4-substituted Benzyl Research Articles

The decomposition of substituted benzoyl peroxides in the presence of dimethoxybenzenes

Benzoyl peroxides, particularly those containing electron withdrawing substituents, undergo rapid decomposition in the presence of m-dimethoxybenzene, p-dimethoxybenzene, 2,5-di-t-butyl-1,4-dimethoxybenzene, and 2,5-dimethyl-1,4-dimethoxybenzene. Reactions are first order in peroxide and dimethoxy benzene, increasing in the order given. Identified products are the acids corresponding to the peroxide and esters involving ring substitution, ring-substitution with elimination of a t-Bu group, and benzylic substitution. It is proposed that reaction involves a rate-determining charge transfer transition state leading to radical ion pairs which collapse to products. No free radicals have been detected.

Regiospecific bromination of condensed tetralones via aryloxydifluoroborn chelates

Bromination (Br2, CCl4) of the anthracenone derivative (1b) under thermal or photochemical conditions gives the expected bromo-compound (1d) whereas photochemical bromination of the aryloxydifluoroboron complexes (2a,b) gives products (2c,d) of benzylic substitution; conversion of (2c) and (3a,b) into anthraquinone derivatives including madeirin (4) is described and extension of the regiospecific bromination procedure to the bicyclic difluoroboron complex (5a) is illustrated.

Kinetics and mechanisms of nucleophilic displacements with heterocycles as leaving groups. 3. N-(substituted benzyl)-2,4,6-triphenylpyridiniums: effects of benzyl substitution on first- and second-order rates

Kinetics and mechanisms of nucleophilic displacements with heterocycles as leaving groups. 3. N-(substituted benzyl)-2,4,6-triphenylpyridiniums: effects of benzyl substitution on first- and second-order rates

ChemInform Abstract: REACTIVITY OF ISOCOUMARINS. III. REACTION OF 1‐ETHOXYISOCHROMAN WITH BENZYLAMINES

As a part of our studies on the reactions of 1-ethoxyisochroman (1) with nucleophilic reagents, the reaction of 1 with benzylamines was examined. Heating of 1 with benzylamine or its derivatives having an electron-releasing or-attracting group at the 4-position gave 1-benzylaminoisochroman (2) or the corresponding 1-(4-substituted benzylamino) isochromans (6 and 7). Pyrolysis of 2, 6, and 7 gave 4-benzylisoquinoline (3) and 4-(4-substituted benzyl)-isoquinolines (8 and 9), respectively. Compound 3 was also obtained by heating 2-(2-hydroxyethyl) benzaldehyde with benzylamine, or by heating 2-vinylbenzylidenebenzylamine (4), while the reaction of 1 with N-methylbenzylamine afforded 1-(N-methylbenzylamino) isochroman (5) and did not give the 4-benzylisoquinoline derivative at all. The reaction mechanism giving 4-benzylisoquinolines is proposed to be as shown in Chart 3.

Reactivity of isocoumarins. III. Reaction of 1-ethoxyisochroman with benzylamines.

As a part of our studies on the reactions of 1-ethoxyisochroman (1) with nucleophilic reagents, the reaction of 1 with benzylamines was examined. Heating of 1 with benzylamine or its derivatives having an electron-releasing or-attracting group at the 4-position gave 1-benzylaminoisochroman (2) or the corresponding 1-(4-substituted benzylamino) isochromans (6 and 7). Pyrolysis of 2, 6, and 7 gave 4-benzylisoquinoline (3) and 4-(4-substituted benzyl)-isoquinolines (8 and 9), respectively. Compound 3 was also obtained by heating 2-(2-hydroxyethyl) benzaldehyde with benzylamine, or by heating 2-vinylbenzylidenebenzylamine (4), while the reaction of 1 with N-methylbenzylamine afforded 1-(N-methylbenzylamino) isochroman (5) and did not give the 4-benzylisoquinoline derivative at all. The reaction mechanism giving 4-benzylisoquinolines is proposed to be as shown in Chart 3.

Coplanar vs. orthogonal bimolecular substitution at a benzylic carbon

Bimolecular substitution at the benzylic centre in dibenzylethylsulphonium fluoroborate (8) with thiocyanate anion is 8000 times faster than the corresponding reaction in the cyclic sulphonium fluoroborate (4) in which the attacking and leaving groups must remain in approximately the plane of the benzene ring thereby precluding conjugation in the transition state; it is estimated that a ca. thousand-fold increase in rate is attributable to conjugation in unconstrained benzylic substitution.

Attack of S‐ vs N‐Nucleophiles on 2‐halomethylquinazoline 3‐Oxides

AbstractA comparison is made of thiols with amines in their mode of reaction with different substituted 2‐halomethylquinazoline 3‐oxides. Whereas the reaction of some amines (particularly small primary ones), as has long been known, leads to ring‐enlarging rearrangement under certain conditions, all thiol nucleophiles we have observed, ranging from small to large, lead without rearrangement to direct benzylic substitution only. Preformed aminomethylquinazoline 3‐oxides are shown not to rearrange to the corresponding 1,4‐benzodiazepine 4‐oxides. The mechanistic implications of these and other observations are discussed. Data on over forty new compounds are presented.

The effect of steric crowding on an E2 transition state

The mechanism of the reaction of 9-(4-substituted benzyl)fluorene-9-trimethylammonium ions with ethoxide is a normal E2 process. The magnitude of the primary hydrogen–deuterium isotope effect at 60 °C increased with increasing electron-donating ability of the 4-substituent, i.e., 4.15, 5.10, 5.34, 5.65, 5.75, and 5.91 for the 4-CF3, 4-Br, 4-Cl, 4-H, 4-CH3, and 4-OCH3 substituents, respectively. The magnitude of the nitrogen isotope effect at 70 °C decreased with increased electron-donating power of the 4-substituent, i.e., [(k14/k15)–1]100 = 1.24, 0.95, 0.92, 0.91, and 0.80 for the 4-CF3, 4-F, 4-H, 4-CH3, and 4-OCH3 substituents, respectively. A small Hammett ρ value of +1.33 was observed for the reaction. It is concluded that the reaction proceeds via a transition state where the proton is more than one-half transferred to base. It is further concluded that for a reaction in which the 4-substituents decrease the rate, both carbon–hydrogen and carbon–nitrogen bond rupture is more advanced in the transition state. This variance with Hammond's postulate is discussed in the light of steric crowding at the transition state.

Potentiometric studies of hydrophobic effect on ion binding of ionic dextran derivatives

AbstractIn order to clarify the effect of degree of substitution of ionic and hydrophobic group on the polyelectrolytic behavior of polysaccharides, potentiometric titration and activity measurement of counterions were made for carboxymethyldextran (Cm‐dextran) having various degrees of substituted carboxyl group and for carboxymethylbenzyldextran (Cm‐Bzl‐dextran) containing various degrees of substituted benzyl group. From the shape of titration curve, no conformational change was observed for both Cm‐dextran and Cm‐Bzl‐dextran. The pK0 value of Cm‐dextran was independent of the degree of the degree of substituted carboxy group. However, the pK0 of Cm‐Bzl‐dextran increased with an increasing degree of substituted benzyl group. The suppression of dissociation of a carboxyl group, caused by the surrounding hydrophobic groups, was discussed mainly in terms of the change of water structure around such groups. From the results of activity measurement for counterions of these dextran derivatives, we proposed the possibility of ion selectivity based on the hydrophobicity.

Comparisons of the formation of cytochrome P-450 complexes absorbing at 455 nm in rabbit and rat microsomes

The formation of 455 nm complexes during the metabolism of various drugs has previously been studied in the rat. The formation of 455 nm complexes during the metabolism of amphetamine congeners and other compounds has now been studied in the rabbit to determine the differences that exist between these two species. Rabbit microsomes, in contrast to those from rat, show stereochemical preference for the l-isomer over the d-isomer of amphetamine. In both species, benzyl and hydroxyl substitutions on the nitrogen increased the rate of 455 nm complex formation, while methyl substitution did not. Much lower rates of 455 nm complex formation from SKF 525-A and propoxyphene were observed in rabbit microsomes than in rat microsomes. Both rat and rabbit were incapable of forming a 455 nm complex from p-hydroxyamphetamine. These and other differences in 455 nm complex formation parallel, in part, the qualitative and quantitative differences observed in the metabolism of these compounds in the two species.

Studies in Solvolysis. Part IV. Substituent and Solvent Isotope Effects in the Solvolysis of a Series of Benzyl Trifluoroacetates

The rates of neutral hydrolysis of a series of 4-substituted benzyl trifluoroacetates 4-X-C6H4CH2OCOCF3, X = NO2, Cl, H, CH3, and OCH3 have been studied in water and deuterium oxide, both solvents containing 0.012 mol fraction of acetone. The alteration of the rates with the nature of the 4-substituent and the kinetic solvent isotope effect (k(H2O)/k(D2O)) are consistent with the proposal that the esters with X = NO2, Cl, H, and CH3 all react by an acyl–oxygen BAc2 mechanism. On the other hand, the same mechanistic criteria indicate that the 4-methoxybenzyl ester reacts by both the BAc2 and the SN1 alkyl–oxygen fission paths in equal amounts.

2- or 4-Thiazolylmethyl Cyclopropanecarboxylates: Their Synthesis and Insecticidal Activities

From a consideration of the structure-activity relationships, nineteen 2- or 4-thiazolylmethyl cyclopropanecarboxylates, including three benzyl-thiazolylmethyl chrysanthemates (IVf, Xb and Xc), were prepared from thioamides and α-haloketones or α-haloaldehydes and examined for insecticidal activity against houseflies. All those with benzyl substitutions on the thiazole ring were ineffective, as were the other substituents. Only 4,5,6,7-tetrahydrobenzothiazolylmethyl chrysanthemate and 2,2,3,3-tetramethylcyclopropanecarboxylate (Xf and Xlf) possessed about the same order of activity as allethrin, and their activities were 0.61 and 1.56 μg/fly respectively.

Electrochemical reduction of 1,4-diphosphoniacyclohexa-2,5-diene salts without accompanying cleavage

Controlled potential electrochemical reduction of 1,4-diphosphoniacyclohexa-2,5-diene salts in aqueous ethanol provides good yields of 1,1,4,4-tetrasubstituted-1,4-diphosphoniacyclohexane dichlorides or dibromides without reductive cleavage of the ring or any external carbon–phosphorus bonds, including those of substituted benzyl groups.

Studies on the decomposition of tetra-alkylammonium salts in solution. Part III: Interpretation of Hammett correlations

Hammett free energy correlations are reported for the decomposition reactions of tetra-alkylammonium halides in chloroform and acetone solution. All the salts contained a substituted benzyl group attached to the nitrogen atom and decomposed to yield a benzyl iodide and dimethylaniline as the only products.The curved Hammett plots for para-substituted benzyl compounds are compared to the linear plot found previously for a series of salts each containing a para-substituted phenyl group, and it is concluded that curved Hammett plots cannot be used as evidence for a change of mechanism, unless direct conjugative effects between substituent and reaction site are absent.

Photo-induced benzyl substitution of flavins by phenylacetate: a possible model for flavoprotein catalysis.

PHOTOREDUCTION of flavins is known to occur with aminoacids1,2 or, intramolecularly, with the ribityl side chain of the flavin3,4 as hydrogen donors. We wish to report here a new photochemical reaction of flavins which could also explain the mechanism of flavin and flavoenzyme catalysis as a whole.