Photochemistry of Flavonoids

Flavonoids and their photochemical transformations play an important role in biological processes in nature. Synthetic photochemistry allows access to molecules that cannot be obtained via more conventional methods. This review covers all published synthetic photochemical transformations of the different classes of flavonoids. It is first comprehensive review on the photochemistry of flavonoids.


Introduction
Flavonoids are polyphenolic compounds based on a C 15 (C 6 C 3 C 6 ) framework.They contain a chroman ring (C-ring) with a second aromatic ring (B-ring) at the C-2, C-3, or C-4 position.The heterocyclic six-membered C-ring is sometimes replaced by a five-membered ring (e.g., aurones) or the acyclic form (chalcones).The oxidation state of the C-ring is used to classify flavonoids into different categories, of which typical examples are flavan-3-ols, flavanones, flavones and flavonols.The term flavonoid can be ambiguous as it may refer either to the class of all C 6 C 3 C 6 compounds, or its meaning may be restricted to 2-arylchromans with a carbonyl group at C-4 (C-ring) [1].Flavonoids Epidemiological studies suggest that the regular consumption of flavonoids protects humans against diseases associated with oxidative stress such as Alzheimer's disease [2], arteriosclerosis [3], cancer [4,5], and ageing [6].The polyphenolic nature of flavonoids equates with ready oxidation and the formation of stable radicals and it is widely believed that flavonoids protect against free radical damage (caused by photolytically generated singlet oxygen and metabolic processes in living organisms) and act as antioxidants [7].Other biological effects include improved blood flow [8], the inhibition of cholesterol absorption [9] and protection from damage by ultraviolet B radiation [10].These have stimulated renewed interest in flavonoid synthesis and photochemical transformations that give access to molecules that are not available via conventional chemistry.The increasing use of flavonoids as food additives for health purposes has also contributed towards the growing interest in flavonoid photostability and photochemistry.Flavonoids are commercially important constituents of red wine [11], adhesives [12], and black tea [13].
The reason for the ubiquitous existence of flavonoid monomers and their oligomers as secondary metabolites in plants is controversial.Their polyphenolic nature allows complexation with proteins, as is evident in the widespread use of tannin extracts to tan leather, hence the name tannin [14].This property renders protein in food indigestible and supports their putative anti-feeding role that provides protection against insect predation.Certain flavonoids are toxic to insects and other organisms.Bark that contains rotenoids is used by tribal communities to poison and harvest fish from rivers [15].
The light absorption properties of flavonoids and anthocyanidins in the visible ultraviolet light region are responsible for the colours associated with flowers and this plays an important role in pollination by insects and thus plant reproduction.
It has been shown that light is important in flavonoid biosynthesis [16,17], and that light is essential for anthocyanidin synthesis [18][19][20][21].Flavonoids play important roles as development regulators and can regulate auxin transport in vivo [22].Their role as antioxidants in plants [23], in stress protection [17] and in photoprotection [24] has been discussed.The influence of light on plant defence against pest and pathogens has been reviewed [25].
The postulate that flavonoids protect plants against ultraviolet light damage is supported not only by the fact that flavonoids absorb UV radiation and may act as sunscreens, but also by observations that exposure to UV radiation induces higher levels of flavonoids in plants.Caldwell [26] demonstrated a correlation between flavonoid content in plants and ambient UV conditions.Alpine plants at high altitudes and tropical plants from regions exposed to intense UV radiation have higher flavonoid content than plants from other regions.Plants exposed to sunlight have short internodes and smaller thicker leaves than plants that grow in shade [17].
It was observed that the biosynthesis of flavonoids with antioxidant properties (e.g., orthodihydroxy or catechol B-ring substitution) in plants is stimulated by UV light at the expense of flavonoids that are not considered as antioxidant (e.g., monohydroxy B-ring substitution) and flavonoids with good sunscreen properties (e.g., hydrocinnamic acid derivatives).This suggested that flavonoids' photoprotection may also involve the removal of reactive oxygen species that form as a result of exposure to strong UV light.
Apart from the photochemical transformations that flavonoids may undergo due to their long daily exposure to sunlight, these compounds may also transfer or accept light energy to or from other molecules, i.e. act as sensitizers or quenchers.
A photochemical transformation requires excitation of an electron from a ground state orbital to an excited state orbital.This is usually achieved via the absorption of ultraviolet light (UV) by a chromophore.All flavonoids have aromatic chromophores, as indicated by UV absorptions in the 250 nm region of their UV spectra.These compounds may undergo π,π* excitation and react from π,π* excited states.Certain flavonoids contain carbonyl chromophores and absorb light in the 300 nm region.They may undergo n,π* excitation to react from n,π* excited states.Carbonyl chromophores that are conjugated with the aromatic ring (e.g., acetophenones and chalcones) absorb UV light in the 350 nm region.The n,π* and π,π* excited states of these compounds are almost degenerate and the state from which their reactions originates is sometimes controversial.Polyphenolic chalcones may absorb light in the visible region as is evident by their colours.Molecules that have no chromophores and cannot absorb light energy may be excited indirectly via sensitisation.This involves the transfer of mostly triplet energy.
The excited states may be in the triplet or singlet form.The triplet excited n,π* state [ 3 (n,π*) state] is associated with radical reaction type products and the singlet excited π,π* state [ 1 (π,π*) state] with ionic reaction type products.Solvent polarity is important and ionic type products are encouraged by polar solvents.Triplet excited states are formed indirectly from the initially formed singlet states via intersystem crossing [27].Triplet excited states usually have much longer lifetimes than the corresponding singlet states, permitting photochemical transformations to compete more effectively with relaxation of the excited state to the photochemical inert ground state.
Much of the older photochemistry work in flavonoid chemistry was on compounds with unsubstituted aromatic rings and high yields were reported (see the review by Gupta et al. [28]).Polyphenolic flavonoids are more representative of naturally occurring molecules and have more interesting biological properties.These compounds generally afford lower yields and require special conditions to react due to deactivation by phenolic hydroxy and methoxy groups [29].
The formation of phthalide 37a was explained in terms of a photoinduced carbon monoxide loss from C-4 via a repeated Norrish type I process (α-fission) of the aliphatic carbonyl group (Scheme 15).The reaction was repeated with a range of substituted flavonols (Scheme 14 and Table 3) and in some cases an aromatic α-ketoacid, of type 36 was isolated.It was concluded that the formation of phthalides was, despite the poor yields, a general photoreaction of flavonols.In some cases a benzoic acid degradation product was also isolated.The presence of metal ions such as Cu 2+ , Ni 2+ , Fe 3+ , Co 2+ , and Be 2+ prevented the photochemical rearrangement of flavonols.In contrast to these ions, Ca 2+ , Mg 2+ , and Hg 2+ had no effects on the photochemical reactivities of flavonols.Ficarra and co-workers [44] obtained only the indandione 35a upon irradiation of flavonol 34a in aerated or oxygen-free acetonitrile and dichloromehane solutions (high pressure mercury lamp with Bausch Lamb monochromator) (Scheme 16).No indication of the formation of photo-oxygenated products was found.This contrasts with the results of Yokoe and co-workers [43], where the oxygenated product dominated.They concluded that photo-rearrangement takes place from a singlet excited phototautomer ( 1 PT) and photo-oxygenation from a triplet phototautomer ( 3 PT).Alcoholic solvents (protic polar solvents) slow down rearrangements from ( 1 PT) and inhibit photo-rearrangement at the expense of photo-oxygenation from ( 3 PT).Aprotic polar solvents have the opposite effect and do not interfere with photo-rearrangement of ( 1 PT).Their formation of only the oxygenated product in heptane and other non-polar solvents was explained by a rapid conversion of ( 1 PT) to ( 3 PT) in non-polar solvents.They thus concluded that molecular oxygen affects photochemical reactions of flavones in alcoholic (protic-polar) and hydrocarbon (non-polar) solutions and does not participate in acetonitrile and dichloromethane (aprotic-polar) (Figure 3).  4.These products resulted from radical addition of 4-ketyl 43 and/or its isomeric 1,2-ketyl anion to flavones, respectively (Scheme 19).Single electron transfer (SET) [46] is a well-known photoreaction between amines and α,β-unsaturated carbonyl compounds.The amine donates an electron to form an exciplex or a contact ion radical pair [47] (CIP) that undergoes hydrogen transfer to yield the radical responsible for dimerisation.
Bhatacharyya and co-workers [52] studied the photophysics of flavones.They concluded that flavone almost instantaneously forms a triplet state with a 90% intersystem crossing (ISC) yield after absorption of UV light.Polar solvents enhanced yields indicating a π,π*-character for the lowest triplet excited state.The flavone's triplet is quenched by several typical triplet quenchers like hydrogen donors [53], including amines [54].
Christoff and co-workers [55] investigated the photophysics of 3-methoxy-and 7-methoxyflavone.A 7-methoxy substituent increases the π,π*-character of the excited state further but does not change the energy level or known flavone deactivation pathways.In contrast, a 3-methoxy substituent leads to a strong geometric constraint which interferes with planar π-orbital conjugation between the carbonyl group and the aromatic ring.This reduces the π,π*-character and increases the n,π*-character and the triplet state energy.The methoxy group becomes an intramolecular hydrogen donor to the excited carbonyl n,π*-triplet.The spectroscopic properties of the transient species are compatible with a 1,4biradical structure.Conventional photolysis indicates that the biradical is transformed into an ethereal ethylene group.The mechanism for the photocyclisation is given in Scheme 23.

Chalcone and Flavanone Photochemistry
Chalcones and α-hydroxychalcones are key intermediates in flavonoid synthesis and biosynthesis and the photochemistry of these compounds has attracted much early interest.Of major interest is cistrans isomerisation of the olefinic bond and reversible interconversion of 2'-hydroxychalcones and flavanes.Lutz and Jordan [56] obtained a photo-stationary mixture of 74% cisand 26% transchalcone upon leaving the chalcone in benzene in sunlight.The trans-isomer absorbs light more efficiently and is depleted compared to the cis-isomer under the reversible reaction conditions.

Scheme 25. Trans-cis -photoinduced isomerisation of α-methoxychalcones.
hν 300 and 350 nm MeOH  Stermitz and co-workers [61] transformed 2'-hydroxychalcone 70 to flavanone 68 (53%) upon irradiation with a Hanovia 450 W lamp with a Pyrex filter in benzene.It is known that the pKa values of phenols increase in the excited state [62] and, thus, the reaction could have been acid self-catalyzed (Scheme 28).Matsushima and co-workers [63] photolysed (100 W high pressure mercury lamp) flavanone 68 in benzene and obtained 2'-hydroxychalcone 70 (14%) via cleavage of the pyrone ring.Repetition of the reaction in 2-propanol gave the pinacols 75 (39%) and solvent adducts 76 (8%) (Scheme 29).Photolysis of 7,8-benzoflavanone 77 in 2-propanol gave no coupling products 79 and 80, but rather the ring-cleaved chalcone 78 (33%) (Scheme 30).The lack of photo-reduction (coupling products) suggested that the lowest triplet state of 7,8-benzoflavanone was 3 (π,π*) and that of the flavanones that had undergone photo-reduction to pinacols were 3 (n,π*).Methoxylated flavanones are assumed to have considerable π,π* character in their lowest triplet state.This is supported by conversion of 4'methoxyflavan to 2'-hydroxy-4-methoxyflavanone in yields of 69% in benzene (compared to the 14% conversion of flavanone), 66% in pyridine, 48% in acetonitrile and 31% in carbon tetrachloride.Nakashima and co-workers [64] investigated the photochemistry of 4′-methoxyflavanone (81).They obtained chalcone 82 (14%), and a mixture of pinacols 83 (23%) upon irradiation of 81 with a high pressure Pyrex lamp in benzene or 2-propanol.5,7,4'-Trimethoxyflavanone was inert in benzene and gave a complex mixture of at least six products that was not identified.5,7-Dimethyl-4'methoxyflavanone (84) yielded bis-flavanone 85, probably via intramolecular hydrogen abstraction by an n,π*-excited carbonyl from the 5-methyl group (Scheme 31).6).They also investigated the effect of triplet quenchers and radical scavengers.All the chalcones were inert in chloroform and t-butyl alcohol and all were reactive in benzene, ethyl acetate, and 1,4-dioxane (Table 7).Light of a shorter wavelength gave slower reaction rates and more side reactions.The best results were obtained with wavelengths above 365 nm (Table 8).Rates were highest in ethyl acetate and dioxane and low in benzene.The yields were the highest in ethyl acetate [e.g., 86% conversion of 86b] (Table 9).Triplet quenchers and radical scavengers had no effect, suggesting that photocyclisation of 2'-hydroxychalcones is an ionic or polar reaction.Solvent effects are ambiguous, but it seems that polar aprotic (basic) solvents gave the best results, supporting the polar mechanism.Photo-enolization of 3-chromanones as described by Padwa et al [66], followed by cis-trans isomerisation that may require a second photon, seems to best explain the experimental results (Scheme 33).Matsushima and Kageyama [67] investigated the scope and mechanism of the photocyclisation of 2'-hydroxychalcones and photolysed a series of B-ring mono-substituted derivatives (Scheme 34).They concluded that visible light (405 nm) gives the best results via selective cyclisation, avoiding secondary reactions of the resulting flavanone such as hydrogen abstraction from the solvent or equilibration of the flavanone and chalcone.Methoxy and phenyl substituents on the B-ring enhanced the reaction rate while halogen atoms and a nitro group had little effect (Table 10).Solvent effects on the consumption rate of 88a are given in Table 11.Reaction rates are the highest in aprotic polar solvents, low in non-polar solvents and extremely low in hydroxylic solvents that interfere with intramolecular hydrogen bonding (except in t-butyl alcohol).Ethyl acetate gave superior results compared to benzene and THF.Free radical inhibitors (2,6-di-t-butylphenol, nitrosobenzene, or acrylonitrile) did not suppress the reaction, suggesting a non-radical mechanism as supported by increased reaction rates in polar solvents.Triplet quenchers ferrocene, cyclohexa-1,3-diene, anthracene, phenanthrene, or acenaphthylene had no effect, suggesting an excited singlet or very shortlived triplet state.Quantum yields were low.In π,π* excited states phenolic groups become more acidic and carbonyl groups more basic [68][69][70] suggesting a charge transfer mechanism.6-Methoxy-, 7-methoxy-, 4'-methoxy, 4'-carbomethoxy-, and 2-methyl-7-methoxyflavanones were also converted to the corresponding 2'-hydroxychalcones (no yields were reported).Scheme 34.Photochemical cyclization of 2'-hydroxychalcones.Jain [71] investigated the photochemistry of flavanones in alkaline medium.Flavanone 90a and 4chloroflavanone 90b rearranged in alkaline medium (2 mL 10% NaOH in 2 mL ethanol) upon irradiation with UV of an unspecified source to the corresponding products 91a and 91b (Scheme 35), but no yields were reported.A concerted mechanism was proposed (Scheme 36).Obara and co-workers [73] repeated the reaction using a high-pressure 100 W mercury arc with 2-, 3-, and 4-hydroxyphenyl cinnamates 94a-c and obtained the corresponding 2',3'-, 2',4'-, and 2',5'dihydroxychalcones 95a-c in yields of 20, 5 and 16%, respectively (Scheme 38).

MeOH
Ramakrishnan and Kagan [76] studied the photo-Fries reaction with the view of obtaining chalcones with the complex substitution patterns found in plants.A variety of chalcone derivatives were irradiated at 254 nm in different solvents, as given in Scheme 41 and Table 12.

Substituent on structure 100 and 101 Solvent Irradiation time (h) a
Yields varied between 20 and 50% and it was postulated that the forming chalcones acted as internal filters and prevented complete conversion of the cinnamates.No cis-chalcones were isolated.After confirming that the photo-Fries reaction proceeded with the sample ester 100a, which yielded 101a as the major rearrangement product, different substituents were introduced on the A ring and it was found that the 2-methoxy-(compound 100b) and 3-hydroxy-(compound 100c) phenylcinnamates yielded the products of ortho migration, namely 101b from 100b and a mixture of 101c and 101d from 100c.Finally the set of compounds 100e-k was photolysed to get 101e-101k.The photo-Fries reaction of the phloroglucinol mono-ester is particularly simple since, for reasons of symmetry, the two products of ortho migration and that of para migration are identical.Scheme 42.Proposed mechanism of the photo-oxygenation of chalcones.
Chawla and Chibber [77] studied the photo-oxygenation of chalcones.Irradiation of 2',4',6'trihydroxychalcone (102) in methanol containing catalytic amounts of methylene blue under air with a 100 W tungsten lamp yielded the corresponding flavonol 103.The suggested mechanism is given in Scheme 42.No yields were reported.No reaction took place in the absence of methylene blue, suggesting the involvement of singlet molecular oxygen.Replacement of methylene blue with rose bengal gave lower yields, probably due to a lower concentration of 1 Δ g oxygen and the formation of 1 E g oxygen which leads to the formation of side products [78].
Subsequently Chawla and coworkers [79] studied the conversion of chalcones into dihydroflavonols.Irradiation of 2'-hydroxy-4',6',3,4-tetramethoxychalcone (104) in 4% aqueous methanol and a catalytic amount of methylene blue with a 100 W tungsten flood lamp yielded the corresponding flavanol 105 (compared to flavonol 103 in previous paper [75]) (Scheme 43), but no 2,3-relative stereochemistry was indicated.No reaction was observed in non-aqueous solvents such as benzene, benzene-methanol mixtures, or absolute methanol.Upon addition of small amounts of water (ca.5%) the product was observed.This suggests that water is the source of the 3-OH in the flavanol product.Quinol, a well known radical quencher, inhibited the reaction, suggesting a radical mechanism.No yield was reported.The reaction was compared to the chlorophyll sensitised oxygenation in plants.13) using triphenylpyrilium tetrafluoroborate (TPT) in dichloromethane with a Pyrex immersion well and 125 W medium pressure lamp (potassium chromate solution as filter).

Substituent
Yield (%) 4'-Nitroflavanone 106d was inert under the reaction conditions.The mechanism was rationalised in terms of an initial single electron transfer from the aromatic B-ring of the flavanone to the excited pyrilium salt to give the radical cation 108 or 110 which disproportionated to the flavones.Prevention of the reaction by an electron-withdrawing nitro group and acceleration by electron-donating methoxy substituents supports this mechanism (Scheme 45).Scheme 45.Proposed single electron transfer mechanism of photosensitized dehydrogenation of flavanones to flavones with 2,4,6-triphenylpyrylium tetrafluoroborate (TPT).
Ramakrishnan and Kagan [83] irradiated the phenyl epoxycinnamate 112 at 250 nm (in benzene under nitrogen) and obtained the 2-hydroxybenzoylacetophenone (β-diketone) 114 in 75% yield.This β-diketone was readily converted to the corresponding flavone 118 with sodium acetate in acetic acid.The same β-diketone 114 was obtained upon irradiation of phenyl epoxycinnamate (112).It was postulated that 2'-hydroxyepoxychalcone 113 was an intermediate in this reaction, via a photo-Fries rearrangement.The isolation of small quantities of dihydroflavonol 115 (3.3%) and flavonol 117 (0.7%) was explained in terms of thermal rearrangements and oxidation of 113 (Scheme 47).No 2,3relative stereochemistry was indicated for 115.Phenol (16%) and stilbene (10%) were also isolated and a carbene mechanism was suggested.Efforts to broaden the scope of this reaction failed because other substituted phenyl cinnamates could not be converted to their corresponding epoxides.

Reactions Initiated via Hydrogen Abstraction by an Excited State Carbonyl
The excited state carbonyl group, generally assumed to be 3 (n,π*), may abstract a suitably positioned hydrogen to form a biradical intermediate that may undergo further rearrangements to novel products.Photochemical keto-enol isomerisation and further transformations of the enol is included in hydrogen abstraction by carbonyls.
Van der Weshuizen and co-workers [88]  In 144a the 2-hydroxy allows incorporation of the aromatic -CH 2 OH group in the heterocyclic ring that changes the five-membered to a six-membered ring.In the case of the fully methylated 2methoxybenzo[b]furan-3(2H)-one (144b), the five-membered ring resisted ring-opening and the product with a free -CH 2 OH (compound 147b) was isolated (11%).It was postulated that the benzylic acid rearrangement has ionic character and takes place from a π,π* excited state which has ionic character and is encouraged by polar solvents [89].Formation of 150 is described in Scheme 60 [90].

Reactions of Flavonoids with a Fully Saturated C-Ring (no Carbonyl Chromophore). Benzyl Ether Fission
Benzyl ethers typically undergo photolytic fission of the C-O bond.This is assisted by the stability of the benzylic radical or ionic intermediates.The heterocyclic C-ring of flavonoids contains an intramolecular benzylic ether bond.Scheme 55.Photochemistry of flavan-3-ols.Fourie and co-workers [86] studied the photochemistry of flavan-3-ols.Irradiation of free phenolic flavan-3-ol 153c, fisetinidol (153a) and its tetra-O-methyl ether 153b at 300 nm in methanol yielded the corresponding optically active 1,3-diarylpropan-2-ols 156a and 156b (in 64 and 40% yield, respectively).The mechanism involves fission of the heterocyclic benzylic O-C bond and trapping of the resulting intermediary benzylic carbocation 155 with methanol.
The methyl ether 153b also yielded 5-methoxy-2-methoxymethylphenol (158), via subsequent fission of the C3-C4 bond of radical 154 and trapping of the resulting ortho quinone methide 157 with methanol.The absence of the free phenolic analogue of 157 probably indicates stabilization of the free-phenolic benzylic carbocation as a para-quinone methide.Irradiation of the tetra-O-methyl ether 153b in benzene did not give any product.Benzene is probably not sufficiently polar to stabilise the intermediate carbocation 155 (Scheme 55).Under identical conditions free-phenolic catechin 153c gave the corresponding diarylpropan-2-ol 156c (20%).Irradiation of flavan-3-ols results in homolysis of the heterocyclic 1,2-(O-C) and 3,4-(C-C) bonds.

4-Phenylchroman-3-one
The photochemistry of these compounds is of interest because of the C4 diaryl functionality that appears in all proanthocyanidins.Grover and Anand [92]  Later Padwa and Lee [93] suggested an alternative mechanism involving an enol tautomer (Scheme 62).Padwa and Au [94], and also Padwa and co-workers [95], subsequently repeated the reaction in benzene or acetonitrile to obtain 2-phenylchroman-3-one (180) in 60% yield and the proposed mechanism explaining this different product is outlined in Scheme 63.They demonstrated tautomer control via use of the appropriate solvent.
Formation of the chalcone 182 was postulated to take place via photocyclisation of the excited triplet state of the enol form of 181 followed by a thermal oxidative step.Formation of the flavanone 183 was assumed to be via photochemical cyclisation in agreement with the work by Matshushima and coworkers (1985) [67].This work represents a unique example of the photochemical conversion of a molecule from one important class of natural products (diarylheptanoids) into another important class (flavonoids).Yokoe and co-workers [96] studied the photochemistry of 2-steryl-4H-chromen-4-ones 184.Irradiation of 184 in benzene with a high-pressure mercury lamp at room temperature under air yielded benzo[a]xanthones 185 (Scheme 65) via cyclization in yields of between 43 and 88%, depending on the aromatic substituents (Table 14).In the case of 184d and 184e, there are two possible directions of cyclization, ortho or para to the methoxy group on the benzene ring.However, the photocyclized products (185d and 185e) each showed a single spot on TLC.This reaction provides a general route to polycyclic xanthene derivatives.Kamboj and co-workers [97] observed similar results upon irradiation of 3-alkoxy-2-styrylchromones 186a-d with a 125 W mercury vapour lamp in methanol under nitrogen to afford six different structures 187-192 (Scheme 66, Table 15).The suggested mechanism for the formation of the photoproduct through dealkylation and excited state intramolecular proton transfer is given in Scheme 67.Dhande and co-workers [98] investigated the photochemistry of E-3-benzylideneflavanones 193.Aroylflavone 194 were obtained upon irradiation of compound 193 in dry benzene in the presence of air or oxygen (125 W high-pressure mercury lamp in quartz) as given in Scheme 70.Yields varied between 27 and 90% depending on the substituent on the aromatic rings.Isomerisation of the double bond to Z-3-benzylideneflavanones 195 was observed in all cases.Under inert atmosphere only the isomerisation product 195 was observed.As the Z-isomer with the C-2 aryl in the equatorial position has the H-2 proton in a suitable axial position for a concerted ene reaction with singlet oxygen, it was suggested that isomerisation to the Z-isomer preceded oxidation to a hydroperoxide intermediate 196.

Scheme 65. Photocyclization of 2-styryl
Efforts to increase the reaction rate with rose bengal (a singlet oxygen source), however, failed.In dichloromethane with a phase transfer catalyst and rose bengal or methylene blue, no oxidation and only E to Z isomerisation was observed.Yields for each different derivative are given in Table 16.
Halogen containing solvents (such as chloro-, bromo-, and iodobenzene) or addition of iodoform reduced the isomerisation time under nitrogen.Addition of iodoform to the benzene reaction mixture under air gave 3-α-hydroxybenzylflavones 197 upon photolysis using a Pyrex immersion well in yields of between 60 and 88% depending on the substituent.This represents a general route to these otherwise unavailable compounds.Arylideneflavanones 193 upon UV irradiation using quartz undergo auto-oxidation to 3-aroyl-flavones 194.Photolysis by using a Pyrex filter in the presence of iodoform  Ishibe and co-workers (1975) [99] irradiated 2-phenyl-7-methoxyisoflavone (198a) in methanol with a medium-pressure mercury lamp and a Pyrex filter and obtained the corresponding 3,4-diphenylisocoumarin 199a (10%) and a pentacyclic structure 200a (42%), presumably via intermediate 201.2-Phenyl-7-hydroxyisoflavone was unreactive in air but gave (200b) in the presence of iodine.Photoisomerisation was not observed with 2-methyl-7-hydroxyisoflavone and 2-methylisoflavone in methanol, indicating that the presence of a 2-phenyl-substituent was a prerequisite (Scheme 71).

Conclusions
A plethora of photochemical transformations of flavonoids has been described over the past 50 years [100] and much progress has been made to better understand the reaction mechanisms and the associated influence of reaction conditions on yields and products.Yet photochemistry still presents the researcher with many challenges and opportunities.Ephemeral goals like chemical trapping of sunlight energy to replace fossil fuels (derived from sunlight) and industrial feedstocks (also derived from sunlight) will receive considerable attention.More humble goals such as the publication of novel flavonoid photochemical transformations will keep academics active and expand our knowledge of flavonoid chemistry [101].Photochemistry in chiral environments [102], including the use of chiral light, promises enantiomerically pure products.The use of monochromatic laser light will allow selective excitation of target chromophores.The use of high energy lasers in combination with a flow reactor will reduce the time that reagents are exposed to UV light to minimize unwanted side reactions and increase yields.Low temperature photochemistry should also yield interesting results.

Table 1
O

Table 3 .
Products obtained by the irradiation of flavonol in methanol.

Table 4 .
Photoinduced reactions of flavone with amines.

Table 5 .
Yields and conditions of photoinduced biflavanone formation with amines.

Table 8 .
Effect of the solvent on the relative rates of photochemical flavanone formation from 2'-hydroxychalcones.

Table 9 .
Effect of irradiation time on the yield of photochemical flavanone 87b formation from 2'-hydroxychalcones.

Irradiation time/h 86b (mM Recovered) a 87b (mM Formed) Yield of 87b (%) b
a Initial concentration of 86b was 1 mM; b The yield of 87b was based on the consumed amount of 86b.

Table 11 .
Cont.Initial concentration of 88a was 1 mM, on visible irradiation.Irradiation times were controlled so that conversions were close to or below 10%.b Relative rate for the consumption of 88a.Solvent effects on the absorption at λ ≥ 400 nm were nil, hence the rate can be regarded as the relative quantum yield.
a c Distilled over fresh sodium.

Table 16 .
Effect of substituents on the yields of phototransformation of 3arylideneflavanones to 3α-hydroxybenzylflavones.