Compounds as Alkylating Agents

As an alkylating agent, cyclophosphamide (Cytoxan) and its active metabolites destroy the rapidly proliferating lymphocytes and, hence, are potent immunosuppressive agents. Those metabolites that are devoid of alkylating properties also lack an immunosuppressive capability. Because the 

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Different amides and anilines have been selectively mono-N-alkylated using catalytic heterogeneous palladium and carbonyl compounds as alkylating agents. The same method has been applied to the synthesis of ethers from alcohols. Reaction parameters have been studied in details and a mechanism is proposed. 

The antitumor activity displayed by the mitosanes and many synthetic aziridines stems from their ability to act as alkylating agents which chemically modify (crosslink) DNA. For this reason, a large number have been screened for antitumor activity, the mechanism of which has been the subject of considerable research effort <75CJC289l). An excellent account of the broad spectrum of biological properties of a multitude of compounds containing the aziridinyl moiety has been published [Pg.93]

Ketones and alcohols are frequently used as alkylating agents Ketones often condense with two molecules of an aromatic compound through an alcohol intermediate [79, 20, 21] T,r,I -Trifluoroacetophenone and aniline afford 1,1 bis(4-ammophenyl) 1 phenyl 2,2,2-trifluoroethane [27] (equation 14)... 

An important application of the potential for bis-alkylation is the use of a dihalide 7 as alkylating agent. This variant allows for the synthesis of cyclic compounds 8 by this route, mainly five- to seven-membered ring compounds have been prepared ... 

Monoanions derived from nitroalkanes are more prone to alkylate on oxygen rather than on carbon in reactions with alkyl halides, as discussed in Section 5.1. Methods to circumvent O-alkylation of nitro compounds are presented in Sections 5.1 and 5.4, in which alkylation of the a.a-dianions of primary nitro compounds and radial reactions are described. Palladium-catalyzed alkylation of nitro compounds offers another useful method for C-alkylation of nitro compounds. Tsuj i and Trost have developed the carbon-carbon bond forming reactions using 7t-allyl Pd complexes. Various nucleophiles such as the anions derived from diethyl malonate or ethyl acetoacetate are employed for this transformation, as shown in Scheme 5.7. This process is now one of the most important tools for synthesis of complex compounds.6811-1 Nitro compounds can participate in palladium-catalyzed alkylation, both as alkylating agents (see Section 7.1.2) and nucleophiles. This section summarizes the C-alkylation of nitro compounds using transition metals. 

One of the crucial factors that must not be ignored is the accuracy, or recovery of the method. It is not sufficient to show sensitivity and selectivity using just standard solutions. Recovery of the analyte from API or drug product (where appropriate) during the method must be sufficient to allow confidence in the method. This is particularly important when reactive compounds such as alkylating agents... 

The behavior of the 2(3//)-furanone 43 and of the 2(5//)-furanone 45 as alkylating agents was studied in an attempt to show the effect of the position of the double bond on the reaction mode. Compound 43 reacts with AICI3 in the presence of benzene, toluene, or anisole to give 4-aryl-2,4-diphenylbut-3-enoic acids (44), which are formed by an intermolecular alkylation reaction. On the other hand, the reaction of 45 under the same... 

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