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Two novel synthetic strategies that allow rapid diversification of the sulfone moiety in sulfonylmethyl pyrimidines, a class of compounds with a wide range of biological activity, which are of interest in a wide variety of drug discovery programmes, are described.

Two different approaches to synthesize 2,4-bis-aminoaryl pyridine derivatives are introduced.

A number of important photophysical properties of C{sub 60} have been determined, including its lowest triplet-state energy (near 33 kcal/mol), lifetime, and triplet-triplet absorption spectrum. The triplet state is formed in near quantitative yield and produces a very high yield of singlet oxygen by energy transfer. C{sub 60} does not react with singlet molecular oxygen and quenches it only slowly by an unknown mechanism. These results are discussed in terms of the unusual geometry of this molecule.

The efficiency of singlet oxygen generation (S Δ ) was measured for acetophenone, p-aminobenzophenone, and Michler's ketone by the time-resolved O 2 ( 1 Δ g ) phosphorescence method in various solvents. The S Δ value for acetophenone is 0.3-0.4 in benzene, cyclohexane, acetonitrile, and alcohols (practically independent of solvent); the lowest triplet state of acetophenone is therefore probably pure n,π * in all solvents. The values for Michler's ketone and p-aminobenzophenone are 0.24-0.4 in all solvents investigated (except in ethanol for Michler's ketone) and are also typical for ketones with n,π * triplet states

Compounds 5 (4,8,13,17,21-pentamethyl-4,8,12,16,20-docasapen- taenyl chloride and tosylate) were prepared starting from squalene and the solvolysis rates were measured in 80% (v/v) aqueous ethanol. a-Deuterium secondary kinetic isotope effects and activation parameters were calculated, and the products were determined. According to the values obtained (/CH/JCD — 0.99 ± 0.06, A H={= = 86.6 kJ mol1, A S+ = —69.3 J mol-1 K-1) and on the basis of isolated aliphatic products (11 and 14) it is concluded that the substrate follows the SN2 type displacement reaction with solvent without jt^participation of the double bond.

The quantum yield of singlet oxygen ( 1 O 2 ) production from 9,10-dicyanoanthracene (DCA) in the presence of trans-stilbene (TS) was determined by measurement of its 1268-nm emission.

The 9,lO-dicyanoanthracene-sensitized photooxidation of 2,3-diphenyl- 1,4-dioxene in CHICN produces ethylene glycol dibenzoate and small amounts of epoxide. Most of the diester is formed from singlet oxygen via the dioxetane, and only a small amount by electron transfer. The epoxide is a primary electron-transfer product. Various mechanistic possibilites for the electron-transfer process are considered.

Structures, energies, and vibrational frequencies of various intermediates and transition states in the reaction between phosphines and singlet oxygen have been calculated using ab initio methods, including RHF, MP2, and CASSCF optimizations, and energy evaluations using various basis sets including electron correlation. A surprising result is that the only intermediate located for the first step of the reaction has the cyclic phosphadioxirane structure. An acyclic intermediate is not stable. This result contrasts strongly with the reaction of sulfides, where both cyclic and open structures are stable. Improved calculations for thiadioxirane and peroxy sulfoxide are reported

Reactions of seven N-acyl indole derivatives with singlet oxygen have been investigated. 1-Acetyl-(1a) and 1-(chloroacetyl)-2,3-dimethylindole (1b) gave exclusively 1-acetyl-(2a) and 1-(chloroacetyl)-2-hydroperoxy-3-methyleneindoline (2b), respectively, in high yields via ene reaction on irradiation with oxygen in the presence of TPP sensitizer. 1-Acetyl-3-methylindole (1c) gave only 1-acetyl-2-hydroperoxy-3-methyleneindoline (2c) in low yield under the same conditions

C 60 undergoes 1,3-dipolar cycloaddition with the azomethine ylide derived from N -benzyl- N -(methoxymethyl)- N -[(trimethylsilyl)methyl]amine to give a C 60 -fused N -benzylpyrrolidine in 50 % isolated yield.

On irradiation with visible and UV light, fullerenes C60 and C70 give high yields of their triplet states. Fluorescence is very weak from both, and phosphorescence has been observed only from C70. The triplet states are also formed efficiently by energy transfer from triplet sensitizers with energies above 35 kcal/mol. Triplet fullerenes transfer energy efficiently to oxygen, giving singlet molecular oxygen, but they react and quench singlet oxygen very inefficiently, making them excellent photosensitizers. The fullerenes C60 and C70 are easily reduced but very difficult to oxidize. Electron transfer to triplet C60 and C70 occurs readily from electron donors to produce the radical anions. C60 can also be oxidized by excited high-potential photosensitizers to the radical cation. Some dihydrofullerenes also give high yields of the triplet state and singlet oxygen on irradiation. Photoreaction of C60 with electron-rich compounds appears to be an efficient route to difunctionalized adducts.

A series of 1-methyl- and 1-(phenylsulfonyl)-substituted 3-vinylindoles with different electronic and steric features has been synthesized and their sensitized photooxygenation in aprotic solvents investigated. 1-Methyl-3-vinyl-(1a), 1,2-dimethyl-3-vinyl-(1b), 1-methyl-3-(α-methoxyvinyl)- (4-Z and 4-E, 1-(phenylsulfonyl)-3-vinyl-(8b), 1-(phenylsulfonyl)-3-(α-methylvinyl) (8b), 1-(phenylsulfonyl)-3-(α-methoxyvinyl)- (8c and 8d), and cis-1-(phenylsulfonyl)-3-(α-methyl-β-methoxyvinyl) indoles (1d-Z) react with 1 O 2 predominantly to give endoperoxides via [4+2] cycloaddition. However, 1,2-dimethyl-3-(β-methoxyvinyl)indole (1c) gives [2+2] cycloaddition with the 3-double bond to give 1,2-dimethyl-3-formylindole (3c); trans-1-(phenylsulfonyl)-3-(α-methyl-β-methoxyvinyl)indole (15-E) gives the 3-indolyl allylic hydroperoxide (17) via ene reaction, along with a small amount of isomerization of the 3-vinyl double bond. A zwitterionic intermediate in the isomerization is proposed. Most of the resulting dioxacarbazole endoperoxides are isolable and inert to reduction by trimethyl phosphite and thiourea except for N-methyldioxacarbazole 5, which undergoes clean rearrangement to indolin-2-one epoxide 7 at -20°C

We report an efficient photochemical [2 + 2] cycloaddition route to a C[sub 60] adduct and its subsequent reaction to give a very high yield of a difunctional dihydrofullerene in one pot. These preliminary studies demonstrate a potentially versatile, high-yield photochemical functionalization of C[sub 60]. The moderately stable cyclobutenamine undergoes interesting chemical changes that lead to useful functionalized dihydrofullerenes that should be easily converted to a wide variety of derivatives. The mechanism of the photochemical [2 + 2] cycloaddition of C[sub 60] with electron-rich compounds is under investigation. 38 refs.

Eight N-acylated indole derivatives (1a-h) react with singlet oxygen at low temperatures (-5 to -78 o C) in methanol-d 4 or methanol-d 4 -methylene chloride-d 2 to afford 1,2-dioxetanes 2a-h, whose structures are characterized by low-temperature 13 C NMR and 1 H NMR spectra and chemical transformations. These strained 1,2-dioxetanes decompose smoothly and exclusively to dicarbonyl cleavage products 3a-h upon warming to room temperature

Reaction of C 60 with benzocyclobutenol (2a) and its methoxy ether (2b) in refluxing toluene gave 1,9-dihydrofullerene cycloadducts (3a) and (3b) in 59% and 50% yields, respectively. The alcohol was converted to pyranyl ether (4), acrylate (5), p-vinylbenzoate (6) and acid succinate esters (7) in good yields under very mild conditions. The adducts exist as two interconverting boat conformers. Acrylate (5) and p-vinylbenzoate (6) should be used for polymerization studies. Acid (7) shows enhanced solubility in polar solvents

[2 + 2] Cycloaddition of C{sub 60} with N,N,N{prime},N{prime}-tetraethylethynediamine (1a) and N,N-diethyl-2-ethylthioethyneamine (1b) gave the stable, 1,2-dihydrofullerene[60]-1,2-cyclobutenediamine 2a and thioenamine 2b, respectively, in good yield. Self-sensitized photooxygenation of 2a and 2b produced 1,2-dihydrofullerene[60]-1,2-diamide 3a and thioester amide 3b, from which 1,2-dihydrofullerene[60]-1,2-dicarboxylic acid anhydride (C{sub 62}O{sub 3}) was readily prepared. Similarly, C{sub 70} reacted with 1a (regiospecifically at the 1,9-bond) to give 1,9-dihydrofullerene[70]-1,9-cyclobutenediamine 5 or 1,9:61,62-biscyclobutenediamine 6 in good yields. In contrast to 2a, self-sensitized photooxygenation of 5 regenerated C{sub 70} and the oxidized ynamine. 1,9-Dihydrofullerene[70]-1,9-dicarboxylic acid anhydride (C{sub 72}O{sub 3}) was prepared from a tert-butylthioester amide 10 in one pot by reaction of N,N-diethyl-2-tert-butylthioethyneamine (1c) with C{sub 70} and photooxygenation of the resultant cycloadduct. 52 refs.

A concise synthesis of the tricyclic furanochroman unit 2 found in the unusual PAF antagonist phomactin A 1 is described. The synthesis is based on elaboration of the novel dihydrofuran enol ether 3 as key intermediate via the iodopyran 6 or the dihydrofuran 20. Treatment of 3 with dimethyldioxirane in acetone-water then gave the furanochroman 2.

A C60-linked deoxyoligonucleotide (C60-DON-1) was prepared from bromoacetate 3. This C60-oligonucleotide conjugate was hybridized to a complementary single-stranded DNA. This system reacted with light and oxygen to damage only guanosines in the single-stranded region which are closest to C60. The damage did not involve 1O2 as the active species but rather resulted from a single electron-transfer mechanism between guanosine and 3C60, as shown by comparison experiments with eosin-attached DON-1 and by the use of singlet oxygen quenchers.

Photooxygenation of a series of isotopically-labeled trimethylethylenes shows that formation of the perepoxide intermediate is rate-determining.

The stereoselectivity of the ene reaction of singlet oxygen with E -2,4-dimethylpent-3-en-2-ol-5,5,5-d 3 depends on solvent; polar solvents favor hydrogen abstraction from the methyl anti to the alcohol; nonpolar solvents favor the opposite.

Photochemical [2 + 2] cycloaddition of C60 with N,N-diethyl-4-methyl-3-penten-1-yn-1-amine (1) afforded the stable C60-fused cyclobutenamine 2 which underwent self-sensitized photooxidation to dihydrofullerenone amide 4 in high yield. Fullerenes C60 and C70 react thermally with tetraalkoxyethylenes to give dihydrofullerene cyclobutanediketals, which undergo a clean cycloreversion to fullerenes on irradiation with visible or UV light. Attempted hydrolysis of the ketals was unsuccessful, but treatment of 1,2-(6161,62,62-tetraethoxycyclobutano)dihydro[60]fullerene (8) with TMSI gave ring-contracted product 11 (by cleavage of the C−C bond to the fullerene fragment) along with reduction product 12.

o-Nitrobenzyloxycarbonyl and a number of related groups have been tested for the photolabile protection of nucleoside 5'-hydroxyls. The rates of photodeprotection were found to vary by approximately 17-fold in a series of 5'-O-protected thymidine derivatives irradiated at 365 nm under identical conditions. The homologous 2-(o-nitrophenyl)ethoxycarbonyl group and its derivatives were found to be removed approximately 2-fold faster than the corresponding o-nitrobenzyloxycarbonyl group, possibly due to an increased rate of α-hydrogen abstraction by the photo-excited nitro group. Photolysis rates were affected by substitutions on both the phenyl ring and α-carbon, with the strongest rate enhancements caused by the presence of a methyl or second o-nitrophenyl group in the α-position. Among the ring-substituted derivatives studied, o-nitro and o-iodo had the strongest enhancement effects on photodeprotection, while an o-fluoro group reduced the rate of photodeprotection. In general, substitutions at other positions on the phenyl ring had less effect on photolysis rates.

Reaction of C 60 with diethylaminopropyne leads to cyclobutene adduct 1 , which upon acid hydrolysis provides a facile synthetic route to fullerene adduct 2 . Subsequent oxidative cyclization involving activated carbon yields the novel fullerene lactone 3 .

The ene reaction of singlet oxygen with (Z)-4-methylpent-3-en-2-ol-2,5,5,5-d4 (1-OH-d4) in nonpolar solvents exhibits a 90% threo diastereoselectivity in the adduct derived from the major syn perepoxide intermediate, but also a moderate threo diastereoselectivity in the adduct derived from the minor anti perepoxide. Photooxygenation of 2,4-dimethylpent-3-en-2-ol (2) exhibits a significant solvent dependence in the syn/anti methyl stereoselectivity, with nonpolar solvents promoting syn methyl reactivity, while polar solvents promote anti methyl reactivity. These results are in agreement with a steering effect between hydroxyl and singlet oxygen in the rate-determining step of the reaction. N-Phenyltriazolinedione addition to the chiral allylic alcohol 4-methylpent-3-en-2-ol (1-OH) is highly threo diastereoselective in nonpolar solvents, with a solvent dependent variation in the threo/erythro ene products. On the other hand, the nonfunctionalized chiral alkene 2,4-dimethyl-2-hexene (1-Et) exhibits poor dias...

The preparation of 7-ethoxy-5-fluoroquinazolin-4-one, starting from 3,5-difluorophenol, is described. Further reaction with alkoxide then gives differentially substituted 5,7-dialkoxyquinazolin-4-ones.