The first efficient method for the intramolecular trapping of benzynes by phenols: A new approach to xanthenes

Article abstract of DOI:10.1039/b103834f

Condensations between the dianion 1 derived from 1-(N-butoxycarbonylamino)-1H-benzotriazole and silyloxysalicylaldehydes 10 give excellent yields of the expected adducts 11. While attempts to remove the N-Boc function were unsuccessful, desilylation and hydrogenolysis delivered the hydroxybenzyl derivative 14 which could be efficiently deprotected to give the amine 15. This then underwent smooth decomposition to the benzyne 16, upon exposure to N-iodosuccinimide, and intramolecular trapping by the phenol group, with incorporation of iodine, to give the iodoxanthene 17. A more efficient protocol featured condensation of dianion 1 with 2-(benzyloxy)aryl aldehydes; hydrogenolysis of the initial products 19 and 22a served both to deprotect the phenol function and to effect hydrogenolysis of the benzylic alcohol group. A final acidic deprotection and exposure to N-iodosuccinimide delivered good yields of the iodoxanthenes 21 and 23, demonstrating for the first time a viable method for the intramolecular trapping of benzynes by phenolic groups.

Full text of DOI:10.1039/b103834f

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The first efficient method for the intramolecular trapping of
benzynes by phenols: a new approach to xanthenes
David W. Knight* and Paul B. Little
1
Chemistry Department, Cardiff University, P.O. Box 912, Cardiff, UK CF10 3TB
Received (in Cambridge, UK) 27th April 2001, Accepted 14th June 2001
First published as an Advance Article on the web 6th July 2001
Condensations between the dianion 1 derived from 1-(N-butoxycarbonylamino)-1H-benzotriazole and
silyloxysalicylaldehydes 10 give excellent yields of the expected adducts 11. While attempts to remove the
N-Boc function were unsuccessful, desilylation and hydrogenolysis delivered the hydroxybenzyl derivative
14 which could be efficiently deprotected to give the amine 15. This then underwent smooth decomposition
to the benzyne 16, upon exposure to N-iodosuccinimide, and intramolecular trapping by the phenol group,
with incorporation of iodine, to give the iodoxanthene 17. A more efficient protocol featured condensation
of dianion 1 with 2-(benzyloxy)aryl aldehydes; hydrogenolysis of the initial products 19 and 22a served both
to deprotect the phenol function and to effect hydrogenolysis of the benzylic alcohol group. A final acidic
deprotection and exposure to N-iodosuccinimide delivered good yields of the iodoxanthenes 21 and 23,
demonstrating for the first time a viable method for the intramolecular trapping of benzynes by phenolic
groups.
In our recent contributions to benzyne chemistry, we have
reported the successful generation and synthetic utility of the
1-amino-1H-benzotriazole derived dianion 1.1 This can be
homologated directly or converted into the iodide 2 which can
Scheme 2
reported,2,3 there are no reports of the efficient intramolecular
trapping of a benzyne by a tethered phenol. One notable excep-
tion of this was reported by Castedo’s group who succeeded in
isolating products arising from the trapping of a benzyne with a
phenoxide anion; however, the yield was only 20%.4 It may well
be that, in common with the corresponding alcohol chemistry,
the hard nature of the phenoxide species renders it unsuitable
for reaction with benzyne intermediates, which are known to be
soft electrophiles.2
then also be manipulated through to a series of alcohol deriv-
atives 3. Subsequent deprotection and benzyne generation,
specifically using N-iodosuccinimide, leads to the reactive
intermediates 4 which undergo smooth intramolecular cyclis-
ations with incorporation of iodine to give various dihydro-
benzofurans and chromane derivatives 5 in good to excellent
yields (Scheme 1). To the best of our knowledge, this represents
Xanthenes constitute some of the oldest known dyes5 and
interest in their photochemistry continues today.6 One notable
feature of xanthenes is their flat rigid structure which has been
used to advantage as a linker for peptide synthesis7 and in
unnatural amino acids and related pharmaceutical precursors.8
There are several well established approaches to xanthenes9
which typically feature formation of the central heterocyclic
ring often by combinations of Friedel–Crafts methodology and
C–O bond formation involving nucleophilic attack by a phenol
residue onto an electron-deficient aryl ring.10 Interestingly,
benzyne chemistry has also been used to form a xanthene
nucleus but in a very different manner to the present work.
Thus, exposure of the diaryl ether 8 to two equivalents of
lithium diisopropylamide causes both ester enolisation and
elimination of hydrogen bromide; subsequent attack onto the
benzyne by the resulting enolate then delivers a good yield of
the highly substituted derivative 9 (Scheme 3).11 Xanthenes can
also be obtained by reduction of the corresponding xanthones
using a number of hydride sources,12 as well as by the Huang-
Minlon modification of the Wolff–Kishner reduction.13
Xanthones themselves can be prepared by a range of well
Scheme 1
the first efficient method for the intramolecular trapping of
benzynes by alcohol groups.2 A natural extension of this was to
investigate whether similar chemistry could be applied to the
cyclisation of benzynes 6 having a phenolic appendage (Scheme
2). The generalised example shown, if successful, would result
in a new approach to xanthenes 7 with, if the foregoing
mechanism applies, incorporation of a potentially useful iodine
atom. To the best of our knowledge, while efficient inter-
molecular reactions between benzynes and phenols have been
DOI: 10.1039/b103834f
J. Chem. Soc., Perkin Trans. 1, 2001, 1771–1777
This journal is © The Royal Society of Chemistry 2001
1771

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Scheme 3
established procedures,14,15 most notably by intramolecular
Friedel–Crafts acylations or formation of the ether bond.
Recent contributions to this area include the reverse of the
Friedel–Crafts method developed by Snieckus in which metal-
lated aryls cyclise by intramolecular attack onto an adjacent
carboxamide function.16 Such structures have also recently been
made by the benzannelation of suitable cyclobut-2-enones.17
Xanthones can also be accessed by oxidation of the corre-
sponding xanthenes using a range of standard oxidizing
agents.18 In view of the foregoing results, we felt that, if success-
ful, the ideas shown in Scheme 2 could make a useful contri-
bution to this area, both for the initial xanthene synthesis and
as an approach to xanthones, by subsequent oxidation.19
Our initial experiments were carried out using 2-(tert-
butyldimethylsilyloxy)benzaldehydes 10 derived from the
corresponding salicylaldehydes. Thus, condensations between
these electrophiles and the benzotriazole dianion 1, in the
presence of both tetraglyme and cerium() chloride gave good
isolated yields of the expected adducts 11, despite concerns that
the steric bulk of the silyloxy group might hinder the reaction
(Scheme 4). Cleavage of the silyl group in the adduct 11b was
Scheme 5
products. Protection of the offending alcohol group seemed to
offer limited prospects and hence we reasoned that removal was
a more likely solution, by exploiting the very feature responsible
for the extreme acid lability—the benzhydrylic positioning of
the hydroxy group—which should also render the function
amenable to hydrogenolysis. In a first model reaction, we were
pleased to find both that exposure of the hydroxyphenol 12 to
hydrogen and 5% Pd–C in methanol under ambient conditions
led cleanly to the desired benzyl derivative 14 and that
subsequent removal of the N-Boc group now also occurred
smoothly, by brief exposure to 20% trifluoroacetic acid in
dichloromethane, to give the key free amine 15. This, due to
its highly polar and somewhat sensitive nature, was not fully
characterised, as attempted complete purification resulted in
significant losses. In principle, a more direct approach to this
type of structure in general would be by direct alkylation of the
dianion 1 without competing N-alkylation by these particularly
reactive electrophiles; however, preliminary attempts were not
promising as dialkylated products were obtained, along with
the desired mono-adducts.
Scheme 4
then readily achieved by treatment with hydrogen fluoride–
pyridine complex and gave an example, 12, of a free phenol,
again in good yield (Scheme 5). However, all attempts to
hydrolyse the N-Boc function using the standard protocol of
20% trifluoroacetic acid in dichloromethane proved fruitless
and resulted in extensive decomposition; little or none of the
required product 13 was obtained. This was not entirely
unexpected as protonation of the secondary benzylic alcohol
group and subsequent loss of water would lead to a highly
stabilized benzhydryl carbocation, whose longevity might also
be aided by the flanking ortho nitrogen and oxygen atoms.
Similar problems at this deprotection stage were encountered
during some of our related work on chromane synthesis.1
Milder, Lewis-acidic reagents including aluminium() chlor-
ide,20 boron tribromide,21 trimethylsilyl iodide22 and cerium()
ammonium nitrate23 also proved unsuccessful and led to a
range of unrecognizable products. As xanthenes can be readily
oxidised to xanthones and the latter, in turn, reduced to
xanthenes (see above), we attempted to oxidise the initial alco-
hols 11 to the corresponding ketones; however, using either
manganese() oxide or Jones reagent again led to many
Returning to the free amine 15, we were delighted to find that
addition of two equivalents of N-iodosuccinimide (NIS) to a
solution of this in dichloromethane at ambient temperature
resulted in the rapid and clean formation of the iodoxanthene
17, presumably via the benzyne 16, in much the same way as
we were able to form iodochromanes from 1-amino-7-hydroxy-
propylbenzotriazoles.1 Only traces of unidentified products
1
were evident in the H NMR spectrum of the crude product
and the iodoxanthene 17 was readily isolated in the pure state in
81% yield. The product 17 was identified in the usual manner.
Particularly characteristic was the appearance of a two-proton
singlet at δH 3.97 due to the 9-CH2 of the xanthene and a
particularly high field sp2 quaternary carbon at δC 83.6, due to
the new C–I group, shifted to this position by the heavy atom
effect. Molecular weight determination from mass spectral data
was also unique for this structure. This successful sequence led
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to the idea of using o-benzyloxybenzaldehydes 18 as the
electrophiles in the initial condensations with the benzotriazole
dianion 1, as removal of both this alternative protecting group
and the benzylic hydroxy should be possible in a single
operation.
In the event, condensations between dianion 1 and represen-
tative o-benzyloxybenzaldehydes 18 proceeded uneventfully
to give good to excellent yields of the desired alcohols 19
(Scheme 6). Subsequent hydrogenolysis then delivered the
manner as the foregoing compound. We were therefore sur-
prised to find that the product obtained following the general
deprotection–cyclisation protocol was an approximately 1 : 1
mixture of the 6,8- and 6,9-diiodotetrahydrobenzo[a]xanthenes
26 and 27. Fractional crystallization from dichloromethane
allowed the separation of a sample of the 6,8-isomer 26. Pre-
sumably, the tetralin ring is sufficiently electron rich to allow
electrophilic iodination to occur during the cyclisation. As yet,
we have not found a method to avoid this additional reaction.
An extension of this methodology featured an attempt to
incorporate a substituent at the 9-position of the final xanthene.
To this end, the tertiary alcohol 29 was formed by condensation
between the dianion 1 and 2-benzyloxyacetophenone 28,
in 72% isolated yield. Unfortunately, various attempts at
hydrogenolysis failed to remove the tertiary hydroxy group,
even after extended reaction times. Attempts to dehydrate this
compound were similarly unproductive and, not unexpectedly,
a single attempt to effect removal of the Boc group led to
intractable material. Therefore, as the scheme stands, it is not
amenable to preparation of 9-substituted xanthenes.
Scheme 6
required phenols 20, again in good yields. The reaction required
four hours to reach completion, but TLC and 1H NMR analysis
showed that the debenzylation step was complete after the first
hour. The central conversion into the iodoxanthenes 21 was
then carried out by a combined deprotection–cyclisation
sequence which gave highly respectable overall yields in all
cases. Again, there was no benefit in isolating and purifying the
intermediate aminophenols (cf. 15). This sequence could be
extended to naphthols. Thus, 2-benzyloxy-1-naphthaldehyde
underwent condensation with the dianion 1 to provide a 55%
isolated yield of the expected adduct 22a, double hydrogen-
olysis of which gave the phenol 22b in 82% isolated yield. The
final deprotection–cyclisation sequence then gave the iodo-
benzoxanthene 23 in 75% isolated yield. Unexpectedly, when
the final reaction mixture was left stirring for an additional
hour, the initial xanthene 23 was converted into the correspond-
ing xanthone 24, presumably by interaction with the excess
N-iodosuccinimide and/or by aerial oxidation. This new
product was identified by its molecular weight, along with
disappearance of the xanthene 9-methylene resonances and the
appearance of a carbonyl group (183.2 ppm in the 13C NMR
In summary, we have shown that using this aminobenzotri-
azole methodology it is indeed possible to secure good yields of
products from the intramolecular trapping of benzynes with
phenolic groups, for the first time. There are clearly some limit-
ations, in particular the further iodination of electron-rich
products (i.e. products 26 and 27) and the difficulties associated
with the incorporation of a 9-substituent. On the credit side, the
incorporation of the additional iodine atom into the xanthenes
clearly offers many opportunities for further homologation by
a wide variety of functionalities using the plethora of metal-
catalysed coupling reactions currently available and should
allow access to many types of xanthene and xanthone deriv-
atives. Further modifications of this overall scheme are in
progress both to address these problems and also to extend
this chemistry to the synthesis of other ring sizes and related
heterocyclic systems.
spectrum and a C᎐O stretch at 1644 cmϪ1 in the infrared
᎐
spectrum). Traces of this xanthone could be detected in the
original crude product, obtained from the shorter reaction time
leading to the iodobenzoxanthene 23.
A further example featured extended hydrogenation of the
naphthaldehyde derivative 22a which delivered an excellent
yield of the tetralin (1,2,3,4-tetrahydronaphthalene) derivative
25, which we expected would undergo cyclisation in the same
J. Chem. Soc., Perkin Trans. 1, 2001, 1771–1777
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(Mϩ ϩ 1, 100%) and 120 (100) [Found: C, 59.91; H, 7.42; N,
11.36. C25H36N4O5Si requires C, 59.97; H, 7.25; N, 11.20%].
Experimental
For general experimental details, see ref. 1.
1-(tert-Butoxycarbonylamino)-7-[hydroxy(2-hydroxy-3-meth-
oxyphenyl)methyl]-1H-benzotriazole 12. Benzotriazole 11b
(0.15 g, 0.30 mmol), in dichloromethane (10 ml), was stirred
with hydrogen fluoride–pyridine complex (1 ml) for 48 h.
Potassium carbonate (2 g) was added and the mixture was
stirred for a further 0.5 h before being acidified with hydro-
chloric acid (2 M, ∼10 ml). The mixture was separated and the
aqueous layer extracted with dichloromethane (3 × 10 ml). The
combined organic extracts were washed with water (10 ml) and
brine (10 ml), then dried and evaporated to yield the phenol 12
as a brown solid (0.096 g, 83%), mp 155–156 ЊC, νmax/cmϪ1 3148,
2966, 2840, 2797, 2697, 2647, 1749, 1615, 1540, 1483, 1442,
1396, 1371, 1277, 1156, 1125, 1057, 1037, 905, 865, 816 and 759;
δH 1.35–1.52 (9H, br s, C(CH3)3), 3.91 (3H, s, CH3O), 6.17–6.23
(1H, br s, OH), 6.51–6.55 (1H, br s, CHOH), 6.66 (1H, d, J 7.5,
1 × Ar-H), 6.81–6.89 (2H, m, 2 Ar-H), 7.27–7.37 (2H, m,
2 × Ar-H), 7.98 (1H, d, J 7.8, 4-H) and 8.40–8.52 (1H, br s
NH); δC 28.4 (C(CH3)3), 56.5 (CH3O), 84.0 (C(CH3)3), 111.1
(CHOH), 120.2, 120.5, 120.7, 124.8 (all CH), 126.0 (C), 127.6
(CH), 130.2, 140.8, 143.8, 143.6, 146.2, 147.1 (all C) and 154.5
Metallation and homologation of 1-(tert-butoxycarbonylamino)-
1H-benzotriazole: general procedure
Anhydrous cerium() chloride was prepared from the hepta-
hydrate by drying in a vacuum oven at 140 ЊC and 0.1 mmHg
for 4 days with regular turning and crushing of the sample. The
dry salt (1.1 equivalents) was slurried in dry tetrahydrofuran
(30 ml mmolϪ1) for 16 h. In a separate flask, butyllithium (2.2
equivalents of a 1.6 M solution in hexanes) was added to
a stirred solution of dry tetraglyme (5 equivalents) in dry
tetrahydrofuran (10 ml mmolϪ1) maintained below Ϫ70 ЊC
using a dry ice–acetone bath. After 0.5 h, a solution of 1-(tert-
butoxycarbonylamino)-1H-benzotriazole1 (1 equivalent) in dry
tetrahydrofuran (10 ml mmolϪ1) was added dropwise. The
resulting deep purple solution of the dianion 1 was stirred at the
same temperature for 0.5 h. During this period, the cerium()
chloride suspension was cooled in a dry ice–acetone bath and
titrated with butyllithium (1.6 M in hexanes) until a faint but
permanent orange colour appeared; typically this required 0.1
ml mmolϪ1. The purple dianion solution was then rapidly trans-
ferred via syringe into the cerium() chloride suspension. The
resulting mixture was warmed to 0 ЊC during 3 h, then recooled
to Ϫ78 ЊC and treated with a solution of an electrophile (1.1
equivalents) in tetrahydrofuran (1 ml mmolϪ1). The mixture was
then allowed to warm slowly to ambient temperature and
stirred for 16 h before quenching with saturated aqueous
ammonium chloride (10 ml mmolϪ1 of benzotriazole), followed
by acidification using 2 M hydrochloric acid. The resulting
mixture was extracted with ether (3 × 30 ml mmolϪ1). The com-
bined extracts were washed with saturated aqueous sodium
hydrogen carbonate (10 ml mmolϪ1), water (10 ml mmolϪ1) and
brine (10 ml mmolϪ1) then dried and evaporated. Column
chromatography (CC) of the residue (ca. 20 g silica per mmol)
in petrol–ether (7 : 3), unless otherwise stated, separated the
pure product.
(C᎐O), m/z (APcI) 387 (Mϩ ϩ 1, 100%) and 287 (30) [Found:
᎐
Mϩ ϩ 1, 387.1667. C19H23N4O5 requires M, 387.1668].
1-(tert-Butoxycarbonylamino)-7-[(2-hydroxy-3-methoxy-
phenyl)methyl]-1H-benzotriazole 14. Benzotriazole 12 (0.20 g)
was subjected to the general dehydroxylation conditions
described below to give the phenol 14 (0.18 g, 87%) as a colour-
less solid which showed mp 59–62 ЊC, νmax/cmϪ1 3296, 2978,
2941, 1746, 1616, 1480, 1442, 1394, 1370, 1275, 1275, 1254,
1158, 1118, 1077, 911 and 734; δH 1.31–1.63 (9H, br s, C(CH3)3),
3.91 (3H, s, MeO), 4.32–4.41 (2H, br s, CH2
(Ar )), 6.61 (1H, dd,
2
J 7.8 and 6.4, 1 Ar-H), 6.71–6.80 (2H, m, 2 × Ar-H), 7.28 (1H,
t, J 8.1, Ar-H), 7.32 (1H, t, J 7.4, 5-H), 7.91 (1H, d, J 7.4, 6-H)
and 8.54–8.65 (1H, br s, NH); δC 29.0 (C(CH3)3), 30.4 (CH2),
57.0 (MeO), 84.6 (C(CH3)3), 110.2, 119.0, 120.8 and 123.0 (all
CH), 124.7 (C), 126.0 and 130.8 (both CH), 132.1, 144.2 and
147.4 (all C) and 154.3 (C᎐O), m/z (APcI) 371 (Mϩ ϩ 1, 100%)
᎐
1-(tert-Butoxycarbonylamino)-7-[hydroxy(2-tert-butyldimeth-
ylsilyloxyphenyl)methyl]-1H-benzotriazole 11a. Following the
general procedure, treatment of dianion 1 generated from the
corresponding aminobenzotriazole (0.234 g, 1 mmol) with
2-(tert-butyldimethylsilyloxy)benzaldehyde 10a (0.228 g, 1.1
mmol) yielded the alcohol 11a as a beige, crystalline solid (0.389
g, 82%), mp 163–168 ЊC, νmax/cmϪ1 3249, 2931, 2857, 1754,
1600, 1457, 1370, 1253, 1158, 1075 and 1004; δH Ϫ0.1 (3H, s,
Si(CH3)), 0.07 (3H, s, Si(CH3)), 0.94 (9H, s, Si(CH3)3), 1.37–
1.58 (9H, br s, C(CH3)3), 6.77 (1H, t, J 6.1, 5Љ-H), 6.84–6.88
(2H, m, 6Љ-H and 1Ј-H), 7.08 (1H, t, J 6.1, 4Љ-H), 7.14 (1H, d,
J 6.1, 3Љ-H), 7.40 (1H, t, J 8.0, 5-H), 7.07 (1H, d, J 8.0, 6-H),
7.94 (1H, d, J 8.0, 4-H) and 8.84 (1H, br s, NH); δC 14.6 (CH3),
18.5 (CH3), 26.1 (Si(CH3)3), 28.5 (C(CH3)3), 60.9 (CH, 1Ј-C),
84.5 (C(CH3)3), 117.3, 119.5, 120.7, 125.3, 128.1, 128.2, 129.5
and 314 (30) [Found: C, 61.72; H, 6.11; N, 15.04. C19H22N4O4
requires C, 61.59; H, 5.99; N, 15.13%].
Material that showed identical analytical properties was
given when benzotriazole 19b (0.47 g, 1 mmol) was subjected to
the general dehydroxylation conditions giving phenol 14 (0.30 g,
82%) as a colourless solid, mp 59–61 ЊC (see below).
Deprotection and cyclisation: general procedure
The N-tert-butoxycarbonylaminobenzotriazole (14, 20, 22b or
25) (n mmol) was dissolved in dichloromethane (10 ml mmolϪ1
)
containing trifluoroacetic acid (2 ml mmolϪ1) and the resulting
solution stirred at ambient temperature until TLC analysis
showed disappearance of the starting material (ca. 0.5 h). The
reaction mixture was then basified with aqueous sodium
hydroxide (2 M, ∼10 ml mmolϪ1) and the pH of the solution
reduced to ∼5 with hydrochloric acid (2 M, ∼3 ml mmolϪ1). The
aqueous phase was separated and saturated with sodium chlor-
ide then extracted with dichloromethane (3 × 10 ml mmolϪ1).
The combined organic solutions were washed with brine (10 ml
mmolϪ1), then dried and filtered. Solid N-iodosuccinimide (~2.5
eq.) was then added to the filtrate in the dark. The resulting
purple solution was stirred for a further 0.5 h then washed with
saturated aqueous sodium thiosulfate (5 ml mmolϪ1), water (5
ml mmolϪ1) and brine (5 ml mmolϪ1), then dried and evapor-
ated to give the crude product, column chromatography of
which (eluent, petrol) gave the pure product.
(all CH), 145.1 (C) and 172.3 (C᎐O); m/z (APcI) 471 (Mϩ ϩ 1,
᎐
100%) [Found: C, 61.01; H, 7.20; N, 11.90. C24H34N4O4Si
requires C, 61.25; H, 7.29; N, 11.91%].
1-(tert-Butoxycarbonylamino)-7-[hydroxy(2-tert-butyldimeth-
ylsilyloxy-3-methoxyphenyl)methyl]-1H-benzotriazole 11b. Fol-
lowing the general procedure, treatment of dianion 1 generated
from the corresponding aminobenzotriazole (0.936 g, 4 mmol)
with
2-(tert-butyldimethylsilyloxy)-3-methoxybenzaldehyde
10b (1.17 g, 4.4 mmol) yielded the alcohol 11b as a beige, crystal-
line solid (1.56 g, 78%), mp 164–165 ЊC, νmax/cmϪ1 3342, 2928,
1747, 1480, 1251, 1158, 1064, 827 and 778; δH Ϫ0.02 (3H, s,
CH3Si), 0.02 (3H, s, CH3), 3.88 (3H, s, CH3O), 6.74 (1H, dd,
J 8.0 and 1.9, 6Љ-Ar-H), 6.78 (1H, t, J 7.9, 4-H), 6.90 (1H, dd,
J 8.0 and 1.9, Ar-4Љ-H), 7.41 (1H, t, J 8.0, Ar-5Љ-H), 7.89 (1H,
br d, J 7.9, 6-H) and 7.93 (1H, d, J 7.9, 4-H); m/z (APcI) 501
4-Iodo-5-methoxyxanthene 17. Benzotriazole 14 (0.11 g, 0.3
mmol) was subjected to the general deprotection–cyclisation
protocol described above to yield the xanthene 17 as a yellow
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solid (0.08 g, 81%), mp 92–95 ЊC, νmax/cmϪ1 3055, 2983, 2926,
2848, 1594, 1497, 1446, 1240, 1089, 886, 800 and 790; δH 3.90
(3H, s, MeO), 3.97 (2H, s, CH2Ar2), 6.69–6.72 (2H, m, 2 ×
Ar-H), 6.76 (1H, d, J 8.1, Ar-H), 6.90 (1H, t, J 7.6, Ar-H) and
7.06 (1H, d, J 7.6, Ar-H); δC 27.6 (CH2), 55.8 (MeO), 83.6 (C-I),
110.3, 119.3 (both CH), 120.4, 120.5 (both C), 122.3, 123.6
(both CH), 124.9 (C), 127.9, 136.5 (both CH), 150.3 and 153.2
(both C); m/z (APcI) 339 (Mϩ ϩ 1, 100%) [Found (EI):
337.9809. C14H11IO2 requires 337.9806].
General hydrogenation procedure for ‘one pot’ debenzylation–
dehydroxylation
The benzyl ether (n mmol) was stirred in methanol (20 ml
mmolϪ1) with 5% palladium on activated charcoal (0.05 g
mmolϪ1) under a hydrogen atmosphere for 4 h. The reaction
mixture was then filtered through a plug of Celite. The solids
were washed with methanol (30 ml mmolϪ1) and dichlorometh-
ane (2 × 30 ml mmolϪ1), and the combined filtrates dried and
evaporated to give the product.
1-(tert-Butoxycarbonylamino)-7-[hydroxy(2-benzyloxyphenyl)-
methyl]-1H-benzotriazole 19a. Following the general procedure,
treatment of dianion 1 generated from the corresponding
aminobenzotriazole (0.936 g, 4 mmol) with 2-(benzyloxy)-
salicylaldehyde 18a (0.827 g, 4.4 mmol) yielded the alcohol
19a as a beige, crystalline solid (1.145 g, 68%), mp 67–68 ЊC,
νmax/cmϪ1 3263, 3041, 2976, 2933, 1744, 1601, 1490, 1454, 1366,
1242, 1152, 1020 and 737; δH (323 K) 1.41–1.48 (9H, br s,
C(CH3)3), 3.21–3.25 (1H, br d, J 4.4, CHOH), 4.98 (1H, d,
J 11.1, CHaAr), 5.05 (1H, d, J 11.1, CHbAr), 6.62 (1H, d, J 4.4,
CHOH), 7.02–7.06 (2H, m, 5 and Ar-H), 7.1 (1H, d, J 7.1, 6-H),
7.25–7.38 (8H, m, 8 × Ar-H), 7.80–7.85 (1H, br s, NH) and 7.99
(1H, dd, J 7.1 and 7.1, 4-H); δC 28.4 (C(CH3)3), 70.7 (CH2), 84.0
(C(CH3)3), 112.1, 120.4, 121.8, 124.8 (all CH), 126.8 (C), 127.9,
128.0, 129.0, 129.3, 129.7 (all CH), 130.3, 136.4, 145.5, 154.2
1-(tert-Butoxycarbonylamino)-7-[(2-hydroxyphenyl)methyl]-
1H-benzotriazole 20a. Benzotriazole 19a (0.16 g, 0.36 mmol)
was subjected to the general hydrogenation procedure to yield
the phenol 20a as a colourless solid (0.095 g, 78%), mp
97–98 ЊC, νmax/cmϪ1 3268, 3069, 2976, 2933, 1723, 1595, 1456,
1371, 1253, 1157, 910 and 733; δH (323 K) 1.22–1.50 (9H, br s,
C(CH3)3), 4.30–4.39 (2H, br s, CH2Ar2), 6.80–6.89 (2H, m,
2 × Ar-H), 6.99 (1H, d, J 7.5, Ar-H), 7.12 (1H, t, J 7.5, Ar-H),
7.19 (1H, d, J 7.5, 5-H), 7.19 (1H, d, J 7.5, 6-H), 7.25 (1H, t,
J 7.8, Ar-H), 7.81 (1H, d, J 7.5, 4-H) and 8.75–8.82 (1H, br s,
NH); δC 28.4 (C(CH3)3), 30.3 (CH2), 84.3 (C(CH3), 116.3, 118.3,
121.0 (all CH), 124.3 (C), 125.4 (CH), 125.7 (C), 128.6, 129.9,
131.2 (all CH), 131.4, 136.2, 144.8 (all C) and 154.4 (C᎐O);
᎐
m/z (APcI) 341 (Mϩ ϩ 1, 100%) [Found: Mϩ ϩ 1, 341.1615.
C18H21N4O3 requires M, 341.1614].
(all C) and 156.1 (C᎐O); m/z (APcI) 447 (Mϩ ϩ 1, 100%)
᎐
[Found: C, 67.04; H, 5.63; N, 12.29. C25H26N4O4 requires C,
67.25; H, 5.87; N, 12.55%].
1-(tert-Butoxycarbonylamino)-7-[(2-hydroxy-5-methoxy-
phenyl)methyl]-1H-benzotriazole 20b. Benzotriazole 19c (0.47 g,
1.0 mmol) was subjected to the general hydrogenation pro-
cedure to yield the title compound 20b as a beige, crystalline
solid (0.28 g, 75%), mp 70–71 ЊC (EtOAc–hexane), νmax/cmϪ1
3254, 2982, 2933, 2833, 1724, 1605, 1510, 1434, 1395, 1370,
1255, 1209, 1157, 1042, 911, 871, 816 and 736; δH 1.20–1.49
(9H, br s, C(CH3)3), 3.56 (3H, br s, MeO), 4.09–4.21 (2H, br s,
CH2), 6.52 (1H, br s, Ar-H), 6.56 (1H, br d, J ∼7, Ar-H), 6.68
(1H, br d, J ∼7, Ar-H), 6.99–7.12 (2H, br m, 5- and 6-H), 7.59
(1H, br app. s, 4-H) and 9.22–9.27 (1H, br s, NH); δC 28.4
(C(CH3)3), 30.5 (CH2), 56.3 (MeO), 84.3 (C(CH3)3), 110.8,
115.5, 116.8 (all CH), 122.8 (C), 124.1, 125.5, 128.5 (all CH),
1-(tert-Butoxycarbonylamino)-7-[hydroxy(2-benzyloxy-3-
methoxyphenyl)methyl]-1H-benzotriazole 19b. Following the
general procedure, treatment of dianion 1 generated from the
corresponding aminobenzotriazole (1.18 g, 5 mmol) with
2-(benzyloxy)-3-methoxybenzaldehyde 18b (1.33 g, 5.5 mmol)
yielded the alcohol 19b as a beige, crystalline solid (1.64 g, 69%),
mp 59–61 ЊC, νmax/cmϪ1 3370, 2977, 2933, 2840, 1752, 1586,
1479, 1370, 1275, 1158, 1019, 912 and 733; δH 1.31–1.39 (9H, br
s, C(CH3)3), 3.02–3.19 (1H, br app. s, CHOH), 3.85 (3H, s,
MeO), 4.77 (1H, d, J 11.0, CHAAr), 4.89 (1H, d, J 11.0,
CHBAr), 6.41 (1H, d, J 4.1, CHOH), 6.71 (1H, br d, J 5.6, Ar-
H), 6.89 (1H, dd, J 8.4 and 1.3, Ar-H), 6.95–7.06 (2H, m,
2 × Ar-H), 7.12–7.26 (5H, m, 5 × Ar-H), 7.89 (2H, app. d,
J 8.0, 2 × Ar-H); δC 29.4 (C(CH3)3), 57.4 (MeO), 68.7 (CHOH),
76.3 (CH2), 85.2 (C(CH3)3), 114.0, 121.0, 121.6, 125.8, 125.9 (all
CH), 128.1, 128.9 (both C), 129.7, 129.9, 130.0 (all CH), 132.1,
136.2 (both C), 138.7 (CH), 146.5, 153.9 (all C) and 154.0
129.8, 143.2, 147.0, 152.4 (all C) and 155.4 (C᎐O) (one aryl
᎐
quaternary resonance obscured); m/z (APcI) 371 (Mϩ ϩ 1,
100%), 315 (40) and 271 (72) [Found: C, 61.97; H, 6.23; N,
15.20. C19H22N4O4 requires C, 61.59; H, 5.99; N, 15.13%].
4-Iodoxanthene 21a. Benzotriazole 20a (0.088 g, 0.26 mmol)
was subjected to the deprotection–cyclisation protocol to yield
the xanthene 21a as a yellow solid (0.066 g, 86%), mp 73–74 ЊC,
νmax/cmϪ1 3062, 2962, 2926, 1622, 1597, 1445, 1426, 1246, 1099,
891 and 754; δH 3.95 (2H, s, CH2Ar2), 6.69 (1H, t, J 7.7, Ar-H),
6.99 (1H, t, J 7.6, Ar-H), 7.03–7.26 (4H, m, 4 × Ar-H) and 7.58
(1H, d, J 7.6, Ar-H); δC 27.4 (CH2), 83.7 (C-I), 115.8 (CH),
119.6, 120.8 (both C), 122.5, 123.4, 126.7, 127.5, 128.0, 136.5
(all CH), 150.1 and 150.9 (both C); m/z (EI) 308 (Mϩ, 100%)
and 181 (32) [Found: 307.9693. C13H9IO requires 307.9700].
(C᎐O); m/z (APcI) 477 (Mϩ ϩ 1, 100%) [Found: C, 65.60; H,
᎐
5.97; N, 11.82. C26H28N4O5 requires C, 65.52; H, 5.93; N,
11.76%].
1-(tert-Butoxycarbonylamino)-7-[hydroxy(2-benzyloxy-5-
methoxyphenyl)methyl]-1H-benzotriazole 19c. Following the
general procedure, treatment of dianion 1 generated from the
corresponding aminobenzotriazole (1.18 g, 5 mmol) with
2-(benzyloxy)-5-methoxybenzaldehyde 18c (1.33 g, 5.5 mmol)
yielded the alcohol 19c as a beige, crystalline solid (1.73 g, 73%),
mp 65–69 ЊC, νmax/cmϪ1 3266, 3062, 2976, 2933, 2833, 1751,
1497, 1370, 1251, 1210, 1158, 1043, 910, 732 and 697; δH 1.32–
1.45 (9H, br s, C(CH3)3), 3.34–3.39 (1H, br app. s, CHOH), 3.74
(3H, s, MeO), 4.88 (1H, d, J 11.0, CHAAr), 4.95 (1H, d, J 11.0,
CHBAr), 6.53 (1H, d, J 4.4, CHOH), 6.76 (1H, dd, J 5.6 and
2.7, Ar-H), 6.88–6.93 (1H, m, Ar-H), 7.05 (2H, br app. d, J ∼10,
2 × Ar-H), 7.25–7.40 (6H, m, 6 × Ar-H), 7.89–7.97 (1H, br s,
NH) and 7.99 (1H, dd, J 7.7 and 1.7, 4-H); δC 28.4 (C(CH3)3),
56.1 (Me), 67.9 (CHOH), 71.3 (CH2), 84.0 (C(CH3)3), 113.3,
113.8, 114.0, 120.1, 124.9, 128.0, 128.1 (all CH), 128.3 (C),
128.9, 129.2 (both CH), 129.9, 130.2, 131.9, 136.2, 145.5, 150.2
4-Iodo-7-methoxyxanthene 21b. Benzotriazole 20b (0.15 g,
0.40 mmol) was subjected to cyclisation protocol to yield the
xanthene 21b (0.11 g, 81%), mp 99–101 ЊC, νmax/cmϪ1 3055,
2998, 2941, 2826, 1618, 1564, 1496, 1447, 1268, 1237, 1203,
1176, 1150, 1038, 884, 854, 807, 764 and 714; δH 3.81 (3H, s,
MeO), 4.03 (2H, s, CH2Ar2), 6.72 (1H, d, J 7.9, Ar-H), 6.76–
6.82 (2H, m, 2 × Ar-H), 7.11–7.16 (2H, m, 2 × Ar-H) and 7.65
(1H, dd, J 8.0 and 8.1, 2-H); δC 29.3 (CH2), 56.1 (MeO), 85.1
(C-I), 113.4, 113.8, 117.9 (all CH), 121.7, 121.8 (both C), 124.6,
129.4, 137.9 (all CH), 146.4, 151.7 and 156.1 (all C); m/z (APcI)
339 (Mϩ ϩ 1, 100%) [Found: C, 49.51; H, 3.22. C14H11IO2
requires C, 49.71; H, 3.28%].
(all C) and 154.4 (C᎐O); m/z (APcI) 477 (Mϩ ϩ 1, 100%)
᎐
[Found: C, 65.45; H, 6.08; N, 11.81. C26H28N4O5 requires C,
65.53; H, 5.92; N, 11.76%].
1-(tert-Butoxycarbonylamino)-7-[hydroxy(2-benzyloxy-1-
naphthyl)methyl]-1H-benzotriazole 22a. Following the general
J. Chem. Soc., Perkin Trans. 1, 2001, 1771–1777
1775

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procedure treatment of dianion 1 (4 mmol) with 2-(benzyloxy)-
1-naphthaldehyde (1.15 g, 4.4 mmol) yielded the alcohol 22a as
a pale yellow, crystalline solid (1.10 g, 55%), mp 94–97 ЊC
(ether–pentane), νmax/cmϪ1 3256, 3062, 2948, 2926, 2848, 1748,
1625, 1596, 1513, 1454, 1370, 1252, 1157, 1085, 1021, 911, 816,
734 and 697; δH 1.47 (9H, s, C(CH3)3), 5.12 (1H, d, J 11.5,
CHaAr), 5.18 (1H, d, J 11.5, CHbAr), 6.66 (1H, d, J 7.2,
CHOH), 6.93 (1H, d, J 10, Ar-H), 7.00–7.07 (3H, m, 3 × Ar-
H), 7.15–7.20 (3H, m, 3 × Ar-H), 7.28–7.32 (2H, m, 2 × Ar-H),
7.38 (1H, d, J 8.0, Ar-H), 7.61–7.65 (1H, m, Ar-H), 7.78–7.82
(1H, m, Ar-H), 7.88 (1H, d, J 8.0, Ar-H), 7.93 (1H, d, J 8.3,
Ar-H) and 8.90 (1H, s, NH); δC 28.5 (C(CH3)3), 68.4 (CHOH),
72.0 (CH2), 83.9 (C(CH3)3), 114.9 (CH), 120.2 (C), 120.9 (CH),
122.9 (C), 124.4, 124.8 (both CH), 126.3 (C), 126.9, 127.9,
128.9, 129.1 (all CH), 129.2, 129.8 (both C), 131.1 (CH), 132.3,
lation procedure for 18 h to yield the tetrahydronaphthol 25 as a
colourless solid (0.31 g, 79%), mp 102–103 ЊC, νmax/cmϪ1 3254,
2976, 2934, 2862, 1724, 1592, 1488, 1455, 1395, 1370, 1253,
1158, 1056, 1019, 910, 812 and 733; δH 1.20–1.55 (9H, br s,
C(CH3)3), 1.60–1.70 (4H, br res, 2 × CH2), 2.35–2.40 (2H, br
res, CH2), 2.65–2.72 (2H, br res, CH2), 4.15–4.20 (2H, br res,
Ar2CH2), 6.55 (1H, br d, J ∼8, Ar-H), 6.60 (1H, br d, J ∼8,
Ar-H), 6.78 (1H, br d, J ∼8, 6-H), 6.98 (1H, br t, J ∼8, 5-H),
7.52 (1H, br d, J ∼8, 4-H) and 8.80–8.95 (1H, br s, NH); δC 22.9,
23.2, 25.0 and 26.6 (all CH2), 28.1 (C(CH3)3), 29.6 (CH2), 83.9
(C(CH3)3), 113.4, 117.7 (both CH), 122.1, 123.7 (both C), 125.0,
126.8, 128.8 (all CH), 129.8, 131.1, 137.2, 144.4, 152.3 (all C)
and 153.9 (C᎐O); m/z (APcI) 395 (Mϩ ϩ 1, 100%) and 339 (20)
᎐
[Found: C, 66.68; H, 6.88; N, 14.14. C22H26N4O3 requires C,
66.97; H, 6.65; N, 14.21%].
135.9, 146.1 (all C) and 155.2 (C᎐O) (3 × CH resonances
᎐
coincidental); m/z (ES) 497 (Mϩ ϩ 1, 100%) [Found: C, 70.39;
H, 5.80; N, 11.41. C29H28N4O4 requires C, 70.13; H, 5.69; N,
11.29%].
6,8- and 6,9-Diiodo-1,2,3,4-tetrahydro-12H-benzo[a]xanthene
26 and 27. Benzotriazole 25 (0.40 g, 1.0 mmol) was subjected
to the general deprotection–cyclisation protocol to yield the
xanthenes 26 and 27 (0.27 g, 77%) as an approximately 1 : 1
mixture. A sample of the 6,8-diiodide 26 was separated by
fractional crystallization from dichloromethane–petrol and
showed mp 87–89 ЊC, δH 1.72–1.79 (2H, br m, 8-CH2), 1.83–
1.91 (2H, br m, 9-CH2), 2.61 (2H, br app. t, J 6.5, 7-CH2), 2.72
(2H, br app. t, J 6.3, 10-CH2), 3.90 (2H, s, CH2Ar2), 6.79 (1H, t,
J 7.7, 2-H), 7.16 (1H, d, J 7.7, 1-H), 7.48 (1H, s, 6-H) and 7.69
(1H, d, J, 7.7, 3-H); δC 21.4, 21.8, 25.2, 25.3, 28.1 (all CH2),
79.7, 83.2 (both C-I), 112.9 (C), 123.7 (CH), 124.8, 127.2 (both
C), 127.9 (CH), 128.3 (C), 136.8, 136.8 (both CH), 147.9 and
150.3 (both C); m/z (APcI) 489 (Mϩ ϩ 1, 100%).
1-(tert-Butoxycarbonylamino)-7-[(2-hydroxy-1-naphthyl)-
methyl]-1H-benzotriazole 22b. Benzotriazole 22a (0.43 g, 0.87
mmol) was subjected to the general hydrogenation procedure
to yield naphthol 22b as a colourless solid (0.28 g, 82%), mp
117–120 ЊC, νmax/cmϪ1 3263, 3062, 2984, 2833, 1720, 1629, 1513,
1439, 1370, 1272, 1252, 1157, 993, 909, 815 and 733; δH (323 K)
1.51–1.59 (9H, br s, C(CH3)3), 4.83 (2H, s, CH2Ar2), 6.00–6.30
(1H, br s, OH), 6.75 (1H, d, J 7.2, Ar-H), 7.01 (1H, t, J 7.6,
5-H), 7.20 (1H, d, J 7.6, 6-H), 7.35 (1H, t, J 7.9, Ar-H), 7.41
(1H, t, J 7.9, Ar-H), 7.70 (1H, d, J 7.6, Ar-H), 7.78 (2H, d, J 8.8,
2 × Ar-H), 7.84 (1H, d, J 7.6, 4-H) and 8.68–8.72 (1H, br s,
NH); δC 23.0 (CH2), 28.5 (C(CH3)3), 84.7 (C(CH3)3), 115.7 (C),
118.6, 123.4, 123.7 (all CH), 123.8, 124.4 (both C), 125.5, 128.2,
129.0, 129.5 (all CH), 129.7, 131.2, 134.1, 144.7 (all C) and
From spectra of the mixture, the 6,9-diiodide 27 showed δH
1.72–1.79 (2H, br m, 8-CH2), 1.83–1.91 (2H, br m, 9-CH2), 2.65
(2H, br app. t, J 6.5, 7-CH2), 2.77 (2H, br app. t, J 6.3, 10-CH2),
3.90 (2H, s, CH2Ar2), 6.75 (1H, t, J 7.7, 2-H), 6.99 (1H, s, 6-H),
7.16 (1H, d, J 7.7, 1H) and 7.62 (1H, d, J 7.7, 3-H).
152.5 (C᎐O) (2 × CH coincidental); m/z (APcI) 391 (Mϩ ϩ 1,
᎐
100%) [Found: C, 67.31; H, 5.42. C22H22N4O3 requires C, 67.66;
H, 5.68%].
1-(tert-Butoxycarbonylamino)-7-[1-(2-benzyloxyphenyl)-1-
hydroxyethyl]-1H-benzotriazole 29a. Following the general
procedure, treatment of dianion 1 (5 mmol) with 2-(benzyl-
oxy)acetophenone 28 (1.24 g, 5.5 mmol) yielded the alcohol 29a
as a beige, crystalline solid (1.65 g, 72%), mp 67–68 ЊC (ether–
petrol), νmax/cmϪ1 3279, 3062, 2980, 2933, 1753, 1600, 1488,
1453, 1370, 1252, 1159, 1052, 911, 806, 751 and 699; δH 1.25–
1.56 (9H, br s, C(CH3)3), 2.05 (3H, s, 1Ј-Me), 4.82–4.91 (1H, br
app. s, CHaAr), 4.95–5.05 (1H, br res., CHbAr), 5.32–5.40 (1H,
br s, OH), 6.72–7.32 (10H, br res., 10 × Ar-H), 7.40 (1H, t,
J 7.7, Ar-H), 8.05 (1H, d, J 8.4, 4-H) and 9.10–9.42 (1H, br s,
NH); δH (323 K) 1.40–1.45 (9H, br s, C(CH3)3), 2.05 (3H, s,
1Ј-Me), 4.90 (1H, br d, J ∼10, CHaAr), 5.02 (1H, br d, J ∼10,
CHbAr), 5.27 (1H, s, OH), 6.80–6.92 (2H, br res, 2 × Ar-H),
7.01 (1H, t, J 7.5, 5-H), 7.09 (1H, d, J 7.5, 6-H), 7.11–7.19 (2H,
m, 2 × Ar-H), 7.20–7.27 (4H, m, 4 × Ar-H), 7.36 (1H, t, J 8.2,
Ar-H), 8.04 (1H, d, J 7.5, 4-H) and 8.81–9.00 (1H, br s, NH);
δC 28.5 (C(CH3)3), 29.3 (CH3), 71.3 (CH2), 77.9 (MeCOH), 83.2
(C(CH3)3), 113.6, 120.6, 122.0, 124.2, 126.1, 127.8, 129.0, 129.1
(all CH), 129.7 (C), 130.1 (CH), 134.0, 135.6, 141.1, 146.8,
8-Iodo-12H-benzo[a]xanthene 23. Benzotriazole 22b (0.12 g,
0.31 mmol) was subjected to the deprotection–cyclisation
protocol to yield the xanthene 23 (0.08 g, 75%), mp 131–133 ЊC,
νmax/cmϪ1 3062, 2962, 2926, 2855, 1645, 1595, 1437, 1252, 1066
and 816; δH 4.33 (2H, s, CH2Ar2), 6.77 (1H, t, J 7.6, 10-H), 7.22
(1H, dd, J 7.5 and 7.5, 5-H), 7.31 (1H, d, J 7.6, 9-H), 7.39 (1H,
t, J 7.1, 4-H), 7.52 (1H, t, J 7.1, 3-H), 7.64 (1H, d, J 8.3, 6-H),
7.70 (1H, d, J 8.3, 7-H) and 7.77–7.81 (2H, m, 2- and 11-H);
δC 29.4 (CH2), 81.2 (C-I), 117.0, 117.1 (both CH), 122.3 (C),
123.6, 124.8 (both CH), 125.2 (C), 126.2, 127.4, 127.5, 127.5 (all
CH), 128.8, 129.1 (both C), 136.1 (CH), 136.7 and 142.1 (both
C); m/z (APcI) 360 (Mϩ ϩ 2, 24%) and 356 (100) [Found: C,
57.11; H, 3.26. C17H11IO requires C, 56.99; H, 3.10%].
8-Iodo-12H-benzo[a]xanthen-12-one 24. Benzotriazole 22b
(0.12 g, 0.31 mmol) was subjected to the deprotection–
cyclisation protocol and the solution allowed to stir for an
additional 1 h before workup, as before, to yield the xanthone 24
as a beige, crystalline solid (0.09 g, 84%) (1H NMR showed
essentially quantitative conversion), mp 110–112 ЊC, νmax/cmϪ1
2962, 2926, 2855, 1781, 1644, 1452, 1373, 1337, 1258, 1223,
1158, 1044 and 808; δH 6.73 (1H, d, J 8.2, 5-H), 7.36 (1H, t,
J 7.7, 10-H), 7.74–7.85 (3H, m, 3-, 4- and 7-H), 8.20 (1H, d,
J 7.7, 11-H), 8.60 (1H, d, J 7.7, 9-H), 8.79 (1H, s, 6-H) and
10.21 (1H, d, J 8.2, 2-H); δC 92.1 (C-I), 126.5 (CH), 128.4, 128.9
(both C), 129.4, 129.6, 129.7 (all CH), 130.2, 131.4 (both C),
132.4, 134.5 (both CH), 135.0, 137.7 (both C), 136.0, 147.6
151.9 (all C) and 156.2 (C᎐O); m/z (APcI) 461 (Mϩ ϩ 1, 100%)
᎐
[Found: C, 67.98; H, 6.21; N, 12.20. C26H28N4O4 requires C,
67.79; H, 6.13; N, 12.17%].
1-(tert-Butoxycarbonylamino)-7-[1-hydroxy-1-(2-hydroxy-
phenyl)ethyl]-1H-benzotriazole 29b. Benzotriazole 29a (0.46 g,
1.0 mmol) was subjected to the general hydrogenation pro-
cedure to yield the phenol 29b as a colourless solid (0.29 g,
79%), mp 102–103 ЊC, νmax/cmϪ1 3279, 2976, 1713, 1581, 1496,
1366, 1287, 1225, 1151, 901, 808 and 743; δH 1.16–1.50 (9H, br
s, C(CH3)3), 1.97–2.02 (3H, s, Me), 6.05–6.12 (1H, br d, J ∼7,
6Љ-H), 6.38–6.49 (1H, br t, J ∼7, 5Љ-H), 6.82–6.90 (1H, br d,
J ∼8, 6-H), 7.02–7.11 (1H, br t, J ∼8, 5-H), 7.13–7.25 (1H, br t,
J ∼7, 4Љ-H), 7.35–7.42 (1H, br d, J ∼7, 3Љ-H), 7.57–7.71 (1H, br
(both CH) and 183.2 (C᎐O) (one C obscured).
᎐
1-(tert-Butoxycarbonylamino)-7-[(2-hydroxy-5,6,7,8-tetra-
hydro-1-naphthyl)methyl]-1H-benzotriazole 25. Benzotriazole
22a (0.50 g, 1.0 mmol) was subjected to the general dehydroxy-
1776
J. Chem. Soc., Perkin Trans. 1, 2001, 1771–1777

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Heterocyclic Chemistry, II, eds. A. R. Katritzky, C. W. Rees and E. F.
s, NH) and 7.72–7.81 (1H, br d, J ∼8, 4-H); δC 28.3 (C(CH3)3),
28.4 (Me), 78.5 (MeCOH), 83.8 (C(CH3)3), 118.4, 120.2, 121.0,
124.5, 126.7 (all CH), 128.9, 129.7 (both C), 129.9 (CH), 130.1
V. Scriven, Elsevier Science Ltd., Oxford, 1996, vol. 5, p. 379.
10 For recent contributions, see C. Scala-Valero, D. Doizi and
G. Guillaumet, Tetrahedron Lett., 1999, 40, 4803; O. Sirkecioglu,
N. Talinli and A. Akar, J. Heterocycl. Chem., 1998, 35, 457; M. Ruth
and W. Steglich, Synthesis, 2000, 677; M. B. Dinger and M. J. Scott,
J. Chem. Soc., Perkin Trans. 1, 2000, 1741; L. Novak, P. Kovacs,
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11 R. Vázquez, M. C. de la Fuente, L. Castedo and D. Domínguez,
Synlett, 1994, 433.
12 A. Mustafa, W. Asker and M. E. E. D. Sebhy, J. Am. Chem. Soc.,
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4418.
(C), 130.5 (CH), 146.0, 153.9 (both C) and 155.5 (C᎐O); m/z
᎐
(APcI) 371 (Mϩ ϩ 1, 100%) and 353 (55) [Found: C, 61.29; H,
5.52; N, 14.86. C19H22N4O4 requires C, 61.61; H, 5.99; N,
15.13%].
Acknowledgements
We are grateful to the EPSRC Mass Spectrometry Service
at University College, Swansea for the provision of high
resolution mass spectral data, to Mrs F. Godwin for helpful
assistance and to Cardiff University for financial support.
13 N. D. Xuong and N. P. Buu-Hoi, J. Chem. Soc., 1952, 3741.
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