Phenacyl alcohol derivatives

Table 1. Molecular properties of phenacyl alcohol derivatives...

The analysis of a molecule with one site of action is a good indicator for the LD50, such as in phenacyl alcohol derivatives. Steroids, however, are complex molecules, and their metabolites contribute to the experimentally measured LD50 values. If the toxicity can be related to superoxide, the measurement of chemiluminescence intensity can be used for a drug candidate screening. Further studies of the substituent effect of steroids are required before LD50 values can be estimated from computational chemical calculations. 

The ape of atoms was correlated with the relative sensitivity of phenacyl alcohol derivatives and steroids. The correlation coefficients for several keto-form steroids varied from 0.221 to 0.842, and for enol forms from 0.163 to 0.800, as summarized in Table 11.3. 

Photolytic cleavage reactions (e.g., of o-nitrobenzyl, phenacyl, nitrophenylsul-fenyl derivatives) take place in high yield on irradiation of the protected compound for a few hours at 254-350 nm. For example, the o-nitrobenzyl group, used to protect alcohols, amines, and carboxylic acids,has been removed by irradiation. Protective groups that have been removed by photolysis are described at the appropriate places in this book in addition, the reader may wish to consult five review articles. 

Lobinine, CjgHggOgN. First isolated by Wieland, Ishimasa and Koschara who, on the evidence then available, regarded it as 2-phenacyl-l-methyl-7-)3-hydroxypropylhexamethyleneimine, CjgHjjOjN (XXI), which was modified to (XX) in 1989. It furnishes an oxime (B. HCl, m.p. 182°) and a benzoyl derivative (B. HCl, m.p. 146-7°). On reduction by sodium in acetic acid it is converted into the unsaturated dihydric alcohol for which th original name lobinol has been changed to /3-lobinanidine,... 

The formation of cyano ketones by this method is illustrated by the conversion of phenacyl halides to the corresponding nitriles. Ring closure to cyclopropane derivatives is a side reaction which has been encountered with y-halo ketones. Benzalacetophenone dibromide is converted by alcoholic potassium cyanide to the fi-cyaao ketone, the a-halogen atom being reduced. Several a-chloro ketones have been found to yield a-cyano epoxides. ... 

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]. 

Perimidine has an acidic NH proton and therefore behaves differently from pyrimidine and quinazoline. The product is a neutral molecule. Like imidazoles, perimidines are best A-alkylated in alkaline media (79) in an inert atmosphere. Alkylation with primary alkyl bromides or iodides can be performed in an alcoholic solution. Dimethyl sulfate is recommended for methylation. Yields drop with secondary halides. A-Substitution reactions are sensitive to steric interference from 2-and 4(9)-substituents 2-alkyl or aryl derivatives can be methylated but not alkylated by benzyl chloride or isopropyl, allyl or phenacyl bromides. 4(9)-Substituted perimidines are preferentially alkylated at the remote nitrogen. 

Treatment of 2-amino-3- mercapto -pyrazines 8 with a-halo ketones has been used on several occasions to prepare derivatives of this ring system. When the reaction is performed in the presence of alcoholic potassium hydroxide at <0°C, the dihydro compounds 9 are obtained. At room temperature with substituted phenacyl bromides, the ring-opened derivatives 10 are the main products. " The latter compounds may be cyclized in acetic anhydride" to give the substituted pyrazinothiazines 11. These may also be obtained directly from the pyrazine 8 by performing the reaction in a chloroform-aqueous potassium hydroxide mixture at room temperature. ... 

Adding an alcoholic solution of phenacyl or 4-bromophenacyl bromide to[a solution of a carboxylic acid that has been neutralized with sodium carbonate gives an ester of a)-hydroxyaceto-phenone or of its 4-bromo derivative these esters crystallize well from ethanol and are useful for characterization of liquid acids. 

Examples of additives are the following EA = iodonium salt, e.g. diphenyliodonium hexafluorophosphate (more rarely, a sulfonium salt) and related derivatives [113], alkyl halide, e.g. phenacyl bromide [1.14] and triazine, e.g. 2,4,6-tris(trichloromethyl)-l,3,5-triazine ED = borate disulfide, group IVb dimetal [1.15] HD = alcohol, THE, thiol, benzoxazine, aldehyde, acetal, silane (e.g. tris(trime1hylsilyl)silane = (TMS)3Si-H) [1.16]), germane, borane, stannane, alkoxyamine, silyloxyamine, polymer substrate, etc. EPD = amine [1.17], thiol, etc. The generated radicals (e.g. Ph, R, RsSi, RR C R R in [1.13]-[1.17] ) are the initiating species. Efficient novel or newly modified dye structures in the Dye/amine, Dye/iodonium salt or Dye/silane two-component PISs have been proposed within the last 4 years (see section 1.3.5). 

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