Active alkylation

Which of these two opposite stereochemical possibilities operates was determined in experiments with optically active alkyl halides In one such experiment Hughes and Ingold determined that the reaction of 2 bromooctane with hydroxide ion gave 2 octanol having a configuration opposite that of the starting alkyl halide... 

Although this mechanistic picture developed from experiments involving optically active alkyl halides chemists speak even of methyl halides as undergoing nucleophilic substitution with inversion By this they mean that tetrahedral inversion of the bonds to carbon occurs as the reactant proceeds to the product... 

Single-electron transfer from a borate anion particle to the excited polymethine cation generates a dye radical and an aLkylphenylbotanyl radical. The aLkylphenylbotanyl radical fragments to form an active alkyl radical. It is the alkyl radical particles that initiate the polymerization reactions (101). 

Enzymatic acylation reactions offer considerable promise in the synthesis of specific ester derivatives of sucrose. For example, reaction of sucrose with an activated alkyl ester in /V, /V- dim ethyl form am i de in the presence of subtilisin gave 1 -0-butyrylsucrose, which on further treatment with an activated fatty acid ester in acetone in the presence of Hpase C. viscosum produced the 1, 6-diester derivative (71,72). 

In recent years the application of photocycloaddition reactions to organic synthesis has been growing in importance. - The procedure described is illustrative of a general method based on a photocycloaddition reaction for the introduction of an activated alkyl group specifically to the a-carhon atom of an a,/3-unsaturated cyclohexenone. Especially significant is the fact that the method is also applicable to... 

The isosteric relationship of benzene and thiophene has often led medicinal chemists to substitute the sulfur containing heterocycle for benzene drugs in biologically active molecules. That this relationship has some foundation in fact is attested by the observation that the resulting analogs often possess full biologic activity. Alkylation of the diamine, 71 (obtained from aniline and the chloroethylamine), with 2-chloromethylthiophene affords the antihistamine methaphenylene (72) The correspond-... 

Further substitution of benzoic acid leads to a drug with antiemetic activity. Alkylation of the sodium salt of p-hydroxy-benzaldehyde (8) with 2-dimethylaminoethyl chloride affords the so-called basic ether (9). Reductive amination of the aldehyde in the presence of ammonia gives diamine, 10. Acylation of that product with 3,4,5-trimethoxybenzoyl chloride affords trimetho-benzamide (11). ... 

Introduction of an additional double bond into the tricyclic nucleus, on the other hand, is consistent with antidepressant activity. Alkylation of the potassium salt, obtained on treatment of hydrocarbon, 38, with ammonia, with the chlorocarbamate, 39, affords the intermediate, 40. Basic hydrolysis leads to protrip-tylene (41). ... 

Attachment of a basic amino group to the side chain leads to a compound with antiparkinsonian activity. Alkylation of the carbanion from phenylacetonitrile with 2-chlorotriethylamine affords the product, 36. Conjugate addition of the anion from this to acrylonitrile gives the glutarodinitrile (37). Partial hydrolysis of this in a mixture of sulfuric and acetic acid leads to phenglutarimide (38). ... 

Inclusion of iodine in the thiouracyl molecule similarly proves compatible with antithyroid activity. Alkylation of thiouracyl proper (85) with benzyl chloride affords the thioether,... 

The anxiolytic agent buspirone (131) is notable for the fact that it does not interact with the receptor for the benzodiazepines. This difference in biochemical pharmacology is reflected in the fact that buspirone (131) seems to be devoid of some of the characteristic benzodiazepine side effects. The spiran function is apparently not required for anxiolytic activity. Alkylation of 3,3-dimethylglutarimide with dichlorobutane in the presence of strong base yields the intermedi-... 

Ethylene is an active alkylating agent. It can be used to alkylate aromatic compounds using Friedel-Crafts type catalysts. Commercially,... 

Ortho- and Para-Directing Activators Alkyl Groups... 

Hydrostannation of chiral menthyl esters of substituted acrylic acids proceeds stereoselectiveiy, providing a route to optically active alkyl-... 

The method is quite useful for particularly active alkyl halides such as allylic, benzylic, and propargylic halides, and for a-halo ethers and esters, but is not very serviceable for ordinary primary and secondary halides. Tertiary halides do not give the reaction at all since, with respect to the halide, this is nucleophilic substitution and elimination predominates. The reaction can also be applied to activated aryl halides (such as 2,4-dinitrochlorobenzene see Chapter 13), to epoxides, " and to activated alkenes such as acrylonitrile. The latter is a Michael type reaction (p. 976) with respect to the alkene. 

Dihydro-2iy-thiopyrans, derived from dimethylbuta-1,3-dienes, Na2S203-5H20 and various activated alkyl h des, ring contract on treatment with a strong base leading to vinyl cyclopropanes and cyclopentenes <96JOC4725>. 

It is possible to replace one isocyanide by triphenylphosphine, or to replace two isocyanides with diphos, giving phosphine analogues of these complexes. These species are not available from analogous reactions of phosphine-palladium(O) and (II) complexes. Reactions with active alkyl halides proceeds with oxidation nitric oxide also oxidizes these complexes. [Eqs. (31, 32)]. 

The reaction of alkyllithium reagents with diaryl or alkyl aryl sulphoxides results in a displacement of the aromatic group by the alkyl group from the alkyllithium (equation 369) . Johnson and coworkers ° were the first to apply this reaction for the synthesis of optically active alkyl methyl sulphoxides. Later on. Durst and coworkers found that the aromatic group which can best carry a negative charge is the most readily displaced, and that the lowest yields of displacement were observed when methyllithium was used as a nucleophilic reagent. The results are summarized in Table 28. 

Oxime carbamates have high polarity and solubility in water and are relatively chemically and thermally unstable. They are relatively stable in weakly acidic to neutral media (pH 4-6) but unstable in strongly acidic and basic media. Rapid hydrolysis occurs in strongly basic aqueous solutions (pH > 9) to form the parent oxime/alcohol and methylamine, which is enhanced at elevated temperature. Additionally, oxime carbamates are, generally, stable in most organic solvents and readily soluble in acetone, methanol, acetonitrile, and ethyl acetate, with the exception of aliphatic hydrocarbons. Furthermore, most oxime carbamates contain an active -alkyl (methyl) moiety that can be easily oxidized to form the corresponding sulfoxide or sulfone metabolites. 

A disubstituted butyramide, disopyramide, distantly related to some acyclic narcotics interestingly shows good antiarrhythmic activity. Alkylation of the anion from phenylacetonitrile with 2-bromopyridine yields 99. Alkylation of the anion from the latter with N,N-diisopropyl-2-chloroethyl-amine leads to the amine 100. Hydration of the... 

A possible mechanism proposed by Kuivila was based on the fact that retardation by hydroquinone has been observed 72) (see however 73)) and that optically active alkyl halides RX have been transformed into racemic RD 72). 

In the case of 67g which has a chiral alkyl group, optically pure 67g was included at the complexation process with 2a, and (—)-67g of 100% ee [[a]D —66.8° (c 0.22, CHClj)] was obtained. Irradiation of the 1 1 inclusion complex of 2a and (—)-67g of 100% ee gave 69g of 100% ee which has three optically pure chiral centers 40). This is not the result of a chiral induction by the optically active alkyl group, since irradiation of 67g of 100% ee in benzene gave 69g of only 12% de (diastereomeric excess). 

Among the most active alkylating agents used against cancer are nitrosoureas and aziridines. 

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