Primary alkyl ring opening

Finally the aminoquinoline bearing a primary amine at the terminal carbon atom of the side chain is itself an effective antimalarial drug. Ring opening of 2-methyltetrahydrofuran by bromine gives the dibromide, 99. The primary halide is sufficiently less hindered so that reaction with potassium phthalimide affords exclusively the product of displacement of that halogen (100). Alkylation of the aminoquinoline with lOO affords the secondary amine, 101. Removal of the phthalimide group by means of hydrazine yields primaquine (102). ... 

The reaction of a -halocarboxylic acids with sodium nitrite has been used to synthesize ni-tromethane, nitroethane and nitropropane, although the reaction fails for higher nitroalkanes. " A number of other reactions have been reported which use nitrite anion as a nucleophile, including (1) reaction of alkyl halides with potassium nitrite in the presence of 18-crown-6, (2) reaction of alkyl halides with nitrite anion bound to amberlite resins, (3) synthesis of 2-nitroethanol from the acid-catalyzed ring opening of ethylene oxide with sodium nitrite, and (4) reaction of primary alkyl chlorides with sodium nitrite in the presence of sodium iodide. ... 

Synthesis of primidolol (65) can be carried out by a convergent scheme. One branch consists in application of the usual scheme to o-cresol (62) ring opening of the intermediate oxirane with ammonia leads to the primary amine (63). The side chain fragment (64) can be prepared by alkylation of pyrimidone (63) with ethylene dibromide to afford Alkylation of ami noalcohol with halide ... 

The same regiochemistry is observed when nitroimidazole (48-2, 48-3) acts as a nucleophile in unionized form. Thus, the reaction of a compound with benzoyl-aziridine (49-1) in the presence of boron trifluoride probably involves an initial salt formation with an amide attack by the imidazole results in a ring opening and the formation of the alkylated product (49-2) the free primary amine (49-3) is obtained on basic hydrolysis. Acylation of the primary amine with methyl thiochloroformate gives the corresponding thiourethane, carnidazole (49-4) [52]. 

The Novozym 435-catalyzed ring-opening polymerization of e-caprolactone shown in Figure 6.2 was also performed in the presence of methyl or ethyl gluco-pyranosides. In this way, polyesters with low polydispersity index (PDI) values and initiated by alkyl glucopyranosides (acylated at their primary OH) could be prepared [48]. 

Deprotonation reactions if the 2-benzopyrylium cation has an a-alkyl substituent or a group with a mobile hydrogen atom in any other fragment of the molecule. This conversion takes place over a wide range of conditions, and it often accompanies nucleophilic additions. Moreover, the problem of the acid-base and nucleophilic-electrophilic interactions for 2-benzopyrylium salts concerns not only the primary step of their reactions with nucleophiles, but also the ring-open forms, as shown in Section III,C,4. 

Asymmetric synthesis of primary amines by nucleophilic 1,2-addition of alkyl-lithiums to aldehyde SAMP/RAMP hydrazones has been reported in detail.105 On reaction with a range of lithium alkyls, 1,3,5-triazinc has been found to form 1,4-adducts which yield 1,4-dihydrotriazines on hydrolysis 106 in contrast LiNR2 or LiCR3(thf)2 promote 1,3,5-triazine ring-opening reactions. 

Figure 7.2 illustrates the phosphorus pentoxide-mediated dehydration of a primary amide to a nitrile, using the transformation of nicotine amide (A) into nicotine nitrile (B) as an example. The reaction of phosphorus pentoxide at the carboxyl oxygen furnishes the partially ring-opened iminium ion E (simplified as F) via the polycyclic iminium ion C. E is deprotonated to give the mixed anhydride G from imidic acid and phosphoric acid. Imidic acids are characterized by the functional group R-C(=NH)-OH. This anhydride is transformed into the nitrile B by an El elimination via the intermediate nitrilium salt D. Nitrilium salts are iV-pro-tonated or V-alkylated nitriles. 

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