Ethers benzyl, hydrogenation

The second acceleration effect is based on the radical promotion and mainly depends on nature of the substituents on the benzene ring of the benzyl alcohol. In this case, benzyl ether groups containing hydrogen atoms, which are labile to abstraction, are attached to ends of the polymer chains (see Equation 11.106 in Scheme 11.38). In the subsequent stage, benzyl ether hydrogens are abstracted by aryl radicals produced as a result of the photolysis of the onium salt, and benzyl ether radicals are formed (Equation 11.107). These more stable radicals, in turn, are oxidized by the onium salt to corresponding carbocations, which are also stable and able to initiate a new polymerization chain more rapidly (Equation 11.108), as described by Ledwith [82], This process also results in increase in the quantum yield of the photolysis of the onium salt. 

Catalytic hydrpgenation in acetic anhydride-benzene,- moves the aromatic benzyl ether and forms a monoacetate hydrogenation in ethyl acetate re-moves the aliphatic benzyl ether to give, after acetylation, the diacetate. ... 

The 2,6-dimethylbenzyl ether is considerably more stable to hydrogenolysis than is the benzyl ether. It has a half-life of 15 h at 1 atm of hydrogen in the presence of Pd-C whereas the benzyl ether has a half-life of —45 min. This added stability allows hydrogenation of azides, nitro groups, and olefins in the presence of a di-methylbenzyl group. ... 

Esters and amides are quite resistant to hydrogenation under almost all conditions so their presence is not expected to cause difficulties. Alkyl ethers and ketals are generally resistant to hydrogenolysis but benzyl ethers are readily cleaved, particularly over palladium or Raney nickel catalysts. ... 

Cr03/AcOH, 25°, 50% yield, ROCOPh ROH + PhC02H)]. This method was used to remove benzyl ethers from carbohydrates that contain functional groups sensitive to catalytic hydrogenation or dissolving metals. Esters are stable, but glycosides or acetals are cleaved. 

Platinum may be more useful than palladium in reduction of nitro compounds containing functions easily reduced by palladium. Hydrogenation of I over 5% Pd-on-C was nonselective with hydrogenolysis of the benzyl ethers competing with nitro hydrog ation, but over PtO in ethanol 2 was obtained in 96% yield (4). 

To a stirred solution of 5.7 g (0.02 m) of 4-benzyloxy-2-ureidoacetophenone in 100 ml of chloroform is added 3.2 g (0.02 m) of bromine. The mixture is stirred at room temperature for about 45 minutes and the solution is concentrated in vacuo at 25°-30°C. The amorphous residue (hydrobromide selt of 4-benzyloxy-a-bromo-3-ureidoacetophenone) is dissolved in 80 ml of acetonitrile and 98 g (0.06 m) of N-benzyl-N-t-butylamine is added. The mixture is stirred and refluxed for 1.5 hours, then it is cooled toOt in an ice bath. Crystalline N-benzyl-N-t-butylamine hydrobromide is filtered. The filtrate is acidified with ethereal hydrogen chloride. The semicrystalline product is filtered after diluting the mixture with a large excess of ether. Trituration of the product with 60 ml of cold ethanol gives 4-banzyloxy-Of-( N-benzyl-N-t-butylamino)-3-ureidoacetophenone hydrochloride, MP 200°-221°C (decomposition). 

Hydrogenolysis (Section 26.7) Cleavage of a bond by reaction with hydrogen. Benzylic ethers and esters, for instance, are cleaved by hydrogenolysis. 

The general features of the monensin synthesis conducted by Kishi et al. are outlined, in retrosynthetic format, in Scheme 1. It was decided to delay the construction of monensin s spiroketal substructure, the l,6-dioxaspiro[4.5]decane framework, to a very late stage in the synthesis (see Scheme 1). It seemed reasonable to expect that exposure of the keto triol resulting from the hydrogen-olysis of the C-5 benzyl ether in 2 to an acidic medium could, under equilibrating conditions, result in the formation of the spiroketal in 1. This proposition was based on the reasonable assumption that the configuration of the spiroketal carbon (C-9) in monensin corresponds to the thermodynamically most stable form, as is the case for most spiroketal-containing natural products.19 Spiro-ketals found in nature usually adopt conformations in which steric effects are minimized and anomeric effects are maximized. 

With a secure route to pentacyclic amine 2, the completion of the total synthesis of 1 requires only a few functional group manipulations. When a solution of 2 in ethanol is exposed to Pd-C in an atmosphere of hydrogen, the isopropenyl double bond is saturated. When a small quantity of HCI is added to this mixture, the hydro-genolysis of the benzyl ether is accelerated dramatically, giving alcohol 15 in a yield of 96%. Oxidation of the primary alcohol in 15 with an excess of Jones reagent, followed by Fischer esterification, gives ( )-methyl homosecodaphniphyllate [( )-1] in an overall yield of 85 % from 2. 

The catalytic system employing (2 - Fur)3P as ligand was applied to the coupling of methyl vinyl ketone and ethyl vinyl ketone to aromatic, aliphatic, acetylenic, and olefinic aldehydes (Scheme 23) [37]. Despite the hydrogenation conditions, alkyne and alkene moieties, as well as benzylic ether and nitro functional groups all remained intact. Furthermore, extremely high lev-... 

The last reaction perhaps involves an intermediate such as 33a which expells a proton and dimethyl sulfide. Formation of the Schiff s base with t-butylamine, reduction with sodium borohydride and hydrogenolysis of the benzyl ether produces sulfonterol (28). Despite the fact that the methylene hydrogen of sulfonterol must be much less acidic than of the corresponding urea proton on carbuterol or the sulfonamide proton on soterenol, good bioactivity is retained. 

The disadvantages of the general method using supported palladium and hydrogen are a lack of selectivity and overreduction. Where selectivity is not an important requirement, Pd/C is a widely used catalyst for the hydrogenolysis of the C-O bond in benzyl ethers. 

Examples In a typical experiment, a benzyl ether in absolute methanol was added to a tube containing Pd/C and a stir bar. Three drops of concentrated HCl were added and the mixture was stirred under a gentle flow of hydrogen for 5 minutes. The tube was sealed and pressurized with hydrogen (40 psi) and stirring was continued for 6 hours. During these circumstances, the benzyl group was completely removed.65... 

Boc-O-benzyl-L-homoserine (Boc = t-butoxicarbonyl) was transformed to L-proline methyl ester, and the benzyl ether was removed by hydrogenolysis. The compound was dissolved in 50% acetic acid in methanol and the reaction mixture was degassed by bubbling nitrogen for 5 minutes then 10% Pd/C was added. The system was evacuated for 5 minutes and then pressured to 45 psi of hydrogen for 48 hours at room temperature.66... 

Pd/CaC03 is also used for the hydrogenolysis of benzyl-oxygen bonds.152 Hydrogenation and hydrogenolysis of an unsaturated benzyl ether over 5% Pt/ C and Pd(OH)2 gave the saturated and deprotected product.153 In contrast, transfer hydrogenolysis with 1,4-cylohexadiene or ammonium formate failed to provide the product cleanly, rapidly, or dependably. 

Hydrogenolysis of a benzyl ether C-O bond in a phosphoric acid dimethyl ester was done in MeOH in the presence of Pd(OH)2 at room temperature under atmospheric hydrogen pressure for 12 hours (Scheme 4.36).167,168... 

In some cases the hydrogenation of the double bond in an unsaturated benzyl ether is necessary without debenzylation. To hydrogenate the carbon-carbon double bond 5% Pd/C in AcOEt was used for 1.5 hours (Scheme 4.40).136 The benzyl ether-protecting group was removed over Pd(OH)2 in AcOEt for 1 hour. 

Treatment of the 0,0-dibenzyl derivative of norneoenactin with 10% Pd/C in MeOH under hydrogen atmosphere resulted in the rapid deprotection (within 1 h) of the starting material. However, reduction of the benzyl ether functionality, without the concomitant hydrogenolysis of the N-O bond, required fine tuning of the conditions. When the hydrogenolysis was carried out using 20-25 mol % of 10% Pd/C at 20 or 30 mM concentrations for 22-31 hours, a... 

Usually the benzyl ether is dissolved in EtOH and cyclohexene, and 20% Pd(OH)2/C is added (1 10 catalyst-substrate by weight) and stirred under reflux for the required period (thin layer chromotography monitoring).246 Without cyclohexene, the benzyl ether was usually recovered, signifying that the EtOH solvent is not a good hydrogen donor under these conditions. 

The Delft synthesis makes use of an acid-catalyzed ring closure - in fact an intramolecular aromatic alkylation - of a l-(3,5-dihydroxy-4-methoxybenzyl) isoquinoline derivative that is prepared starting from (natural) gallic acid. One of the hydroxyl groups is removed via a Pd/ C hydrogenation of the benzyl ether. Other catalytic steps play an important role some steps were improved recently [27]. The crucial step in the Rice synthesis makes use of a l-(2-bromo-5-hydroxy-4-methoxybenzyl)isoquinoline derivative that is also cyclized in an acid-catalyzed ring closure to the morphinan skeleton, followed by catalytic removal of the bromo substituent (Scheme 5.8). 

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