and remained unchanged for two days. 1H NMR data are
reported in Table 1.
3.2.8. Compound 13
Disappearance of the substrate was quite complete after 25 min. The compound 12
became quite prevalent and isolated. The main oxidation product (13, 13 mg, yield
90%) was obtained by chromatography on silica gel column eluted by CHCl3 :
1
MeOH ¼ 9 : 1. [M–H]ꢀ ¼ 285.3. H NMR data are reported in Table 1. Elemental
analysis of C16H14O5 (286.29): Calcd: C 67.13, H 4.93, Found: C 66.98, H 5.01.
3.2.9. Compound 14
The quinone (25) formation was complete after 10 reaction min. The disappearance
of 25 was quite complete after 72 h. The main product (14, 13 mg, 95% yield)
remained unchanged for ten days, which was successively isolated by chromatog-
raphy on silica gel column eluted by CHCl3 : MeOH ¼ 9 : 1. 1H NMR data are
reported in Table 2. [M–H]ꢀ ¼ 277.4. Elemental analysis of C9H8O4 (278.39): Calcd:
C 73.35, H 9.41 Found: C 73.01, H 9.44.
1
Compound 25 (quinone): H NMR (ppm): 0.86 (3H, t, J ¼ 7.0 Hz, CH3); 1.1–1.6
(12H, m, H-20, H-30, H-40, H-50, H-60, H-70); 1.77 (2H, m, H-10); 2.71 (2H, m, H-3);
3.62 (1H, m, H-4a); 3.95 (1H, m, H-4b); 4.41 (1H, m, H-1); 6.12* (1H, s, H-5); 6.14*
(1H, s, H-8).
3.2.10. Compound 15
The reaction was not complete after two days, the main oxidation product (15,
14 mg, 93% yield) was isolated by chromatography on silica gel column eluted by
CHCl3 : MeOH ¼ 9 : 1. 1H NMR data are reported in Table 2. [M–H]ꢀ ¼ 205.3.
Elemental analysis of C9H8O3 (206.29): Calcd: C 75.69, H 8.80, Found: C 75.71,
H 8.87.
3.2.11. Compound 16
The main oxidation product of 16 became clearly prevalent after 1 h and remained
1
unchanged for one day. H NMR data are reported in Table 3.
3.2.12. Compound 17
The main oxidation product (17, 19 mg, 90% yield) was obtained by chromatog-
raphy on silica gel column eluted by CHCl3. 1H NMR data are reported in Table 3.
13C NMR (CD3COCD3)(ppm): 192.8 (R2C¼O); 189.9 (HC¼O); 163.0 (C–OCH3);
159.1 (C-40); 138.0 (C-3a); 132.3 (C-10); 131.4 (C-20, C-60); 131.1 (C-6); 130.0 (C-7a);
118.6 (C-6); 114.3 (C-5); 113.0 (C30, C50); 54.4 (OCH3). [M–H]ꢀ ¼ 255.1. Elemental
analysis of C15H12O4 (256.26): Calcd: C 70.31, H 4.72, Found: C 69.58, H 4.87.

Natural Product Research
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3.2.13. Compound 18
The main oxidation product of 18 became clearly prevalent after 10 min and
1
remained unchanged for one day. H NMR data are reported in Table 3.
3.2.14. Compound 19
The main oxidation product of 19 became clearly prevalent after 90 min and
1
remained unchanged for one day. H NMR data are reported in Table 3.
3.2.15. Compound 20
The oxidation product was formed in 1 h, but it resulted to be less stable. Many
1
signals attributable to aldehydic protons were observed after this time. H NMR
data are reported in Table 1.
4. Conclusions
It is interesting to note that the first involved position in this oxidation
reaction is always the benzylic or dibenzylic tertiary C-1 carbon. The lactone
formation at C-1, that is the classical oxidative product of the C-1 unsubstituted
isochroman or phthalan derivatives, is observed when the substituent at
C-1 is aliphatic. This is in accordance with the easy cleavage of the aliphatic
moiety.
The different stability of the phthalan oxidation products could be explained on
the basis of the different substitution pattern of the parent benzylic alcohol; in fact,
the presence of two hydroxyl groups on the alcoholic aromatic ring makes further
oxidation easier.
The hydroxybenzophenone derivatives obtained from oxidation reaction may be
interesting also for their antioxidant properties; already, some hydroxybenzophe-
nones are used to inhibit the oxidation process of polymers and other kinds of
compounds (Dobashi, Kondou, & Ohkatsu, 2005).
Acknowledgement
Authors acknowledge the financial support from MIUR.
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