Potential Alkylating Agents

These reactions introduce a new substituent a to the carbonyl group and constitute an important method for this transformation. In the retrosynthetic sense, the disconnection is between the a-carbon and a potential alkylating agent. 

The sulphur atom of alkyl(thioalkyl)phosphonium salts forms a new onium centre on triethyloxonium tetrafluoroborate alkylation in nitromethane848,849 (thiocetals see above). Phosphonium ketene acetals are potential alkylating agents for phosphorus dithioic acid anions in non-aqueous, aprotic and aqueous media and in phase-transfer catalysis conditions296 (reaction 263). It is suggested that onium ketene acetals react by nucleophilic attack on the methyl group of the acetal. 

Halmos, T., et al. 1997. Synthesis of O-methylsulfonyl derivatives of D-glucose as potential alkylating agents for targeted drug delivery to the brain. Evaluation of their interaction with the human erythrocyte GLUT1 hexose transporter. Carbohydr Res 299 15. 

When phosphine is formed, it decomposes to several lesser known intermediates such as P2H4, a potential alkylating agent, finally forming HjPC (phosphoric acid), salts, and water. In... 

Reactive alkyl radicals and nonradical products generated by lipid peroxidation chain reactions are potential alkylating agents. Reactive methyl radicals can also arise by the irradiation or oxidation of methyl compounds such as methylhydrazine (33). 

In their synthesis of Baylis-Hillman adducts as potential alkylating agents, Lawrence et al. attempted the oxidation of diol 56 under standard Swem conditions, with unexpected results.41 Instead of the required a-methylene-P-keto ester, the formation of an allylic chloride 57 was detected. The substitution is thought to take place via a conjugate-elimination process through enolate 59 involving the ester group, which is clearly implicated since the Swem oxidation of related alcohols such as 60 proceeds as expected. 

Olefin O) and alcohols are other potential alkylating agents. Studies have been done on the gas phase methylatlon and ethylation of benzene over the polymeric perfluorlnated sulfonic acid. At 185°C, methylatlon of benzene with methyl alcohol gives toluene In only 4.1% (50). On the other hand, ethylation of benzene at 175°C gave ethylbenzene In 88% selectivity with 100% conversion of ethylene at a weight hourly space velocity, WHSV, of 8.0 ( ). 

The choice of potential alkylating agents is quite wide. Complexes of alkyl... 

Figure 7 Proposed mechanism for formation of free radicals and porential alkylating agents by anchracyclines in the presence of redox enzymes (flavc oteins IF]), which reduce die anihracy-dine in a one-electron step to the semiquinone. The Cj-quinone methide, a potential alkylating agent, is a tautomer of the deoxyaglycone produced from this reaction. (Redrawn and modified from Ref. 206.)...

Handling, Storage, and Precautions potential alkylating agent use in a fume hood. 

The choice of potential alkylating agents is quite wide. Complexes of alkyl halides with Lewis acids, especially AICI3, protonated alcohols, and protonated alkenes can all provide carbonium ions or other reactive alkylating agents ... 

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 ... 

Amine bases in nucleic acids can react with alkylating agents in typical Sjsj2 reactions. Look at the following electrostatic potential maps, and tell which is the better nucleophile, guanine or adenine. The reactive positions in each are indicated. 

There is much evidence to suggest that carcinogenic N-nitros-amines are metabolised by an oxidative process to produce an alkylating agent (J f2) One potential metabolite is therefore the corresponding N-nitrosamide resulting from 2-electron oxidation at the oc-carbon atom, and, indeed, such compounds appear to induce tumours at the site of application without metabolic activation (3) It follows that the chemical properties of N-nitrosamides are relevant to the etiology of cancer ... 

SCHEME 7.2 Examples of potential bioreductive alkylating agents reported by Lin et al.17. 

Moore, H. W. Czemiak, R. Naturally occurring quinones as potential bioreductive alkylating agents. Med. Res. Rev. 1981, 1, 249-280. 

Lin, A. J. Shansky, C. W. Sartorelli, A. C. Potential bioreductive alkylating agents. 3. Synthesis and antineoplastic activity of acetoxymethyl and corresponding ethyl carbamate derivatives of benzoquinones. J. Med. Chem. 1974, 17, 558-561. 

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