Benzyl derivatives carbonates

Monoalkylation of optically active 1-phenylethylamine with benzyl bromide in N,N-dimethylpropyleneurea (249a) at 100 °C in the presence of sodium carbonate gives the enantiomerically pure A-benzyl derivative. Isopropyl iodide and neopentyl iodide behave analogously275. 

Nucleophilic Substitution at Benzyl Derivatives. The sharp break from a stepwise to a concerted mechanism that is observed for nucleophilic substitution of azide ion at X-l-Y (Figs. 2.2 and 2.5) is blurred for nucleophilic substitution at the primary 4-methoxybenzyl derivatives (4-MeO,H)-3-Y. For example, the secondary substrate (4-MeO)-l-Cl reacts exclusively by a stepwise mechanism through the liberated carbocation intermediate (4-MeO)-T, which shows a moderately large selectivity toward azide ion ( az/ s = 100 in 50 50 (v/v) water/ trifluoroethanol). The removal of an a-Me group from (4-MeO)-l-Cl to give (4-MeO,H)-3-Cl increases the barrier to ionization of the substrate in the stepwise reaction relative to that for the concerted bimolecular substitution of azide ion. The result is that both of these mechanisms are observed concurrently for nucleophilic substitution of azide ion at (4-MeO,H)-3-Cl in water/acetone solvents. These concurrent stepwise and concerted nucleophilic substitution reactions of azide ion with (4-MeO,H)-3-Cl show that there is no sharp borderline between mechanisms for substitution at primary benzylic carbon, but instead a region of overlap where both mechanisms are observed. 

Fig. 36 Plot of geometrical progression vs charge development on the benzyl carbon for a nucleophilic substitution reaction of a benzyl derivative...

C-Alkylation of 1-methyl-1,2,3,4-tetrahydro-6//-pyrimido[l,2-b]isoquino-lin-6-one with benzyl bromide in boiling methylene chloride overnight in the presence of potassium carbonate, and with excess methyl iodide gave 11-substituted derivatives (113 and 114) (88HCA77). The treatment of hydrobromide salt of 11-benzyl derivative 113 with a base yielded 11-benzyl-1 -methyl-1,2,3,4-tetrahydro-6//-pyrimido[l, 2-6]isoquinolin-6-one (115). 

DMF in the dark at room temperature for many hours [40-43] (for this compound, a two-step procedure based on regioselective tosylation of OH-6 followed by SN2 displacement with sodium benzoxide proved more practical [44, 45]). Barium carbonate [46] or sodium hydroxide [43] as a base have also been used. Without protection ofOH-3, the order of reactivity seems to be OH-6 > OH-3 > OH-4 40% of 3,6-di-O-benzyl and 20% of 3,4,6-tri-O-benzyl derivative have been isolated after 4 days stirring with 2 molar equiv. of benzyl bromide [41], Ultrasonication increases the rate of this benzylation substantially [47]. 

For sodium cyanoborohydride — hydrogen chloride reagent the direction of the reductive opening of the dioxolane acetals obeys the same rule, it depends on the stereochemistry at the asymetric, benzylidene acetal carbon [168, 169]. Methyl exo-2,3 4,6-di-0-benzylidene-a-D-mannopyranoside is cleaved in oxolane solution to give 50 % of the 3,6-di-O-benzyl derivative, which is also the major product in the reaction of methyl 3-0-benzyl-4,6-0-benzylidene-a-D-mannopyranoside. The 2-O-benzyl isomer (20) was cleaved nonselectively, indicating again the effect of the bulk of the C-3 substituent [169]. A compatibility of this reagent, as well as of borane — tri-... 

The incorporation of cyclic substituents, such as propane-1,3-diyldioxy, its ethyl and benzyl derivatives substituted at the (1-thiophene carbons of 21,23-dithiaporphyrins 240b and 21-monothiaporphyrins 241b (Scheme 95), has also been reported (04BCJ1173) by condensing the substituted thiophene diols 239b with benzaldehyde and pyrrole. The cyclic substituents at the (5-thiophene carbon atoms alter electronic properties of porphyrin. 

For a five-membered dioxolane ring, the regioselectivity depends on the stereochemistry of the benzylidene acetalic carbon atom. For example, treatment of the methyl endo 2,3-0-benzylidene protected rhamnoside with LiAlILi-AlClj gave a 2-0-benzyl derivative, but the same reaction with the 2-exo isomer yielded mainly the 3-0-benzyl derivative.32... 

Low asymmetric induction is observed when (R)-3-benzyloxycarbonylamino-5-hexenoic acid (1, R = H) is iodolactonized under kinetic conditions (iodine/potassium iodide/sodium hydrogen carbonate). A mixture of the cis- and trww-iodo-5-lactones (60 40) in 94% yield is obtained. Better stereoselectivity can be obtained when the. V-benzyl derivative 1 (R = Bn) is cyclized under the same conditions. In fact, an 86 14 cisjtram) ratio is observed, showing that halolactonization is kinetically favored over halocarbamation, with the bulky substituent at nitrogen inducing high selectivity7. n n... 

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