Phenacyl Derivatives

The nature of the solvent is important (small amounts of water can increase the photolysis rate fivefold), but air or triplet quenchers should be excluded, as they create an up to fourfold slowdown. 

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Phenacyl esters can be prepared from the phenacyl bromide, a carboxylic acid, and potassium fluoride as base. These phenacyl esters can be cleaved by irradiation (313 nm, dioxane or EtOH, 20°, 6 h, 80-95 % yield, R = amino acids > 300 nm, 30°, 8 h, R = a gibberellic acid, 36-62% yield ). Another phenacyl derivative, RC02CH(C0C6H5)C6H3 3,5-(0CH3)2, cleaved by irradiation, has also been reported. ... 

The 1,3-dipolar cycloaddition of dienes 86 with phenacyl derivatives 85 gave the pyrrolo[l,2-a]quinoline 87 regio- and stereoselectively (90DOK1156) (Scheme 15). 

Valproic acid was determined in plasma by treatment with 2,4-dibromoacetophe-none or 2-bromoacetonapththalone and with dicyclohexano-18-crown-6 and heated at 70 °C for 40 min. The solution was subjected to TLC on C8F octyl plates or to high performance TLC on RP 8 254 S or Kieselgel 60 F254 plates with developing solvents of aq. 63% ethanol, aq. 73% ethanol or CHCl3-cyclohexane (2 1), respectively, with detection at 280 or 254 nm for the naphthoylmethyl or phenacyl derivative, respectively. The limits of detection were 9.7 and 4.9 pg/mL of valproic acid for the TLC RP 8 and HPTLC RP 8 plates, respectively. Recovery was 84-92.74% [28],... 

Carbonyl compounds are also suited to the investigation of the role of solvent reorganization in the dynamics of intramolecular dissociative electron transfer as observed in a series of phenacyl derivatives bearing various leaving groups.199... 

Cyclization of phenacyl derivatives 676 and 678 with phosphorus oxychloride and pentachloride gave 677 and 679, respectively (87KGS533). 

Selective oxidation of polymethylpyrimidines. 2,4-Di- and 2,4,6-trimethyl-pyrimidines are selectively oxidized to 4-carboxylic acids by a slight excess of Se02 in pyridine. Yields are about 40-65%. This increased reactivity of a 4-methyl group of polymethylpyrimidines is also observed in reaction with ethyl nitrite in liquid ammonia to form 4-aldoximcs and with ethyl benzoate in the presence of KOC2H to form phenacyl derivatives. 

Table 1 Elution Conditions Used to Separate Fatty Acid Phenacyl Derivatives...

An acetonitrile-water mobile phase could not resolve adjacent peaks of palmitoleic (16 1) and arachidonic (20 4) acids. Partial separation could be achieved with a decreased ratio of acetonitrile to water in the mobile phase, as reported by Borch (25), but this was inconvenient, owing to the substantial prolongation of the elution time (up to 4 h at a flow rate of 2 ml/min) and the specific column requirements (90 X 0.64-cm ID). These results demonstrate the importance of the carbon chain length and the number of double bonds with respect to the solubility of phenacyl derivatives in these two solvents. The retention time of phenacyl esters increases with increasing chain length and decreasing number of double bonds. 

With samples containing a wide range of components, such as hydrogenated fats, the column was eluted with solvent A for 13 min, then changed in one step to A-B (75 25), with a gradient to 100% B over 20 min. The free fatty acids were converted into the phenacyl derivatives and, prior to HPLC analysis, were purified by elution from a BOND ELUT NH2 column with hexane-diethyl ether (9 1). 

Fig. 14 Separation of the phenacyl derivatives of C16 0 llt-C18 l, 9t-C 18 1, Ilc-C18 1, and 9c-C18 1 by HPLC in the silver ion mode. The column temperature was 38°C and the mobile phase was 1,2-dichloroethane/dichloromethane (1 1 v/v) at a flow rate of 1.5 ml/min, with detection at 242 nm.

A commercially available column containing silver ions has recently been developed by Chrompack (ChromSpher Lipids HPLC column). A solvent system (43) composed of dichloro-methane, dichloroethane, and small amounts (0.01-0.025%) of acetonitrile (ACN) is used with both the Nucleosil and Chrompack HPLC columns. Because chlorinated solvents are opaque at the wavelengths (200-210 nm) used for FAME analyses, the use of UV detectors is precluded unless the phenacyl derivatives of the fatty acids are first prepared. 

Cyclazines are an interesting class of compounds that can be synthesized by intramolecular cyclization to the 3-position of the indolizine ring.200 The reactivity of the methyl group in 5-methylindolizine is similar to that in 2-picoline, and this provides the means of preparing cycl[3,2,2]azines. Thus, the reaction of 5-methyl-2-phenylindolizine with butyl lithium followed by JV,JV-dimethylbenzamide yielded the 5-(phenacyl) derivative, which could be ring-closed to 133 by heating... 

Interestingly, phenacyl derivatives bearing an easily abstractable hydrogen might undergo a competitive Norrish type II pathway, and this has been exploited to release fragrant carbonyl compounds (Scheme 13.25) [59]. 

Other phenacyl derivatives were introduced by Klan et al. to release amines (if protected as carbamates) in high chemical yields upon irradiation (up to 97%) [89-93], The mechanism proceeds through an ortho-quinoid aromatic triplet photoenol, which can either cyclize/eliminate or be trapped by the solvent if it is nucleophilic (e.g., MeOH), as shown in Scheme 13.26. 

Photocleavage of phenacyl derivatives was first reported by Sheehan and Umezawa in 1973.40 In contrast to the 2-nitrobenzyl protecting groups, choice of solvent is important because the solvent acts as a hydrogen donor. The cleavage takes place by a radical mechanism as shown in Scheme L21. Typical solvents include ethanol dioxane and benzene containing cumene as hydrogen donor. 

A thiete intermediate (225a) was proposed in the photochemical reaction of dimethyl acetylenedicarboxylate with 225,and similar intermediates were proposed in the addition of thiones or dithioesters to heteroatom-substituted acetylenes. Thiete 227 was suggested as an intermediate in the reaction of 226 with carbon disulfide. Reactions of aryl vinyl sulfide derivatives (2,4,6-trinitrobenzenesulfonate of a phenylthiovinyl alcohol, a phenacyl derivative )... 

Phenacyl phenyl sulfide can be reduced in aqueous-alcoholic medium to acetophenone and thiophenol [119] this is analogous to several other phenacyl derivatives see Eq. (8). This reaction has been used to cleave some phenacylthio-substituted thiophenes by reduction at a mercury cathode in DMF containing 2 Eq. phenol [120]. 

The passing of the years has not diminished the interest in photolabile protecting groups. Many such systems are available and have been described in the literature. A new method has been proposed for the protection of amino acids. This involves the conversion of the amino acid into the phenacyl derivatives 120. Irradiation of these derivatives in a buffered aqueous solution results in the release of the amino acid and the transformation of the phenacyl group into a phenylacetic acid. This occurs via the triplet state within which there is intramolecular displacement of the amino acid moiety as represented in 121. The resultant intermediate 122 undergoes ring opening by attack by water to afford the... 

Reaction of 3-amino-4-phenylthiazolin-2-thione with phenacyl bromides in methanol leads to thiadiazinium cation 463. The latter compounds, on treatment with triethylamine, is converted to pyrazolo[5,l-Z>]thiazole derivative (465). The same reaction in benzene first gives the S-phenacyl derivative 464, which is transformed to 465 in the presence of bases (87H1323). 

The nitrogen atom of 31 is readily alkylated. The 2-phenacyl derivative (38) rearranges to 2-benzoyl-2//-l,3-benzothiazin-4(3//)-one (39) in mild base,51 illustrating once again the ease with which the S—N bond is broken. 

In the presence of suitable nucleophiles (such as benzoyl acetic acid) the primary imines can be spontaneously further modified in situ. A convenient approach to obtain phenacyl-derivatives, building blocks in the synthesis of certain alkaloids, was reported 38. In some cases, diamine oxidases exhibit activities complementary to monoamine oxidases. For example vanillylamine is far more efficiently converted into vanillin by a diamine oxidase from Aspergillus niger than by the monoamine oxidase from E. coIi[1 L... 

Some further monosubstituted furoxans which have been reported are either of very doubtful authenticity or have been discredited. The phenacyl derivatives of Harries and Tietz,462 formed by the nitrosation of /J-aryl-oc,/ -unsaturated oximes, have been shown to be pyrazolone di-JV-oxides 463 The degradation of Holleman s peroxide (29) by hydroxylamine and alkali was reported to form structure 218, or its 3-substituted isomer, by Boyer and Chang.29 It does, however, seem unlikely that a monosubstituted furoxan could withstand such reaction conditions. Decarboxylation of furoxandi-carboxylic acid has been suggested to provide the 4-monocarboxylic acid,464 but Ponzio and De Paolini465 have assigned a nitrile oxide structure to the product. 

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