Benzylic substitution

The birefringence for phenyl-substituted PC (4) (T = 176 C) is reduced to about 50%, for benzyl substituted PC (5) (T = 138 C) to about 25%, and for four-ring bisphenol PC (6) to 8% of the value for BPA-PC (183,190,195,197,198) on condition of an optimum conformation of the phenyls in the side groups perpendicular to the aromatic rings in the backbone. In reaUty, however, these low birefringence values are not achieved, because the optimum conformation of the phenyl rings cannot be achieved in injection-stamped disks. 

Pentafluorophenylnitrene generated by the photolysis of pentafluorophenyl-azide in toluene at 25 gives pentafluoroaniline and benzyl-substituted anilines At low temperatures (-78 to -196 °C), perfluoroazobenzene also is formed [7] (equation 8)... 

In 1909, Robinson demonstrated the utility of acylamidoketones as intermediates to aryl-and benzyl-substituted 1,3-oxazoles through cyclization with sulfuric acid. Extension of sulfuric acid cyclization conditions to alkyl-substituted oxazoles can give low yields, for example 10-15% for 2,5-dimethyl-l,3-oxazole. Wiegand and Rathbum found that polyphosphoric acid can provide alkyl-substituted oxazoles 4 in yields equal to or greater than those obtained with sulfuric acid. Significantly better yields are seen in the preparation of aryl- and heteroaryl-substituted oxazoles. For example, reaction of ketoamides 5 with 98% phosphoric acid in acetic anhydride gives oxazoles 6 in 90-95% yield. ... 

Alkylation at the ind-N of l,2,3,4-tetrahydro-j8-carbolines has been carried out with alkyl halide after treatment with sodamide in the usual manner. Cyanoethylation of a p /r-V-substituted tetrahydro-jS-carboline in the presence of Triton B yields the corresponding 9-cyanoethyl derivative. Similarly, treatment of p / -V-methyl-l,2,3,4,4a,9b-hexahydro-y-carboline with sodamide, followed by benzyl chloride, leads to the ind-A -benzyl-substituted derivatives. l-Oxo-l,2,3,4-tetrahydro-j8-carboline yields the ind-A -methyl derivative directly with dimethyl sulfate.Prolonged treatment with sodium hydride, followed by methyl iodide, yields the 2,9-dimethyl derivative. Heating with sodium hydride in acetone followed by the addition of dimethyl sulfate gives rise to the ind-V-methyl derivative. ... 

The enantioselective synthesis of the V-benzyl-substituted /3-lactam 274a (NR2 = PhCH2NH), a precursor for carbapenem antibiotics, was described starting from the chiral synthon 5(R)-menthyloxy-2(5//)-furanone 170 (Scheme 71)... 

The regeneration of carbonyl compounds from 1,3-dithianes can be achieved using potassium hydrogen persulfate, Oxone , supported on wet alumina <96SL767> and by periodic acid under non-aqueous conditions <96TL4331>. The deprotection of benzyl substituted 1,3-dithianes can be achieved using the one electron oxidant [Fe(phen)3](PF6)3 <96SL315>. 

Loss of catalytic activity resulting from internal displacements is not usually a serious problem below temperatures of about 100 C. However, highly active R-groups, such as benzyl, methyl and allyl, undergo internal displacement more readily, particularly in the presence of strong nucleopfiles. For instance, the presence phenolates and thiolates may lead to the formation of benzyl alcohol, ethers, or sulphides from benzyl-substituted quaternary ammonium salts. 

A range of different functional groups has been introduced into the V-position of the C3 side chain, as shown in Table 6.10. A number of different functionalities were shown to be tolerated in this position, with lipophilic groups such as methyl and dithiolane being preferred over polar groups such as ketones and alcohols. Ketone (118) had similar CBi receptor affinity to the unfunctionalised -heptyl compound (84), while alcohol (120) had lower affinity. The phenyl ketone (119) had lower CBi receptor affinity than the simple benzyl-substituted compound (116), but higher CB2 affinity, with about 12-fold selectivity for CB2 over CBi. 

The photochemistry of benzyl-substituted digermanes is thus basically the same as that observed for vinyl- and styryl-substituted digermanes reported in Section in. In comparison, the equivalent disilane compounds exhibit only Si—Si bond homolysis, with no Si—C cleavage or silylene formation39. 

Moreover, the Nb complex hydrogenates catalytically aryl- and benzyl-substituted phosphine under similar conditions (Scheme 6.16) [149]. Kinetic studies show that the hydrogenation of triphenylphosphine into the monocyclohexyl, dicyclohexyl, and tricyclohexylphosphine are successive reactions, and the rate of hydrogenation of the arylphosphine decreases as the number of cyclohexyl substituents increases [153]. 

Secondary phosphine oxides are known to be excellent ligands in palladium-catalyzed coupling reactions and platinum-catalyzed nitrile hydrolysis. A series of chiral enantiopure secondary phosphine oxides 49 and 50 has been prepared and studied in the iridium-catalyzed enantioselective hydrogenation of imines [48] and in the rhodium- and iridium-catalyzed hydrogenation functionalized olefins [86]. Especially in benzyl substituted imine-hydrogenation, 49a ranks among the best ligands available in terms of ex. 

R2 = Benzyl, Substituted benzyl, Naphtylmethyl, Alkyl, 2-Hydroxymethyl groups... 

Tanner et al. (58) investigated the use of chelating diaziridines (85) as ligands for transition metals. The cyclopropanation of styrene using CuOTf complexes of phenyl-substituted aziridine (85a) proceeds in modest enantioselectivity and dias-tereoselectivity, but improved enantioselectivity is observed with complexes derived from benzyl-substituted bis(aziridine) (85b), Eq. 42 (59). Complexes derived... 

The efficient addition-cyclization sequence described above could be successfully applied to the preparation of the polyhydroxylated y-amino acid (-)-detoxinine [73], The crucial key step in this fairly short synthesis is the chelate-controlled addition of lithiated benzyloxyallene 120 (R = Bn) to the chiral N-benzyl-substituted imine 121 as shown in Scheme 8.31. The required skeleton of the natural product was generated in good overall yield. 

We next contemplated whether the unsaturation site could be encompassed in the context of a properly positioned benzo linkage. We were intrigued to discover that excellent diastereoface selectivity was obtained in the aldol condensation of the Z-lithium enolate with the benzyl-substituted formyl moiety, entry g. 

Benzylic CH bonds Benzylic CH bonds can be preferentially substituted at the anode by oxidation of the aromatic ring to a radical cation, which can undergo side-chain substitution at the benzylic carbon atom and/or nuclear substitution. Benzylic substitution preponderates, when there is an alkyl substituent at the aromatic carbon bearing the highest positive charge density in the radical cation, while a hydrogen at this position leads to a nuclear substitution [16]. Anodic benzylic substitution is used in technical processes for the conversion of alkyl aromatics into substituted benzaldehydes [17, 18]. Anodic benzylic substitution has been used for the regioselective methoxylation of estratrienone at C9 (Fig. 4) [19]. 

The ion pairing between the enolate of 5 and the catalyst should make the asymmetric induction sensitive to the electronic effects of substituents on the N-benzyl group. A Hammett plot of log ee/eeQ vs the substituent constant o of the para N-benzyl substituted catalysts (R = CH3O, CH3 H, F, Cl, CF3) gave a reaction constant of p - 0.21 + 0.02 with ee s in the range of 60% to 92% demonstrating that substituents with increasing... 

The proposed mechanism is depicted in Scheme 38. The aldehyde is activated due to coordination on the silicon atom. A hydrogen bond between the aldehyde function and the benzyl substituted tertiary nitrogen atom stabilizes the transition state, and the benzyl group ensures that the cyclopentadiene attacks the dienophile only from one side. 

In the benzyl-substituted spiro compound 30 (Scheme 18), the phenyl ring (due to a weak intramolecular interaction) was folded over the 1,3-dioxan-3,6-dione moiety (78M1263) the ABMNX spin system in the H NMR spectrum therefore was analyzed in detail (in CDCI3). 

The second way differs little from the previous, and consists of the initial formation of 4-hydroxy-3-acetoxybromoacetophenone (11.1.27) by acylation of methyl ester salicylic acid using bromoacetyl chloride. This is also reacted with iV-benzyl-tcrt-buty-lamine, and the resulting product (11.1.28) is completely hydrolyzed by lithium aluminum hydride into the (V-benzyl substituted albuterol (11.1.29), the benzyl group of which is removed by hydrogen over a palladium catalyst to give the desired albuterol (11.1.26) [31]. 

Substituents R and have been alkyl, ethoxycarbonylethyl, benzyl, substituted benzyl, and phenyl the latter gave the lowest yield. Cyclobutanone gave a rearranged product, due apparently to ring strain. ... 

Similarly to their 2-aryl-substituted analogs <1996CHEG-II(6)301>, 2-methyl- and 2-benzyl-5-phenyl-l,3-oxazine-4,6(57T)-diones 26B proved to be less favored tautomers than the corresponding 4-hydroxy-l,3-oxazin-6-ones 26A in (003)280. H NMR measurements showed the ratio of the tautomers 26A and 26B to be 55 45 for the 2-methyl- and 60 40 for the 2-benzyl-substituted derivative <2005ARK(xv)88>. 

Reduction of cycloalkane-condensed 2-phenyl-5,6-dihydro-4//-l,3-benzoxazines 144 with lithium aluminium hydride (LAH) afforded A -benzyl-substituted 2-(aminomethyl)cycloalkanols 145 in a reductive ring opening via the ring-chain tautomeric tetrahydro-l,3-oxazine intermediates. Catalytic reduction of 1,3-oxazines 144 under mild conditions in the presence of palladium-on-carbon catalyst similarly resulted in formation of the A -benzyl-1,3-amino alcohols 145. When the catalytic reduction was performed at elevated temperature at hydrogen pressure of 7.1 MPa, the N-unsubstituted 2-(aminomethyl)cycloalkanols 146 were formed in good yields (Scheme 22) <1998SC2303>. 

One of the oldest-known reactions of N-nitrosamines is their reduction to 1,1-disubstituted hydrazines discovered by Fischer (19) The most common method to perform this transformation has been zinc dust in acid, generally acetic acid tetrazenes are sometimes formed as by-products (20) and denitrosation can also occur. Several other reducing methods have been investigated reduction with lithium aluminum hydride and catalytic hydrogenation are sometimes useful. Sodium dithionite reduction of benzyl substituted N-nitrosamines in base can result in fragmentation to... 

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