Synthesis and Photochromism of Novel Pyridyl-Substituted Naphthopyrans

Article abstract of DOI:10.1021/acs.joc.0c01296

Multitarget synthetic strategies to access novel photochromic 3H-naphtho[2,1-b]pyrans decorated with pyridyl units are described. The new pyridyl-substituted 3H-naphtho[2,1-b]pyrans display good photochromic properties with reversible generation of photomerocyanines, which exhibit mainly orange/red hues. Photochromic parameters including photocolorability and persistence of color vary tremendously on structural modification of the naphthopyran core.

Full text of DOI:10.1021/acs.joc.0c01296

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Article
Synthesis and Photochromism of Novel Pyridyl Substituted Naphthopyrans
Orlando Delfim Carvalho Couto de Azevedo, Paul I. Elliott, Christopher
D. Gabbutt, B. Mark Heron, Kyle Jack Lord, and Christopher Pullen
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c01296 • Publication Date (Web): 27 Jul 2020
Downloaded from pubs.acs.org on July 27, 2020
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Synthesis and Photochromism of Novel Pyridyl Substituted Naphthopyrans
*
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*‡
Orlando D. C. C. de Azevedo , Paul I. P. Elliott, Christopher D. Gabbutt, B. Mark Heron ,
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Kyle J. Lord, and Christopher Pullen
Department of Chemical Sciences, School of Applied Sciences, University of Huddersfield,
Queensgate, Huddersfield, HD1 3DH, UK
*†
Orlando.DeAzevedo@hud.ac.uk
*‡
M.Heron@hud.ac.uk
Abstract – Multi-target synthetic strategies to access novel photochromic 3H-naphtho[2,1-
b]pyrans decorated with pyridyl units are described. The new pyridyl substituted 3H-
naphtho[2,1-b]pyrans display good photochromic properties with the reversible generation of
photomerocyanines which exhibit mainly orange/red hues. Photochromic parameters including
photocolourability and persistence of colour vary tremendously on structural modification of
the naphthopyran core.
Keywords: Naphthopyrans, Benzochromenes, Heterocycles, Synthesis, Photochromism
Introduction
Photochromism is succinctly defined as the light-induced reversible transformation of a
chemical entity into one or more isomeric species that possess different absorption spectra.1
Photochromism occurs in both organic and inorganic compounds, as well in biological
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systems. Major organic photochromic families include diarylethenes, naphthopyrans
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(
benzochromenes), spiropyrans, spirooxines, benzopyrans (chromenes), azobenzenes,
stilbenes, anils, viologens,11 fulgides,12 and flavyliums.13 The coloured transient species
resulting from a photochromic reaction can possess different physicochemical properties, such
as, luminescence, electron conductivity, refractive index, dielectric constant,
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oxidation/reduction potential and geometry in addition to the expected colour change. As a
result, photochromic molecules have been widely employed as switches to modulate various
physical properties e.g. conductance, shape, viscosity, fluorescence, in addition to their
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inherent colour switching. Photochromes have been applied in many fields such as optical
information storage media, ophthalmic lenses, chemical sensors and intelligent stimuli-
responsive materials.15,16,17 Naphthopyrans although possessing interesting biological
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activities, are essentially known for their photochromic properties as they are one the most
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commercially important classes of photochromic molecules. In this regard, naphthopyrans
have been applied to commercially available ophthalmic photochromic sun and contact
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lenses. Other commercial applications of naphthopyrans include fuel and security markers,
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UV light intensity indicators, solar cell sensitizer dyes and hair dyes. The commercial
success of naphthopyrans can be attributed to the fact that functional groups can be readily
introduced in a cost-effective way allowing a wide range of hues that span across the visible
spectrum from yellows to blues.19 Of the three isomeric geminal diaryl substituted
naphthopyrans, the linear isomer 2H-naphtho[2,3-b]pyran displays no significant
photochromic response at ambient temperature (Figure 1).25 On the other hand, 2H-
naphtho[1,2-b]pyran and 3H-naphtho[2,1-b]pyran have received much attention since they
display good photochromic properties in both solution and polymers under ambient
conditions.26
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Ar 2 Ar
2
Ar
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O 2
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H-naphtho[2,3-b]pyran 2H-naphtho[1,2-b]pyran
3H-naphtho[2,1-b]pyran
Figure 1. Isomeric geminal diaryl substituted naphthopyrans
Naphthopyrans are the stable colourless ground state heterocycles that undergo a photoinduced
electrocyclic ring-opening to the corresponding open-forms, the photomerocyanines, which
due to the extended delocalized -system absorb at a longer wavelength, typically in the visible
region (Figure 2).27,28
Ar
Ar
O
Ar
Ar
Ar
Ar
UV
 Vis
UV
O
O

 Vis
Naphthopyran
Transoid-Cis (TC)
Transoid-Trans (TT)
short-lived
long-lived
colourless
coloured photomerocyanines
Figure 2. Photoisomerization of 3H-naphtho[2,1-b]pyran
In recent years, there has been a significant interest in developing transition metal containing
photochromic complexes that can perform multi-responsive tasks.29 The major organic
photochromic families have been employed to modulate the physical and chemical properties
of transition metal complexes,30 however naphthopyrans have yet to receive attention as
photoresponsive ligands. In this work, we devise and implement multi-target synthetic
strategies to obtain novel naphthopyrans decorated with pyridyl units, and to characterize their
photochromic response. It was envisioned that the foregoing pyridyl substituted naphthopyrans
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and 2 could be employed as 'dynamic' ligands in transition metal complexes for a variety of
applications (Figure 3).
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Figure 3. Target pyridyl substituted naphthopyrans
When conceiving strategies for the preparation of the pyridyl substituted 3H-naphtho[2,1-
b]pyrans different factors were considered e.g. the starting material availability and price, the
predicted overall yield, and the number of steps for a given pathway. A straightforward strategy
(
Strategy A) involved performing Suzuki cross-coupling reactions, after ‘chromenization’,31
between the pyridylboronic acids 3 and either the halo- or pseudo halo- substituted
naphthopyrans 4 (Figure 4). Furthermore, the naphthopyran precursors 4 would be prepared by
a variant of the established acid-catalysed condensation between the appropriate 1,1-
3
2
diarylprop-2-yn-1-ols 5 and the 2-naphthols 6. The foregoing strategy was employed to the
forward synthesis of the 10-, 9-, 8-, 7- and 5-pyridyl substituted 3H-naphtho[2,1-b]pyrans.
Incorporation of either basic or electron-withdrawing groups at C-3 of the 3H-naphtho[2,1-
b]pyrans by acid-catalysed condensation between 2-naphthol and the corresponding prop-2-
3
3
yn-1-ol has been previously accomplished only in very poor yields. Inspired by the work of
34
Putala et al., it was envisioned that a Heck cross-coupling reaction could be employed to
prepare the 3-pyridyl-3H-naphtho[2,1-b]pyrans 7 from commercially available and easily
attainable 1-halo-2-naphthols 8 (Strategy B). Furthermore, it was envisioned an additional
strategy (Strategy C) that involved effecting a late-stage ‘chromenization’ by the acid-
catalysed cyclization of the alkene 9, the latter prepared by the Heck cross-coupling reaction
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between the appropriate prop-2-en-1-ol 10 and the 1-halo-4-pyridyl-2-naphthol 11. This route
would require the synthesis of the Heck coupling partner 11 by the regioselective halogenation
of pyridyl-2-naphthol 12, the latter prepared by an early-stage Suzuki cross-coupling reaction.
The foregoing strategy was employed to the forward synthesis of the 6-pyridyl substituted 3H-
naphtho[2,1-b]pyrans.
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Strategy A
OH
BPin
Ar
Ar
Ar
Ar
Ar
N
3
Ar
5
3
2 OH
3
O
O
X
Suzuki
reaction
X
Acid-catalysed
condensation
N
4
6
Strategy B
N
N
HO
Ar
Ar
O
HO
Ar
X
OH
N
OPG
Acid-catalysed
cyclization
Protection
Heck Reaction
7
8
Strategy C
OH
Ar
Ar
HO
Ar
Ar
Ar
Ar
3
X
10
OPG
2
O
2
OPG
Acid-catalysed
cyclization
Heck
reaction
N
N
N
9
11
Halogenation
Protection
PG = protecting group
X = Br, I or OTf
Pin = pinacol
BPin
N
1
2
OH
2 OH
Ar = aryl
X
Suzuki
N
reaction
12
Figure 4. Retrosynthesis of the pyridyl substituted 3H-naphtho[2,1-b]pyrans
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There was no interest in synthesizing naphthopyrans with pyridyl substituents at C-1 and C-2
of the naphthopyran scaffold in the present work as it was predicted that the resulting
photochromes would show poor colorability under UV irradiation at room-temperature.35
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Results and Discussion
Synthesis of 10-pyridyl-3H-naphtho[2,1-b]pyrans (Strategy A)
To prepare the 10-pyridyl-3H-naphtho[2,1-b]pyrans, it was first necessary to synthesize an 8-
halo-2-naphthol, as 8-iodo-2-naphthol was not commercially available and 8-bromo-2-
naphthol was expensive. Thus, 8-iodo-2-naphthol 13 was obtained in good yield (73%) from
the commercially available and comparatively cheaper 8-amino-2-naphthol by a Sandmeyer-
type reaction (Scheme 1).36 To access the 10-(4-pyridyl)-3H-naphtho[2,1-b]pyran 15, the
precursor 10-iodo-3H-naphtho[2,1-b]pyran 14 was first prepared by the acid-catalysed
condensation between 8-iodo-2-naphthol 13 and the readily available 1,1-bis(4-
methoxyphenyl)prop-2-yn-1-ol, following a modification of a procedure from Carreira and co-
worker.32 The poor yield (39%) was attributed to decomposition of the iodonaphthopyran
during the column chromatography separation. Even though it was isolated with only
approximately 83% purity, due its proclivity to decomposition, it was used directly in the next
step without further purification. The Suzuki cross-coupling reaction between 14 and 4-
pyridineboronic acid pinacol ester afforded the 10-(4-pyridyl)-3H-naphtho[2,1-b]pyran 15 in
good yield (66%) after 5 days of reflux.37 By H NMR spectroscopy it was determined that 1-
1
3
8
H, that usually resonates as a doublet at ca. 7.3 ppm, appeared upfield at 6.01 ppm as it was
shielded by the induced anisotropic field from the pyridyl substituent at C-10.
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Ar
Ar
3
1
OH
Ar
NH2
I
I
1
) NaNO , H SO ,
2 2 4
8
8
10
2
OH
2 OH
O
H O, 0  5 °C
Ar
2
2
) KI, 0  5 °C
PPTS,
(
1
CH O) CH,
,2-DCE, reflux
3 3
1
3 73%
14 39% (83% Purity)
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Pd(PPh ) , KF,
BPin
Ar = 4-MeOC H4
Pin = pinacol
3 4
6
PhMe:EtOH
N
(
1:1), reflux, N2
N
Ar
Ar
3
1
1
0
O
15 66%
Scheme 1. Synthesis of 10-pyridyl-3H-naphtho[2,1-b]pyran 15
Overall, 10-(4-pyridyl)-3H-naphtho[2,1-b]pyran 15 was synthesized from 8-amino-2-naphthol
in a three step linear route in 19% yield.
Synthesis of 9-pyridyl-3H-naphtho[2,1-b]pyrans (Strategy A)
The commercially available and relatively inexpensive 2,7-dihydroxynaphthalene was chosen
as starting material for the synthesis of the 9-pyridyl-3H-naphtho[2,1-b]pyrans. In a first route
(
Route A), the transformation of 2,7-dihydroxynaphthalene into 7-bromo-2-naphthol 16 was
accomplished by reacting the former with a triphenyldibromophosphorane intermediate,
formed in situ by mixing Br and triphenylphosphine in acetonitrile, followed by heating,
2
3
9
affording the desired product 16 in 48% yield (Scheme 2). The acid-catalysed condensation
between 16 and 1,1-bis(4-methoxyphenyl)prop-2-yn-1-ol led to the isolation of the 9-bromo-
3
H-naphtho[2,1-b]pyran 17 in very good yield (86%). Suzuki cross-coupling reactions between
either 4- or 3- pyridineboronic acid pinacol esters and 17 afforded the corresponding 9-pyridyl
4
0
substituted 3H-naphtho[2,1-b]pyrans 18 and 20 in fair to good yields (57 – 70%). Besides the
desired targets, minor amounts of the naphthofurans 19 and 21 (10 – 11%) were isolated as by-
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products of the Suzuki reactions, being the result of the ring-contraction of the 9-pyridyl-3H-
naphtho[2,1-b]pyrans.37 The slightly fluorescent non-photochromic naphthofurans are
structural isomers of the corresponding 9-pyridyl-3H-naphtho[2,1-b]pyrans, and their
formation, during the Suzuki cross-coupling reactions, made it extremely complicated to purify
each of the 9-pyridyl-3H-naphtho[2,1-b]pyrans and the corresponding naphthofurans by flash
0
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column chromatography as a consequence of their similar R values on a variety of TLC plates
F
and solvent systems.
Ar
Ar
3
OH
HO
7
2 OH
Br
7
2 OH
Br
O
Ar
Ar
9
Br .PPh , MeCN
2
3

PPTS,
(
CH O) CH,
3 3
1,2-DCE, reflux
16 48%
17 86%
Pd(PPh ) , K CO ,
Ar = 4-MeOC H
Pin = pinacol
3 4
2
3
6
4
BPin PhMe:EtOH (1:1),
reflux, N2
N
Ar
Ar
3
Ar
2
Ar
R1
O
R1
8
O
9
+
1
1
1
8 (R = 4-pyridyl) 57%
19 (R = 4-pyridyl) 10%
1
1
2
0 (R = 3-pyridyl) 70%
21 (R = 3-pyridyl) 11%
Scheme 2. Synthesis of 9-pyridyl-3H-naphtho[2,1-b]pyrans 18 and 20 (Route A)
In an alternative route (Route B), the acid-catalysed condensation between 2,7-
dihydroxynaphthalene and 1,1-bis(4-methoxyphenyl)prop-2-yn-1-ol afforded the target 9-
hydroxy-3H-naphtho[2,1-b]pyran 22 in poor yield (28%) which was a result of the poor
regioselectivity of the reaction, in conformity with literature observations (Scheme 3).41
Treatment of 22 with triflic anhydride in the presence of triethylamine generated the 9-
triflyloxy-3H-naphtho[2,1-b]pyran 23 in very good yield (87%).42 Suzuki cross-coupling
reactions between either 4- or 3- pyridineboronic acid pinacol esters and 23 rendered the
corresponding 9-pyridyl substituted 3H-naphtho[2,1-b]pyrans 18 and 20 in poor to fair yields
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(
21 – 56%). Besides the desired targets, the corresponding naphthofurans 19 and 21 were again
isolated from the Suzuki reactions (9 – 31%).
Ar
Ar
Ar
Ar
3
3
OH
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4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
HO
7
2 OH
HO
9
O
TfO 9
O
Ar
Ar
PPTS,
Tf O, Et N,
2
3
(
1
CH O) CH,
,2-DCE, reflux
3 3
DCM, 0 °C, N2
22 28%
23 87%
Pd(PPh ) , K CO ,
3
4
2
3
BPin PhMe:EtOH (1:1),
reflux, N2
N
Ar = 4-MeOC H
6
4
Pin = pinacol
Tf = triflyl
Ar
Ar
3
Ar
2
Ar
R1
O
R1
8
O
9
+
1
1
1
8 (R = 4-pyridyl) 21%
19 (R = 4-pyridyl) 31%
1
1
2
0 (R = 3-pyridyl) 56%
21 (R = 3-pyridyl) 9%
Scheme 3. Synthesis of 9-pyridyl-3H-naphtho[2,1-b]pyrans 18 and 20 (Route B)
In summary, Route A afforded the 9-(4-pyridyl)-3H-naphtho[2,1-b]pyran 18 and 9-(3-pyridyl)-
3
H-naphtho[2,1-b]pyran 20 in a three step linear route in 24% and 29% yield, respectively. On
the other hand, Route B afforded the 9-(4-pyridyl)-3H-naphtho[2,1-b]pyran 18 and 9-(3-
pyridyl)-3H-naphtho[2,1-b]pyran 20 in a three step linear route in 5% and 14% yield,
respectively. As a result, Route A provided the desired targets with a higher overall yield in the
same number of steps when compared to Route B. Interestingly, 9-triflyloxy-3H-naphtho[2,1-
b]pyran 23 has proven to be a less effective coupling partner than 9-bromo-3H-naphtho[2,1-
b]pyran 17, since the yield of the Suzuki cross-coupling reaction involving the former (21 –
5
6%) was lower than the latter (57 – 70%).
Synthesis of 8-pyridyl-3H-naphtho[2,1-b]pyrans (Strategy A)
The synthesis of the 8-pyridyl-3H-naphtho[2,1-b]pyrans was accomplished by starting from
the inexpensive and commercially available 6-bromo-2-naphthol. The acid-catalysed
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1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
condensation between 6-bromo-2-naphthol and either 1,1-bis(4-methoxyphenyl)prop-2-yn-1-
ol or 1-(2,4-dimethoxyphenyl)-1-(4-methoxyphenyl)prop-2-yn-1-ol afforded the 8-bromo-3H-
naphtho[2,1-b]pyrans 24 and 25 in very good yields (88 – 97%) (Scheme 4). Suzuki cross-
coupling reactions between either 4- or 3- pyridineboronic acid pinacol esters and the 8-bromo-
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
3
H-naphtho[2,1-b]pyrans 24 and 25 led to the corresponding 8-pyridyl substituted 3H-
naphtho[2,1-b]pyrans 26, 28 and 30 in fair to good yields (60 – 70%). Besides the desired
targets, the corresponding naphthofurans 27, 29 and 31 were again isolated (3 – 11%), after
extensive flash column chromatography separations, being the result of the ring-contraction of
the 8-pyridyl-3H-naphtho[2,1-b]pyrans. In summary, 8-pyridyl-3H-naphtho[2,1-b]pyrans 26,
28 and 30 were prepared in a two step linear route from 6-bromo-2-naphthol in 53 – 68% yield.
OMe
OH
Ar
Ar
3
O
R1
2 OH
R1
OMe
PPTS, (CH CH O) CH,
1,2-DCE, reflux
3
2
3
Br
8
Br
6
1
2
4 97% (R =H)
1
2
5 88% (R = OMe)
Pd(PPh ) , K CO ,
BPin PhMe:EtOH (1:1),
reflux, N2
3 4
2
3
Ar = 4-MeOC H
Pin = pinacol
6
4
N
OMe
Ar

Ar
OMe
2
3
O R1
O
R1
+
R2
8
2 7
R
1
2
1
2
26 (R = H, R = 4-pyridyl) 63%
27 (R = H, R = 4-pyridyl) 3%
1
2
1
2
2
8 (R = H, R = 3-pyridyl) 70%
29 (R = H, R = 3-pyridyl) 6%
1
2
1
2
3
0 (R = OMe, R = 4-pyridyl) 60%
31 (R = OMe, R = 4-pyridyl) 11%
Scheme 4. Synthesis of 8-pyridyl-3H-naphtho[2,1-b]pyrans 26, 28 and 30
The frailty of pyridine-2-boronic acids under Suzuki cross-coupling conditions is known.43
Given this fact, it was envisioned that the 8-(2-pyridyl)-3H-naphtho[2,1-b]pyran 33 could be
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prepared by the Suzuki cross-coupling reaction between the inverted coupling partners 8-
boronyl-3H-naphtho[2,1-b]pyran 32 – prepared from the borylation of 8-bromo-3H-
naphtho[2,1-b]pyran 24 – and the stable 2-bromopyridine. The boronic acid was first prepared
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
from 8-bromo-3H-naphtho[2,1-b]pyran 24 by a two-step metalation protocol,44 and then
esterified with pinacol affording the 8-boronyl-3H-naphtho[2,1-b]pyran 32 in 49% yield after
four steps (Scheme 5). Hence, 32 was successfully coupled to 4-bromopyridine, liberated from
its hydrochloride salt by the addition of excess base, under Suzuki-Miyaura conditions,
affording the 8-(4-pyridyl)-3H-naphtho[2,1-b]pyran 26 in 67% yield. The corresponding
naphthofuran 27 was formed during the reaction but it was not isolated in this instance. In a
similar fashion, Suzuki cross-coupling reaction between 32 and 2-bromopyridine rendered the
8
-(2-pyridyl)-3H-naphtho[2,1-b]pyran 33 in very good yield (84%). Once again, the
corresponding naphthofuran 34 was isolated as a by-product (4%). In summary, 8-(4-pyridyl)-
3H-naphtho[2,1-b]pyran 26 was prepared from 6-bromo-2-naphthol in a five step linear route,
via a two-step metalation protocol, in 32% yield and similarly 8-(2-pyridyl)-3H-naphtho[2,1-
b]pyran 33 was prepared from 6-bromo-2-naphthol in a five step linear route in 40% yield.
Ar
Ar
Ar
Ar
3
3
1
) n-BuLi, THF,
-58 °C, N2
O
O
i
2
) B(O Pr)3
6
Ar = 4-MeOC H4
8
PinB 8
Br
3) HCl (aq)
) Pinacol, PhMe,
Pin = pinacol
4
24
32 49% after 4 steps
reflux (Dean-Stark)
Br
.HCl
N
Br
N
Pd(PPh ) , K CO ,
Pd(PPh ) , K CO ,
3
4
2
3
3 4
2
3
PhMe:EtOH (1:1),
reflux, N2
Ar
PhMe:EtOH (1:1),
reflux, N2
Ar


Ar
Ar
Ar
Ar
Ar
Ar
3
2
3
2
O
O
O
O
+
+
8
7
8
7
N
N
N
N
26 67%
27 (not isolated)
33 84%
34 4%
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1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Scheme 5. Synthesis of 8-pyridyl-3H-naphtho[2,1-b]pyrans 26 and 33
Synthesis of 7-pyridyl-3H-naphtho[2,1-b]pyrans (Strategy A)
For the synthesis of the 7-pyridyl-3H-naphtho[2,1-b]pyrans it was first necessary to prepare 5-
bromo-2-naphthol 37 as it was not commercially available. The latter was derivatized from the
readily accessible 5-amino-2-naphthol by a Sandmeyer reaction. Thus, 5-bromo-2-naphthol 37
was prepared in three steps from 5-amino-2-naphthol in 25% overall yield following a literature
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
4
5
procedure described by Abelt et al. (Scheme 6). First, the sulfonation of 5-amino-2-naphthol,
by treatment with H SO , generated 1-sulfonyl-5-amino-2-naphthol 35. The sulfonyl group at
2
4
C-1 was intended to favour the Sandmeyer reaction and block this activated position from
potential complications arising from azo-coupling. The Sandmeyer reaction of 35 generated 1-
sulfonyl-5-bromo-2-naphthol 36, which was immediately hydrolysed to 5-bromo-2-naphthol
3
7 by treatment with aq. H SO . The acid-catalysed condensation between 37 and 1,1-bis(4-
2 4
methoxyphenyl)prop-2-yn-1-ol afforded the 7-bromo-3H-naphtho[2,1-b]pyran 38 in 62%
yield. Hence, the Suzuki cross-coupling reaction between 38 and 4-pyridineboronic acid
pinacol ester afforded the 7-(4-pyridyl)-3H-naphtho[2,1-b]pyran 39 in fair yield (66%). Similar
to previous Suzuki cross-coupling reactions, the naphthofuran derived from the ring-
contraction of 39 was formed as a by-product of the reaction, but could not be isolated in a pure
state.
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SO H
SO H
3
3
1
1
2
OH
2 OH
2 OH
H SO , 55 °C
1) NaNO , H SO
2 2 4
2
4
2) CuBr, CuBr2,
5
5
5
Br
HBr, 70 °C
NH2
NH2
35
36
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
H SO (20% aq)
2
4
Ar
Ar
3
OH
Ar
O
2 OH
Ar
BPin
N
PPTS,
7
5
Pd(PPh ) , K CO ,
3
4
2
3
(
CH CH O) CH,
Br
3 2 3
Br
PhMe:EtOH (1:1),
1,2-DCE, reflux
reflux, N2
38 62%
37 25% after 3 steps
Ar
Ar
3
Ar = 4-MeOC H
6 4
Pin = pinacol
O
7
N
39 66%
Scheme 6. Synthesis of 7-pyridyl-3H-naphtho[2,1-b]pyran 39
In summary, 7-(4-pyridyl)-3H-naphtho[2,1-b]pyran 39 was prepared from 5-amino-2-naphthol
in a five step linear route in 10% yield.
Synthesis of 5-pyridyl-3H-naphtho[2,1-b]pyrans (Strategy A)
The widely available and relatively inexpensive 2,3-dihydroxynaphthalene was used as the
starting material for the synthesis of the 5-pyridyl-3H-naphtho[2,1-b]pyrans. The acid-
catalysed condensation between 2,3-dihydroxynaphthalene and 1-(2,4-dimethoxyphenyl)-1-
(
4-methoxyphenyl)prop-2-yn-1-ol afforded the 5-hydroxy-3H-naphtho[2,1-b]pyran 40 in 36%
yield (Scheme 7). Similar to the ‘chromenization’ of 2,7-dihydroxynaphthalene, the poor yield
was attributed to the poor regioselectivity of the reaction.
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1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
OMe
OMe
OH
MeO
MeO
3
3
Ar
MeO
PPTS, (CH O) CH,
Ar
Ar
2
3
OH
OH
O
O
OMe
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
5
Tf O, Et N,
DCM, 0 °C
5
3
3
OH
2
3
OTf
5%
1
,2-DCE, reflux
40 36%
41
9
Ar = 4-MeOC H
Tf = Triflyl
6
4
BPin
Pd(PPh ) , K PO ,
3
4
3
4
DMAc, 110 °C,
0 min, N2
2
N
OMe
MeO
3
Ar
O
5
N
42 51%
Scheme 7. Synthesis of 5-pyridyl-3H-naphtho[2,1-b]pyran 42
Moreover, 5-hydroxy-3H-naphtho[2,1-b]pyran 40 forms a naphthopyran : photomerocyanine
(
85 : 15) equilibrium mixture in CDCl , due to the particular stabilizing hydrogen-bond
3
1
formation in the photomerocyanine (Scheme 8). This hypothesis is supported by the H NMR
spectrum of the mixture that clearly shows a doublet at 8.95 ppm (J = 12 Hz) corresponding to
the resonance of 2-H of the transoid-cis (TC), a doublet at 6.87 ppm (J = 8.9 Hz) corresponding
to the resonance of 3′, 5′-H protons (anisyl) and three singlets at 3.65, 3.85 and 3.93 ppm
corresponding to the resonance of the methoxy hydrogens (TC) (Figure S41). The doublet (J =
1
2 Hz) corresponding to the resonance of 3-H (TC) is underneath a multiplet at 7.85 ppm, and
it is identified by COSY NMR as it correlates with 2-H (TC) (Figures S43 and S44). The
chemical shifts and coupling constants of the signals shown in Figure S41 are identical to the
1
signals from H NMR spectra of analogous photomerocyanines reported in the literature.46
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3
'
OMe
MeO
OMe
OMe
1
2
5'
MeO
3
3
OMe
O
5
O
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
H
CDCl3
6 O
5
OH
40
Photomerocyanine (TC)
Scheme 8. Equilibration of 5-hydroxy-3H-naphtho[2,1-b]pyran 40 in CDCl solution
3
Triflation of 5-hydroxy-3H-naphtho[2,1-b]pyran 40 afforded the 5-triflyloxy-3H-naphtho[2,1-
b]pyran 41 in excellent yield (95%) – the photomerocyanine was no longer discernible in the
1
H NMR spectrum in CDCl as no hydrogen bond could be established. Suzuki cross-coupling
3
reaction between 41 and 4-pyridineboronic acid pinacol ester rendered the desired 5-(4-
pyridyl)-3H-naphtho[2,1-b]pyran 42 in fair yield (51%). Overall, 5-(4-pyridyl)-3H-
naphtho[2,1-b]pyran 42 was prepared from 2,3-dihydroxynaphthalene in a three step linear
route in 17% yield.
Synthesis of 3-pyridyl-3H-naphtho[2,1-b]pyrans (Strategy B)
For the synthesis of the 3-pyridyl-3H-naphtho[2,1-b]pyrans, the commercially available 1-
bromo-2-naphthol was used as starting material. In order to facilitate the key Heck cross-
coupling reaction, the hydroxyl group of 1-bromo-2-naphthol was first protected as a
methoxymethyl ether by reaction with chloromethyl methyl ether to afford 43 in excellent yield
47
(
99%). A successful Heck reaction between 43 and prop-2-en-1-ol 44, derived from the
addition of vinylmagnesium chloride to 4-benzoylpyridine, resulted in the formation of 47 in
moderate yield (41%), when employing Pd(OAc) (8 mol%), K CO (1.5 equiv), TBAB (1.5
2
2
3
4
8
equiv), KCl (1 equiv) in DMF at 100 °C (Scheme 9; Entry 1, Table 1). In order to understand
the scope of the reaction, the same phosphine-free conditions were applied to the Heck reaction
between 43 and the more electron-rich prop-2-en-1-ol 45. However, these conditions proved
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1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
to be less effective as the Heck product 48 was isolated in very poor yield (9%) (Scheme 9;
Entry 2, Table 1). When employing Pd(OAc) (5 mol%), N-methyldicyclohexylamine
2
[Cy NMe] (1.5 equiv), PPh (10 mol%), TBAC (11 mol%) in DMAc at 80 °C, the Heck adduct
2
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
4
8 was again isolated in very poor yield (8%) (Scheme 9; Entry 3, Table 1). It was rationalized
that by mixing Pd(dba)2 (2 mol%) with tri-tert-butylphosphonium tetrafluoroborate
TTBP·HBF ] (4 mol%), the very active bis(tri-tert-butylphosphine)palladium(0) (Pd(t-
[
4
Bu P) ) would be formed in situ. The t-Bu P is a strong electron-rich phosphine ligand that
3
2
3
4
9
stabilise proficiently the palladium(II) salt obtained from the oxidative addition step. On the
other hand, the bulkiness of the t-Bu P favours the reductive elimination step. Thus, when using
3
Pd(dba) (2 mol%), TTBP·HBF (4 mol%), Cy NMe (1.5 equiv), TBAC (10 mol%) in DMAc
2
4
2
at 80 °C, the 3H-naphtho[2,1-b]pyran 49 was isolated directly in a much improved yield (50%)
Scheme 9; Entry 4, Table 1).50 It was possible that either the strong acid HBF or the
(
4
conjugated acid of Cy NMe formed during the reaction promoted the unmasking of the
2
naphthol unit with concomitant acid-catalysed cyclization of the Heck product 48 to the
corresponding 3H-naphtho[2,1-b]pyran 49. However, the same non-optimized conditions did
not prove to be as successful when employed to the more electron-deficient prop-2-en-1-ol 46,
as the 3H-naphtho[2,1-b]pyran 50 was isolated in only 25% yield (Scheme 9; Entry 5, Table
1
).
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Heck Partner:
N
OH
Ar
Ar
OMe
OH
F
Ar
Ar
3
1
Br
1
1
2
OMOM
Heck Partner
2 OMOM
O
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
Catalyst, Base,
Ligand, Phase
Transfer Catalyst, KCl,
Solvent,
Acid-catalysed
cyclization
OH
OH
MeO
F
4
3
47 or 48
49 or 50
44
45
46
Temperature
MOM = methoxymethyl ether
Ar = aryl
Scheme 9. Heck reactions between 1-bromo-2-naphthol 43 and either prop-2-en-1-ols 44, 45 or 46 under different conditions
Table 1. Summary of Heck reactions between 1-bromo-2-naphthol 43 and either prop-2-en-1-ols 44, 45 or 46 under different conditions
Entry
Heck Partner
Catalyst
Base
Ligand
Phase
Transfer
Catalyst
TBAB (1.5
equiv)
TBAB (1.5
equiv)
TBAC (11
mol%)
KCl
Solvent Temp.
Yield (%)
1
2
3
4
5
44 (1.1 equiv)
45 (1.2 equiv)
45 (1.2 equiv)
45 (1.4 equiv)
46 (1.3 equiv)
Pd(OAc)
2
2
2
(8 mol%)
K
K
2
2
CO
CO
3
(1.5 equiv)
(1.5 equiv)
N/A
N/A
1 equiv
1.1 equiv
N/A
DMF
DMAc
DMAc
DMAc
DMAc
100 °C
100 °C
80 °C
80 °C
80 °C
47 (41%)
48 (9%)
48 (8%)
49 (50%)
50 (25%)
Pd(OAc)
Pd(OAc)
(9 mol%)
(5 mol%)
(2 mol%)
(2 mol%)
3
Cy
Cy
Cy
2
2
2
NMe (1.5 equiv)
NMe (1.5 equiv)
NMe (1.5 equiv)
PPh
TTBP·HBF
TTBP·HBF
3
(10 mol%)
Pd(dba)
Pd(dba)
2
4
(4 mol%)
(4 mol%)
TBAC (10
mol%)
N/A
2
4
TBAC (10
mol%)
N/A
Temp. = Temperature
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1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Hence, unmasking of the naphthol function of 47 was attended by the concomitant cyclisation
to the 3-pyridyl-3H-naphtho[2,1-b]pyran 51 in fair yield (61%) upon treatment with TFA at
room temperature (Scheme 10).
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
N
OH
3
1
N
1
2 OMOM
O
TFA, DCM, rt
MOM = methoxymethyl ether
47
51 61%
Scheme 10. Synthesis of 5-pyridyl-3H-naphtho[2,1-b]pyran 51
In summary, 3-pyridyl-3H-naphtho[2,1-b]pyran 51 was prepared from 1-bromo-2-naphthol in
a three step linear route in 25% yield.
Synthesis of 6-pyridyl-3H-naphtho[2,1-b]pyrans (Strategy C)
The commercially available 1,3-dihydroxynaphthalene was chosen as starting material for the
synthesis of the 6-pyridyl-3H-naphtho[2,1-b]pyrans. First, 3-methoxy-1-naphthol 52 was
synthesized in 86% yield by the regioselective O-methylation of 1,3-dihydroxynaphthalene by
treatment with dry methanolic HCl generated in situ from the reaction between acetyl chloride
and methanol (Scheme 11).51 Triflation of 52 by reaction with triflic anhydride and
triethylamine in dichloromethane afforded the desired 3-methoxy-1-triflyloxynaphthalene 53
in very good yield (81%). Subsequently, 53 was successfully coupled to 4-pyridine- and 3-
pyridine- boronic acid pinacol ester rendering the corresponding 2-methoxy-4-
pyridylnaphthalenes 54 and 55 in good to excellent yield (79 – 91%). The latter were
demethylated by hydrobromic acid (45% w/v) in acetic acid:H O at reflux giving the
2
corresponding 4-pyridyl-2-naphthols 56 and 57 in good to excellent yield (75 – 93%).
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O
3
OH
3 OMe
3
OMe
Cl
Tf O, Et N,
DCM, 0 °C, N2
MeOH,
°C
2
3
1
1
1
0
rt
OH
OH
OTf
53 81%
5
2 86%
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Tf = triflyl
An = 4-MeOC H
Pd(PPh ) , K CO ,
3 4 2 3
BPin PhMe:EtOH (1:1),
reflux, N2
6
4
N
MOM = methoxymethyl ether
2
OH
2 OMe
HBr (45% w/v in AcOH),
AcOH:H O (2:1),
reflux
4
R1
4
R1
2
1
1
56 (R = 4-pyridyl) 93%
54 (R = 4-pyridyl) 79%
55 (R = 3-pyridyl) 91%
1
1
5
7 (R = 3-pyridyl) 75%
Scheme 11. Synthesis of 4-pyridyl-2-naphthols 56 and 57
Attempts to perform the direct acid-catalysed condensation between pyridyl-2-naphthols 56
and 57 and 1,1-bis(4-methoxyphenyl)prop-2-yn-1-ol systematically failed to provide the
desired products (Scheme 12). It was rationalized that the pyridinium-2-naphthol p-
toluenesulfonate salts, formed in situ under the reaction conditions, were too deactivated to
undergo acid-catalysed condensations. Alternatively, the Heck partners 62 and 63 were
prepared from the regioselective bromination of 56 and 57 with NBS in fair yields (54 – 57%),
followed by protection of the hydroxyl groups of the naphthols 60 and 61 as methoxymethyl
ethers by treatment with MOMCl in good yields (74 – 78%). Even though a previous Heck
reaction between 43 and prop-2-en-1-ol 45 led to an unsatisfactory outcome (Scheme 9; Entry
2
, Table 1), for comparison, the same conditions were applied to the Heck reactions between
6
2 and 63 and 1,1-bis(4-methoxyphenyl)prop-2-en-1-ol. Surprisingly, TLC analysis indicated
that the cross-coupling reactions were virtually finished after two days of reaction as there were
just minor amounts of the starting materials in the crude mixture. Thus, flash column
chromatography purification rendered the Heck products 64 and 65 in 29% and 55% yield,
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1
1
1
1
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1
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1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
respectively. In a final step, the acid-catalysed unmasking of the hydroxyl group of 64 and 65
with concomitant cyclization afforded the corresponding 6-pyridyl-3H-naphtho[2,1-b]pyrans
58 and 59 in fair yield (61 – 69%).
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
In summary, 6-pyridyl-3H-naphtho[2,1-b]pyrans 58 and 59 were prepared from 1,3-
dihydroxynaphthalene in a eight step linear route in 4% and 8% yield, respectively.
Ar
Ar
3
OH
Ar
2
OH
O
Ar
PPTS,
4
R1
6
R1
(CH3O)3CH,
,2-DCE, reflux
1
1
1
56 (R = 4-pyridyl)
58 (R = 4-pyridyl)
NBS, DMF,
2 °C, N2
1
1
57 (R = 3-pyridyl)
59 (R = 3-pyridyl)
5
Ar = 4-MeOC H
6
4
MOM = methoxymethyl ether
OH
Ar
Ar
Br
Br
Ar Ar
OH
Pd(OAc) , K CO ,
1
1
1
2 OH
2 OMOM
2 OMOM
MOMCl, K CO ,
DMF, 0 °C, N2
2
2
3
2
3
4
R1
4
R1
4
TBAB, KCl, DMF,
00 °C, N2
R1
1
1
1
1
6
0 (R = 4-pyridyl) 54%
62 (R = 4-pyridyl) 74%
64 (R = 4-pyridyl) 29%
1
1
1
6
1 (R = 3-pyridyl) 57%
63 (R = 3-pyridyl) 78%
65 (R = 3-pyridyl) 55%
TFA,
DCM:AcOH (1:1)
Ar
3
Ar
O
6
R1
1
5
8 (R = 4-pyridyl) 61%
1
5
9 (R = 3-pyridyl) 69%
Scheme 12. Synthesis of 6-pyridyl-3H-naphtho[2,1-b]pyrans 58 and 59 from 4-pyridyl-2-
naphthols 56 and 57
Photochromic Properties
5
2
Whilst there are reports of naphthopyrans bearing electron-withdrawing groups, there is a
5
3
paucity of data concerning their influence on their photochromic properties. In contrast, much
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has been reported concerning the photochromic response of the 3H-naphtho[2,1-b]pyran
isomer decorated around the periphery of the naphthalene unit with electron-donating methoxy
substituents.54 For electron-donating methoxy and dialkylamino groups, influential
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
54
naphthalene ring positions have been identified. The presence of a methoxy group at C-8
induces a bathochromic shift in the wavelength of maximum absorption (max) of the derived
photomerocyanine accompanied with augmented absorption at the photostationary state
55
56
57
(
PSS), and the presence of either a dialkylamino or a methoxy group at C-6 exhibits a
similar hyperchromism but with a hypsochromic shift in the max. The hyperchromic effect of
various electron-donating substituents has, in some instances, been associated with increased
populations of the photomerocyanine isomers at the PSS as a consequence of an increase in the
5
8
half-life (t ) / decrease of the thermal bleaching rate constant (k ). However, hyperchromism
½

has been observed for 2-naphthol derived keto-hydrazone dyes purely as a consequence of the
59
location of a dialkylamino substituent at C-4. It is well established that the UV irradiation of
a naphthopyran generates two major photomerocyanines, the TC and TT isomers in varying
proportions.60 Whilst only minor differences in the max and in the molar attenuation
coefficients () have been observed for the isomeric photomerocyanines derived from 3H-
6
0
naphtho[1,2-b]pyrans, the differential fade rates of these isomeric photomerocyanines from
either angular naphthopyran isomer, in particular the very slow fading of the TT isomer, has
been noted and much interesting exploration of the design of naphthopyrans has been
6
1
undertaken to obviate the formation of this persistent photomerocyanine. With the foregoing
features considered the photochromic response of the new series of pyridyl substituted 3H-
naphtho[2,1-b]pyrans was explored (Figure 5). Their photochromic behaviour was studied in
aerated toluene solutions under continuous UV irradiation (300-Watt xenon arc lamp source
set at 150 W coupled with an UG11 filter, exc 325 nm) at 23 °C. The following standard
6
2
photochromic parameters were analysed: 1) wavelength of maximum absorption (max) of the
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1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
derived photomerocyanines; 2) persistence of colour in the dark which was measured by
recording the thermal bleaching rates constants (k ), and 3) photocolourability which is the

induced optical density (A) of the coloured species at its λmax achieved after irradiation (10
min) to a constant value – photostationary state (PSS). Thus, variations in concentration were
considered in the photocolourability by calculation of the parameter AConc which is defined
as the colour generated at the PSS after continuous UV irradiation of 1 mole of a given
naphthopyran in solution. 4) Fatigue resistance was evaluated for selected examples.
Additionally, electronic emission spectra of the pyridyl substituted naphthopyrans were also
recorded.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Figure 5. UV-Vis absorption spectra of the pyridyl substituted 3H-naphtho[2,1-b]pyrans
in aerated toluene in the closed form (black) and in the PSS (coloured) after continuous
(10 min) UV irradiation (λ 325 nm) by employing an Oriel 300-Watt xenon arc lamp
irr
source (set at 150 W): (a) 15 (1.1 mM); (b) 18 (1.7 mM); (c) 20 (1.7 mM); (d) 26 (1.7 mM);
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(
e) 28 (1.8 mM); (f) 33 (5.2 mM); (g) 30 (0.040 mM); (h) 39 (0.69 mM); (i) 58 (4.0 mM in
toluene:dichloromethane (1:1)); (j) 59 (1.7 mM); (k) 42 (0.065 mM); (l) 51 (0.15 mM)
The majority of the pyridyl substituted naphthopyrans produced orange/red hues (λmax 458 –
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
4
90 nm) in toluene solution under UV irradiation (Table 2), one exception being the 3-(4-
3
-1
pyridyl)-3H-naphtho[2,1-b]pyran 51 (λmax 412 nm; AConc 6.5 × 10 M ; Entry 12, Table 2)
that produced an intense pale yellow hue. The introduction of the 4-pyridyl group at C-3 on the
naphthopyran core induced a large hypsochromic shift in accordance to reported examples of
6
3
naphthopyrans with electron-withdrawing groups at this position. From the series, the 3-(4-
pyridyl)-3H-naphtho[2,1-b]pyran 51 was the only example that showed photodecomposition
after two fatigue cycles when irradiated for 10 min (Figure S177). The 10-pyridyl-3H-
2
-1
naphtho[2,1-b]pyran 15 (λmax 458 nm; AConc 2.1 × 10 M ; Entry 1, Table 2) produced a more
predominantly orange hue than most of the other naphthalene ring substituted isomers,
corresponding to a hypsochromic shift of 17 nm when compared to the simple 3,3-bis(4-
methoxyphenyl)-3H-naphtho[2,1-b]pyran (λmax 475 nm; Entry 13, Table 2). It was rationalized
that the blue shift was a result of the steric clash between the bulky 4-pyridyl group at C-10
and the hydrogens of the diene unit, which led to a more twisted conformation and consequently
to less efficient conjugation. The introduction of pyridyl substituents at C-6, C-7 and C-9
(Entries 2, 3, 8, 9, 10, Table 2) had a small effect on the λmax, in accord with previous
5
4
observations on the substitution of methoxy groups at these positions. Thus, there was a poor
electronic conjugation of the pyridyl groups at these positions with the photo-generated

systems irrespective of the orientation of the pyridyl moiety. The weak colour (AConc 1.3
2
-1
2
-1
× 10 M – 2.2 × 10 M ) generated for these isomers (λ
468 – 472 nm) was slightly
max
hypsochromic shifted when compared to the simple 3,3-bis(4-methoxyphenyl)-3H-
naphtho[2,1-b]pyran (λmax 475 nm; Entry 13, Table 2), most likely as a result of the small
negative inductive effect of the pyridyl unit.
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1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Table 2. Summary of the spectrokinetic properties of the target pyridyl substituted 3H-
naphtho[2,1-b]pyrans and respective PSS obtained after continuous (10 min) UV
irradiation (λ 325 nm, 150 W) in toluene solution
irr
Entry
NP
Conc /
mM
R1
R2
R3
R4
λ
max
A
A
k / s-1
(Amplitude %)
λem / nm
(λexc / nm)
Conc
-1
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
/ nm
458
472
472
486
478
N/A
490
468
472†
472
490
412
/ M
1
2
15
18
20
26
28
33
30
39
58
59
42
51
1.1
1.7
10-(4-Py)
9-(4-Py)
9-(3-Py)
8-(4-Py)
8-(3-Py)
8-(2-Py)
8-(4-Py)
7-(4-Py)
6-(4-Py)
6-(3-Py)
5-(4-Py)
H
4-MeOC
4-MeOC
4-MeOC
4-MeOC
4-MeOC
4-MeOC
4-MeOC
4-MeOC
4-MeOC
4-MeOC
4-MeOC
4-Py
6
6
6
6
6
6
6
6
6
6
6
H
H
H
H
H
H
H
H
H
H
H
4
4
4
4
4
4
4
4
4
4
4
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
H
H
H
0.227
0.366
0.322
0.487
0.415
N/A
2.1 × 102
> 10
-1
Not
recorded
407 (370)
-6
<
10
2.2 × 102
6.5 × 10 (4)
-1
-4
3
.2 × 10 (96)
1.9 × 102
-1
3
1.7
H
6.9 × 10 (3)
391 (360)
450 (367)
387 (353)
-4
3.2 × 10 (97)
4
1.7
H
2.9 × 102
2.3 × 102
N/A
5.3 × 10 (3)
-1
-5
1
.8 × 10 (97)
-1
5
1.8
H
6.0 × 10 (4)
-5
2
.3 × 10 (96)
6
5.2
H
N/A
Not
recorded
402 (337)
7
0.040
0.69
4.0†
1.7
OMe
H
0.553
0.087
0.267†
0.268
0.735
0.975
1.4 × 104
3.1 × 10 (17)
-1
-3
2
.7 × 10 (83)
1.3 × 102
-1
8
9.1 × 10 (1)
411 (352)
405 (360)
419 (360)
413 (364)
375 (346)
-5
1
.3 × 10 (99)
-1†
9
H
67†
7.3 × 10
.4 × 10 (100)
-4
†
2
-1
10
H
1.6 × 102
1.1 × 104
6.5 × 103
7.3 × 10
-
5
3
.4 × 10 (100)
-1
1
1
3
1
0.065
0.15
OMe
H
4.2 × 10 (21)
-3
2.2 × 10 (79)
-1
2
4.1 × 10 (39)
-5
4
.2 × 10 (61)
26a
1
1
N/A
N/A
N/A
N/A
H
H
4-MeOC
4-MeOC
6
6
H
H
4
OMe
OMe
H
OMe
475
476
N/A
N/A
N/A
N/A
N/A
N/A
N/A
N/A
464
4
†
Table S1 includes all 14 structures and can be found in the ESI. toluene:dichloromethane (1:1). NP = naphthopyran. Conc = concentration of the naphthopyran
in solution prior to UV irradiation (mM). λmax = maximum wavelength of absorption at the photostationary state. A = induced optical density at λmax. AConc

= colour generated at the photostationary state after continuous UV irradiation of 1 mole of a given naphthopyran in solution, calculated as A / Conc. k =
6
3a
thermal bleaching rate constant. Amplitude (%).
λem = maximum wavelength of emission of the naphthopyrans in aerated toluene. λexc = excitation
wavelength, corresponding to the maximum wavelength of absorbance of the naphthopyran.
R3
R2
2
1
3
10
O4 R4
9
8
R1
5
7
6
2
-1
The introduction of a 4-pyridyl substituent at C-8 (26) (λmax 486 nm; AConc 2.9 × 10 M ;
Entry 4, Table 2) induced a bathochromic shift (11 nm) when compared to the 3,3-bis(4-
methoxyphenyl)-3H-naphtho[2,1-b]pyran (λmax 475 nm; Entry 13, Table 2). It is pertinent to
note that the introduction of an electron-donating methoxy group at C-8 results in a more
substantial red shift in the max.54 A larger bathochromic shift (15 nm) was observed for the
trimethoxy substituted 8-(4-pyridyl)-3H-naphtho[2,1-b]pyran 30 (λmax 490 nm; AConc 2.1 ×
4
-1
1
1
0 M ; Entry 7, Table 2) and 5-(4-pyridyl)-3H-naphtho[2,1-b]pyran 42 (λ 490 nm; AConc
max
4
-1
.1 × 10 M ; Entry 11, Table 2) when compared to the simple trimethoxy substituted 3H-
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naphtho[2,1-b]pyran (λmax 476 nm; Entry 14, Table 2). For the 8-substituted 3H-naphtho[2,1-
b]pyrans 26 (Entry 4, Table 2), 30 (Entry 7, Table 2) and 5-substituted 3H-naphtho[2,1-b]pyran
42 (Entry 11, Table 2), the red shift of the λmax was presumably a consequence of the balance
between the more extended conjugated π system of the corresponding photomerocyanines and
the electron-withdrawing nature of the pyridyl ring. The augmentation of the max by 25 nm
1
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through extension of the merocyanine chromophore by introduction of an acetoxy group at C-
65
5
has been noted by Van Gemert. Similarly, the introduction of the electron-withdrawing N-
phenylamido group at C-5 has also been reported to induce a substantial bathochromic shift in
6
6
the λmax by 60 nm accompanied by faster bleaching kinetics. By changing the orientation of
2
-1
the pyridyl at C-8 in 28 (λmax 478 nm; AConc 2.3 × 10 M ; Entry 5, Table 2) the electronic
conjugation was disturbed which resulted in a negligible shift when compared to 3,3-bis(4-
methoxyphenyl)-3H-naphtho[2,1-b]pyran (λmax 475 nm; Entry 13, Table 2). This contrasts with
data reported for the photomerocyanines derived from 3,3,8-triphenyl-3H-naphtho[2,1-b]pyran
where similar conjugation of the merocyanine upon introduction of the 8-phenyl substituent
6
7
affords a red shift of 30 nm. Distinct from the 8-(4-pyridyl)- (26) (Entry 4, Table 2) and 8-
(3-pyridyl)- (28) (Entry 5, Table 2) isomers, the insertion of a 2-pyridyl substituent at C-8, to
afford 33 (Entry 6, Table 2), resulted in a weak yellow background hue accompanied by very
poor photochromic response.
The location of the pyridyl unit on the naphthopyran core has an influence on the persistence
of the photogenerated colour. It is well established that the absorption spectrum of the irradiated
naphthopyran results from an equilibrium mixture of photomerocyanine isomers at the PSS,
and that the TC isomer fades relatively quickly while the TT isomer can fade over many hours,
leading to the impression of the generation of a permanent dye. Such differential fading has led
to the report of thermal bleaching rate constants (k ) for the initial rapidly fading TC isomer

-1
-3 -1
traditionally in the order of 10 – 10 s and then a second k for the slower fading TT isomer

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-4
-6 -1 63a,68
generally in the order of 10 – 10 s .
In this work it should be noted that the 3H-
naphtho[2,1-b]pyrans displayed such dual fading characteristics with the majority of the
-1
-1
-5 -1
examples exhibiting a first k in the order of 10 s and the second k in the order of 10 s ,


0
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irrespectively of the position and orientation of the pyridyl group (Table 2). A few exceptions,
solely characterized by changes in the second k  include naphthopyrans 18 (Entry 2, Table 2)

and 20 (Entry 3, Table 2) in which the pyridyl at C-9 led to a one order of magnitude smaller
-4
-1
second k (10 s ). A more pronounced effect was recorded for naphthopyran 15 (Entry 1,

Table 2) in which the pyridyl at C-10 led to the generation of a particularly thermally stable
photochrome as no fading of colour was detected after 30 min of standing in the dark (Figure
S165). The combined effect of the introduction of a pyridyl substituent in the naphthopyran
scaffold and an ortho methoxy in one of the anisyl substituents at C-3 for naphthopyrans 30
(
Entry 7, Table 2; also Figure 6) and 42 (Entry 11, Table 2) led to a second k in the order of

-
3 -1
1
0 s .
The UV-Vis absorption spectra of the pyridyl substituted 3H-naphtho[2,1-b]pyrans revealed
absorption bands centred at 337 – 370 nm assigned to π → π* electronic transitions (Figures
6
9
S166 – S176). Besides triggering the photochromic reaction, excitation at these transitions
resulted in the evolution of structured and high energy emission bands centred at 375 – 450 nm
attributed to π → π* fluorescence (Figure S179). Considering the electron-withdrawing nature
of the pyridyl substituent, the fluorescence behaviour of the naphthopyrans may be justified by
a potential charge-transfer (CT) character of the π → π* transition. Curiously, for the selected
examples 30 and 42, the photochromic reaction appears to disrupt the CT character of the
bathochromic shifted π → π* transition as no emission was recorded at the PSS (Figure S180).
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Figure 6. Thermal bleaching of the PSS in aerated toluene after continuous (10 min) UV
irradiation (λ 325 nm) by employing an Oriel 300-Watt xenon arc lamp source (set at
irr
1
50 W): (a) UV-Vis absorption spectra of the bleaching in the dark of the PSS of 51 (0.15
mM) with a 240 seconds scan interval; (b) Bi-exponential fit of absorbance of 51 at 412
nm = f (t); (c) UV-Vis absorption spectra of the bleaching in the dark of the PSS of 30
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(
0.040 mM) with a 40 seconds scan interval; (d) Bi-exponential fit of absorbance of 30 at
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90 nm = f(t); (e) UV-Vis absorption spectra of the bleaching in the dark of the PSS of 28
(1.8 mM) with a 240 seconds scan interval; (f) Bi-exponential fit of absorbance of 28 at
78 nm = f (t)
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The ideal combination of photochromic properties for variable optical transmission devices is
the rapid intense colour generation from a colourless inactivated state with a reasonably rapid
rate of fade (seconds) of the coloured form at room temperature. It is also important that the
photochromes exhibit good fatigue resistance; the photochromic cycles must be repeatable
many times without loss of performance. From the series, the two examples that better combine
strong photocolourability and relatively fast bleaching kinetics are the trimethoxy substituted
4
-1
8
-(4-pyridyl)-3H-naphtho[2,1-b]pyran 30 (λmax 490 nm; AConc 2.1 × 10 M ; t 190 s; Entry
½
4
-1
7, Table 2) and 5-(4-pyridyl)-3H-naphtho[2,1-b]pyran 42 (λmax 490 nm; AConc 1.1 × 10 M ;
t½ 210 s; Entry 11, Table 2). Considering their potential interest to the community, the fatigue
resistance of naphthopyrans 30 and 42 was evaluated. The fatigue resistance plots showed that
the photochromes possess good photostability (Abs = 0.02) after continuous irradiation for
1
30 min with a strong light source (Figure 7). Furthermore, the bleaching of colour, besides
occurring thermally, was assisted by irradiation with visible light, revealing the mixed P- and
T-type photochromic character of the pyridyl substituted 3H-naphtho[2,1-b]pyrans.
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Figure 7. Fatigue resistance plots – PSS reached after continuous (10 min) UV irradiation
(λ 325 nm) by employing an Oriel 300-Watt xenon arc lamp source (set in 150 W) and
irr
bleaching effected by continuous irradiation (3 min) with visible light (λ > 420 nm) by
irr
employing an Oriel 300-Watt xenon arc lamp source (set in 150 W): (a) 30 (0.040 mM in
aerated toluene); (b) 42 (0.040 mM in aerated toluene)
Conclusions
A series of twelve novel pyridyl substituted 3H-naphtho[2,1-b]pyrans were synthesized by
following different strategic ideas: a) a Suzuki reaction after ‘chromenization’ was employed
to the synthesis of the 10-, 9-, 8-, 7- and 5-pyridyl substituted 3H-naphtho[2,1-b]pyrans
(Strategy A); b) a Heck reaction was used to prepare a 3-pyridyl substituted 3H-naphtho[2,1-
b]pyran (Strategy B); (c) a Suzuki reaction prior to ‘chromenization’ effected by a late stage
Heck reaction was employed to prepare the 6-pyridyl substituted 3H-naphtho[2,1-b]pyrans
(Strategy C).
The majority of the target pyridyl substituted 3H-naphtho[2,1-b]pyrans exhibited fully
reversible positive photochromism, generating predominantly orange/red hues (λmax 458 – 490
nm) in toluene solution under UV irradiation, with the colour reverting back to the original
colourless state either thermally or with assistance of visible light. Photocolourability was
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