Functionalization of furans via phenacyl sulfides

A mild, efficient, photochemical method for the functionalization of furans via phenacyl sulfides is described.     

The structure of the diazonium coupling products of phenacyl thiocyanate and phenacyl selenocyanate with diazotized 3-phenyl-5-aminopyrazole

The reaction of diazotized 3-phenyl-5-aminopyrazole with phenacyl thiocyanate 1a and phenacyl selenocyanate 1b afforded directly 2-imino-3-(3-phenyl-5-pyrazolyl)-5-benzoyl-2,3-dihydro-1,3,4-thiadiazole monohydrate 9a and 2-imino-3-(3-phenyl-5-pyrazolyl)-5-benzoyl-2,3-dihydro-1,3,4-selenadiazole monohydrate 9b , respectively. The products 9a and 9b were also obtained from the reaction of C-benzoyl-N-(3-phenyl-5-pyrazolyl)formohydrazidoyl bromide 10 with potassium thiocyanate and potassium selenocyanate, respectively. Acetylation, benzoylation, and nitrosation of 9 afforded the corresponding diacetyl, dibenzoyl, and nitroso derivatives 11-13 , respectively. Cyclization of C-benzoyl-N-(3-phenyl-5-pyrazolyl)-nitrilimine 6 was shown to give the pyrazolo [5,1-d]triazole 8 and not the pyrazolo[5,1-c]-as-triazine derivative 7 , as previously reported.     

Determination of thioureas by reaction with phenacyl bromide

Thioureas react quantitatively with phenacyl bromide in ethanolic solution to give hydrobromides of aminothiazoles/iminodihydrothiazoles which can be titrated with sodium carbonate, Thymol Blue being used as indicator.     

Diminished reactivity of ortho-substituted phenacyl bromides toward nucleophilic displacement

A systematic increase of substitution rates by tert-butylamine on alpha-bromopropiophenones is observed with meta or para substituents with increasing electron-withdrawing ability (k x 10(3) L M(-1) min(-1) = 12.7 (p-CH(3)), 15.7 (o-F), 20.5 (H), 20.0 (p-Cl), 23.6 (m-Cl), 27.3 (p-CF(3))). Within an ortho-substituted series, the reactivities decrease (k x 10(3) L M(-1) min(-1) = 7.64 (o-OCH(3)), 5.31 (o-CH(3)), 2.85 (o-Cl), 2.40 ( o-CF(3))). Ortho-substitution results occur from rotational barrier effects and an Adelta(sigma)+ Bdelta(sigma)+ repulsion. The major bonding contribution between reaction and alpha-substituent centers (A-B) is only the sigma bond. When pi bonding is allowed between A and B (meta/para-substitution), delocalization and stabilization of the reacting center occurs.     

Regioselective alkylation of isopropylidene- and cyclohexylidenepropanedinitrile with phenacyl bromides

Alkylation of isopropylidene- and cyclohexylidenepropanedinitrile with phenacyl bromides gave 2,2-bis(2-aryl-2-oxoethyl)propanedinitriles. Direct alkylation of propanedinitrile with phenacyl bromides afforded only 2-(2-aryl-2-oxoethyl)propanedinitriles.     

Synthesis of imidazolyl dithiocarbamates and their reactions with phenacyl bromides

The reactions of ethyl (5-carbamoyl-3H-imidazol-4-yl)dithiocarbamate with phenacyl bromides afford the S-alkylation products as a mixture of E/Z-isomers, which undergo cyclization to 5-(2-oxo-4-arylthiazol-3-yl)-1H-imidazole-4-carboxamides under the action of a base.     

Carbon-13 NMR spectra of some 4-substituted phenacyl bromides

The ¹³C NMR signals for some 4- substituted phenacyl bromides were assigned. The experimental chemical shifts of the aromatic ring carbons are in close agreement with those calculated using substituent chemical shifts. Both the carbonyl and the α-methylene carbons exhibit upfield shifts compared with those of the corresponding 4-substituted acetophenones.     

Kinetics and mechanism of the pyridinolysis of phenacyl bromides in acetonitrile

Kinetic studies of the reactions of substituted phenacyl bromides (YC6H4COCH2Br) with pyridines (XC5H4N) are carried out in acetonitrile at 45.0 degrees C. A biphasic Bronsted plot is obtained with a change in slope from a large (betaX approximately equals 0.65-0.80) to a small (betaX approximately 0.36-0.40) value at pKa = 3.2-3.6, which can be attributed to a change in the rate-determining step from breakdown to formation of a tetrahedral intermediate in the reaction path as the basicity of the pyridine nucleophile increases. This mechanism is supported by the faster rates with pyridines than with anilines and the change of cross-interaction constant rhoXY from a large positive (rhoXY = +1.4) to a small positive (rhoXY approximately +0.1) value. The large magnitude of Hammett rhoX (= -5.5 to -6.9) values for the pyridines with electron-withdrawing substituents and positive deviations of the pi-acceptors, p-CH3CO and p-CN, are quite similar to those for the pyridinium ion formation equilibria. The activation parameters are also in line with the proposed mechanism.     

Reactions of ortho oxy-substituted benzyl and phenacyl bromides in dimethyl sulphoxide

o-Acetoxy- and o-benzoyloxy-benzyl bromides and tosylates oxidatively rearrange in moist dimethyl sulphoxide to o-hydroxybenzyl esters; o-acetoxy- and o-benzoyloxy- phenacyl bromides rearrange to mixtures of 2-hydroxycoumaran-3-ones and o-hydroxyphenacyl esters; o-hydroxyphenacyl bromides also yield 2-hydroxycoumaran-3-ones, together with o-hydroxyphenacyl alcohols. 2-Acetoxybenzaldehyde is reductively rearranged by sodium borohydride to o-hydroxybenzyl acetate.     

Quantitation of phenacyl esters of retinal fatty acids by high-performance liquid chromatography.

A high-performance liquid chromatographic (HPLC) method for the separation and quantitation of retinal fatty acids containing long-chain polyunsaturated fatty acids is described. Fatty acids from frog retinal lipids were converted to the corresponding phenacyl derivatives which were separated on a C18 reversed-phase column and detected at 242 nm. Molar absorptivities (peak area units/nmol) of up to seventeen fatty acid phenacyl derivatives were determined and used for quantitation of fatty acids separated by HPLC. Compared with gas chromatography, the HPLC method gave a similar molar percent distribution of the fatty acids and was twenty to fifty times more sensitive. This HPLC method provides a useful means for the study of chemistry and metabolism of long-chain polyunsaturated fatty acids in retina and other tissues where amounts of material may be limited or recovery of individual components desirable.     

Electronic-state switching strategy in the photochemical synthesis of indanones from o-methyl phenacyl epoxides

An electronic excited-state switching strategy has been utilized to control the selectivity of a key photochemical step in the total synthesis of indanorine. The excited-state character of 4,5-dimethoxy-2-methylphenacyl epoxide was changed from an unfavorable (3)π,π* state to a productive (3)n,π* state by a temporary structural modification, resulting in a relatively efficient and high-yielding formation of an indanone derivative. The corresponding structural modification was selected on the basis of quantum chemical calculations prior to the synthesis.     

Laser photolysis studies of β-bond cleavage of phenacyl phenyl sulfide in acetonitrile

Photo-induced β-bond dissociation of phenacyl phenyl sulfide (PPS) has been investigated in acetonitrile by laser photolysis techniques. Direct excitation of PPS at 295 K provided the acetylmethyl and phenylthiyl radicals with a quantum yield (Φ_rad) of 0.18, whereas triplet sensitization using xanthone revealed an efficiency for β-cleavage of triplet PPS (α _rad) of ≥0.64. From disagreement between the Φ_rad and α _rad values, it was concluded that both the lowest excited single and triplet states are reactive for β-bond dissociation in PPS. The photochemical processes of excited PPS, including β-cleavage, are discussed in detail.     

Determination of trace levels of ethylenethiourea by HPLC following derivatisation with phenacyl halides

Summary The HPLC determination of ethylenethiourea (ETU, imidazolidine-2-thione) has been carried out by derivatisation with phenacyl halides to give imidazole-[2,1-b]thiazoles, which were separated on a polystyrenedivinylbenzene (PS-DVB) column. A number of different phenacyl halides including p-phenyl-, and naphthyl, were studied and the p-nitro reagent was selected as the most suitable for residue analysis. The analysis was more sensitive than direct HPLC analysis and had a limit of detection of 0.04 ng ETU. Presented at the 15th International Symposium on Chromatography, Nürnberg, October 1984     

Synthesis of phenacyl derivatives of frangula-emodin and their HIV-1 RNase H activity

New functionally substituted phenacyl derivatives of frangula-emodin were synthesized and tested as inhibitors of HIV-1 RNase H activity.