Hydrolysis nucleophilic displacements

The regioselecdvity in tin-mediated monotosyladons of diols has been studied use of dibutyldn oxide or hexamethylenetin oxide in the example shown in Scheme 8 gave the primaiy-62 and secondary tosylate 63 in the rados 3 7 and 20 1, respecdvely. A rqxnt on the leacdons of dimesylated methyl hexopyranosides and glucofuranoses with superoxide (KOj) to give hydroxy products, either by direct hydrolysis, nucleophilic displacement, or via transient epoxides, has been published. Amberlite IRA-410 (Cl form) resin in DMF has been recommended for the selective displacement by chlorine of the primary sulfonyloxy groups in 3,5-disulfonate derivatives of 1,2-0-cyclohexylidene-a-D-xylofuranose. ... 

Pyrimidine, I-alkyl-2-methyltetrahydro-C-thioacylation, 4, 807 Pyrimidine, 4-alkylsulfinyl-nucleophilie displaeement reaetions, 3, 97 Pyrimidine, 6-alkylsulfinyl-nucleophilic displacement reactions, 3, 97 Pyrimidine, 2-alkylsulfonyl-nueleophilie displaeement reactions, 3, 97 Pyrimidine, 4-alkylsulfonyl-nucleophilic displacement reactions, 3, 97 Pyrimidine, 6-alkylsulfonyl-nucleophilie displaeement reactions, 3, 97 Pyrimidine, alkylthio-dealkylation, 3, 95 desulfurization, 3, 95 oxidation, 3, 96 synthesis, 3, 135, 136 Pyrimidine, 2-alkylthio-aminolysis, 3, 96 hydrolysis, 3, 95 Prineipal Synthesis, 3, 136 Pyrimidine, 4-alkylthio-aminolysis, 3, 96 hydrolysis, 3, 95 Pyrimidine, 6-alkylthio-aminolysis, 3, 96 hydrolysis, 3, 95 Pyrimidine, 4-allenyloxy-rearrangement, 3, 93 Pyrimidine, 4-allyloxy-2-phenyl-rearrangement, 3, 93 Pyrimidine, 4-allynyloxy-rearrangement, 3, 93 Pyrimidine, 4-anilino-2,5,6-trifluoro-NMR, 3, 63 Pyrimidine, 2-aryl-pyrroleaeetic aeid from, 4, 152 Pyrimidine, arylazo-synthesis, 3, 131 Pyrimidine, 4-arylazo-reduetion, 3, 88... 

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 formation of ethyl cyano(pentafluorophenyl)acetate illustrates the intermolecular nucleophilic displacement of fluoride ion from an aromatic ring by a stabilized carbanion. The reaction proceeds readily as a result of the activation imparted by the electron-withdrawing fluorine atoms. The selective hydrolysis of a cyano ester to a nitrile has been described. (Pentafluorophenyl)acetonitrile has also been prepared by cyanide displacement on (pentafluorophenyl)methyl halides. However, this direct displacement is always aecompanied by an undesirable side reaetion to yield 15-20% of 2,3-bis(pentafluoro-phenyl)propionitrile. 

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. ... 

The final step is the nucleophilic displacement of the oxyphosphonium group by the carboxylate anion via a SN2-mechanism, yielding ester 3 with inverted configuration at the stereogenic center, and triphenylphosphine oxide. A hydrolysis of the ester 3 will leave the new configuration unchanged, and yield the inverted alcohol 4 ... 

Although the foregoing reactions involve dehalogenation by reduction or elimination, nucleophilic displacement of chloride may also be important. This has been examined with dihalomethanes using HS at concentrations that might be encountered in environments where active anaerobic sulfate reduction is taking place. The rates of reaction with HS exceeded those for hydrolysis and at pH values above 7 in systems that are in equilibrium with elementary sulfur, the rates with polysulfide exceeded those with HS. The principal product from dihalomethanes was the polythio-methylene HS (CH2-S) H (Roberts et al. 1992). 

Nucleophilic displacement including hydroxylation, hydrolysis, and glutathione-mediated reactions... 

The Delepine reaction Involves nucleophilic displacement of active halides by hexamethylenetetramine, followed by hydrolysis of Intermediate quaternary ammonium salt to release the amine. 

The rate of appearance of p-nitrophenolate ion from p-nitrophenyl methylphosphonate (7), an anionic substrate, is moderately accelerated in the presence of cycloheptaamylose (Brass and Bender, 1972). The kinetics and pH dependence of the reaction are consistent with nucleophilic displacement of p-nitrophenolate ion by an alkoxide ion derived from a cycloheptaamylose hydroxyl group to form, presumably, a phosphonylated cycloheptaamylose. At 60.9° and pH 10, the cycloheptaamylose-induced rate acceleration is approximately five. Interestingly, the rate of hydrolysis of m-nitrophenyl methylphosphonate is not affected by cycloheptaamylose. Hence, in contrast to carboxylate esters, the specificity of cycloheptaamylose toward these phosphonate esters is reversed. As noted by Brass and Bender (1972), the low reactivity of the meta-isomer may, in this case, be determined by a disadvantageous location of the center of negative charge of this substrate near the potentially anionic cycloheptaamylose secondary hydroxyl groups. 

The most effective catalyst for the hydrolysis of p-nitrophenyl acetate was reported to be a cycloheptaamylose derivative containing approximately two imidazole groups per cycloheptaamylose molecule (Cramer and Mackensen, 1970). At pH 7.5 and 23°, this material accelerates the rate of release of phenol from p-nitrophenyl acetate by a factor of 300 when compared with the hydrolysis of this substrate in the absence of catalyst. However, when compared with an equivalent concentration of imidazole, which is an effective catalyst for ester hydrolysis at neutral pHs, the rate accelerations imposed by this cycloheptaamylose derivative are only two- to threefold. Cramer and Mackensen attributed this rate enhancement to nucleophilic displacement of phenol from the included ester by a cycloheptaamylose hydroxyl group, assisted internally by the attached imidazole group... 

Nuclear motion, the principle of least, and the theory of stereoelectronic control, 24, 113 Nucleophiles, partitioning of carbocations between addition and deprotonation. 35, 67 Nucleophilic aromatic photosubstitution, 11,225 Nucleophilic catalysis of ester hydrolysis and related reactions, 5,237 Nucleophilic displacement reactions, gas-phase, 21, 197... 

Chloromethylphosphonamide 104 has been alkylated with diastereoselectivities up to >95%. The corresponding azido compounds 106 were obtained by nucleophilic displacement, with partial to full stereospecificity <2000HA528>. This two-step process can lead to aminophosphonic acids after reduction of the azido group and hydrolysis of the chiral appendage (Scheme 7). 

This is why SN2 type of displacements are more facile at the silicon atom than at the carbon. This is particularly so with nucleophiles derived from the more electronegative element. In compounds of the type of R3SiX (where X = leaving group), the nucleophilic displacements and hydrolysis in aqueous media occur rapidly. 

The reaction is believed to begin with the metalation of the substrate via aromatic electrophilic substitution (SEAr) followed by CO insertion and nucleophilic displacement by water or another protic nucleophile such as tri-fluoroacetic acid (TFFA) to give, respectively, the aromatic carboxylic acid or its mixed anhydride derivative, from which the acid is freed by hydrolysis (Scheme 24). 

Reactions.—Alkaline Hydrolysis. The first total resolution of a heterocyclic phosphonium salt containing an asymmetric phosphorus atom (128) has been reported, providing ready access to optically active phospholan derivatives of value for studies of the stereochemistry of nucleophilic displacement at phosphorus.124 Alkaline hydrolysis of (128) proceeds with retention of configuration at phosphorus to form the oxide (129). Stereochemical studies in the phospholan series have also been facilitated by the X-ray investigation125 of an isomer of l-iodomethyl-l-phenyl-3-methylphospholanium iodide, which is shown to have the structure (130). 

In the hope of gaining further experimental insight into the mechanism of nucleophilic displacement at sulfur, the alkaline hydrolysis of chiral dialkoxysulfonium salts was investigated (162). At least two interesting features of these model systems for nucleo-phihc substitution studies should be accentuated both alkoxy groups are of comparable leaving group ability, and there are essentially two identical tetrahedral faces to be attacked by the nucleophile. 

Another example of the effects of ultrasound on a solvolysis reaction can be found in the homogeneous hydrolysis of 2-chloro-2-methylpropane in aqueous alcoholic media (Eq. 3.3). This system has been the subject of numerous kinetic studies since it is one of the classic examples of a unrmolecular nucleophilic displacement reaction (termed... 

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