2-chloro nucleophilic substitution, relative

In phenazine At-oxides, substituents show enhanced activation towards nucleophilic substitution relative to the parent unoxidized system. Electron-withdrawing groups potentiate this effect. Halogen atoms at the 1 and 2 positions with respect to the A -oxide function are most easily displaced, e.g. 2,7-dichlorophenazine 5-oxide is transformed to the 7-ethoxy derivative, and l-chloro-2-methylsulfanylphenazine 5-oxide is formed from 1,2-dichlorophenazine 5-oxide. In this reaction, small amounts of 1,2-disubstituted product (2%) and deoxygenat-ed compound (11 %) are formed. 

The relatively poor resonance activation of the 2-Le-3-aza orientation in bicyclics (cf. Section IV, A) is illustrated by nucleophilic substitutions below. Vigorous conditions are required for methoxylation (110°, 17 hr, quantitative yield) of 3-bromocinnoline and for amination (aqueous ammonia, copper sulfate, 20 hr, high yield) of 3-bromo- (at 130°) or of 3-chloro-derivatives (at 165°). 3,4-Dichlorocinnoline gives predominantly 4-substitution in hydra-zination (90% yield, 20°, 4 days in alcohol), amination (70% yield, 150°, 22 hr in alcohol), and hydroxylation (50% yield, 150°, 22 hr, aqueous ammonia). The poorer-leaving phenoxy group in 3-chloro-4-phenoxycinnoline, is displaced with ammonium acetate (160°, few mins, 60% yield). ... 

The synthesis of nitro dyes is relatively simple, a feature which accounts to a certain extent for their low cost. The synthesis, illustrated in Scheme 6.5 for compounds 140 and 141, generally involves a nucleophilic substitution reaction between an aromatic amine and a chloronitroaromatic compound. The synthesis of C. I. Disperse Yellow 14 (140) involves the reaction of aniline with l-chloro-2,4-dinitroaniline while compound 141 is prepared by reacting aniline (2 mol) with compound 144 (1 mol). 

PMR) trends that correspond to relative rates.179 From an examination of the displacement of chloride from l-chloro-5-nitrofuran by potassium iodide in acetic acid or by sodium sulfide in water it was concluded that the substitution need not be a true nucleophilic substitution. Initially there could be a transfer of one electron from the nucleophile to the furan nucleus the resultant radical anion loses chloride to form a furyl radical and product.179... 

The reaction of primary or secondary alcohols with thionyl chloride is a general method for preparing the corresponding chloro compounds. In the first step a chlorosulfne ROSOC) is formed from which S02 is eliminated in a relatively slow step. This decomposition is facilitated by a tertiary amine, e.g. pyridine. The ammonium salt RO-SON+.Cl— formed from the chlorosulftte is subsequently attacked on carbon (in R) by CF. Since nucleophilic substitutions on propargylic carbon proceed more easily than on carbon in saturated compounds, it may be expected that the conversion of propargylic chlorosulfites into the chlorides will take place under relatively mild conditions. 

One important point regarding relative reactivities of Af-unsubstituted and Af-substituted 2-chloroimidazoles with powerful nucleophiles such as alkoxide is that in the former there is competition between proton abstraction from N-1 (which severely hampers any nucleophilic attack at C-2) and the nucleophilic substitution at the 2-position. Thus, chloride is not displaced from 2-chlorobenzimidazole by alkoxide ions, whereas 2-chloro-l-methyl-benzimidazole reacts readily. That steric effects can also be important is evidenced by the lack of reactivity of 2-chloro-l-methylbenzimidazole with t-butoxide, and similar resistance to nucleophilic attack of 2-chloro-l-isopropylbenzimidazole. Alkoxide readily displaces chloride from 2-chloro-1 -isopropenylbenzimidazole, and the N- substituent may be removed subsequently by oxidative cleavage (74CRV279). 

Amino-7-halo-6-nitro derivatives are prepared similarly.Excess piperidine and 2-chloro-7-nitroquinoxaline (11) give 7-nitro-2-piperidinoquinoxaline (12) and large amounts of 6-nitro-2,3-dipiperidinoquinoxaline (13). The mechanism of this unusual nucleophilic substitution of hydrogen is proposed to involve the oxidation of the dipiperidinodihydroquinoxaline intermediate by dissolved oxygen.The relative yields of both products depends on the ratio of the... 

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