New derivatives of the 1,2-benzodiazepine ring system

Article abstract of DOI:10.1039/b005696k

The adducts 10, formed in high yield by condensations between the benzotriazole dianion 2 and enals 9, undergo smooth oxidation by manganese(IV) oxide to provide the expected conjugated enones. These then cyclise at varying rates, depending upon the subst

Full text of DOI:10.1039/b005696k

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New derivatives of the 1,2-benzodiazepine ring system
David W. Knight* and Paul B. Little
Chemistry Department, Cardiff University, P.O. Box 912, Cardiff, UK CF10 3TB
1
Received (in Cambridge, UK) 14th July 2000, Accepted 18th August 2000
First published as an Advance Article on the web 27th October 2000
The adducts 10, formed in high yield by condensations between the benzotriazole dianion 2 and enals 9, undergo
smooth oxidation by manganese() oxide to provide the expected conjugated enones. These then cyclise at varying
rates, depending upon the substitution pattern around the enone function, by intramolecular Michael addition of the
NHBoc group to provide examples 13 of a novel ring system based upon a 4,5,6,7-tetrahydro-1,2-benzodiazepine
core. Allylic acetates 16 derived from the initial adducts 10 also undergo cyclisations via the derived π-allyl palladium
complexes 15 to provide examples of the corresponding 4,5-dihydro-1,2-benzodiazepinenes 17, but in a less general
manner.
Despite the enormous advances in pharmaceutical design and
synthesis in recent times, the bulk of commercially successful
products are still based upon heterocyclic ring systems.1 Clearly,
therefore, there is a continuing need for the definition of
routes to novel heterocyclic arrays. We have recently described
methods for the generation of the dianion 2 from the parent
Fig. 1
benzotriazole derivative 1 (Scheme 1).2 This can be used in a
hydrolysis of one of these groups occurs upon exposure to
warm methanolic sodium hydroxide to provide excellent yields
of the mono(Boc) derivative 1.) We reasoned that it ought
to be possible to exploit this level of nucleophilicity in a more
positive way by using various types of bond formation between
the NHBoc function and electrophilic centres in the newly
introduced 7-substituents in the derivatives 3 (Fig. 1). As con-
densations between the dianion 2 and conjugated aldehydes and
ketones resulted in exclusive [1,2]-addition to give the adducts
8,2 we have examined opportunities for the manipulation of
the resulting allylic alcohol function in order to generate such
systems. Herein, we report that intramolecular additions to the
derived enones and to allylic acetates both provide routes to a
novel 1,2-benzodiazepine ring system.3
Scheme 1
number of ways for the elaboration of the 7-substituted homo-
logues 3, precursors of ortho-substituted benzynes. During this
work, the high nucleophilicity of the N-amino group in such
aminobenzotriazoles manifested itself in a number of ways. For
example, the deprotected free amines 4 were very rapidly trans-
formed into the corresponding imines 5 when dissolved in
acetone. This reaction was so facile that exposure to even traces
of this solvent had to be avoided at all times. The N-Boc func-
tion in derivatives 1 and 3 is also highly nucleophilic. During
the early stages of our studies in this area, chromatographic
solvent systems based on ethyl acetate were often used, which
resulted in the isolation of variable amounts of by-products
(5–20%, depending on time of exposure), manifested by the
appearance of a new singlet at ca. δH 2.5. These were identified
as the N-acetyl derivatives 6, formed by reaction between the
NHBoc group and ethyl acetate. Hence, this and related
solvents were always avoided in subsequent work. Perhaps the
most definitive example of this phenomenon is the unavoidable
formation of the bis(Boc) derivative 7 during protection
of the parent 1-aminobenzotriazole.2 (Fortunately, selective
Results and discussion
Condensations between representative enals 9 and dianion 2
were best carried out after modification of the initial dilithio
derivative of dianion 2 by the addition of cerium() chloride,
resulting in increases in yields of 10–15%. Isolated yields of the
resulting allylic alcohols 10 thus ranged from good to excellent
(71–92%; Scheme 2). The simplest member 12 of the series was
prepared by an alternative route in which the dianion 2 was
3752
J. Chem. Soc., Perkin Trans. 1, 2000, 3752–3757
This journal is © The Royal Society of Chemistry 2000
DOI: 10.1039/b005696k

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Scheme 2 Condensations between dianion 2 and enals.
Scheme 3 Formation of [1,2]benzodiazepin-7-one derivatives.
formylated using DMF as the electrophile and the resulting
evidently the enone 14a according to both infrared and NMR
aldehyde 112 reacted with vinylmagnesium chloride at 0 ЊC in
THF. This gave an essentially quantitative yield of the desired
adduct 12. When the allylic alcohol 10a, derived from croton-
aldehyde, was treated with activated manganese() oxide, pre-
pared by the Attenburrow method,4 in dichloromethane at
ambient temperature, TLC analysis indicated the formation of
a single, less polar product after 3 hours (Scheme 3). Filtration
and evaporation gave a single compound, isolated in 92% yield,
which was evidently devoid of an enone function but which did
contain a new carbonyl group (νmax 1674 cmϪ1; δC 194.0 ppm),
consistent with the expected formation of an aryl ketone. Fur-
data. Fortunately, in terms of the aims of this study, addition
of a slight excess of triethylamine to the reaction mixture, after
completion of the oxidation step, triggered a smooth intra-
molecular Michael addition to this poorer acceptor function
and the anticipated heterocycle 13d was isolated in 76%
yield. The enone 14b proved similarly recalcitrant in terms
of the Michael addition until triethylamine was added and gave
a similarly good isolated yield of the anticipated product
13e. Returning to the simplest allylic alcohol 12, the parent
heterocycle 13f was obtained in less than 3 h without the need
to add triethylamine, as expected.
1
ther, the H and 13C spectra, when obtained at 300 K, showed
very broadened resonances and it was only when these spectra
were run at 340 K that useful analysis could be carried out. This
clearly showed the presence of an ABX system; all of these data
were consistent with formation of the novel benzodiazepinone
structure 13a. It is presumed that the line broadening was due
either to rotation of the NHBoc function or to pseudorotation
around the newly formed ring. Hence, in this case, the high
nucleophilicity of the NHBoc function must have facilitated an
intramolecular Michael addition, while oxidation of the allylic
alcohol 10a to the corresponding enone proceeded. Attempts to
observe the latter intermediate by either TLC or 1H NMR were
not successful, indicating that the Michael addition is faster
than oxidation. Exposure to other oxidants including Jones
reagent or pyridinium chlorochromate (PCC) failed to generate
the enone cleanly.
We then turned to our second strategy, in which formation
of an intermediate π-allyl species 15 (Fig. 2) was a central
feature.5 For this, we required the allylic acetates 16 which, in
the cases of the parent alcohol 12 or the distally alkylated
derivatives 10a,b, were selectively formed by exposure to acetic
anhydride. Subsequent reaction6 of the parent acetate 16a with
catalytic amounts of Pd(PPh3)4 and an equivalent of potassium
carbonate in THF at ambient temperature resulted in dis-
appearance of the starting material after 3 h (Scheme 4). A
The other alkyl-substituted allylic alcohols 10b,c were
similarly converted into the substituted benzodiazepinones
13b,c in excellent isolated yields. While oxidation of the alcohol
10c was significantly slower, the product 13c was nevertheless
isolated in excellent yield and as a single diastereoisomer, which
we presume had the trans stereochemistry although this was not
proven with certainty as, due to the rotameric nature of the
compound, only low quality NOE data could be obtained.
In contrast, oxidation of the cinnamaldehyde-derived alcohol
10d was even slower but was completed cleanly after 36 h.
However, the product, although not fully characterised, was
Scheme 4
single product 17a was subsequently separated by column
chromatography, which evidently had the expected benzo-
diazepine structure. Similarly, the methyl-substituted acetate
16b gave the corresponding heterocycle 17b but the slightly
larger propyl group of acetate 16c slowed the cyclisation
J. Chem. Soc., Perkin Trans. 1, 2000, 3752–3757
3753

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with regular crushing. Anhydrous cerium() chloride (1.1 eq.)
was slurried in dry tetrahydrofuran (30 ml mmolϪ1) for 16 h
under dry nitrogen. In a separate vessel butyllithium (1.6 M
solution in hexanes, 2.2 eq.) was added to a stirred solution of
dry tetraglyme (5 eq.) in dry tetrahydrofuran (10 ml mmolϪ1
)
maintained at Ϫ78 ЊC under dry nitrogen. Stirring was con-
tinued for 0.5 h, after which a solution of 1-(N-Boc-amino)-
benzotriazole 6 (n mmol) in dry tetrahydrofuran (10 ml
mmolϪ1) was added slowly via syringe. The resulting deep
purple dianion solution was stirred for 0.5 h at Ϫ78 ЊC;
concurrently the cerium() chloride suspension was cooled
to Ϫ78 ЊC and titrated with butyllithium (1.6 M solution in
hexanes) until the first faint but permanent orange end point
(typically 0.1 ml mmolϪ1). The dianion solution was then
rapidly transferred via syringe to the cerium() chloride sus-
pension. The reaction mixture was stirred at Ϫ78 ЊC for 3 h,
before rapid addition of freshly purified electrophile (1.1 eq.)
in THF (1 ml mmolϪ1). The reaction mixture was slowly
warmed to ambient temperature and stirring was continued
for 16 h, before the reaction was quenched with saturated
ammonium chloride (10 ml mmolϪ1). The resulting mixture was
carefully acidified using 2 M hydrochloric acid and extracted
with ether (3 × 30 ml mmolϪ1). The combined extracts were
washed with saturated aqueous sodium bicarbonate (10 ml
mmolϪ1), water (10 ml mmolϪ1) and brine (10 ml mmolϪ1),
then dried and evaporated to give crude material which was
subjected to column chromatography (20 g silica mmolϪ1) using
petrol–diethyl ether (7:3) to obtain the purified product, unless
otherwise stated.
Fig. 2
significantly. However, after 24 h, a 59% isolated yield of the
expected product 17c was secured. In all three cases, varying
amounts (5–20%) of the corresponding free amines 18 were
observed; presumably, these are formed by loss of the Boc
group during cyclisation as indicated in structure 19, as at no
stage are the reactants exposed to acidic conditions. Taking the
formation of these three amines 18 into account, overall yields
of these heterocycles are thus respectable; higher yields were
not obtained, despite modifications to the reaction conditions
including heating and changes both of solvent and of catalyst.
Unfortunately, the very nucleophilicity upon which this
chemistry relies precluded extensions to this approach. When
attempts were made to form the corresponding acetates from
the allylic alcohols 10c and 10d, we were surprised to find, in the
light of the foregoing results, that the products instead were the
bis-acetylated species 20. In view of the mechanism indicated
in structure 19, it was reasoned that this might not be a draw-
back in terms of formation of the ring system 18. However,
many attempts to cyclise these intermediates under increasingly
vigorous conditions failed to produce the desired heterocycles.
Presumably, the nitrogen function is now both too hindered and
not sufficiently nucleophilic to participate in such cyclisations.
(E)-1-(tert-Butoxycarbonylamino)-7-(1Ј-hydroxybut-2Ј-en-1Ј-
yl)-1H-1,2,3-benzotriazole 10a
Following the general procedure, treatment of dianion 2 gener-
ated from the aminobenzotriazole 1 (0.234 g, 1 mmol) with
freshly distilled (E)-but-2-enal 9a (0.082 ml, 1.1 mmol) gave
alcohol 10a as a brown solid which recrystallised from ether–
petrol to yield the allylic alcohol 10a as colourless crystals
(0.279 g, 92%), mp 115–118 ЊC, νmax/cmϪ1 3267, 2980, 1750,
1456, 1370, 1253, 1160, 1049, 967 and 751; δH 1.30–1.59 (9H, br
s, C(CH3)3), 1.66 (3H, d, J 7.1, 4Ј-H), 2.55–2.65 (1H, br s, OH),
5.55–5.66 (2H, m, CHOH and 3Ј-H), 5.74 (1H, ddd, J 15.4, 5.9
and 1.5, 2Ј-H), 7.26 (1H, t, J 7.1, 5-H), 7.41 (1H, d, J 7.1, 6-H),
7.97 (1H, d, J 7.1, 4-H) and 8.51–8.62 (1H, br s, NH); δC 18.3
(4Ј-CH3), 28.5 (C(CH3)3), 71.2 (1Ј-CHOH), 84.2 (C(CH3)3),
120.5, 124.8 (both CH), 126.8 (C), 127.0 (both CH), 130.2 (C),
131.8 (CH) and 154.2 (C᎐O); m/z (ES) 305 (Mϩ ϩ 1, 100%)
᎐
[Found: C, 59.31; H, 6.69; N, 18.50. C15H20N4O3 requires C,
59.18; H, 6.63; N, 18.42%].
In conclusion, this chemistry has defined a simple approach
to a new benzodiazepine ring system which, despite some
limitations, should be applicable to the elaboration of many
derivatives beyond those reported herein. Not unexpectedly,
in none of the foregoing examples was formation of the related
five-membered derivatives observed. Presumably, ring strain
prevents the generation of such products, despite the oppor-
tunity for their formation, by attack either onto the aryl ketone
function in enones 14 and relatives or onto the benzylic position
in the π-allyl complexes 15. Efforts to further exploit the nucleo-
philicity of the amino function in such aminobenzotriazoles
in the formation of other, novel ring systems are underway.
(E)-1-(tert-Butoxycarbonylamino)-7-(1Ј-hydroxyhex-2Ј-en-1Ј-
yl)-1H-1,2,3-benzotriazole 10b
Following the general procedure, treatment of dianion 2 gener-
ated from the aminobenzotriazole 1 (0.234 g, 1 mmol) with
freshly distilled (E)-hex-2-enal 9b (0.12 ml, 1.1 mmol) yielded
the alcohol 10b as a colourless crystalline solid (0.289 g, 87%),
mp 138–144 ЊC, νmax/cmϪ1 3264, 2960, 2932, 2873, 1753, 1457,
1394, 1370, 1252, 1160, 1116, 1048, 969 and 771; δH 0.78 (3H,
t, J 7.4, 6Ј-CH3), 1.28 (2H, quintet, J 7.4, 5Ј-CH2), 1.35–1.50
(9H, br s, C(CH3)3), 1.94 (2H, q, J 7.4, 4Ј-CH2), 3.25–3.51 (1H,
br s, OH), 5.58 (1H, app d, J 7.4, 1Ј-CHOH), 5.61 (1H, app t,
J 6.0, 3Ј-H), 5.72 (1H, app dd, J 15.0 and 6.0, 2Ј-H), 7.19 (1H,
t, J 7.1, 5-H), 7.41 (1H, d, J 7.1, 6-H), 7.72 (1H, d, J 7.1, 4-H)
and 8.95–9.05 (1H, br s, NH); δC 13.8 (6Ј-CH3), 22.2 (C(CH3)3),
28.1 (5Ј-CH2), 34.4 (4Ј-CH2), 70.5 (1Ј-CHOH), 83.8 (C(CH3)3),
120.0, 124.5, 126.7 (all CH), 126.7, 129.8 (both C), 130.3, 134.2
Experimental
For general experimental details see ref. 2.
Generation of dianion 2 and condensations with 2-enals:
general procedure
(both CH), 145.2 (C) and 153.9 (C᎐O); m/z (ES) 333 (Mϩ ϩ 1,
᎐
Anhydrous cerium() chloride was prepared from the hepta-
hydrate by drying in a vacuum oven (140 ЊC, 0.1 mmHg, 4 days)
100%) and 98 (92) [Found: C, 61.27; H, 7.42; N, 16.88.
C17H24N4O3 requires C, 61.43; H, 7.28; N, 16.85%].
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J. Chem. Soc., Perkin Trans. 1, 2000, 3752–3757

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(E)-1-(tert-Butoxycarbonylamino)-7-(1Ј-hydroxy-2Ј-methylbut-
2Ј-en-1Ј-yl)-1H-1,2,3-benzotriazole 10c
1371, 1274, 1258, 1100, 990, 912, 804 and 742; δH 1.31–1.78
(9H, app br d, C(CH3)3), 2.88 (1H, s, OH), 5.29–5.32 (2H, m,
2 × 3Ј-H), 5.73 (1H, app d, J 5.0, 1Ј-H), 6.20 (1H, ddd, J 17.2,
10.4 and 4.9, 2Ј-H), 7.34 (1H, t, J 8.2, 5-H), 7.51 (1H, d, J 8.2,
6-H), 7.91 (1H, d, J 8.2, 4-H) and 8.61 (1H, br s, NH); δC 28.5
(C(CH3)3), 71.1 (1Ј-CH), 84.2 (C(CH3)3), 117.2 (CH2), 120.6,
124.9 (both CH), 126.3 (C), 127.5 (CH), 130.2 (C), 138.8 (CH),
By the general procedure, treatment of dianion 2 generated
from the aminobenzotriazole 1 (0.234 g, 1 mmol) with freshly
distilled (E)-2-methylbut-2-enal 9c (0.097 ml, 1.1 mmol) yielded
the allylic alcohol 10c as a colourless crystalline solid (0.283 g,
89%), mp 134–136 ЊC, νmax/cmϪ1 3246, 2978, 1749, 1449, 1370,
1253, 1159, 1050 and 748; δH 1.29–1.50 (9H, br s, C(CH3)3), 1.54
(3H, d, J 9.9, 4Ј-CH3), 1.62 (3H, s, 2Ј-CH3), 3.49–3.60 (1H, br
s, OH), 5.20–5.36 (1H, app br s, 3Ј-H), 5.47–5.52 (1H, app br
s, 1Ј-H), 7.22 (1H, t, J 7.9, 5-H), 7.40 (1H, d, J 7.9, 6-H), 7.77
(1H, d, J 7.9, 4-H) and 8.95–9.05 (1H, br s, NH); δC 13.8
(4Ј-CH3), 14.0 (2Ј-CH3), 28.5 (C(CH3)3), 74.1 (1Ј-CHOH), 83.2
(C(CH3)3), 119.9, 122.9, 124.8, 127.5 (all CH), 128.6, 130.3,
145.6 (C) and 154.1 (C᎐O); m/z (ES) 291 (Mϩ ϩ 1, 100%),
᎐
235 (50) and 179 (24) [Found: C, 57.95; H, 6.38; N, 18.23.
C14H18N4O3 requires C, 57.92; H, 6.25; N, 19.3%].
General oxidation–cyclisation protocol for formation of
1,2-benzodiazepinones 13
The allylic alcohol (n mmol) was stirred in dichloromethane
(20 ml mmolϪ1) at ambient temperature; manganese() oxide
(3.0 g mmolϪ1) was added with vigorous stirring. The progress
of the reaction was monitored by TLC; after all the starting
material had been consumed, the reaction mixture was
passed through a plug of Celite, which was then washed with
copious dichloromethane. The combined filtrates were dried
and evaporated to yield the crude benzodiazepinone which was
purified by column chromatography.
136.4, 145.2 (all C) and 154.2 (C᎐O); m/z (ES) 319 (Mϩ ϩ 1,
᎐
100%), 263 (10) and 175 (11) [Found: C, 60.26; H, 7.08; N,
17.88. C16H22N4O3 requires C, 60.36; H, 6.97; N, 17.60%].
(E)-1-(tert-Butoxycarbonylamino)-7-(1Ј-hydroxy-3Ј-phenylprop-
2Ј-en-1Ј-yl)-1H-1,2,3-benzotriazole 10d
By the general procedure, treatment of dianion 2 generated
from the aminobenzotriazole 1 (0.234 g, 1 mmol) with freshly
distilled (E)-cinnamaldehyde 9d (0.138 ml, 1.1 mmol) yielded
the allylic alcohol 10d as a colourless crystalline solid (0.26 g,
71%), mp 153–155 ЊC, νmax/cmϪ1 3260, 2981, 1749, 1495, 1370,
1273, 1156, 1049 and 969; δH 1.35–1.78 (9H, br s, C(CH3)3),
2.78–2.93 (1H, br s, OH), 5.93 (1H, d, J 5.3, 1Ј-H), 6.52 (1H,
dd, J 15.6 and 5.3, 2Ј-H), 6.68 (1H, app d, J 15.6, 3Ј-H), 7.26–
7.41 (6H, m, 6 × Ar-H), 7.58 (1H, d, J 7.2, 6-H), 7.98 (1H, d,
J 7.2, 4-H) and 8.55 (1H, br s, NH); δC 28.4 (C(CH3)3), 70.9
(1Ј-CHOH), 84.4 (C(CH3)3), 120.8, 125.0 (both CH), 126.5 (C),
127.1, 127.3, 128.6, 129.1, 129.8, 132.7 (all CH), 136.4, 146.1
4-N-(tert-Butoxycarbonyl)-5-methyl-4,5,6,7-tetrahydro[1,2,3]-
triazolo[4,5,1-jk][1,2]benzodiazepin-7-one 13a
Benzotriazole 10a (0.50 g, 1.6 mmol) was subjected to the
general oxidation–cyclisation protocol to yield the benzodiaze-
pinone 13a as colourless crystals (0.45 g, 92%), mp 138–140 ЊC,
νmax/cmϪ1 2978, 1739, 1674, 1594, 1370, 1297, 1157 and 806;
δH (300 K) 1.04–1.18 (3H, br d, 5-CH3), 1.30–1.42 (9H, br s,
C(CH3)3), 3.12 (1H, br d, J ~ 17, 6-HA), 3.30 (1H, br d, J ~ 17,
6-HB), 4.80–4.97 (1H, br res., 5-H), 7.49 (1H, t, J 7.6, 10-H),
8.24 (1H, d, J 7.6, 9-H) and 8.29 (1H, d, J 7.6, 11-H); δH (340 K)
1.21 (3H, d, J 7.2, 5-CH3), 1.37–1.45 (9H, br s, C(CH3)3), 3.14
(1H, dd, J 18.3 and 4.4, 6-HA), 3.32 (1H, dd, J 18.3 and 3.8,
6-HB), 4.58 (1H, m, 5-H), 7.51 (1H, app t, J 7.9, 10-H), 8.29
(1H, d, J 7.9, 9-H) and 8.32 (1H, d, J 7.9, 11-H); δC (340 K)
19.6 (5-CH3), 28.3 (C(CH3)3), 50.2 (CH2), 50.2 (CH), 85.4
(C(CH3)3), 120.1 (C), 125.1, 127.1, 131.0 (all CH), 154.1 and
(both C) and 158.9 (C᎐O); m/z (ES) 367 (Mϩ ϩ 1, 74%) [Found:
᎐
C, 65.56; H, 6.16; N, 15.43. C20H22N4O3 requires C, 65.56;
H, 6.05; N, 15.29%].
1-(tert-Butoxycarbonylamino)-7-[3Ј-(2-furyl)-1Ј-hydroxyprop-
2Ј-en-1Ј-yl]-1H-1,2,3-benzotriazole 10e
Following the general procedure, treatment of dianion 2
generated from the aminobenzotriazole 1 (0.234 g, 1 mmol)
with freshly distilled (E)-3-(2-furyl)prop-2-enal 9e (0.134
g, 1.1 mmol) yielded the allylic alcohol 10e as a brown solid
(0.267 g, 75%), mp 88–91 ЊC, νmax/cmϪ1 3285, 2979, 1747, 1371,
1326, 1158 and 797; δH (323 K) 1.38–1.43 (9H, br s, C(CH3)3),
2.50–2.55 (1H, br s, OH), 5.92–5.99 (1H, br s, 1Ј-H), 6.28 (1H,
d, J 3.2, 4Љ-H), 6.39 (1H, dd, J 3.2 and 2.9, 3Љ-H), 6.45–6.54
(2H, m, 2Ј- and 3Ј-H), 7.32–7.41 (2H, m, 2Љ- and 5-H), 7.65
(1H, d, J 7.5, 6-H), 8.03 (1H, d, J 7.5, 4-H) and 8.29–8.32 (1H,
br s, NH); δC 28.3 (C(CH3)3), 70.3 (1Ј-CHOH), 84.3 (C(CH3)3),
109.6, 111.9, 120.3, 120.5, 125.0 (all CH), 126.4 (C), 127.5,
128.3 (both CH), 130.2 (C), 142.7 (CH), 145.5, 152.2 (both C)
194.0 (both C᎐O); m/z (ES) 303 (Mϩ ϩ 1, 100%) and 247 (74)
᎐
[Found: C, 59.30; H, 5.96; N, 18.44. C15H18N4O3 requires C,
59.59; H, 6.00; N, 18.53%].
4-N-(tert-Butoxycarbonyl)-5-propyl-4,5,6,7-tetrahydro[1,2,3]-
triazolo[4,5,1-jk][1,2]benzodiazepin-7-one 13b
Benzotriazole 10b (0.60 g, 1.8 mmol) was subjected to the
general oxidation–cyclisation protocol to yield the benzodiaze-
pinone 13b as colourless crystals (0.54 g, 91%), mp 145–149 ЊC,
νmax/cmϪ1 2963, 2934, 2874, 1732, 1674, 1596, 1458, 1297, 1294,
1160, 1026 and 1001; δH 0.82 (3H, br t, J 7.0, 3Ј-CH3), 1.10–1.52
(13H, br res., 1Ј- and 2Ј-CH2 and C(CH3)3), 3.20 (1H, br d,
J ~ 17, 6-HA), 3.30 (1H, br d, J ~ 17, 6-HB), 4.62–4.83 (1H,
br res., 5-H), 7.58 (1H, t, J 7.9, 10-H), 8.31 (1H, d, J 7.9, 9-H)
and 8.36 (1H, d, J 7.9, 11-H); δC 13.8 (CH3), 20.2 (CH2), 28.3
(C(CH3)3), 49.8 (CH2), 53.9 (CH), 85.3 (C(CH3)3), 120.0 (C),
125.1, 127.0 (both CH), 128.9 (C), 131.0 (CH), 145.2 (C), 154.3
and 154.2 (C᎐O).
᎐
1-(tert-Butoxycarbonylamino)-7-(1Ј-hydroxyprop-2Ј-en-1Ј-yl)-
1H-1,2,3-benzotriazole 12
Vinylmagnesium chloride (4 eq. of a 15% solution in THF) was
added dropwise to a stirred solution of aldehyde 112 (0.251 g,
1 mmol) in dry ether at 0 ЊC. TLC analysis showed that the
reaction was complete after 5 min. Excess Grignard reagent
was destroyed by the dropwise addition of water (10 ml). The
organic layer was separated and the aqueous layer extracted
with ether (3 × 10 ml). The combined organic solutions were
washed with water (10 ml) and brine (10 ml) then dried
and evaporated to yield a crude product which was purified
by column chromatography (3:7 ether–petrol), followed by
recrystallisation from dichloromethane–petrol, to give the
allylic alcohol 12 as a colourless crystalline solid (0.267 g, 92%),
mp 125–127 ЊC, νmax/cmϪ1 3392, 2984, 2253, 1749, 1477, 1395,
and 193.2 (both C᎐O); m/z (ES) 331 (Mϩ ϩ 1, 100%) [Found: C,
᎐
62.04; H, 7.01; N, 16.55. C17H22N4O3 requires C, 61.80; H, 6.71;
N, 16.96%].
trans-4-N-(tert-Butoxycarbonyl)-5,6-dimethyl-4,5,6,7-tetra-
hydro[1,2,3]triazolo[4,5,1-jk][1,2]benzodiazepin-7-one 13c
Benzotriazole 10c (0.25 g, 0.80 mmol) was subjected to the
general oxidation–cyclisation protocol to yield the benzodiaze-
pinone 13c as colourless crystals (0.215 g, 85%), mp 139–143 ЊC,
νmax/cmϪ1 2980, 2936, 1732, 1676, 1595, 1456, 1371, 1301, 1258,
1157, 1119, 1106 and 1018; δH 1.01 (3H, d, J 7.4, 5-CH3),
1.39–1.54 (12H, m, 6-CH3 and C(CH3)3), 3.21 (1H, br quintet,
J. Chem. Soc., Perkin Trans. 1, 2000, 3752–3757
3755

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J ~ 6.9, 6-H), 4.88 (1H, br quintet, J ~ 6.9, 5-H), 7.69 (1H, t,
J 7.6, 10-H) and 8.31–8.35 (2H, m, 9- and 11-H); δC 12.4, 15.3
(both CH3), 28.8 (C(CH3)3), 54.2, 56.1 (both CH), 85.8
(C(CH3)3), 120.7 (C), 125.1, 127.0 (both CH), 129.3 (C), 131.0
(2H, m, 2 × furyl-β-H), 5.96–5.99 (1H, m, 5-H), 7.01–7.04
(1H, m, Ar-H), 7.47 (1H, t, J 7.4, 10-H), 8.22 (1H, d, J 7.4, 9-H)
and 8.28 (1H, d, J 7.4, 11-H), m/z (ES) 355 (Mϩ ϩ 1, 100%) and
298 (24) [Found: Mϩ ϩ 1, 355.1407. C18H19N4O4 requires M,
355.1406].
(CH), 145.2 (C), 154.7 and 196.0 (both C᎐O); m/z (ES) 317
᎐
(Mϩ ϩ 1, 100%), 245 (40) and 240 (42) [Found: Mϩ ϩ 1,
317.1616. C16H21N4O3 requires M, 317.1614].
4-N-(tert-Butoxycarbonyl)-4,5,6,7-tetrahydro[1,2,3]triazolo-
[4,5,1-jk][1,2]benzodiazepin-7-one 13f
4-N-(tert-Butoxycarbonyl)-5-phenyl-4,5,6,7-tetrahydro[1,2,3]-
triazolo[4,5,1-jk][1,2]benzodiazepin-7-one 13d
Benzotriazole 12 (1.00 g, 3.4 mmol) was subjected to the
general oxidation–cyclisation protocol to yield the parent
benzodiazepinone 13f as colourless crystals (0.93 g, 95%),
mp 164–167 ЊC, νmax/cmϪ1 2984, 2926, 1739, 1675, 1594, 1398,
1313, 1242 and 1153; δH 1.47–1.62 (9H, br s, C(CH3)3), 3.28–
3.42 (2H, app br s, 6-CH2), 4.05–4.42 (2H, app br s, 5-CH2),
7.58 (1H, t, J 7.8, 10-H), 8.32 (1H, d, J 7.8, 9-H) and 8.41 (1H,
d, J 7.8, 10-H); δH (330 K) 1.47–1.50 (9H, br s, C(CH3)3), 3.30
(2H, app br t, J 5.4, 6-CH2), 4.12–4.26 (2H, m, 5-CH2), 7.56
(1H, t, J 7.8, 10-H), 8.33 (1H, d, J 7.8, 9-H) and 8.35 (1H, d,
J 7.8, 11-H); δC 28.4 (C(CH3)3), 44.4, 45.2 (both CH2), 85.5
(C(CH3)3), 119.6 (C), 125.1, 127.1 (both CH), 128.4 (C), 131.1
Benzotriazole 10d (0.25 g, 0.68 mmol) was stirred in dichloro-
methane (20 ml) at ambient temperature; manganese()
oxide (2.3 g) was added with vigorous stirring. The progress of
the reaction was monitored by TLC; after 36 h, all the starting
material had been converted into enone 14a, a small sample
of which showed νmax/cmϪ1 3258, 2982, 1750, 1660, 1604, 1576,
1494, 1448, 1412, 1273, 1253, 1226, 1158, 1094, 1016, 772 and
697; δH 1.32–1.63 (9H, br s, C(CH3)3), 7.50–7.56 (5H, m,
5 × Ar-H), 7.61 (1H, t, J 7.5, 5-H), 7.99 (1H, d, J 15.6, 2Ј-H),
8.18 (2H, app d, J 7.5, 4- and 6-H), 8.21–8.30 (1H, br s, NH)
and 8.92 (1H, d, J 15.6, 3Ј-H).
(CH), 145.5 (C), 153.7 and 194.5 (both C᎐O); m/z (ES) 289
᎐
(Mϩ ϩ 1, 100%), 233 (24) and 142 (29) [Found: C, 58.13;
H, 5.41; N, 19.14. C14H16N4O3 requires C, 58.33; H, 5.59; N,
19.14%].
To the enone 14a, in dichloromethane (20 ml) (i.e. the fore-
going reaction mixture) was added triethylamine (0.14 ml,
1.5 eq.) and stirring continued for a further 3 h before the
mixture was passed through a plug of Celite, which was then
washed with copious dichloromethane. The combined filtrates
were dried and evaporated to yield a crude product which was
purified by column chromatography to yield the benzodiaze-
pinone 13d as yellow crystals (0.189 g, 76%), mp 153–157 ЊC,
νmax/cmϪ1 2780, 1728, 1673, 1595, 1498, 1450, 1371, 1323, 1292,
1268, 1152, 1076, 1045 and 985; δH 1.46–1.64 (9H, br s,
C(CH3)3), 3.67 (1H, br dd, J ~ 16 and 3, 6-HA), 5.05 (1H, br dd,
J ~ 16 and 3, 6-HB), 6.12–6.20 (1H, m, 5-H), 7.00–7.19 (4H, m),
7.35 (1H, d, J 7.6, Ar-H), 7.45 (1H, t, J 7.6, 10-H), 8.15 (1H, d,
J 7.6, 9-H) and 8.25 (1H, d, J 7.6, 11-H); δC 28.3 (C(CH3)3), 47.2
(CH2), 85.8 (C(CH3)3), 119.7 (C), 124.7, 126.7, 126.9, 128.6 (all
CH), 128.8 (C), 129.1, 130.7 (both CH), 134.3, 145.2 (both C),
1-(tert-Butoxycarbonylamino)-7-(1Ј-acetyloxyprop-2Ј-en-1Ј-yl)-
1H-1,2,3-benzotriazole 16a
Acetic anhydride (0.5 ml, ~5 mmol) was added to benzotriazole
12 (0.291 g, 1 mmol) in dichloromethane (10 ml) containing
4-(N,N-dimethylamino)pyridine (~5 mg). The reaction mixture
was stirred overnight and diluted with dichloromethane (20
ml). The resulting solution was washed with water (10 ml) and
brine (10 ml), then dried and evaporated to give a brown solid
which was recrystallised from dichloromethane–petrol to yield
the acetate 16a as a beige crystalline solid (0.256 g, 77%),
mp 116–118 ЊC, νmax/cmϪ1 3274, 2982, 1731, 1496, 1395, 1254,
1159, 1052, 993, 929 and 750; δH 1.32–1.54 (9H, br s, (C(CH3)3)),
2.10 (3H, s, CH3C(O)O), 5.26 (1H, d, J 17.2, 3Ј-HA), 5.31 (1H,
d, J 10.5, 3Ј-HB), 6.11 (1H, ddd, J 17.2, 10.5 and 5.1, 2Ј-H), 6.93
(1H, d, J 5.1, 1Ј-H), 7.40 (1H, t, J 7.6, 5-H), 7.58 (1H, d, J 7.6,
6-H), 8.04 (1H, d, J 7.6, 4-H) and 8.44–8.56 (1H, br s, NH);
δC 21.6 (CH3C(O)O), 28.5 (C(CH3)3), 70.4 (CHOAc), 84.3
(C(CH3)3), 118.4 (CH2), 121.2 (CH), 122.5 (C), 125.0 (CH),
154.2 and 174.0 (both C᎐O); m/z (ES) 365 (Mϩ ϩ 1, 100%), 245
᎐
(22) and 240 (20) [Found: Mϩ ϩ 1, 365.1616. C20H21N40O3
requires M, 365.1614].
(tert-Butoxycarbonylamino)-7-(3Ј-furyl-1-oxoprop-2Ј-en-1Ј-yl)-
1H-1,2,3-benzotriazole 14b and 4-N-(tert-butoxycarbonyl)-5-
furyl-4,5,6,7-tetrahydro[1,2,3]triazolo[4,5,1-jk][1,2]benzo-
diazepin-7-one 13e
128.9 (C), 135.4 (CH), 145.4 (C), 153.5 and 170.4 (both C᎐O);
᎐
m/z (APCI) 333 (Mϩ ϩ 1, 100%) [Found: C, 58.02; H, 6.39;
N, 16.73. C16H20N4O4 requires C, 57.82; H, 6.07; N, 16.87%].
Benzotriazole 10e (0.15 g, 0.42 mmol) was stirred in dichloro-
methane (10 ml) at ambient temperature and manganese()
oxide (1.3 g) was added with vigorous stirring. The progress of
the reaction was monitored by TLC and after 36 h, all the
starting material had been converted into enone 14b. An aliquot
was removed from the reaction mixture, filtered and evaporated
to leave a residue which showed: δH 1.32–1.35 (9H, br s,
C(CH3)3), 6.51 (1H, dd, J 3.3 and 1.8, Ar-H), 6.74 (1H, dd,
J 3.3 and 1.8, Ar-H), 7.32 (1H, d, J 15.5, 3Ј-H), 7.46–7.53 (3H,
m, 2Ј-, 5- and Ar-H), 7.95 (1H, d, J 7.1, 6-H), 8.23 (1H, d, J 7.1,
4-H) and 8.51 (1H, s, NH); δC 28.3 (C(CH3)3), 83.7 (C(CH3)3),
113.4, 118.0, 121.1, 124.4 (all CH), 124.6 (C), 125.3 (CH), 130.1
(C), 130.2, 133.1, 146.2 (all CH), 151.1 (C), 153.7 and 189.7
(E)-1-(tert-Butoxycarbonylamino)-7-(1Ј-acetyloxyhex-2Ј-en-1Ј-
yl)-1H-1,2,3-benzotriazole 16c
Benzotriazole 10b (0.33 g, 1 mmol) was subjected to the fore-
going acetylation conditions to give the acetate 16c as a light
brown, crystalline solid (0.281 g, 75%); δH 0.76 (3H, t, J 8.1,
6Ј-CH3), 1.10–1.54 (11H, br m, 5Ј-CH2 and C(CH3)3), 1.86
(2H, app q, J 7.6, 4Ј-CH2), 1.99 (3H, s, CH3(O)O), 5.65–5.78
(2H, m, 2Ј- and 3Ј-H), 6.80 (1H, d, J 5.7, 1Ј-CHOAc), 7.30 (1H,
t, J 7.2, 5-H), 7.49 (1H, d, J 7.2, 6-H), 7.91 (1H, d, J 7.2, 4-H)
and 8.40–8.46 (1H, br s, NH); δC 14.1, 21.7 (both CH3), 22.3
(CH2), 28.5 (C(CH3)3), 34.7 (5Ј-CH2), 70.4 (1Ј-CHOAc), 84.2
(C(CH3)3), 120.8, 124.7, 125.0 (all CH), 126.5, 129.7 (both C),
(both C᎐O).
᎐
To the remaining reaction mixture, triethylamine (0.08 ml,
1.5 eq.) was then added and stirring was continued for a further
3 h before the mixture was passed through a plug of Celite
and the residue was washed with copious dichloromethane. The
combined filtrates were dried and evaporated to yield a crude
product which was purified by column chromatography to yield
the benzodiazepinone 13e as yellow crystals (0.12 g, 78%), mp
153–157 ЊC, νmax/cmϪ1 2984, 1732, 1674, 1595, 1373, 1284, 1251
and 1153; δH 1.42–1.50 (9H, br s, C(CH3)3), 3.52 (1H, dd, J 12.0
and 3.5, 6-HA), 3.58 (1H, dd, J 12.0 and 3.5, 6-HB), 5.85–5.89
120.7, 135.2 (both CH), 145.3 (C), 153.6 and 162.1 (both C᎐O).
᎐
(E)-1-(tert-Butoxycarbonylacetamido)-7-(1Ј-acetyloxy-2Ј-
methylbut-2Ј-en-1Ј-yl)-1H-1,2,3-benzotriazole 20a
Benzotriazole 10c (0.319 g, 1 mmol) was subjected to the fore-
going acetylation conditions to give the bis(acetate) 20a as a
light brown crystalline solid (0.281 g, 72%), mp 128–131 ЊC,
νmax/cmϪ1 2982, 1744, 1430, 1371, 1289, 1228, 1146, 1028, 916,
3756
J. Chem. Soc., Perkin Trans. 1, 2000, 3752–3757

View Article Online
835 and 750; δH 1.36 (9H, s, C(CH3)3), 1.68 (1H, s, 3Ј-CH3), 1.72
(3H, d, J 9.0, 4Ј-CH3), 2.16 (3H, s, CH3C(O)O), 2.60 (3H, s,
CH3C(O)N), 5.38 (1H, q, J 9.0, 3Ј-H), 6.42 (1H, s, 1Ј-H), 7.41
(1H, t, J 7.8, 5-H), 7.56 (1H, d, J 7.8, 6-H) and 8.05 (1H, d,
J 7.8, 4-H); δC 13.8, 14.1, 21.5, 25.8 (all CH3), 27.9 (C(CH3)3),
79.6 (CH), 87.4 (C(CH3)3), 120.8 (CH), 122.3 (C), 125.0, 125.9,
127.7 (all CH), 130.3, 132.9, 145.4 (all C), 150.2, 169.2 and
4-N-(tert-Butoxycarbonyl)-5-methyl-4,5-dihydro[1,2,3]-
triazolo[4,5,1-jk][1,2]benzodiazepine 17b
The acetate 16b was prepared by the general procedure
and used directly in the cyclisation. Acetate 16b (0.250 g, 0.64
mmol) was subjected to the general palladium cyclisation
protocol to yield the 1,2-benzodiazepine 17b as an orange
crystalline solid (0.098 g, 54%), mp 120–124 ЊC, νmax/cmϪ1 2962,
2926, 2854, 1739, 1674, 1595, 1459, 1365, 1266 and 1158;
δH 1.20 (3H, d, J 11.6, 5-CH3), 1.35–1.40 (9H, br s, C(CH3)3),
5.28–5.36 (1H, m, 5-H), 6.33 (1H, dd, J 11.3 and 6.8, 6-H),
6.68 (1H, d, J 11.3, 7-H), 7.32–7.42 (2H, m, 9- and 10-H) and
7.95 (1H, d, J 7.2, 11-H); δC 17.9 (CH3) 31.3 (C(CH3)3), 82.8
(C(CH3)3), 118.2, 119.3, 124.1 (all CH), 125.0 (C), 125.6, 126.3
170.0 (all C᎐O); m/z (ES) 403 (Mϩ ϩ 1, 100%) and 303 (24).
᎐
(E)-1-(tert-Butoxycarbonylacetamido)-7-(1Ј-acetyloxy-3Ј-
phenylprop-2-en-1Ј-yl)-1H-1,2,3-benzotriazole 20b
Benzotriazole 10d (0.37 g, 1 mmol) was subjected to the fore-
going acetylation conditions to give the bis(acetate) 20b as a
brown crystalline solid (0.35 g, 78%), mp 120–123 ЊC, νmax/cmϪ1
3463, 3230, 2960, 1744, 1648, 1457, 1371, 1252, 1160, 1106,
1021, 951, 802 and 751; δH 1.22 (9H, s, C(CH3)3), 2.02 (3H,
s, CH3C(O)O), 2.45 (3H, s, CH3C(O)N), 6.19 (1H, dd, J 15.4
and 5.3, 2Ј-H), 6.37 (1H, app d, J 15.4, 3Ј-H), 6.70 (1H, d, J 5.3,
1Ј-H), 7.13–7.29 (5H, m, 5 × Ar-H), 7.32 (1H, t, J 7.2, 5-H),
7.55 (1H, d, J 7.2, 6-H) and 7.98 (1H, d, J 7.2, 4-H); δC 21.1,
25.9 (both CH3), 27.9 (C(CH3)3), 70.7 (1Ј-CHOAc), 87.4
(C(CH3)3), 119.9, 121.2 (both CH), 122.6 (C), 125.9, 127.2,
128.1, 128.5, 128.8, 129.0, 129.1, 135.8 (all CH), 135.8, 144.5
(both CH), 130.5, 144.2 (both C) and 154.7 (C᎐O) [Found:
᎐
Mϩ ϩ 1, 287.1511. C15H19N4O2 requires M, 287.1508].
4-N-(tert-Butoxycarbonyl)-5-propyl-4,5-dihydro[1,2,3]triazolo-
[4,5,1-jk][1,2]benzodiazepine 17c
Acetate 16c (0.208 g, 0.5 mmol) was subjected to the general
palladium cyclisation protocol to yield the 1,2-benzodiazepine
17c as an orange crystalline solid (0.092 g, 59%), mp 125–
128 ЊC, νmax/cmϪ1 2961, 2873, 1738, 1504, 1456, 1370, 1290,
1257, 1156, 1117, 1040, 841, 813 and 749; δH 0.88 (3H, t, J 7.4,
3Ј-CH3), 1.22–1.47 (13H, m, 1Ј- and 2Ј-CH2 and C(CH3)3),
5.12–5.20 (1H, m, 5-H), 6.34 (1H, dd, J 11.6 and 6.8, 6-H), 6.65
(1H, d, J 11.6, 7-H), 7.32–7.41 (2H, m, 9- and 10-H) and 7.93
(1H, d, J 7.7, 11-H); δC 12.5 (CH3), 26.7 (CH2), 27.8 (C(CH3)3),
26.7, 32.1 (CH2), 82.8 (C(CH3)3), 118.0, 119.7, 124.0 (all CH),
125.0 (C), 125.4, 126.4 (both CH), 130.1, 144.1 (both C)
(both C), 150.1, 169.5 and 169.9 (all C᎐O); m/z (ES) 451
᎐
(Mϩ ϩ 1, 100%) and 351 (30).
General protocol for the palladium catalysed formation of
4,5-dihydrobenzodiazepines 17
Acetate 16 (n mmol, 1 eq.) in THF (10 ml mmolϪ1) was stirred
under nitrogen with anhydrous potassium carbonate (1 eq.)
at ambient temperature. Tetrakis(triphenylphosphine)-
palladium(0) (20 mol%) was added as a solution in THF
(5 ml mmolϪ1). The resulting mixture was stirred at ambient
temperature until TLC analysis showed complete consumption
of starting material. Water (10 ml mmolϪ1) was added and
stirring continued for 2 h. The organic layer was separated and
the aqueous layer extracted with ether (2 × 10 ml mmolϪ1). The
combined organic solutions were washed with water (10 ml
mmolϪ1) and brine (10 ml mmolϪ1), then dried and evap-
orated to give a crude product which was subjected to column
chromatography (eluent, 1:4 ether–petrol).
and 154.4 (C᎐O); m/z (APCI) 315 (Mϩ ϩ 1, 47%), 279 (96) and
᎐
199 (100) [Found: Mϩ ϩ 1, 315.1819. C17H23N4O2 requires M,
315.1821].
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.
References
4-N-(tert-Butoxycarbonyl)-4,5-dihydro[1,2,3]triazolo[4,5,1-jk]-
[1,2]benzodiazepine 17a
1 Comprehensive Medicinal Chemistry, ed. P. G. Sammes, Pergamon
Press, Oxford, 1990; R. Silverman, The Organic Chemistry of Drug
Design and Drug Action, Academic Press, 1992; Burger’s Medicinal
Chemistry and Drug Discovery, ed. M. E. Wolff, J. Wiley and Sons,
Chichester, 1997.
2 M. A. Birkett, D. W. Knight, P. B. Little and M. B. Mitchell,
Tetrahedron, 2000, 56, 1013; D. W. Knight and P. B. Little, J. Chem.
Soc., Perkin Trans. 1, 2000, 2343.
Acetate 16a (0.250 g, 0.67 mmol) was subjected to the general
palladium cyclisation protocol to yield the 1,2-benzodiazepine
17a as an orange crystalline solid (0.095 g, 52%), mp 120–
123 ЊC, νmax/cmϪ1 2978, 1742, 1435, 1405, 1370, 1240, 1153,
1012, 850, 813 and 748; δH 1.25–1.49 (9H, br s, C(CH3)3), 3.98
(1H, app d, J 16.6, 5-HA), 4.92 (1H, dd, J 16.6 and 6.8, 5-HB),
6.31 (1H, dd, J 11.3 and 6.8, 6-H), 6.80 (1H, dd, J 11.3 and 1.6,
7-H), 7.35–7.40 (2H, m, 9- and 10-H) and 7.95 (1H, dd, J 7.2
and 4.8, 11-H); δC 28.2 (C(CH3)3), 50.5 (CH2), 84.6 (C(CH3)3),
119.8 (CH), 121.4 (C), 125.4, 128.2, 130.1, 130.5 (all CH),
3 For a preliminary communication, see D. W. Knight and P. B. Little,
Tetrahedron Lett., 1997, 38, 5037.
4 J. Attenburrow, A. F. B. Cameron, J. H. Chapman, R. M. Evans,
B. A. Hems, A. B. A. Jansen and T. Walker, J. Chem. Soc., 1952, 1094.
5 S. Godleski, Comprehensive Organic Synthesis, Pergamon Press,
Oxford, 1991, 4, 585; J. Tsuji, Palladium Reagents and Catalysts,
J. Wiley and Sons, Chichester, 1995; C. G. Frost, J. Howarth and
J. M. J. Williams, Tetrahedron: Asymmetry, 1992, 3, 1089.
6 G. J. Dawson, J. F. Bower and J. M. J. Williams, Contemp. Org. Synth.,
1996, 3, 4.
130.6, 144.9 (both C) and 155.5 (C᎐O); m/z (APCI) 273 (Mϩ ϩ 1,
᎐
52%) and 217 (100) [Found: Mϩ ϩ 1, 273.1384. C14H17N4O2
requires M, 273.1351].
J. Chem. Soc., Perkin Trans. 1, 2000, 3752–3757
3757