Hydrogenolysis Hydrolysis

A hydrogenolysis-hydrolysis sequence applied to isoxazolo[4,5-r/]pyridazin-4(5//)-ones and to 7-methoxy-3-methylisoxazolo[4,5-[Pg.81]

Addition of a hydroxy group to alkynes to form enol ethers is possible with Pd(II). Enol ether formation and its hydrolysis mean the hydration of alkynes to ketones. The 5-hydroxyalkyne 249 was converted into the cyclic enol ether 250[124], Stereoselective enol ether formation was applied to the synthesis of prostacyclin[131]. Treatment of the 4-alkynol 251 with a stoichiometric amount of PdCl2, followed by hydrogenolysis with formic acid, gives the cyclic enol ether 253. Alkoxypalladation to give 252 is trans addition, because the Z E ratio of the alkene 253 was 33 1. 

Carboxyl groups of ammo acids and peptides are normally protected as esters Methyl and ethyl esters are prepared by Fischer esterification Deprotection of methyl and ethyl esters is accomplished by hydrolysis m base Benzyl esters are a popular choice because they can also be removed by hydrogenolysis Thus a synthetic peptide protected at both... 

Section 27 16 Carboxyl groups are normally protected as benzyl methyl or ethyl esters Hydrolysis m dilute base is normally used to deprotect methyl and ethyl esters Benzyl protecting groups are removed by hydrogenolysis... 

Tetrafluoropyrimidine was converted to the antiaeoplastic 5-fluorouracil (5-FU) by a novel process based on the sequence partial exchange chlorination (61% yield), selective hydrogenolysis ia triethylamine (71% yield) and hydrolysis (85—93% yield) (464). 

Hydrogenolysis is analogous to hydrolysis and ammonolysis, which involve the cleavage of a bond induced by the action of water and ammonia, respectively. Chemical bonds that are broken by hydrogenolysis reactions include carbon—carbon, carbon—oxygen, carbon—sulfur, and carbon—nitrogen bonds. An example of hydrogenolysis is the hydrodealkylation of toluene to form benzene and methane ... 

Many other polymerization processes have been patented, but only some of them appear to be developed or under development ia 1996. One large-scale process uses an acid montmorrillonite clay and acetic anhydride (209) another process uses strong perfiuorosulfonic acid reski catalysts (170,210). The polymerization product ia these processes is a poly(tetramethylene ether) with acetate end groups, which have to be removed by alkaline hydrolysis (211) or hydrogenolysis (212). If necessary, the product is then neutralized, eg, with phosphoric acid (213), and the salts removed by filtration. Instead of montmorrillonite clay, other acidic catalysts can be used, such as EuUer s earth or zeoHtes (214—216). 

Purines, N-alkyl-N-phenyl-synthesis, 5, 576 Purines, alkylthio-hydrolysis, 5, 560 Mannich reaction, 5, 536 Michael addition reactions, 5, 536 Purines, S-alkylthio-hydrolysis, 5, 560 Purines, amino-alkylation, 5, 530, 551 IR spectra, 5, 518 reactions, 5, 551-553 with diazonium ions, 5, 538 reduction, 5, 541 UV spectra, 5, 517 Purines, N-amino-synthesis, 5, 595 Purines, aminohydroxy-hydrogenation, 5, 555 reactions, 5, 555 Purines, aminooxo-reactions, 5, 557 thiation, 5, 557 Purines, bromo-synthesis, 5, 557 Purines, chloro-synthesis, 5, 573 Purines, cyano-reactions, 5, 550 Purines, dialkoxy-rearrangement, 5, 558 Purines, diazoreactions, 5, 96 Purines, dioxo-alkylation, 5, 532 Purines, N-glycosyl-, 5, 536 Purines, halo-N-alkylation, 5, 529 hydrogenolysis, 5, 562 reactions, 5, 561-562, 564 with alkoxides, 5, 563 synthesis, 5, 556 Purines, hydrazino-reactions, 5, 553 Purines, hydroxyamino-reactions, 5, 556 Purines, 8-lithiotrimethylsilyl-nucleosides alkylation, 5, 537 Purines, N-methyl-magnetic circular dichroism, 5, 523 Purines, methylthio-bromination, 5, 559 Purines, nitro-reactions, 5, 550, 551 Purines, oxo-alkylation, 5, 532 amination, 5, 557 dipole moments, 5, 522 H NMR, 5, 512 pJfa, 5, 524 reactions, 5, 556-557 with diazonium ions, 5, 538 reduction, 5, 541 thiation, 5, 557 Purines, oxohydro-IR spectra, 5, 518 Purines, selenoxo-synthesis, 5, 597 Purines, thio-acylation, 5, 559 alkylation, 5, 559 Purines, thioxo-acetylation, 5, 559... 

A benzylidene acetal is a commonly used protective group for 1,2- and 1,3-diols. In the case of a 1,2,3-triol the 1,3-acetal is the preferred product. It has the advantage that it can be removed under neutral conditions by hydrogenolysis or by acid hydrolysis. Benzyl groups and isolated olefins have been hydrogenated in the presence of 1,3-benzylidene acetals. Benzylidene acetals of 1,2-diols are more susceptible to hydrogenolysis than are those of 1,3-diols. In fact, the former can be removed in the presence of the latter. A polymer-bound benzylidene acetal has also been prepared." ... 

Historically, simple Vz-alkyl ethers formed from a phenol and a halide or sulfate were cleaved under rather drastic conditions (e.g., refluxing HBr). New ether protective groups have been developed that are removed under much milder conditions (e.g., via nucleophilic displacement, hydrogenolysis of benzyl ethers, and mild acid hydrolysis of acetal-type ethers) that seldom affect other functional groups in a molecule. 

The diphenylmethylene ketal prepared from a catechol (Ph2CCl2, Pyr, acetone, 12 h) or (Ph2CCl2, neat, 170°, 5 min, 59%) can be cleaved by hydrogenolysis (H2/ Pd-C, THF). It has also been prepared from a 1,2,3-trihydroxybenzene (Ph2CCl2, 160°, 5 min, 80% yield) and cleaved by acidic hydrolysis (HOAc, reflux, 7 h). ... 

Diphenylmethyl esters are similar in acid lability to r-butyl esters and can be cleaved by acidic hydrolysis from 5-containing peptides that poison hydrogenolysis catalysts. 

The dibenzosuberyl ester is prepared from dibenzosubeiyl chloride (which is also used to protect —OH, —NH, and —SH groups) and a carboxylic acid (Et N, reflux, 4 h, 45% yield). It can be cleaved by hydrogenolysis and, like t-butyl esters, by acidic hydrolysis (aq. HCl/THF, 20°, 30 min, 98% yield). ... 

The 2,4,6-trimethylbenzyl ester has been prepared from an amino acid and the benzyl chloride (Et3N, DMF, 25°, 12 h, 60-80% yield) it is cleaved by acidic hydrolysis (CF COOH, 25°, 60 min, 60-90% yield 2 N HBr/HOAc, 25°, 60 min, 80-95% yield) and by hydrogenolysis. It is stable to methanolic hydrogen chloride used to remove A-o-nitrophenylsulfenyl groups or triphenylmethyl esters. ... 

Sulfobenzyl esters were prepared (cesium salt or dicyclohexylammonium salt, Na03SC6H4CH2Br, DMF, 37-95% yield) from A -protected amino acids. They are cleaved by hydrogenolysis (H2/Pd), or hydrolysis (NaOH, dioxane/water). Treatment with ammonia-or hydrazine results in formation of the amide or hydrazide. The ester is stable to 2 M HBr/AcOH and to CF3SO3H in CF3CO2H. The relative rates of hydrolysis and hydrazinolysis for different esters are as follows ... 

The first, and still widely used, polymer-supported ester is formed from an amino acid and a chloromethylated copolymer of styrene-divinylbenzene. Originally it was cleaved by basic hydrolysis (2 N NaOH, FtOH, 25°, 1 h). Subsequently, it has been cleaved by hydrogenolysis (H2/Pd-C, DMF, 40°, 60 psi, 24 h, 71% yield), and by HF, which concurrently removes many amine protective groups. Monoesterification of a symmetrical dicarboxylic acid chloride can be effected by reaction with a hydroxymethyl copolymer of styrene-divinylbenzene to give an ester a mono salt of a diacid was converted into a dibenzyl polymer. ... 

H2/Pd-C, 10 h, 87% yield. A nitrobenzyl carbamate is more readily cleaved by hydrogenolysis than a benzyl carbamate it is more stable to acid-catalyzed hydrolysis than is a benzyl carbamate, and therefore selective cleavage is possible. 

Benzyl carbamates substituted with one or more halogens are much more stable to acidic hydrolysis than are the unsubstituted benzyl carbamates.For example, the 2,4-dichlorobenzyl carbamate is 80 times more stable to acid than is the simple benzyl derivative. Halobenzyl carbamates can also be cleaved by hydrogenolysis with Pd-C. The following halobeni yl carbamates have been found to be useful when increased acid stability is required. 

Isopropylidene and benzylidene" groups have been used to protect simultaneously amide nitrogens and a neighboring hydroxyl. They can be removed by acid hydrolysis or hydrogenolysis (Pd-C, hydrazine, MeOH, 95% yield), respectively. 

In a penicillin synthesis, the carboxyl group was protected as a / -bromophenacyl ester that was cleaved by nucleophilic displacement (PhSK, DMF, 20°, 30 min, 64% yield). Hydrogenolysis of a benzyl ester was difficult (perhaps because of catalyst poisoning by sulfur) basic hydrolysis of methyl or ethyl esters led to attack at the /3-lactam ring. ... 

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