Solar photochemistry: Optimisation of the photo Friedel-Crafts acylation of naphthoquinones

Article abstract of DOI:10.1039/c3gc41477a

A practical and robust photo Friedel-Crafts acylation of naphthoquinones is described. Although the reaction proceeds slowly in sunlight, the optimised conditions offer a substantial improvement to those already reported, by the utilisation of a more reliable and practical 'sun-mimicking' light source, a less hazardous solvent system (trifluorotoluene) and faster reaction times. Using these conditions, the reaction scope has been expanded to include functionalised aldehyde and naphthoquinone substrates, affording the desired photo-products in acceptable to excellent yields (17-81%). Factors influencing the regiochemistry of the photo Friedel-Crafts reaction on unsymmetrical naphthoquinones have also been investigated.

Full text of DOI:10.1039/c3gc41477a

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Solar Photochemistry: Optimisation of the Photo Friedel-Crafts AcyDlaOIt: i1o0.n103Vo9ie/fwC3AGrtCic4le1O4n7l7inAe
Naphthoquinones †
Lorna J. Mitchell, William Lewis and Christopher J. Moody*
Abstract
A practical and robust photo Friedel-Crafts acylation of naphthoquinones is described.
Although the reaction proceeds slowly in sunlight, the optimised conditions offer a
substantial improvement to those already reported, by the utilisation of a more reliable
and practical ‘sun-mimicking’ light source, a less hazardous solvent system
(trifluorotoluene) and faster reaction times. Using these conditions, the reaction scope
has been expanded to include functionalised aldehyde and naphthoquinone substrates,
affording the desired photo-products in acceptable to excellent yields (17-81%). Factors
influencing the regiochemistry of the photo Friedel-Crafts reaction on unsymmetrical
naphthoquinones have also been investigated.
Introduction
Acylated quinones and their derivatives serve as valuable and versatile precursors for
the construction of numerous biologically active natural products.1-3 For example, several
* School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD,
U.K; Fax: (+44) 115 951 3564; E-mail: c.j.moody@nottingham.ac.uk
† Electronic supplementary information (ESI) available: experimental details for the
preparation of starting materials, X-ray crystal data and copies of NMR spectra.
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members of the pyranonaphthoquinone class of quinone natural products, are accessible
DOI: 10.1039/C3GC41477A
from a common acylated core (Scheme 1).1-3
Scheme 1. Access to pyranonaphthoquinones elutherin 2, isoelutherin 3, deoxyfrenolicin
4 and frenolicin 5 from a common acylated quinone core 1.
Various synthetic routes to such acyl naphthoquinone building blocks have been
described. Common methods, such as the Friedel-Crafts acylation and the Fries
rearrangement are often inefficient,1,4 and require the use of corrosive reagents such as
Lewis acids and acyl chlorides. Such methods also generate significant amounts of
waste, further adding to the environmental burden of such procedures.
Recently, research has shifted towards the implementation of greener synthetic protocols
throughout organic synthesis.5,6 One such example is the photochemical reaction
between a quinone and an aldehyde, often termed the ‘photo Friedel-Crafts acylation’
(Scheme 2), a reaction that can, in principle, be carried out in sunlight.7-14
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However, in undertaking this reaction, the use of hazardous solvents (e.g. benzene) and
DOI: 10.1039/C3GC41477A
impractical photochemical reactors is commonplace.11-14 Whilst the use of supercritical
carbon dioxide as an alternative reaction media has been reported,15 such techniques
also suffer from technical drawbacks (e.g. high pressure vessels). More recently, the use
of room temperature ionic liquids as alternative reaction media has been reported.16
Despite the noted improvement to the sustainability of the reaction, the use of such
solvent systems led to the occurrence of photo-reduction side processes, low isolated
yields, and furthermore, still required the use of specialised photochemical reactors.16
Scheme 2. The photo Friedel-Crafts acylation
In a variation, Schiel and co-workers reported carrying out the reaction in a more
environmentally benign solvent system (t-butanol/acetone) using sunlight as the light
source.9,10 However, the reaction set up was complex and impractical as it required the
use of specialised equipment to both capture and concentrate sunlight. Successful
examples of the reaction have recently been reported using the intense sunlight found in
insolate regions of lower latitude,7,8 although the reactions were carried out in benzene,
greatly compromising the safety of the procedure.
With the aim of developing an efficient, greener and readily accessible photo Friedel-
Crafts acylation suitable for widespread use in the laboratory, we considered that there
was scope for further development, particularly in the use of more environmentally
acceptable solvents, and of a simple experimental protocol that employed direct sunlight
or a readily available sunlight-mimicking light source. Furthermore, to the best of our
knowledge, there are very few examples of the photo Friedel-Crafts acylation on
substituted quinone substrates.7,9,11 Although heterocyclic,8 aromatic11 and aliphatic13
aldehydes have previously been studied, there remains scope for further expansion in
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this field. As quinones possessing additional functionalities are of direct intDeOrIe: 1s0t.10w39it/hC3iGnC41477A
the field of natural products synthesis, there is also opportunity to apply the
methodology to more complex substrates.
Results and Discussion
We began by considering the known photochemical reaction between 1,4-
naphthoquinone and butyraldehyde to give 2-butanoyl-1,4-dihydroxynaphthalene 6a, as
carried out by Schiel and co-workers (Scheme 3).9,10 The first objective of our research
was to transfer these promising conditions into a more practical laboratory set-up.
Scheme 3. Conditions: t-BuOH/acetone (3:1), sunlight, PROPHIS vessel, 5 days, 90%.
Initially the reaction was carried out in sunlight in a glass vessel placed on the window
sill of the laboratory (latitude 52°56’31’’ NE, 32 m above sea level) and left to stir for 3
months during autumn/winter. Under these conditions, little reaction was observed.
When repeating these conditions in summer for a period of 5 days, we observed 45%
conversion to product (36% isolated yield). Using the more desirable weather conditions
to our advantage, the reaction was carried out with various other aliphatic aldehydes
(Scheme 4, Table 1). Disappointingly, although product formation was observed in all
cases, despite prolonged irradiation times, the reactions did not reach completion.
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DOI: 10.1039/C3GC41477A
Scheme 4
Table 1. Variation of aldehyde
Entry
R
Product
Irradiation
time (d)
Conversion
(%)a,b
1
2
Pr
6a
6b
5
45 (36)
75
CH2CHMe2
20
3
4
C5H11
6c
6d
20
34
61 (38)
50
PhCH2CH2
aBracketed conversions represent isolated yields after purification by column
chromatography; bConversion as measured by 1H NMR spectroscopy.
Given the obvious limitations of using sunlight as the photochemical source in regions of
higher latitude, we decided to investigate artificial light sources as a reliable and
predictable alternative. Whilst several of the light sources (Table 2) gave little or no
conversion to product (Entries 1-2, 4), significant conversion was achieved with the UV
sunlamp (Entry 3). Despite this, lack of current manufacture meant that the UV sunlamp
was impractical for long-term use. A more promising result was achieved with the
hydrargyrum quartz iodide (HQI) high intensity discharge (HID) lamp, which, owing to
its wide spectral emittance when compared with conventional bulbs, is a commonly
employed light source in commercial greenhouses. As a result, such bulbs can therefore
be viewed as ‘sunlight-mimicking’ sources. Furthermore, they are economical and also
readily accessed commercially, so are practical for use in the laboratory environment.
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DOI: 10.1039/C3GC41477A
Table 2: Screening of artificial light sources in the reaction of 1,4-naphthoquinone with
butyraldehyde
Entry
Light Source
Power
(W)
Intensity
Reaction
time (h)
Conversion
(cd)a
to 6a (%)b
1
2
3
4
5
Energy saving LED bulbc
Energy saving halogen bulbd
UV Sunlampe
25
55
48
72
0
50
72
0
300
400
400
1500
1900
6678
14.5
14.5
14.5
63 (55)
9 (6)
66 (72)
Halogen flood lightf
HQI-T HID greenhouse lightg
Reactions were carried out in borosilicate (pyrex) glass tubes which filters out 95% of
radiation below 290 nm, at 0.08 M concentrations with 7.8 eq of aldehyde; Wavelength
emission spectra were recorded for Entries 3-5 (see supplementary information).
aMeasured and calculated using readings from a LUX meter; bConversion measured by 1H
NMR spectroscopy, bracketed conversions represent those carried out without the
c
d
presence of acetone; Philips myVision LED bulb 5 W (25 W eq); General Electric GE
halogen light bulb 55 W eq; ePhilips MLU 300 UV lamp, last produced in 1968; fDefender
security floodlight, 400 W halogen bulb; gTrac metal halide floodlight containing a 400 W
Osram Powerstar HQI-T metal halide bulb.
We next focused on further optimisation of the reaction conditions by variation of the
solvent. Whilst the initial study used a 3:1 mixture of t-butanol/acetone, the precise role
of acetone in the reaction was unclear. Although acetone is a commonly employed


photochemical sensitiser, its reported electronic transitions (n- , max = 275 nm,
ε = 15)17 compared to that of naphthoquinone (n-max = 331 nm, ε5934) meant
that this was unlikely to be the case.18-20 Due to its unknown role, reactions were
attempted both with and without acetone (Scheme 5, Table 3).
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Whilst the use of the polar protic solvent t-butanol (Entry 1) gave promising conversion
DOI: 10.1039/C3GC41477A
to product, despite prolonged irradiation, the reaction appeared to stall and no further
product formation was observed. Furthermore, formation of the hydroquinone 7 was also
observed in trace quantities. Additional attempts to develop this further by the use of
alternative green alcoholic solvents such as 1- and 2-butanol also proved unsuccessful,21
as the photo reduction process appeared to dominate in these cases (Entries 2-3).
Due to the widespread use of benzene as a solvent, we considered that aromatic
solvents might be beneficial.8,11-14 However, the documented incompatibility of radical
reactions with several ‘greener’ aromatic solvents such as toluene, xylene, cumene and
mesitylene meant that there was little scope for further optimisation.21,22 However, use
of trifluorotoluene proved successful (Entry 5). Often viewed as a more sustainable and
less hazardous alternative to many aromatic and chlorinated solvents, trifluorotoluene,
although relatively unknown, is a greener alternative to benzene, and as a result is often
viewed as the solvent of choice for radical reactions.23 Although approximately twice as
expensive as benzene, trifluorotoluene is readily accessible in large quantities from
numerous commercial suppliers. Moreover, comparison of the toxicological data of the
respective solvents confirms that trifluorotoluene is unarguably a less toxic alternative to
benzene (oral LD50>5000 mg/kg compared to 930 mg/kg).23,24 Furthermore, its higher
boiling point when compared to benzene, and short atmospheric lifetime thus minimises
its losses and environmental impact.23
Carrying out the reaction in trifluorotoluene led to acylated hydroquinone 6a being
formed with complete conversion in 14.5 hours and it was also successfully isolated in
good yield (62%). These conditions are superior to those carried out in benzene (Entry
4), which gave lower conversion. Furthermore, product precipitation meant that no
column chromatography was required.
Within the small range of solvents studied, the addition of acetone can be concluded to
be insignificant to the overall outcome, as the conversions obtained with and without its
7

presence are similar in each case and are within experimental error. This thus proVvieidweArsticle Online
DOI: 10.1039/C3GC41477A
further evidence that the role of acetone as a triplet sensitiser is unlikely. Whilst the use
of polar protic solvents possessing a hydrogen atom favours the formation of the
hydroquinone by-product, tertiary alcohols and aromatic solvents give a much more
desirable result. Additionally, it could be argued that less polar solvents, such as
benzene, trifluorotoluene and t-butanol ( =0.111, 0.241 and 0.389 respectively) give a
more successful result than more polar solvents, such as 1-butanol and 2-butanol
25
( =0.586 and 0.506, respectively).
Scheme 5. Conditions: solvent/acetone (3:1), HQI-T HID 400 W bulb, 14.5 h.
Table 3: Solvent optimisation
Entry
Solvent
Conversion to
Conversion
6a (%)a-c
to 7 (%)a-c
1
2
3
4
5
t-butanold
2-butanol
66 (72)
19 (4)
8 (3)
81 (93)
78 (84)
0
1-butanol
20 (14)
81
benzene
trifluorotoluene
100e (62)f
0
All reactions were carried out in Pyrex tubes at 0.08 M concentrations;
1
b
aConversion measured by H NMR spectroscopy; Un-bracketed conversions represent
those carried out in a 3:1 mixture of solvent: acetone; cBracketed conversions represent
those carried out without acetone; dReaction mixture was irradiated for 30 h; eThe same
result was achieved without the presence of acetone and also by irradiating in direct
sunlight for 5 d; fIsolated Yield.
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These optimised conditions were then applied to a range of aldehydesDO(I:T1a0.b10le39/C43)G.C41477A
Pleasingly, in several cases (Entries 1-3), the isolated yields matched, or were superior
to those previously reported.13 Furthermore, they were achieved after shorter irradiation
times under our more sustainable and practical laboratory conditions. With the aim of
expanding the reaction scope, in addition to the literature examples, our optimised
conditions were applied to a range of previously unexplored aliphatic aldehydes (Entries
4-9). In these cases, unfunctionalised aliphatic moieties (Entries 4-5) appear to be the
most successful and product precipitation meant that no further purification was
required. Halides, ether, alkene and unconjugated aromatic functionalities in the
aldehyde are also tolerated (Entries 6-9). Moderate success was achieved with the use of
aromatic and heterocyclic aldehydes (Entries 10-15). However, in several of these cases
(Entries 11-13) the reactions proceeded far more slowly and prolonged irradiation times
were necessary. Furthermore, yields were often compromised by the formation of O-
acylated hydroquinone monoesters (Entries 11 and 13), which despite prolonged
irradiation, did not rearrange to the desired C-acylated hydroquinone.
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DOI: 10.1039/C3GC41477A
Scheme 6
Table 4: Variation of the aldehyde
Entry
1
R
Product
Isolated Yield (%)
81 (75)a
Me
6e
2
3
4
Et
Pr
6f
6a
6b
73 (73)a
62 (58)a
61
CH2CHMe2
5
6
C5H11
6c
6g
71
(CH2)3Cl
30b
7
8
CH2CH2OTBS
6h
6i
28
34
CH2CH2CH=CH2
9
PhCH2CH2
4-FC6H4
6d
6j
55
10
11
12
13
60b,c
17b-e
69b,d
35b-e
2,6-F2C6H3
4-OMeC6H4
2-thienyl
6k
6l
6m
14
15
4-OHC6H4
3-NO2C6H4
6n
6o
0
0
All reactions were carried out in Pyrex tubes at 0.08 M concentrations in trifluorotoluene
a
and were irradiated for 14.5 h using a 400 W Powerstar HQI-T bulb. Bracketed yields
represent those reported in the literature. Literature Conditions: RPR-3000
b
photochemical reactor, benzene, 23 h13; Mixture was vigorously degassed with argon
prior to irradiation; cBased on recovered starting material; dMixture was irradiated for 72
h; eFormation of the hydroquinone monoester was also observed.
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After expansion of the reaction scope by variation of the aldehyde, the regiochemistry of
DOI: 10.1039/C3GC41477A
the acylation was investigated with unsymmetrical quinone substrates. To the best of our
knowledge, there exist only a few successful examples of the photo Friedel-Crafts
acylation on 5-substituted naphthoquinones,9,11 whilst the application of the
methodology to 6-substituted substrates remains unexplored. As a number of
biologically active quinone natural products, such as the pyranonaphthoquinones
(Scheme 1) contain such functionalities, it was of interest to expand the breadth of our
optimised conditions. The regiochemistry of the reaction was first investigated with 5-
substituted naphthoquinones 8b-e that were readily synthesised by alkylation reactions
of commercially available juglone 8a (Scheme 7).
Scheme 7. Conditions: a) 8b: MeI, Ag2O, CH2Cl2, rt, 20 h, 90%; c) 8c: EtI, Ag2O,
CH2Cl2, rt, 20 h, 90%; d) 8d: 2-iodopropane, Ag2O, CH2Cl2, rt, 20 h, quant.; e) 8e:
MOMCl, DIPEA, CH2Cl2, 16 h, 79%.
When carrying out the reaction on 5-substituted naphthoquinones, two regioisomeric
hydroquinone products: 2,5-isomer 9 and 2,8-isomer 10, are possible. It was
anticipated that the regiochemical outcome may be influenced by the nature of the
substituent in naphthoquinone substrates 8a-e (Scheme 8, Table 5).
No reaction was observed with juglone 8a itself (Entry 1), perhaps unsurprisingly, as
there is literature precedent to suggest that such hydroxyquinones undergo a
phototautomerisation (intramolecular hydrogen transfer) process.11,26-29 However, in the
case of each successful reaction (Entries 2-5), the formation of 2,8-isomer 10 appeared
to dominate over 2,5-isomer 9. Pleasingly, the outcome of the photochemical reaction
with methoxy naphthoquinone 8b (Entry 2) is consistent with the results observed by
11

11
Oelgemöller,
where 2,8-isomer 10 was isolated in a ratio of 1.7 to 1 relative toVi2ew,5Ar-ticle Online
DOI: 10.1039/C3GC41477A
isomer 9.
However, in several cases (Entries 3-5), the isolated ratios of 2,5-isomer 9 and 2,8-
isomer 10 did not match the ratio in the initial reaction mixture. Moreover, it was the
2,5-isomer 9 that was isolated as the major product. Whilst unexpected, reasons for this
can be attributed to the difference in the ease of purification of the two regioisomers.
Scheme 8
Table 5: Variation of 5-substituted naphthoquinone
Entry
R
Quinone
Products
Initial Ratio
Isolated
Yield of 9
(%)b
Isolated
Yield of 10
(%)b
of 9:10a
1
2
H
8a
8b
9a/10a
9b/10b
0
0
0
Me
1:1.3
20 (23)c
39 (38)c
(1:1.7)c
3
4
5
Et
iPr
8c
8d
8e
9c/10c
9d/10d
9e/10e
1:1.5
1:1.3
1:1.3
17
18
19
16d
17d
16d
MOM
1
aCrude ratios are calculated from H NMR spectroscopic analysis of the crude reaction
mixture before subsequent purification; bYield after the crude reaction mixture is
subjected to purification by column chromatography; cYields/ratios reported by
Oelgemöller et al.11 using the literature conditions: benzene, 5 d, high pressure mercury
vapour lamp (125 W); dRecovered yield after rigorous chromatography/recrystallisation.
Mechanistically, two possible pathways have been proposed (Scheme 9). The ‘in-cage’
12

scenario,
as
first
proposed
by
Schenck30
and
developed
further View Article Online
by
DOI: 10.1039/C3GC41477A
Maruyama,31,32 suggests the formation of a ‘caged’ triplet biradical which directly
combine to afford the acylated product. Conversely, the ‘out-of-cage’ scenario, as first
proposed by Moore33 and later reinforced by Bruce,26,34,35 suggests dissociation of the
triplet biradical and the reaction of the resultant acyl radical with the ground state
quinone. Later research conducted by Maruyama on the acetylation of corresponding
1,2-naphthoquinones suggested the operation of both pathways, in a manner that is
dependent on the specific conditions for each photo-acylation reaction.36
Scheme 9. Mechanistic scenarios for the photo Friedel-Crafts acylation
For 5-substituted naphthoquinones, the formation of 2,8-isomer 10 as the major product
in all cases can be rationalised by consideration of the ‘out-of-cage’ scenario. Since acyl
radicals are considered nucleophilic,11,37 it is predicted that they will predominately
attack the most electrophilic carbon atom on the quinone substrate. Preliminary AM1
calculations indicate that the C-3 position on quinone 8a bears the larger LUMO
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coefficient and thus will be the preferential site of attack by nucleophiles. This would lead
DOI: 10.1039/C3GC41477A
to the preferential formation of 2,8-isomer 10 as the major regioisomer, which is
observed.11,38
The structures of the regioisomers were initially assigned by analysis of their 1D and 2D
NMR spectra (Figure 1). Firstly, the protons on the aryl ring system can be assigned
based on their multiplicities and interactions with C-5, in the case of 2,5-isomer 9 or C-
8, in the case of 2,8-isomer 10 (interaction A). The 1-OH and 4-OH groups can be as-
signed with ease as significant differences in chemical shifts are observed in the 1H spec-
tra; the hydroxyl group positioned ortho and hydrogen bonded to the carbonyl is largely
de-shielded compared to the other. From the information in the HMBC spectra, the car-
bons bound to OH-1 and 4 can be assigned (interactions B and C). Finally, further exam-
ination of the long-range interactions between C-1 and C-4 with the H-5 and H-8 on the
aryl ring system using the HMBC spectra (interaction D) leads to the assignment of the
regiochemistry. The structure of hydroquinones 9e and 10c were unambiguously con-
firmed by X-ray diffraction (Figure 2).
Figure 1. Assignment of 2,5-Regioisomer 9 and 2,8-Regioisomer 10.
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DOI: 10.1039/C3GC41477A
Figure 2. X-Ray crystal structures of acylated hydroquinones 9e and 10c
After investigation of the regiochemical outcome of the photo Friedel-Crafts acylation of
unsymmetrical 5-substituted naphthoquinones, a corresponding series of 6-substituted
naphthoquinones was studied. Unsymmetrical 6-substituted naphthoquinones 12b-e
were synthesised by functionalisation reactions of isojuglone 12a which was prepared
from the oxidation of commercially available 2,6-dihydroxynaphthalene 11 (Scheme 10).
Scheme 10. Conditions: a) O2, salcomine, DMF, rt, 16 h, 46%; b) 12b: MeI, Ag2O,
CH2Cl2, rt, 3 d, 100%; c) 12c: EtI, Ag2O, CH2Cl2, rt, 16 h, 76%; d) 12d: 2-iodopropane,
Ag2O, CH2Cl2, rt, 20 h, quant.; e) 12e: MOMCl, DIPEA, CH2Cl2, 16 h, 66%.
15

For the substituted 6-hydroxy-naphthoquinone substrates, the reverse regiocheVmiewicAartlicle Online
DOI: 10.1039/C3GC41477A
outcome was expected (Scheme 11, Table 6). As in this case, preliminary AM1
calculations indicated that the C-2 double bond position of the naphthoquinone substrate
bears the larger LUMO coefficient, it was anticipated that 2,6-isomer 13 would be
formed preferentially to 2,7-isomer 14.
Pleasingly, this hypothesis was shown to be correct as in the case of each successful
example (Entries 2-4), 2,6-isomer 13 was formed and subsequently isolated as the
major regioisomer relative to 2,7-isomer 14. Although the reaction with naphthoquinone
12e was successful (Entry 5), both regioisomers co-eluted in all trialled solvent systems
and as a result could not be successfully isolated. As with juglone 8a, no reaction was
observed with isojuglone 12a (Entry 1).
Scheme 11
Table 6: Variation of the 6-Substituted Naphthoquinone Substrate
Entry
R1
Quinone
Products
Crude Ratio
Isolated
Yield of 13
(%)b
Isolated
Yield of 14
(%)b
of 13:14a
1
2
H
12a
12b
13a/14a
13b/14b
0
0
0
Me
1.4:1
30
20
(1.5:1)c
3
4
5
Et
iPr
12c
12d
12e
13c/14c
13d/14d
13e/14e
1.2:1
27
20
-
9
15
-
(3:1)c,d
1.3:1
(1.3:1)c
MOMe
-
1
aReference ratios are calculated from H NMR analysis of the crude reaction mixture
b
before subsequent purification; Yield after the crude reaction mixture is subjected to
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c
d
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purification by column chromatography; Actual (isolated) ratio of 13:14; Reasons for
DOI: 10.1039/C3GC41477A
the inaccuracy of this ratio can be attributed to the challenging purification process; eDue
to co-elution in all solvent systems trialled in our hands, the regioisomers could not be
successfully isolated.
As before, the structures of the regioisomers were assigned by analysis of their 2D NMR
spectra (Figure 3). By considering the HMBC interactions between hydroxyl protons 1
and 4, the carbon atoms bound to them could be assigned (Interactions A and B). By
further analysis of the HMBC correlations between carbon atoms 1 and 4 and the protons
5 and 8 on the ring system (interactions C and D), regioisomers 13 and 14 could be
assigned with certainty. The structure of hydroquinone 13b was unambiguously
confirmed by X-ray diffraction (Figure 4).
Figure 3. Assignment of 2,6-Regioisomer 13 and 2,7-Regioisomer 14.
Figure 4. X-Ray Crystal structure of acylated hydroquinone 13b
Conclusion
The photo Friedel-Crafts acylation offers an efficient method for the preparation of
acylated hydroquinones. However, in order to transfer this promising reaction into a
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more reliable and sustainable laboratory protocol, further development was required. By
DOI: 10.1039/C3GC41477A
optimisation of the literature conditions, we have developed an improved procedure, that
utilises a less hazardous solvent and a reliable commercially available ‘sun-mimicking’
light source. Moreover, we have expanded the scope of the reaction by its application to
a wider range of aldehydes, including those with additional functionality (halide, ether,
alkene), and investigated factors that influence the regiochemistry of the acylation of
unsymmetrical naphthoquinone substrates. In future, we will seek to adapt the reaction
for use on larger scale, and for application in the synthesis of more complex target
molecules.
Experimental Section
General Information
Starting materials were obtained from commercial suppliers and were used as
purchased, except for aldehydes which were distilled immediately prior to use.
Anhydrous solvents were used without further purification, except for the
dichloromethane which was distilled from calcium hydride under nitrogen. Light
petroleum refers to the fraction with bp 40-60 °C. Reactions were monitored by TLC
using Merck Kieselgel 60GF254 aluminium-backed plates. The plates were visualised using
UV light (254 nm) and/or chemical staining. Flash chromatography was carried out using
using Devisil 35-70u 60 Å silica gel under medium pressure with the solvent system
specified.
NMR spectra were recorded at 270 MHz on a Jeol EX270, 400 MHz on Bruker Avance III-
400, Bruker Avance 400 or Bruker DPX 400 spectrometers or 500 MHz on a Bruker
Avance III-500 spectrometer (corresponding 13C frequencies are 68, 100 and 125 MHz
respectively). NMR samples were analysed as dilute solutions with the solvent specified
at 298 K. Chemical shifts are expressed in parts per million (ppm) downfield with the
residual solvent peak as an internal standard (CDCl3 H 7.26, C 77.16). Coupling
constants (J) are reported in Hz and the multiplicities of each peak are quoted as
18

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follows: s singlet, d doublet, t triplet, q quartet, m multiplet and app. b. DdO.I: 1a0p.1p03a9r/eC3nGtC41477A
broad doublet or combinations thereof. The signals were assigned by the analysis of
DEPT, COSY, NOESY, HMBC and HSQC experiments where appropriate. Infrared spectra
were recorded on a Perkin Elmer 1600 series FT-IR spectrometer as dilute chloroform
solutions using NaCl cells. Low and high-resolution mass spectra were obtained for all
compounds where possible. Electrospray ionisation (ESI) and high resolution mass
spectrometric (HRMS) analyses were measured on a Bruker MicroTOF spectrometer.
Electron ionization (EI) analyses were performed on the Waters Autospec or Bruker Apex
IV instrument.
Melting points are uncorrected and were measured using Riechert-Kofler hot stage
apparatus. CHN microanalysis was carried out using an Exeter Analytical CE-440
Elemental Analyser.
The wavelength output of the light source was measured using a compact CCD (Model:
CCS150) spectrometer, produced by Thorlabs, or by a USB Miniature Fiber Optic
Spectrometer, produced by Ocean Optics. Light intensities were measured using a digital
light meter, produced by Sinometer (Model: MS6612), with an operating range of 20-
200000 lux.
Photo Friedel-Crafts Acylation of 1,4-Naphthoquinones
Standard Procedure
Reaction mixtures were irradiated using a 400 W Trac metal halide floodlight containing
a 400 W Osram Powerstar HQI-T metal halide bulb (max 590 nm), at a distance of 29 cm
from the reaction vessel (illuminance: 79405 lux). Reactions were carried out in 15 mL
pyrex tubes, held from the rim and placed in front of the light source for a fixed and
measured period of time. The temperature of the reaction vessels was between 25 and
35 °C.
To a stirred solution of the 1,4-naphthoquinone (50 mg) in trifluorotoluene
(0.08 M) was added the aldehyde (7.8 eq) and the reaction mixture stirred and
19

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irradiated for 14.5 h. The products were obtained either by precipitation (light
DOI: 10.1039/C3GC41477A
petroleum) or by column chromatography on silica gel (95:5 ethyl acetate:light
petroleum).
1-(1,4-Dihydroxy-2-naphthyl)-1-butanone 6a
Standard procedure was used. 1,4-Naphthoquinone (50 mg, 0.316 mmol) and
butyraldehyde (0.18 mL, 2.46 mmol) in trifluorotoluene (4 mL) gave the title compound
6a (45 mg, 62%) as a yellow solid; mp 145-146 °C (lit.,39 mp 144-145 °C); (Found:
M–H+, 229.0881. C14H13O3- requires 229.0870); max (CH2Cl2)/nm 275 (log  4.18), 388
(3.22); max (CHCl3)/cm-1 3600, 3012, 2967, 1629, 1467, 1396, 1193; H (400 MHz;
d6-DMSO) 13.58 (1 H, s, OH), 9.81 (1 H, s, OH), 8.31 (1 H, app. br d, J 8.2, ArH), 8.13
(1 H, d, J 8.2, ArH), 7.71 (1 H, app. td, J 6.9, 1.3, ArH), 7.61 (1 H, app. td, J 6.9, 1.3,
ArH), 7.14 (1 H, s, ArH), 3.05 (2 H, t, J 7.2, CH2), 1.73 (2 H, sxt., J 7.3, CH2), 1.00 (3
H, t, J 7.4, CH3); C (100 MHz; d6-DMSO) 206.6 (C), 154.3 (C), 144.7 (C), 129.4 (C),
129.3 (CH), 126.4 (CH), 125.1 (C), 123.6 (CH), 122.1 (CH), 112.1 (C), 104.4 (CH), 39.9
(CH2), 17.3 (CH2), 13.6 (CH3); m/z (ESI) 229 (M–H+, 100%).
1-(1,4-Dihydroxy-2-naphthyl)-3-methyl-1-butanone 6b
20

Standard procedure was used. 1,4-Naphthoquinone (50 mg, 0.316 mmol)VieawnAdrticle Online
DOI: 10.1039/C3GC41477A
isovaleraldehyde (0.26 mL, 2.46 mmol) in trifluorotoluene (4 mL) gave the title
compound 6b (47 mg, 61%) as a yellow solid; mp 166–168 °C; (Found: M–H+,
243.1030. C15H15O3- requires 243.1027); max (CHCl3)/nm 276 (log  6.35), 398 (3.28);
max (CHCl3)/cm-1 3838, 3012, 2413, 1642, 1578, 1239, 929; H (400 MHz; d6-DMSO)
13.65 (1 H, s, OH), 9.79 (1 H, s, OH), 8.32 (1 H, app. b. d, J 8.2, ArH), 8.13 (1 H, d, J
8.2, ArH), 7.72 (1H, app. td, J 6.9, 1.3, ArH), 7.62 (1 H, app. td, J 6.9, 1.3, ArH), 7.16–
7.12 (1 H, m, ArH), 2.92 (2 H, d, J 6.8, CH2), 2.25 (1 H, hep., J 6.8, CH), 1.01 (6 H, d, J
6.8, CH3); C (100 MHz; d6-DMSO) 206.3 (C), 154.6 (C), 144.6 (C), 129.4 (C), 129.3
(CH), 126.5 (CH), 125.1 (C), 123.7 (CH), 122.1 (CH), 112.3 (C), 104.5 (CH), 47.1
(CH2), 15.0 (CH), 22.5 (CH3); m/z (ESI) 243 (M–H+, 100%).
1-(1,4-Dihydroxy-2-naphthyl)-1-hexanone 6c
Standard procedure was used. 1,4-Naphthoquinone (50 mg, 0.316 mmol) and hexanal
(0.3 mL, 2.46 mmol) in trifluorotoluene (4 mL) gave the title compound
6c (58 mg, 71%) as a yellow solid; mp 166–167 °C; (Found: M–H+, 257.1184. C16H17O3-
requires 257.1183); max (CHCl3)/nm 397 (log  3.57); max (CHCl3)/cm-1 3438, 3012,
1631, 1397, 1273; H (400 MHz; d6-DMSO) 13.58 (1 H, s, OH), 9.80 (1 H, s, OH), 8.31
(1 H, app. b. d, J 8.2, ArH), 8.13 (1 H, d, J 8.2, ArH), 7.71 (1 H, app. td, J 6.9, 1.2,
ArH), 7.61 (1 H, app. td, J 6.9, 1.2, ArH), 7.15–7.12 (1 H, m, ArH), 3.05 (2 H, t, J 7.4,
CH2), 1.75–1.60 (2 H, m, CH2), 1.40–1.30 (4 H, m, CH2), 0.95–0.85 (3 H, m, CH3);
C (100 MHz; d6-DMSO) 206.7 (C), 154.3 (C), 144.6 (C), 129.4 (C), 129.3 (CH), 126.4
21

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(CH), 125.1 (C), 123.6 (CH), 122.0 (CH), 112.1 (C), 104.4 (CH), 38.2 (CH2),D3OI0: 1.08.1(03C9H/C23)G,C41477A
23.6 (CH2), 22.0 (CH2), 13.8 (CH3); m/z (ESI) 257 (M–H+, 100%).
1-(1,4-Dihydroxynaphthalen-2-yl)-3-phenylpropan-1-one 6d
Standard procedure was used. 1,4-Naphthoquinone (50 mg, 0.316 mmol) and 3-
phenylpropanal (0.3 mL, 2.46 mmol) in trifluorotoluene (4 mL) gave the title compound
6d (51 mg, 55%) as a yellow solid; mp 137-138 °C; (Found: M-H+, 291.1015. C19H15O3
requires 291.1027); max (MeOH)/nm 218 (log 4.40), 276 (4.24), 397 (3.68); max
(CHCl3)/cm-1 3852, 3066, 1629, 1397, 1190, 1066, 1016; H (400 MHz; d6-DMSO) 13.45
(1 H, s, OH), 9.77 (1 H, s, OH), 8.30 (1 H, d, J 8.2, ArH), 8.11 (1 H, d, J 8.2, ArH), 7.70
(1 H, app. b. t, J 7.3, ArH), 7.60 (1 H, app. b. t, J 7.3, ArH), 7.35-7.25 (4 H, m, ArH),
7.25-7.10 (2 H, m, ArH), 3.41 (2 H, t, J 7.2, CH2), 3.02 (2 H, t, J 7.2, CH2); C (100
MHz; d6-DMSO) 205.4 (C), 154.3 (C), 144.7 (C), 140.9 (C), 129.4 (C), 129.3 (CH),
128.3 (2 × CH), 126.5 (CH), 126.0 (CH), 125.1 (C), 123.7 (CH), 122.1 (CH), 112.1 (C),
104.3 (CH), 39.9 (CH2), 29.5 (CH2); m/z (ESI) 291 (M-H+, 100).
1-(1,4-Dihydroxy-2-naphthyl)-1-ethanone 6e
22

Standard procedure was used. 1,4-Naphthoquinone (50 mg, 0.316 mmol)VieawnAdrticle Online
DOI: 10.1039/C3GC41477A
acetaldehyde (0.14 mL, 2.46 mmol) in trifluorotoluene (4 mL) gave the title compound
6e (52 mg, 81%) as a yellow solid; mp 208–210 °C (lit.,40 mp 205–207 °C);
H (400 MHz; d6-DMSO) 13.50 (1 H, s, OH), 9.83 (1 H, s, OH), 8.30 (1 H, d, J 8.3, ArH),
8.12 (1 H, d, J 8.3, ArH), 7.70 (1 H, app. td, J 7.0, 1.2, ArH), 7.61 (1 H, app. td, J 7.0,
1.2, ArH), 7.12–7.08 (1 H, m, ArH), 2.66 (3 H, s, CH3); C (100 MHz; d6-DMSO) 204.7
(C), 154.2 (C), 144.6 (C), 129.4 (C), 129.3 (CH), 126.4 (CH), 125.0 (C), 123.6 (CH),
122.1 (CH), 112.4 (C), 105.0 (CH), 27.1 (CH3). Data are consistent with those reported
in the literature.40,41
1-(1,4-Dihydroxy-2-naphthyl)-1-propanone 6f
Standard procedure was used. 1,4-Naphthoquinone (50 mg, 0.316 mmol) and
propionaldehyde (0.18 mL, 2.46 mmol) in trifluorotoluene (4 mL) gave the title
compound 6f (50 mg, 73%) as a yellow solid; mp 164–166 °C; (lit.,13 mp 164–166 °C);
(Found: M–H+, 215.0720. C13H11O3- requires 215.0714); max (CH2Cl2)/nm 274 (log 
4.78), 382 (3.95); max (CHCl3)/cm-1 3821, 3392, 3069, 2361, 1521; H (400 MHz; d6-
DMSO) 13.52 (1 H, s, OH), 9.82 (1 H, s, OH), 8.30 (1 H, d, J 8.3, ArH), 8.12 (1 H, d, J
8.3, ArH), 7.70 (1 H, app. td, J 6.9, 1.2, ArH), 7.61 (1 H, app. td, J 6.9, 1.2, ArH), 7.14–
7.10 (1 H, m, ArH), 3.10 (2 H, q, J 7.2, CH2), 1.16 (3 H, t, J 7.2, CH3); C (100 MHz; d6-
DMSO) 207.0 (C), 154.1 (C), 144.7 (C), 129.3 (C), 129.2 (CH), 126.4 (CH), 125.1 (C),
123.6 (CH), 122.2 (CH), 112.0 (C), 104.3 (CH), 31.5 (CH2), 8.1 (CH3); m/z (ESI) 215
(M–H+, 100%).
23

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DOI: 10.1039/C3GC41477A
4-Chloro-1-(1,4-dihydroxynaphthalen-2-yl)butan-1-one 6g
Standard procedure was used, and the reaction mixture was vigorously degassed with
argon prior to irradiation. 1,4-Naphthoquinone (50 mg, 0.316 mmol) and 4-
chlorobutanal (261 mg, 2.47 mmol) in trifluorotoluene (4 mL) gave the title compound
6g (25 mg, 30%) as a yellow solid; mp 96-101 °C; (Found: M-H+, 263.0435.
C14H1235ClO3 requires 263.0553); max (MeOH)/nm 399 (3.78); max (CHCl3)/cm-1 3598,
3011, 1630, 1397, 1044, 827; H (400 MHz; d6-DMSO) 13.36 (1 H, s, OH), 9.82 (1 H, s,
OH), 8.30 (1 H, app. b. d, J 8.3, ArH), 8.12 (1 H, d, J 8.0, ArH), 7.70 (1 H, td, J 7.6,
1.3, ArH), 7.61 (1 H, td, J 7.6, 1.3, ArH), 7.13 (1 H, s, ArH), 3.77 (2 H, t, J 6.6, CH2),
3.25 (2 H, t, J 7.1, CH2), 2.14 (2 H, pent, J 7.2, CH2); C (100 MHz; d6-DMSO) 205.1
(C), 154.2 (C), 144.8 (C), 129.4 (C), 129.3 (CH), 126.5 (CH), 125.1 (C), 123.7 (CH),
122.2 (CH), 112.2 (C), 104.1 (CH), 44.8 (CH2), 35.5 (CH2), 26.5 (CH2); m/z (ESI)
265/263 (M-H+, 34/100).
3-(t-Butyldimethylsiloxy)-1-(1,4-dihydroxynaphthalen-2-yl)1-propanone 6h
Standard procedure was used. 1,4-Naphthoquinone (50 mg, 0.316 mmol) and
3-(t-butyldimethylsiloxy)propanal (0.464 g, 2.47 mmol) in trifluorotoluene (4 mL) gave
the title compound 6h (14 mg, 20%) as a gummy yellow solid; mp 128-131 °C;
24

(Found: M-, 346.1598. C19H26O4Si- requires 346.1606); max (CH2Cl2)/nm 276 (log 3.41),
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DOI: 10.1039/C3GC41477A
391 (2.82); max (CHCl3)/cm-1 3599, 3009, 1631, 1471, 1398, 1152; H (400 MHz;
CDCl3) 13.68 (1 H, s, OH), 8.46 (1 H, app. br d, J 8.4, ArH), 8.12 (1 H, app. br d, J 8.2,
ArH), 7.69 (1 H, app. t. d., J 7.0, 1.3, ArH), 7.59 (1 H, app t.d, J 7.0, 1.3, ArH), 7.04 (1
H, s, ArH), 4.11 (2 H, t, J 6.8, CH2), 3.21 (2 H, t, J 6.8, CH2), 0.88 (9 H, s, CH3), 0.07 (6
H, s, CH3); H (100 MHz; CDCl3) 204.2 (C), 157.5 (C), 142.9 (C), 129.8 (CH), 129.4 (C),
126.5 (CH), 126.1 (C), 124.6 (CH), 121.6 (CH), 112.2 (C), 105.7 (CH), 59.2 (CH2), 41.7
(CH2), 25.9 (CH3), 18.3 (C), -5.39 (CH3); m/z (ESI) 346/345 (M-, 56/100).
1-(1,4-Dihydroxynaphthalen-2-yl)pent-4-en-1-one 6i
Standard procedure was used. The reaction mixture was irradiated for 28 h. 1,4-
Naphthoquinone (50 mg, 0.316 mmol) and pent-4-enal (0.24 mL, 2.46 mmol) in
trifluorotoluene (4 mL) gave the title compound 6i (26 mg, 34%) as a yellow solid; mp
125-129 °C; (Found: M-H+, 241.0861. C15H13O3 requires 241.0870); max (MeOH)/nm
251 (log 4.11), 276 (4.21), 397 (3.65); max (CHCl3)/cm-1 3600, 3009, 1630, 1468,
1397, 1066; H (400 MHz; d6-DMSO) 13.48 (1 H, s, OH), 9.82 (1 H, s, OH), 8.31 (1 H, d,
J 8.3, ArH), 8.13 (1 H, d, J 8.3, ArH), 7.71 (1 H, app. b. t, J 7.4, ArH), 7.62 (1 H, app. b.
t, J 7.4, ArH), 7.15 (1 H, s, ArH), 6.00-5.85 (1 H, m, CH), 5.15-5.00 (2 H, m, CH), 3.18
(2 H, t, J 7.2, CH2), 2.46 (2 H, t, J 6.8, CH2); C (100 MHz; d6-DMSO) 205.6 (C), 154.3
(C), 144.7 (C), 137.3 (CH), 129.4 (C), 129.3 (CH), 126.4 (CH), 125.1 (C), 123.7 (CH),
122.2 (CH), 115.4 (CH2), 112.1 (C), 104.3 (CH), 37.3 (CH2), 27.7 (CH2); m/z (ESI) 241
(M-H+, 100).
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DOI: 10.1039/C3GC41477A
(1,4-Dihydroxynaphthalen-2-yl)(4-fluorophenyl)methanone 6j
Standard procedure was used with minor modifications. The reaction mixture was
degassed vigorously with argon prior to irradiation. 1,4-Naphthoquinone (50 mg, 0.316
mmol) and 4-fluorobenzaldehyde (0.26 mL, 2.46 mmol) in trifluorotoluene (4 mL) gave
the title compound 6j (35 mg, 60% brsm) as a yellow solid; mp 170-173 °C; (Found:
M-H+, 281.0608. C17H10FO3 requires 281.0619); max (MeOH)/nm 221 (log 4.83), 269
(4.82), 419 (4.17); max (CHCl3)/cm-1 3685, 3012, 2414, 1602, 1520, 1241; H (400
MHz; d6-acetone) 13.42 (1 H, s, OH), 8.65 (1 H, s, OH), 8.46 (1 H, d, J 8.4, ArH), 8.24
(1 H, d, J 8.3, ArH), 7.88-7.84 (2 H, m, ArH), 7.76 (1 H, td, J 7.6, 1.3, ArH), 7.66 (1 H,
td, J 7.6, 1.3, ArH), 7.40-7.36 (2 H, m, ArH), 6.98 (1 H, s, ArH); C (100 MHz; d6-
acetone) 200.6 (C), 165.6 (d, JFC 250, C), 158.1 (C), 145.4 (C), 135.8 (C, d, JFC 3.1),
132.7 (CH, d, JFC 9.2), 130.9 (C), 130.7 (CH), 127.5 (CH), 126.9 (C), 125.0 (CH), 123.3
(CH), 116.3 (CH, d, JFC 22), 112.8 (C), 107.8 (CH); F (377 MHz, d6-acetone) 109.4; m/z
(ESI) 281 (M-H+, 100).
(2,6-Difluorophenyl)(1,4-dihydroxynaphthalen-2-yl)methanone 6k
Standard procedure A was used with minor modifications. The reaction mixture was
degassed vigorously with argon prior to irradiation and the reaction was irradiated for 72
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h. 1,4-Naphthoquinone (50 mg, 0.316 mmol) and 2,6-difluorobenzaldehyde (349 mg,
DOI: 10.1039/C3GC41477A
2.46 mmol) in trifluorotoluene (4 mL) gave the title compound 6k (16 mg, 17%) as a
bright orange solid; mp 159-164 °C; (Found: M-H+, 299.0516. C17H9F2O3 requires
299.0525); max (MeOH)/nm 424 (log 3.84), 299 (3.85), 297 (3.96); max (CHCl3)/cm-1
3684, 3045, 2415, 1637, 1241, 661; H (400 MHz; d6-acetone) 13.15 (1 H, s, OH), 8.73
(1 H, s, OH), 8.49 (1 H, d, J 8.4, ArH), 8.23 (1 H, d, J 8.4, ArH), 7.82-7.68 (3 H, m,
ArH), 7.28 (2 H, t, J 7.8, ArH), 6.66 (1 H, s, ArH); C (100 MHz; d6-acetone) 194.3
(C=O), 161.4 (C, dd, JCF 249), 158.3 (C), 146.3 (C), 134.0 (CH, t, JCF 9.6), 131.6 (C),
131.5 (CH), 127.9 (CH), 126.5 (C), 125.2 (CH), 123.4 (CH), 114.3 (C), 113.12 (CH, d,
JCF 24.5), 113.11 (d, JCF 15, C), 105.9 (CH); m/z (ESI) 299 (M-H+, 100).
(1,4-Dihydroxynaphthalen-2-yl)(4-methoxyphenyl)methanone 6l
Standard procedure was used with minor modifications. The reaction mixture was
degassed vigorously with argon prior to irradiation and the reaction was irradiated for 72
h. 1,4-Naphthoquinone (50 mg, 0.316 mmol) and p-anisaldehyde (335 mg, 2.46 mmol)
in trifluorotoluene (4 mL) gave the title compound 6l (64 mg, 69%) as a bright orange
solid; mp 108-110 °C; (Found: M-H+, 293.0805. C18H13O4 requires 293.0819); max
(MeOH)/nm 416 (log 3.70), 299 (4.20), 297 (4.19); max (CHCl3)/cm-1 3684, 3045,
2434, 1670, 1250, 821; H (400 MHz; d6-acetone) 13.52 (1 H, s, OH), 8.64 (1 H, s, OH),
8.45 (1 H, d, J 8.3, ArH), 8.24 (1 H, d, J 8.3, ArH), 7.29 (2 H, d, J 8.9, ArH), 7.74 (1 H,
td, J 7.5, 1.2, ArH), 7.14 (2 H, d, J 8.9, ArH), 7.07 (1 H, s, ArH), 3.97 (3 H, s, OMe); C
(100 MHz; d6-acetone) 200.7 (C), 163.8 (C), 157.7 (C), 145.2 (C), 132.5 (CH), 131.7
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(C), 130.4 (CH), 127.3 (CH), 126.9 (C), 124.9 (CH), 123.3 (CH), 115.1 (C),D1O1I:410.6.10(39C/HC3)G,C41477A
113.0 (C), 108.2 (CH), 56.1 (CH3); m/z (ESI) 293 (M-H+, 100).
(1,4-dihydroxynaphthalen-2-yl)(thiophen-2-yl)methanone 6m
Standard procedure was used with minor modifications. The reaction mixture was
degassed vigorously with argon prior to irradiation and the reaction was irradiated for
72 h. 1,4-Naphthoquinone (50 mg, 0.316 mmol) and 2-thiophenecarboxaldehyde (0.23
mL, 2.46 mmol) in trifluorotoluene (4 mL) gave the title compound 6m (30 mg, 35%) as
a bright red solid; mp 136-138 °C; (Found: M-H+, 269.0266. C15H9O3S requires
269.0278); max (MeOH)/nm 431 (log 3.98), 302 (4.43), 298 (4.42); max (CHCl3)/cm-1
3684, 3045, 2415, 1634, 1588, 1476, 1241; H (400 MHz; d6-acetone) 13.28 (1 H, s,
OH), 8.78 (1 H, s, OH), 8.44 (1 H, d, J 8.3, ArH), 8.26 (1 H, d, J 8.5, ArH), 8.05 (1 H, d,
J 5.0, ArH), 7.98 (1 H, d, J 3.7, ArH), 7.76 (1 H, app. t. d., J 7.2, ArH), 7.66 (1 H, app.
b. t., J 7.4, ArH), 7.50 (1 H, s, ArH), 7.35 (1 H, t, J 4.3, ArH); C (100 MHz; d6-acetone)
190.4 (C), 156.7 (C), 144.9 (C), 142.4 (C), 134.4 (CH), 134.2 (CH), 129.6 (CH), 129.5
(C), 128.2 (CH), 126.5 (CH), 125.9 (C), 124.0 (CH), 111.8 (C), 105.9 (CH); m/z (ESI)
269 (M-H+, 100).
1-(1,4-Dihydroxy-5-methoxynaphthalen-2-yl)butan-1-one
Dihydroxy-8-methoxynaphthalen-2-yl)butan-1-one 10b
9b
and
1-(1,4-
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DOI: 10.1039/C3GC41477A
Standard procedure was used. Reaction was carried out in duplicate and crude mixtures
combined for purification. 1,4-Naphthoquinone 8b (50 mg, 0.266 mmol) and
butyraldehyde (0.19 mL, 2.07 mmol) in trifluorotoluene (3.4 mL) gave acylated
hydroquinone 9b (26 mg, 20%) as a bright yellow solid; mp 97-99 °C; (Found: M–H+,
259.0975. C15H15O4- requires 259.0976); max (CH2Cl2)/nm 275 (log  5.94), 318 (3.66),
329 (3.70), 411 (3.94); max (CHCl3)/cm-1 3607, 2961, 2933, 1781, 1723, 1464, 1329;
H (400 MHz; d6-acetone) 13.50 (1 H, s, 1-OH), 8.86 (1 H, s, 4-OH), 8.00 (1 H, dd, J
8.6, 1.0, H-8), 7.49 (1 H, app. b. t, J 8.3, H-7), 7.23 (1 H, app. b. d, J 8.0, H-6), 7.06 (1
H, s, H-3), 4.15 (3 H, s, H-9), 3.09 (2 H, t, J 7.3, H-11), 1.78 (2 H, sxt, J 7.4, H-12),
1.04 (3 H, t, J 7.6, H-13); C (100 MHz; d6-acetone) 207.9 (C-10), 157.0 (C-5), 154.9
(C-1), 146.9 (C-4), 128.5 (C-8a), 127.4 (CH-7), 120.1 (C-2), 118.3 (CH-8), 114.4 (C-
4a), 110.0 (CH-6), 107.2 (CH-3), 57.10 (CH3-9), 41.2 (CH2-11), 18.5 (CH2-12), 14.1
(CH3-13); m/z (ESI) 259 (M–H+, 100%), 244 (M–CH5+, 47).
Also isolated regioisomer 10b (49 mg, 39%) as dark orange solid; mp 179-182 °C;
(Found: M–H+, 259.0967. C15H15O4- requires 259.0976); max (CH2Cl2)/nm 275 (log 
7.47), 314 (3.51), 326 (3.54), 401 (3.88); max (CH2Cl2)/cm-1 3708, 3009, 2961, 1780,
1723, 1277; H (400 MHz; d6-acetone) 13.50 (1 H, s, 1-OH), 8.86 (1 H, s, 4-OH), 7.80
(1 H, dd, J 8.3, 1.0, H-5), 7.56 (1 H, app. b. t., J 8.0, H-6), 7.23 (1 H, s, H-3), 7.07 (1
H, app. b. d., J 7.8, H-7), 4.04 (3 H, s, H-9), 3.03 (2 H, t, J 7.3, H-11), 1.75 (2 H, sxt., J
7.6, H-12), 1.00 (3 H, t, J 7.4, H-13); C (100 MHz; d6-acetone) 204.9 (C-10), 160.2 (C-
8), 157.2 (C-1), 145.0 (C-4), 132.7 (C-8a), 130.3 (CH-6), 117.6 (C-4a), 115.7 (CH-5),
115.4 (C-2), 108.0 (CH-7), 107.4 (CH-3), 56.70 (CH3-9), 43.2 (CH2-11), 18.8 (CH2-12),
14.2 (CH3-13); m/z (ESI) 259 (M–H+, 100%), 244 (M–CH5+, 2/16).
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