Synthesis and photochromic properties of substituted 3H-naphtho[2,1-b] pyrans

Article abstract of DOI:10.1016/j.tet.2004.10.069

The synthesis and spectroscopic properties of novel 3H-naphtho[2,1-b]pyrans are described. Subtle variation of the colour of the photo-generated merocyanine dyes derived from these naphthopyrans can be accomplished by controlling the steric interactions between a terminal pyrrolidine donor group and a proximal substituent.

Full text of DOI:10.1016/j.tet.2004.10.069

Tetrahedron 61 (2005) 463–471
Synthesis and photochromic properties of substituted
3H-naphtho[2,1-b]pyrans
a
b
Christopher D. Gabbutt,a B. Mark Heron,a, Alicia C. Instone, Peter N. Horton
*
and Michael B. Hursthouseb
aDepartment of Colour and Polymer Chemistry, The University of Leeds, Leeds LS2 9JT, UK
bDepartment of Chemistry, The University of Southampton, Highfield, Southampton SO17 1BJ, UK
Received 30 July 2004; revised 24 September 2004; accepted 21 October 2004
Abstract—The synthesis and spectroscopic properties of novel 3H-naphtho[2,1-b]pyrans are described. Subtle variation of the colour of the
photo-generated merocyanine dyes derived from these naphthopyrans can be accomplished by controlling the steric interactions between a
terminal pyrrolidine donor group and a proximal substituent.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
been detected by NMR spectroscopy in this equilibrium
mixture.7
The isomeric naphthopyrans 1 and 2 are presently the
systems of choice to impart a photochromic response into a
host matrix. The ophthalmic sun lens industry makes
extensive use of these isomers1 and related fused carbo-
cyclic2 and heterocyclic3 analogues in commercial lens
formulations. Furthermore, the application of these isomers
in other light induced colour change applications, e.g. fuel
markers4 and security markers,5 continues to grow.
The photochromic response of the 3H-naphtho[2,1-b]pyran
system 2 is typified by the generation of vibrant yellow to
purple colours that fade relatively rapidly on removal of the
source of irradiation.8 Unfortunately, this rapid fade of the
photo-generated colour gives the overall impression to an
observer of weak colour generation and may be perceived as
an undesirable property of this naphthopyran isomer. The
intensification of the photo-generated colour of 2 has been
accomplished through the incorporation of an amino or
methoxy group at the 6-position, e.g. 3,9 or alternatively, by
introduction of a group into at least one of the ortho
positions of one of the aryl groups attached to 3-C, e.g. 410
and 5a.11 In the former compounds 3 the intensification of
colour, termed hyperchromism, has been rationalised by a
contribution from an additional resonance form that
The mechanism of the reversible colour generation operates
through a facile electrocyclic ring-opening of the 2H-pyran
moiety to afford an equilibrium mixture of coloured
geometrical isomers that gradually electrocyclise to the
colourless pyran ring on cessation of irradiation (type T
photochromism) (Scheme 1).6 Recently, the formation of an
additional photo-generated species, an allenylnaphthol, has
Scheme 1.
Keywords: Naphthopyrans; Photochromism; Steric effects; X-ray crystallography; Synthesis.
* Corresponding author. Tel.: C44 113 3432925; fax: C44 113 3432947; e-mail: b.m.heron@leeds.ac.uk
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.10.069

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C. D. Gabbutt et al. / Tetrahedron 61 (2005) 463–471
stabilises the ring-opened form (merocyanine dye). In the
latter compounds 4 and 5a the ortho substituent hinders the
ring closure to the colourless pyran form. The net result of
these electronic and steric effects is a photostationary state
in which there is an appreciable concentration of the
merocyanine valence tautomer, which results in intensifica-
tion of the developed colour.
The 1,1-diarylprop-2-yn-1-ols can be conveniently accessed
by addition of lithium trimethylsilylacetylide (LiTMSA) to
a benzophenone with subsequent removal of the TMS
group.14 In this present work we required access to several
new benzophenones each with a pyrrolidine ring at 4-C and
a substituent at 3-C. Traditional Friedel–Crafts chemistry15
was employed to construct the benzophenone from benzene
and an appropriately substituted 4-halogenobenzoyl
chloride. Nucleophilic displacement of the activated halo-
gen with pyrrolidine was then investigated. Chlorobenzoic
acids 6a,b were readily obtained from 3-amino-4-chloro-
benzoic acid using diazonium salt methodology.16 Treat-
ment of 6a,b with thionyl chloride gave the requisite acid
chlorides which were used directly to obtain the benzo-
phenones 7a,b, respectively. The acid chlorides derived
from commercial benzoic acids 6c,d were similarly
converted into the respective benzophenones 7c,e
(Scheme 2). 4-Chloro-3-methoxybenzophenone 7f was
accessed by a different strategy involving addition of the
Grignard reagent derived from 2-chloro-5-bromoanisole to
the Weinreb amide 8.17
The nucleophilic displacement of the activated halogen in
the benzophenones 7 was investigated. Pyrrolidine (bp
88 8C) was the amine of choice used in this study since it is
an excellent donor group18 that provides a large batho-
chromic shift in lmax of the photogenerated isomers.11
Furthermore, pyrrolidine is highly nucleophilic and less
volatile than other secondary amines with similar donor
properties, e.g. diethylamine (bp 55 8C); a feature which
facilitates the nucleophilic displacement reaction. Heating
the benzophenones 7 in an excess of pyrrolidine effected the
smooth formation of the 4-pyrrolidinobenzophenones 9a–f
in 41–89% yield after purification (Scheme 3). The
reaction time was markedly influenced by the nature of
the 3-substituent: with the difluorobenzophenone 7d show-
ing high conversion to 9d in ca. 2 h whilst the 3-methoxy
analogue 7f required 4 days to afford 9f in only 41% yield.
Clearly the efficiency of the SNAr reaction is decreased by
the electron donating effect of the ortho methoxy group in
7f.
We were interested in exploring photochromic naphtho-
pyrans of type 5b in which the influence of replacing an H
atom with a bulky substituent adjacent to the terminal
pyrrolidine unit could be investigated.
2. Results and discussion
The most versatile and efficient route to 3,3-diaryl-3H-
naphtho[2,1-b]pyrans relies upon the one pot, acid-cata-
lysed reaction of a 2-naphthol with a 1,1-diarylprop-2-yn-1-
ol;12 a transformation that was developed from an original
naphthopyran synthesis reported by Iwae and Ide in 1962.13
The benzophenones 9 were efficiently transformed into the
Scheme 2. Reagents: (i) concd HCl, NaNO2, H2O, 0 8C then either CuBr or Kl and heat; (ii) SOCl2, heat; (iii) AlCl3, PhH, heat; (iv) Mg, anhyd. Et2O, heat; (v)
amide 8, anhyd. Et2O, heat then aqueous HCl.

C. D. Gabbutt et al. / Tetrahedron 61 (2005) 463–471
465
Scheme 3. Reagents: (i) pyrrolidine, heat; (ii) LiTMSA, anhyd. THF, 0 8C—RT; (iii) KOH, MeOH then AcOH.
prop-2-yn-1-ols 10 on reaction with an excess of LiTMSA
which was derived from n-butyllithium and trimethyl-
silylacetylene. Removal of the TMS group from the initial
adduct was accomplished in the same flask by addition of
methanolic KOH (2 equiv). Yields for this conversion are
typically high (58–99%); though the alkynol can be
markedly sensitive to over acidification with AcOH during
work-up resulting in the formation of intractable multi-
We have previously observed the formation of such
aldehydes12 as by-products from the acid-catalysed reaction
between naphthols and prop-2-yn-1-ols and have rational-
ised their formation by either a Meyer–Schuster20 or Rupe
rearrangement.21
component tars.
The naphthopyrans 11a–f were obtained on heating the
propynols 10 with 2-naphthol in toluene in the presence of
acidic alumina (Scheme 4). The H NMR spectra of 11
1
displayed a doublet at wd 6.2 with a coupling constant of
10 Hz characteristic of 2-H in 3H-naphtho[2,1-b]pyrans.12,19
The doublet for 1-H was obscured by the aromatic
protons, however, 2D 1H–1H COSY experiments on a
range of 11 (e.g., Fig. 1 for 11d) revealed that 3-H resonated
at d 7.3.
The spectroscopic data (Table 1) obtained for the naphtho-
pyrans (11a–h) merit some comment. It is apparent from
these data that as the size of the substituent X increases lmax
gradually decreases until a limit where XZBr (11b).
Replacement of the bromine atom with the larger iodine
atom (11a) has a negligible influence on lmax. We have
attributed this gradual hypsochromic shift to decreasing
conjugation between the pyrrolidine donor unit and the
remaining chromophore. This diminished conjugation arises
as a consequence of torsion of the pyrrolidine unit about
the Cphenyl–N bond to alleviate steric pressure exerted by the
proximal X group on the N-methylene units of the
pyrrolidine ring. These results compare favourably with
literature data for a series of 4-aminophenylazo dyes (e.g.,
13a,b) where similar hypsochromic shifts in lmax are noted
when a terminal dimethylamino function is crowded by
adjacent methyl group.22 A theoretical account of these
steric effects in azo dyes has been presented.23 Interestingly,
the effect of congestion about a terminal donor group in
triarylmethine dyes is complex with both bathochromic and
Naphthopyrans 11e (24%) and 11f (16%) were isolated in
significantly lower yields compared with those recorded for
11a–d (ca. 60%). Interestingly, a significant amount of a by-
product was isolated from the reaction between 2-naphthol
and 10f. This material, which darkened on standing in air,
was characterised as a mixture of geometrical isomers of the
a,b-unsaturated aldehyde 12. The 1H NMR spectrum of this
compound displayed a doublet at d 9.60 (minor isomer) and
at d 9.36 (major isomer) with coupling constants of 8.0 and
8.2 Hz, respectively, which are assigned to the aldehyde
proton of each isomer. From the signals for the methoxy
groups at d 3.82 (minor) and d 3.73 (major), the isomer ratio
is 1.0:4.2.
Scheme 4. Reagents: (i) acidic alumina, PhMe, heat.

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C. D. Gabbutt et al. / Tetrahedron 61 (2005) 463–471
Figure 1. 1H–1H COSY NMR spectrum of 11d.
hypsochromic shifts in lmax noted.24 We believe that the
twist of the pyrrolidine unit is maximised when XZBr and
that no further reduction in steric congestion by twisting can
be achieved. It is noteworthy that the position of lmax for
11e, where XZMe, is comparable with that for 11c; this
feature is in accord with observations that a chlorine atom
and a methyl group have similar spatial requirements.25 lmax
for 11f, with an ortho methoxy substituent, is apparently at
odds with the observed trend. However, previous results
would suggest that a methoxy group is not as spatially
demanding as a methyl group,11 but is significantly more
electron donating. In this instance we suggest that the
reduced conjugation of the pyrrolidine unit induced by
twisting to minimise crowding with the adjacent methoxy
group is countered by the donating power of the methoxy
unit which, although located in a non conjugating site, is
Table 1. Spectroscopic data for naphthopyrans 11
Entry
X
lmax (nm)
t (s)
½
11a
11b
11c
11d
11e
11f
I
494
493
513
529
517
557
538
5
Br
Cl
F
Me
OMe
H
4
4
4
3
5
5
11h
Figure 2. X-ray crystallographic structure of compound 11a.

C. D. Gabbutt et al. / Tetrahedron 61 (2005) 463–471
467
Comparative space filling model representations of 11a and
11d showing the steric interactions between the halogen
substituent and the pyrrolidine units are provided in
Figure 4. These representations confirm an increasing steric
interaction between the halogen and pyrrolidine ring as the
size of the halogen increases. If we consider the situation in
the coloured ring-opened form, where there is appreciable
N–Caryl double bond character in the excited state, then such
steric interactions are more pronounced and significant
twisting about the N–Caryl bond must occur resulting in
diminished conjugation and a hypsochromic shift in lmax
.
Hallas has discussed the influence of cyclic terminal groups
and associated steric interactions on lmax of aminoazo-
benzene dyes.18
The half-life, t , is the time taken for the intensity of the
½
absorbance to fade to half its original value recorded under
steady state conditions. It is interesting to note that whilst
variation of the X group changes lmax, only minor variations
in the t values are noted. This is somewhat surprising since
½
it has been established that the electronic properties of the
group located at the para position of the geminal aryl rings
influence the persistence of the ring-opened form, with
Figure 3. X-ray crystallographic structure of compound 11d.
powerful electron donor groups resulting in decreased t
½
values.6 Presumably, t is less sensitive than lmax to the
significant. This balance of properties has been observed for
azo dye 14a which has lmax virtually identical with its
methoxy substituted analogue 14b.26
½
subtle variations in the electron donating properties of the
terminal pyrrolidine ring induced by steric interactions.
In summary, a series of novel substituted photochromic 3H-
naphtho[2,1-b]pyrans 11 have been accessed from the
reaction between 2-naphthol and a prop-2-yn-1-ol 10. The
colour of the reversibly photo-generated merocyanine dyes
has been manipulated through control of steric interactions
between a terminal pyrrolidine donor function and neigh-
bouring substituents. As the magnitude of these steric
interactions increase lmax is shifted hypsochromically until
a maximum interaction is observed between the pyrrolidine
X-ray crystal structures of naphthopyrans 11a (XZI)27 and
11d (XZF)28 are presented in Figures 2 and 3, respectively.
Figure 4. Space filling representations of 11a (left) and 11d (right).

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C. D. Gabbutt et al. / Tetrahedron 61 (2005) 463–471
methylene and a bromine atom. The data recorded for the
electron donating methoxy group is at odds with the
observed trend indicating that its electronic effect is
significant despite it being located in a non-conjugating
position. The rate of fade of the photo-generated colour is
relatively insensitive to the subtle changes in electron donor
group strength induced by steric interactions with an
adjacent substituent.
chloride was removed from the cooled reaction mixture
and the remaining acid chloride was dissolved in benzene
(130 mmol). Aluminium chloride (29 mmol) was added
portion-wise over ca. 10 min to this solution and the
resulting suspension was refluxed for ca. 1 h. The reaction
mixture was poured onto ice (300 g) and conc. HCl (50 ml).
The organic layer was separated and the aqueous layer
extracted with ethyl acetate (3!100 ml). The combined
organic phases were washed with 5% aqueous NaOH
solution (50 ml), water (3!50 ml) and dried (anhyd.
Na2SO4). Removal of the solvent gave the crude benzo-
phenones that were recrystallised from hexane and ethyl
acetate. The following benzophenones were obtained by this
protocol:
3. Experimental
3.1. General
Melting points were determined in capillary tubes and
are uncorrected. Visible spectra were recorded for ca. 1!
10K5 mol dmK3 solutions in spectroscopic grade toluene in
10 mm quartz cells at 20 8C using an Analytik Jena Specord
S100 diode array spectrophotometer. Samples were
irradiated to a steady state of absorbance using a Spectroline
8 W lamp (365 nm). Infrared spectra were recorded on a
Perkin-Elmer 882 spectrophotometer in KBr discs unless
otherwise specified. NMR spectra were recorded on a
Bruker Avance 400 MHz instrument for solutions in CDCl3
unless otherwise stated; J values are given in Hz. Flash
chromatography separations were performed on chroma-
tography silica (40–60 mm particle size distribution) as
supplied by Fluorochem Ltd.
3.3.1. 4-Chloro-3-iodobenzophenone, (7a). From 4-chloro-
3-iodobenzoic acid as pale brown microcrystals, (46%), mp
96–98 8C, nmax 1651 cmK1; dH 7.50 (2H, m, Ar-H), 7.55
(1H, d, JZ8.3 Hz, 5-H), 7.62 (1H, m, Ar-H), 7.70 (1H, dd,
JZ8.3, 2.0 Hz, 6-H), 7.76 (2H, m, Ar-H), 8.28 (1H, d, JZ
2.0 Hz, 2-H). (Found: C, 45.93; H, 2.39 C13H8ClIO requires
C, 45.58; H, 2.35%).
3.3.2. 3-Bromo-4-chlorobenzophenone, (7b). From
3-bromo-4-chlorobenzoic acid as pale brown micro-
crystals, (67%), mp 89–91 8C (lit. mp 109 8C30); dH 7.52
(2H, m, Ar-H), 7.57 (1H, m, Ar-H), 7.63 (2H, m, Ar-H),
7.78 (2H, m, Ar-H), 7.90 (1H, d, JZ1.9 Hz, 2-H).
3.2. Preparation of 3-substituted-4-chlorobenzoic acids
(6)
3.3.3. 3,4-Dichlorobenzophenone, (7c). From 3,4-
dichlorobenzoyl chloride as off-white microcrystals,
(54%), mp 102–104 8C (lit. mp 101.5–102.0 8C31); dH
7.51 (2H, m, Ar-H), 7.57 (1H, d, JZ8.3 Hz, 5-H), 7.63
(2H, m, Ar-H), 7.77 (2H, m, Ar-H), 7.89 (1H, d, JZ1.9 Hz,
2-H).
A solution sodium nitrite (102 mmol) in water (15 ml) was
added slowly to a cold (0 8C) stirred solution of 3-amino-4-
chlorobenzoic acid (100 mmol) in water (250 ml) and conc.
HCl (75 ml). On completion of the addition the solution was
stirred for 5 min and then a solution of the appropriate
halide (102 mmol) in water (25 ml) was added. The cooling
bath was removed and the mixture stirred for a further 5 min
before carefully heating the suspension to 90 8C for 10 min.
The mixture was cooled to room temperature and the
precipitated solid collected and washed with water (3!
50 ml). The crude product was recrystallised from ethanol
and water. The following acids were prepared in this way:
3.3.4. 4-Fluoro-3-methylbenzophenone, (7e). From
4-fluoro-3-methylbenzoyl chloride as cream micro-
crystals, (79%), mp 50–52 8C (lit. mp 52–54 8C32); dH
2.34 (3H, s, CH3), 7.09 (1H, m, Ar-H), 7.49 (2H, m, Ar-H),
7.58 (2H, m, Ar-H), 7.63 (1H, m, Ar-H), 7.77 (2H, m, Ar-H).
3.4. Preparation of 4-chloro-3-methoxybenzophenone
(7f)
3.2.1. 4-Chloro-3-iodobenzoic acid, (6a). From potassium
iodide as an off-white powder (72%), mp 215–217 8C (Lit.
mp 216–217 8C29); dH(CDCl3, d6-DMSO) 3.67 (1H, bs,
OH), 7.69 (1H, d, JZ8.3 Hz, 5-H), 7.91 (1H, dd, JZ8.3,
2.0 Hz, 6-H), 8.00 (1H, d, JZ2.0 Hz, 2-H).
A solution of 4-bromo-2-chloroanisole (23 mmol) in anhyd.
diethyl ether (20 ml) was added dropwise to magnesium
turnings (23 mmol) in anhyd. diethyl ether (20 ml). After ca.
1/3 of the solution of 4-bromo-2-chloroanisole had been
added one crystal of iodine was added and the mixture
stirred. Upon initiation of the reaction mixture the
remaining solution of 4-bromo-2-chloroanisole was added
at such a rate so as to maintain a steady reflux. On
completion of the addition the suspension was refluxed for a
further 1 h and then cooled to room temperature. A solution
of N-methoxy-N-methylbenzamide (18 mmol) in anhyd.
diethyl ether (20 ml) was added dropwise via syringe to this
solution of the Grignard reagent so as to maintain a constant
reflux. On completion of the addition the mixture was
refluxed for a further 2 h and then left to stand overnight at
room temperature. The mixture was poured onto ice
(w200 g) and aqueous HCl (w100 ml, 2 M) and the
organic layers separated. The aqueous layer was extracted
3.2.2. 3-Bromo-4-chlorobenzoic acid, (6b). From
copper(I) bromide as an off-white powder (30%), mp
214–216 8C (Lit. mp 215–216 8C29); dH(CDCl3, d6-DMSO)
3.55 (1H, bs, OH), 7.71 (1H, d, JZ8.3 Hz, 5-H), 7.82 (1H,
dd, JZ8.3, 1.6 Hz, 6-H), 8.00 (1H, d, JZ1.6 Hz, 2-H).
3.3. Preparation of 3-substituted-4-halogenobenzo-
phenones (7)
The 3-substituted-4-halogenobenzoic acid (26 mmol), thio-
nyl chloride (40 mmol) and one drop of N,N-dimethyl-
formamide were refluxed for 2 h. The excess thionyl

C. D. Gabbutt et al. / Tetrahedron 61 (2005) 463–471
469
with ethyl acetate (3!100 ml) and the combined organic
phases were washed with water (3!50 ml), dried (anhyd.
Na2SO4) and evaporated to afford a sticky gum. Elution of
this crude product from silica using 40% ethyl acetate/
hexane gave the title compound, 7f, as cream microcrystals,
(54%), mp 52–54 8C, nmax 1650, 1574 cmK1; dH 3.97 (3H, s,
OCH3), 7.27 (1H, dd, JZ8.1, 1.9 Hz, 6-H), 7.46 (2H, m,
Ar-H), 7.50 (2H, m, Ar-H), 7.61 (1H, m, Ar-H), 7.79 (2H,
m, Ar-H). (Found: C, 67.91; H, 4.40; C14H11O2Cl requires
C, 68.16; H, 4.49%).
4-fluoro-3-methylbenzophenone as yellow microcrystals,
(65%), mp 78–81 8C, nmax 1635, 1597, 1589 cmK1; dH 1.97
(4H, m, (CH2)2), 2.16 (3H, s, CH3), 3.43 (4H, m, N(CH2)2),
6.71 (1H, d, JZ8.6 Hz, 5-H), 7.45 (2H, m, Ar-H), 7.53 (1H,
m, Ar-H), 7.59 (1H, dd, JZ8.6, 2.0 Hz, 6-H), 7.66 (1H, m,
Ar-H), 7.73 (2H, m, Ar-H). (Found: C, 81.45; H, 7.21; N,
5.27; C18H19NO requires C, 81.48; H, 7.22; N, 5.28%).
3.5.6. 3-Methoxy-4-pyrrolidinobenzophenone, (9f). From
4-chloro-3-methoxybenzophenone as a viscous orange oil,
(41%), bp 278 8C at 0.4 mmHg; nmax 1634, 1584 cmK1; dH
1.94 (4H, m, (CH2)2), 3.52 (4H, m, N(CH2)2), 3.85 (3H, s,
OCH3), 6.54 (1H, d, JZ8.4 Hz, 5-H), 7.32 (1H, dd, JZ8.4,
2.0 Hz, 6-H), 7.45 (2H, m, Ar-H), 7.51 (2H, m, Ar-H), 7.73
(2H, m, Ar-H). (Found: [MCH]C 282.1485; C18H19NO2
requires [MCH]C 282.1489).
3.5. Preparation of 3-substituted-4-pyrrolidinobenzo-
phenones (9)
The halogenobenzophenone (23 mmol) was dissolved in
pyrrolidine (140 mmol) and stirred at room temperature for
10 min and then refluxed until TLC examination of the
reaction mixture indicated that no further changes were
apparent (2 h–4 days). The cooled mixture was poured into
water (300 ml) and the organic layer was separated. The
aqueous layer was extracted with ethyl acetate (3!100 ml)
and the combined organic phases were washed with water
(6!50 ml), dried (anhyd. Na2SO4) and evaporated to afford
the crude product. Purification was effected by either flash
chromatography or by repeated recrystallisation from
hexane and ethyl acetate. The following benzophenones
were prepared in this manner:
3.6. Preparation of prop-2-yn-1-ols (10)
n-Butyllithium (1.6 M in hexanes) (15 mmol) was added
slowly via syringe to a cold (K10 8C), stirred solution of
trimethylsilylacetylene (15 mmol) in anhyd. tetrahydro-
furan (60 ml) under nitrogen atmosphere. On completion
of the addition (ca. 5 min) the cold solution was allowed to
stir for 1 h. The benzophenone (12 mmol) was added in a
single portion and the mixture stirred until TLC examin-
ation of the reaction mixture indicated that none of the
benzophenone remained (ca. 3 h). The reaction mixture was
re-cooled to 0 8C and a solution of methanolic potassium
hydroxide (from potassium hydroxide (31 mmol) in metha-
nol (20 ml) was added in a single portion. The cooling bath
was then removed and the mixture warmed to room
temperature, after ca. 15 min TLC examination indicated
that deprotection was complete. The mixture was acidified
to pH w7 using glacial acetic acid and then poured into
water (500 ml). The organic layer was separated and the
aqueous layer extracted with ethyl acetate (3!100 ml). The
organic phases were combined, washed with water (3!
50 ml) and dried (anhyd. Na2SO4). Removal of the solvent
gave the prop-2-yn-1-ol that was sufficiently pure for
subsequent use. Analytically pure samples were obtained by
recrystallisation from hexane and ethyl acetate. The
following alkynols were obtained in this way:
3.5.1. 3-Iodo-4-pyrrolidinobenzophenone, (9a). From
4-chloro-3-iodobenzophenone as yellow microcrystals,
(49%), mp 43–45 8C, nmax 1640, 1573 cmK1; dH 1.98 (4H,
m, (CH2)2), 3.56 (4H, m, N(CH2)2), 6.73 (1H, d, JZ8.7 Hz,
5-H), 7.47 (2H, m, Ar-H), 7.54 (1H, m, Ar-H), 7.70 (3H, m,
Ar-H), 8.35 (1H, d, JZ2.1 Hz, 2-H). (Found: [MCH]C
378.0353, C17H16INO requires [MCH]C 378.0349).
3.5.2. 3-Bromo-4-pyrrolidinobenzophenone, (9b). From
3-bromo-4-chlorobenzophenone as yellow microcrystals,
(60%), mp 59–60 8C, nmax 1644, 1589 cmK1; dH 1.97 (4H,
m, (CH2)2), 3.60 (4H, m, N(CH2)2), 6.75 (1H, d, JZ8.8 Hz,
5-H), 7.47 (2H, m, Ar-H), 7.53 (1H, m, Ar-H) 7.64 (1H, m,
Ar-H), 7.72 (2H, m, Ar-H), 7.82 (1H, d, JZ2.1 Hz, 2-H).
(Found: C, 61.51; H, 4.69; N, 4.06; C17H16NOBr requires C,
61.83; H, 4.88; N, 4.24%).
3.6.1. 1-(3-Iodo-4-pyrrolidinophenyl)-1-phenylprop-2-
yn-1-ol, (10a). From 3-iodo-4-pyrrolidinobenzophenone as
pale brown microcrystals, (74%), mp 86–89 8C, nmax 3285,
1602 cmK1; dH 1.77 (4H, m, (CH2)2), 2.73 (1H, s, alkynic-
H), 2.77 (1H, bs, OH), 3.14 (4H, m, N(CH2)2), 6.68 (1H, d,
JZ8.6 Hz, 5-H), 7.18 (4H, m, Ar-H), 7.44 (2H, m, Ar-H),
7.93 (1H, d, JZ2.2 Hz, 2-H). (Found: C, 56.41; H, 4.10; N,
3.17; C19H18NOI requires C, 56.59; H, 4.50; N, 3.47%).
3.5.3. 3-Chloro-4-pyrrolidinobenzophenone, (9c). From
3,4-dichlorobenzophenone as yellow microcrystals, (71%),
mp 54–56 8C, nmax 1635, 1589 cmK1; dH 1.99 (4H, m,
(CH2)2), 3.60 (4H, m, N(CH2)2), 6.75 (1H, d, JZ8.7 Hz,
5-H), 7.47 (2H, m, Ar-H), 7.55 (1H, m, Ar-H) 7.64 (1H, dd,
JZ8.7, 2.0 Hz, 6-H), 7.72 (2H, m, Ar-H), 7.82 (1H, d, JZ
2.1 Hz, 2-H). (Found: C, 71.04; H, 5.68; N, 4.90;
C17H16NOCl requires C, 71.45; H, 5.64; N, 4.90%).
3.5.4. 3-Fluoro-4-pyrrolidinobenzophenone, (9d). From
3,4-difluorobenzophenone as yellow microcrystals, (89%),
mp 127–129 8C, nmax 1632, 1595 cmK1; dH 1.99 (4H, m,
(CH2)2), 3.54 (4H, m, N(CH2)2), 6.57 (1H, m, 5-H), 7.45
(2H, m, Ar-H), 7.54 (3H, m, Ar-H) 7.70 (2H, m, Ar-H).
(Found: C, 75.64; H, 6.07; N, 5.19; C17H16NOF requires C,
75.82; H, 5.99; N, 5.20%).
3.6.2. 1-(3-Bromo-4-pyrrolidinophenyl)-1-phenylprop-2-
yn-1-ol, (10b). From 3-bromo-4-pyrrolidinobenzophenone
as pale brown microcrystals, (58%), mp 86–89 8C, nmax
3286, 1595 cmK1; dH 1.77 (4H, m, (CH2)2), 2.72 (1H, s,
alkynic-H), 2.77 (1H, bs, OH), 3.22 (4H, m, N(CH2)2), 6.66
(1H, d, JZ8.6 Hz, 5-H), 7.15 (4H, m, Ar-H), 7.39 (1H, d,
JZ2.2 Hz, 2-H), 7.44 (2H, m, Ar-H). (Found: C, 63.64; H,
4.85; N, 3.91; C19H18NOBr requires C, 64.06; H, 5.09; N,
3.93%).
3.5.5. 3-Methyl-4-pyrrolidinobenzophenone, (9e). From

470
C. D. Gabbutt et al. / Tetrahedron 61 (2005) 463–471
3.6.3. 1-(3-Chloro-4-pyrrolidinophenyl)-1-phenylprop-
2-yn-1-ol, (10c). From 3-chloro-4-pyrrolidinobenzo-
phenone as an off-white powder, (73%), mp 93–95 8C,
nmax 3285, 1604 cmK1; dH 1.91 (4H, m, (CH2)2), 2.82 (1H,
bs, OH), 2.86 (1H, s, alkynic-H), 3.36 (4H, m, N(CH2)2),
6.79 (1H, d, JZ8.6 Hz, 5-H), 7.30 (4H, m, Ar-H), 7.53 (1H,
d, JZ2.3 Hz, 2-H), 7.59 (2H, m, Ar-H). (Found: C, 72.85;
H, 6.01; N, 4.47; C19H18NOCl requires C, 73.19; H, 5.82; N,
4.49%).
C29H24INO requires MC 529.0897; C, 65.79; H, 4.57; N,
2.65%).
3.7.2. 3-(3-Bromo-4-pyrrolidinophenyl)-3-phenyl-3H-
naphtho[2,1-b]pyran, (11b). From 1-(3-bromo-4-pyrro-
lidinophenyl)-1-phenylprop-2-yn-1-ol as off-white micro-
crystals, (58%), mp 126–129 8C, nmax 1605 cmK1; dH 1.88
(4H, m, (CH2)2), 3.33 (4H, m, N(CH2)2), 6.19 (1H, d, JZ
9.9 Hz, 2-H), 6.75 (1H, d, JZ8.6 Hz, Ar-H), 7.17 (2H, m,
Ar-H, 1-H), 7.25 (5H, m, Ar-H), 7.43 (4H, m, Ar-H), 7.64
(1H, d, JZ8.8 Hz, Ar-H), 7.69 (1H, d, JZ8.8 Hz, Ar-H),
3.6.4. 1-(3-Fluoro-4-pyrrolidinophenyl)-1-phenylprop-2-
yn-1-ol, (10d). From 3-fluoro-4-pyrrolidinobenzophenone
as colourless microcrystals, (76%), mp 118–120 8C, nmax
3281, 1571 cmK1; dH 1.91 (4H, m, (CH2)2), 2.78 (1H, bs,
OH), 2.84 (1H, s, alkynic-H), 3.35 (4H, m, N(CH2)2), 6.57
(1H, m, 2-H), 7.18 (2H, m, Ar-H), 7.27 (1H, m, Ar-H), 7.32
(2H, m, Ar-H), 7.58 (2H, m, Ar-H). (Found: C, 77.05; H,
6.22; N, 4.67; C19H18NOF requires C, 77.27; H, 6.14; N,
4.74%).
7.93 (1H, d, JZ8.5 Hz, 10-H). (Found: MC 481.1028; C,
79
71.96; H, 5.41; N, 3.12; C29H BrNO requires MC
481.1036; C, 72.20; H, 5.01; N, 2.90%).
24
3.7.3. 3-(3-Chloro-4-pyrrolidinophenyl)-3-phenyl-3H-
naphtho[2,1-b]pyran, (11c). From 1-(3-chloro-4-pyrro-
lidinophenyl)-1-phenylprop-2-yn-1-ol as pale pink micro-
crystals, (64%), mp 138–140 8C, nmax 1605 cmK1; dH 1.86
(4H, m, (CH2)2), 3.31 (4H, m, N(CH2)2), 6.18 (1H, d, JZ
10.0 Hz, 2-H), 6.74 (1H, d, JZ8.6 Hz, Ar-H), 7.17 (2H, m,
Ar-H, 1-H), 7.24 (5H, m, Ar-H), 7.43 (4H, m, Ar-H), 7.63
(1H, d, JZ8.8 Hz, Ar-H), 7.69 (1H, d, JZ8.8 Hz, Ar-H),
7.93 (1H, d, JZ8.4 Hz, 10-H). (Found: [MCH]C 438.1623;
3.6.5. 1-(3-Methyl-4-pyrrolidinophenyl)-1-phenylprop-
2-yn-1-ol, (10e). From 3-methyl-4-pyrrolidinobenzo-
phenone as pale brown microcrystals, (99%), mp 71–
74 8C, nmax 3285, 1600 cmK1; dH 1.78 (4H, m, (CH2)2), 1.93
(1H, s, OH), 2.16 (3H, s, CH3), 2.70 (1H, s, alkynic-H), 3.04
(4H, m, N(CH2)2), 6.64 (1H, d, JZ8.4 Hz, 5-H), 7.15 (5H,
m, Ar-H), 7.47 (2H, m, Ar-H). (Found: C, 82.41; H, 7.07; N,
4.59; C20H21NO requires C, 82.44; H, 7.26; N, 4.81%).
C, 79.50; H, 5.60; N, 3.20; C29H ClNO requires [MCH]C
35
24
438.1624; C, 79.53; H, 5.52; N, 3.20%).
3.7.4. 3-(3-Fluoro-4-pyrrolidinophenyl)-3-phenyl-3H-
naphtho[2,1-b]pyran, (11d). From 1-(3-fluoro-4-pyrro-
lidinophenyl)-1-phenylprop-2-yn-1-ol as pale pink micro-
crystals, (68%), mp 167–169 8C, nmax 1625 cmK1; dH 1.88
(4H, m, (CH2)2), 3.32 (4H, m, N(CH2)2), 6.19 (1H, d, JZ
10.0 Hz, 2-H), 6.54 (1H, m, Ar-H), 7.07 (2H, m, Ar-H), 7.17
(1H, m, Ar-H), 7.24 (5H, m, Ar-H, 1-H), 7.47 (3H, m, Ar-
H), 7.63 (1H, d, JZ8.8 Hz, Ar-H), 7.69 (1H, d, JZ8.8 Hz,
Ar-H), 7.94 (1H, d, JZ8.4 Hz, 10-H). (Found: [MCH]C
422.1922; C, 82.29; H, 5.84; N, 3.33; C29H24NOF requires
[MCH]C 422.1920; C, 82.64; H, 5.74; N, 3.32%).
3.6.6. 1-(3-Methoxy-4-pyrrolidinophenyl)-1-phenylprop-
2-yn-1-ol, (10f). From 3-methoxy-4-pyrrolidinobenzo-
phenone as a dark brown gum (61%) which decomposed
on attempted purification, dH (crude) 1.89 (4H, m, (CH2)2),
2.07 (1H, bs, OH), 2.85 (1H, s, alkynic-H), 3.27 (4H, m,
N(CH2)2), 3.79 (3H, s, OMe), 6.67 (1H, d, JZ8.2 Hz, 5-H),
7.08 (2H, m, Ar-H), 7.34 (3H, m, Ar-H), 7.59 (2H, m,
Ar-H).
3.7. Preparation of 3,3-diaryl-3H-naphtho[2,1-b]pyrans
(11)
3.7.5. 3-(3-Methyl-4-pyrrolidinophenyl)-3-phenyl-3H-
naphtho[2,1-b]pyran, (11e). From 1-(3-methyl-4-pyrro-
lidinophenyl)-1-phenylprop-2-yn-1-ol as cream micro-
crystals, (24%), mp 111–114 8C, nmax 1606, 1590 cmK1
;
A stirred solution of 2-naphthol (3.3 mmol) and the prop-2-
yn-1-ol (3.3 mmol) in toluene (40 ml) was warmed to 50 8C.
Acidic alumina (2.5 g) was added and the mixture was
refluxed until TLC examination indicated that none of the
prop-2-yn-1-ol remained (ca. 1.5 h). The mixture was
cooled to w50 8C, filtered and the alumina was washed
with hot toluene (2!20 ml). Removal of the toluene from
the combined washings and filtrate gave a gum that was
eluted from silica (40% ethyl acetate/hexane) to afford the
naphthopyran. The following naphthopyrans were obtained
using this protocol:
dH 1.89 (4H, m, (CH2)2), 2.27 (3H, s, CH3), 3.16 (4H, m,
N(CH2)2), 6.25 (1H, d, JZ10.0 Hz, 2-H), 6.75 (1H, d, JZ
8.4 Hz, Ar-H), 7.11 (1H, m, Ar-H), 7.21 (2H, m, Ar-H, 1-H),
7.24 (2H, m, Ar-H), 7.30 (3H, m, Ar-H), 7.44 (1H, m, Ar-H),
7.49 (2H, m, Ar-H), 7.63 (1H, d, JZ8.8 Hz, Ar-H), 7.69 (1H,
d, JZ8.8 Hz, Ar-H), 7.94 (1H, d, JZ8.5 Hz, 10-H). (Found:
M
M
C 417.2088; C, 86.38; H, 6.50; N, 3.32; C30H27NO requires
C 417.2087; C, 86.30; H, 6.52; N, 3.35%).
Two fractions were isolated from 1-(3-methoxy-4-pyrro-
lidinophenyl)-1-phenylprop-2-yn-1-ol and 2-naphthol.
3.7.1. 3-(3-Iodo-4-pyrrolidinophenyl)-3-phenyl-3H-
naphtho[2,1-b]pyran, (11a). From 1-(3-iodo-4-pyrro-
lidinophenyl)-1-phenylprop-2-yn-1-ol as pale brown micro-
crystals, (56%), mp 123–126 8C, nmax 1591 cmK1; dH 1.86
(4H, m, (CH2)2), 3.23 (4H, m, N(CH2)2), 6.18 (1H, d, JZ
9.9 Hz, 2-H), 6.79 (1H, d, JZ8.5 Hz, Ar-H), 7.23 (7H, m,
Ar-H, 1-H), 7.46 (3H, m, Ar-H), 7.63 (1H, d, JZ8.8 Hz,
Ar-H), 7.69 (1H, d, JZ8.8 Hz, Ar-H), 7.94 (2H, m, Ar-H,
10-H). (Found: MC 529.0906; C, 65.87; H, 4.79; N, 2.63;
3.7.6. Fraction 1. 3-(3-Methoxy-4-pyrrolidinophenyl)-3-
phenyl-3H-naphtho[2,1-b]pyran, (11f). As dark green
microcrystals, (16%), mp 117–119 8C; dH 1.88 (4H, m,
(CH2)2), 3.25 (4H, m, N(CH2)2), 3.74 (3H, s, OCH3), 6.25
(1H, d, JZ10.0 Hz, 2-H), 6.64 (1H, d, JZ8.3 Hz, Ar-H),
6.86 (1H, dd, JZ8.3 Hz, 1.8, Ar-H), 6.98 (1H, d, JZ1.6 Hz,
Ar-H), 7.19 (1H, d, JZ8.8 Hz, Ar-H), 7.28 (5H, m, Ar-H,
1-H), 7.48 (3H, m, Ar-H), 7.64 (1H, d, JZ8.8 Hz, Ar-H),

C. D. Gabbutt et al. / Tetrahedron 61 (2005) 463–471
471
13. Iwai, I.; Ide, J. Chem. Pharm. Bull. 1962, 10, 926.
7.70 (1H, d, JZ8.0 Hz, Ar-H), 7.95 (1H, d, JZ8.5 Hz,
10-H). (Found: [MCH]C 434.2115; C30H27NO2 requires
[MCH]C 434.2114).
14. Gabbutt, C. D.; Hepworth, J. D.; Heron, B. M.; Partington,
S. M.; Thomas, D. A. Dyes Pigments 2001, 49, 65.
15. In Friedel–Crafts and Related Reactions, Olah, G. A., Ed.;
Wiley-Interscience: New York, Vols. I–IV, 1963.
3.7.7. Fraction 2. 3-(3-Methoxy-4-pyrrolidinophenyl)-3-
phenylprop-2-enal, (12). As an inseparable mixture of
geometrical isomers (ratio 1.0:4.2), dH mixture 1.95 (8H, m,
(CH2)2), 3.43 (8H, m, N(CH2)2), 3.73 (3H, s, OCH3
(major)), 3.82 (3H, s, OCH3 (minor)), 6.5–7.7 (18H, m,
Ar-H and alkene-H), 9.36 (1H, d, JZ8.2 Hz, aldehyde-H
(major)) 9.60 (1H, d, JZ8.0 Hz, aldehyde-H (minor)).
(Found for mixture: [MCH]C 308.1646; C20H21NO2
requires [MCH]C 308.1645).
16. (a) Hodgson, H. H. Chem. Rev. 1947, 40, 251. (b) Zollinger, H.
Angew. Chem. 1978, 90, 151. (c) Nonhebel, D. C. Chem. Soc.
Special Publ. 1970, 409.
17. Nahm, S.; Weinreb, S. M. Tetrahedron Lett. 1981, 22, 3815.
18. Hallas, G. J. Soc. Dyers Colourists 1994, 110, 342.
19. Gabbutt, C. D.; Gelbrich, T.; Hepworth, J. D.; Heron, B. M.;
Hursthouse, M. B.; Partington, S. M. Dyes Pigments 2002, 54,
79.
20. Swaminathan, S.; Narayanan, K. V. Chem. Rev. 1971, 71, 429.
21. Rupe, H. Helv. Chim. Acta 1920, 9, 672.
Acknowledgements
22. Griffiths, J.; Roozpeikar, B.; Thomasson, J. J. Chem. Res. (S)
1981, 302.
We thank the EPSRC for the provision of a mass
spectrometry service, University of Wales (Swansea) and
an X-ray crystallographic service, University of
Southampton. James Robinson Ltd, (Huddersfield) and the
University of Leeds are thanked for financial support to
A.C.I.
23. Gordon, P. F.; Gregory, P. Organic Chemistry in Colour;
Springer: Berlin, 1983; p. 157.
24. (a) Barker, C. C.; Hallas, G.; Stamp, A. J. Chem. Soc. 1960,
3790. (b) Castelino, R. W.; Hallas, G. J. Chem. Soc. (B) 1971,
1471. (c) Hallas, G.; Paskins, K. N.; Waring, D. R.; Humpston,
J. R.; Jones, A. M. J. Chem. Soc. Perkin Trans. 2 1977, 450. (d)
Brindle, I.; Jones, A. M. Dyes Pigments 2000, 47, 117.
25. Collings, P. J.; Hird, M. Introduction to Liquid Crystals:
Chemistry and Physics; Taylor Francis: London, 1997; p 70.
26. Mustroph, H.; Gussmann, F. J. Prakt. Chem. 1990, 332, 93.
27. Crystal data for 11a: C29H24INO, MZ529.39, monoclinic,
References and notes
1. Mann, C.; Melzig, M.; Weigand, U. PCT WO 03/080595 A1,
2003. Chan, Y. -P.; Breyne, O.; Jean, P. PCT WO 01/36424 A2
2001. Lin, J.; Van Gemert, B. PCT WO 99/31082, 1999.
Clarke, D. A.; Heron, B. M.; Gabbutt, C. D.; Hepworth, J. D.;
Partington, S. M.; Corns, S. N. PCT WO 00/18755 A1, 2000.
2. Breyne, O.; Chan, Y. -P.; Jean, P. PCT WO 02/30916 A1 2002.
Izumi, S.; Nagoh, H. PCT WO 02/090342 A1, 2002. Kumar,
A. PCT WO 98/32037, 1998.
˚
˚
space group P21, aZ8.575(5) A, bZ22.507(5) A, cZ
3
˚
˚
˚
11.773(5) A, bZ93.701(5) A, UZ2267.4(17) A , Dcalcd
Z
1.551 Mg mK3, ZZ4, Mo Ka radiation (gZ0.71073 A), mZ
1.434 mmK1, TZ120(2) K, 31,310 measured reflections,
10,150 observed reflections (RintZ0.0623), R1Z0.0578
[F2O2s(F2)], wR2Z0.0809 (all data). The structure was
solved and refined using the SHELXL-97 suite of programs.33
Crystallographic data (excluding structure factors) for this
structure have been deposited with the Cambridge Crystal-
lographic Data Centre as supplementary publication no.
CCDC243892.
˚
3. Melzig, M.; Weigand, U. PCT WO 02/22594 A1, 2002.
Breyne, O.; Chan, Y. -P.; Jean, P. PCT WO 00/77007 A1,
2000. Qin, X. PCT WO 03/025638 A1, 2003.
4. McCallien, D. W. J.; Bezer, M. GB Pat. No. 2344599, 2000.
5. Camus, M. Eur. Pat. No. 488902, 1992.
28. Crystal data for 11d: C29H24FNO, MZ421.49, monoclinic,
˚
˚
space group P21/n, aZ15.1016(3) A, bZ8.3820(2) A, cZ
6. (a) Delbaere, S.; Luccioni-Houze, B.; Bochu, C.; Teral, Y.;
Campredon, M.; Vermeersch, G. J. Chem. Soc. Perkin Trans. 2
¨
1998, 1153. (b) Gorner, H.; Chibisov, A. K. J. Photochem.
3
˚
˚
17.3016(4) A, bZ105.9620(10), UZ2105.62(8) A , Dcalcd
Z
1.330 Mg mK3, ZZ4, Mo Ka radiation (lZ0.71073 A), mZ
0.086 mmK1, TZ120(2) K, 27,595 measured reflections, 4807
observed reflections (RintZ0.0617), R1Z0.0581 [F2O
2s(F2)], wR2Z0.1157 (all data). The structure was solved
and refined using the SHELXL-97 suite of programs.33
Crystallographic data (excluding structure factors) for this
structure have been deposited with the Cambridge Crystal-
lographic Data Centre as supplementary publication no.
CCDC243891.
˚
Photobiol. A: Chem. 2002, 149, 83. (c) Jockusch, S.; Turro,
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chromic Compounds, Volume 1: Main Photochromic
Families; Crano, J. C., Guglielmetti, R. J., Eds.; Plenum:
New York, 1998; p 113. (b) Hepworth, J. D.; Gabbutt, C. D.;
Heron, B. M. In Colour Science ’98, Volume 1: Dye and
Pigment Chemistry; Griffiths, J., Ed.; University of Leeds:
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29. Hodgson, H. H.; Beard, H. G. J. Chem. Soc. 1927, 20.
30. Cam-Van, N. T.; Diep, B. K.; Buu-Hoi, N. P. Tetrahedron
1964, 20, 2195.
9. Rickwood, M.; Smith, K. E.; Gabbutt, C. D.; Hepworth, J. D.
PCT WO 94/22850, 1994.
31. Wagner, P. J.; Truman, R. J.; Puchalski, A. E.; Wake, R. J. Am.
Chem. Soc. 1986, 108, 7727.
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11. Gabbutt, C. D.; Heron, B. M.; Instone, A. C. Heterocycles
2003, 60, 843.
32. Bomben, A.; Marques, C. A.; Selva, M.; Tundo, P. Synthesis
1996, 1109.
12. Gabbutt, C. D.; Heron, B. M.; Instone, A. C.; Thomas, D. A.;
Partington, S. M.; Hursthouse, M. B.; Gelbrich, T. Eur. J. Org.
Chem. 2003, 1220.
33. Sheldrick, G. M. SHELXL-97 Program System; University of
¨
Gottingen: Germany, 1997.