2.4- dichloro-, nucleophilic substitution

Pyrido[2,3-d]pyridazine, 1 -chloro-4-hydrazino-biological activity, 3, 261 Pyrido[2,3-(i]pyridazine, 4-chloro-l-hydrazino-biological activity, 3, 261 Pyrido[2,3-(i]pyridazine, 5,8-dichloro-nucleophilic substitution, 3, 242 Pyrido[2,3-(i]pyridazine, polyhalo- H NMR, 3, 234... 

The selective reaction of anionic 3,6-dichloro-4-sulfanilamidopy-ridazine with excess methanolic methoxide at the 3-position is another indication of the absence of major steric effects in most nucleophilic substitutions, as a result of the direction of nucleophilic attack (cf. Section II, A, 1). The selectivity at the 3-position is an example of the interaction of substituent effects. The sulfonamide anion deactivates both the 3-chloro (ortho direct deactivation) and... 

A paper concerned with the synthesis of pyridazino[3,4-fe]indoles 18 included a study of various conversions of 4,5-dichloro-2-methylpyridazin-3-one 17 including nucleophilic substitutions, Suzuki reactions and electrophilic substitution (nitration), combined with reductive dehalogenation, and usefully summarised previous work <06T121>. 

An 8000-member library of trisamino- and aminooxy-l,3,5-triazines has been prepared by use of highly effective, microwave-assisted nucleophilic substitution of polypropylene (PP) or cellulose membrane-bound monochlorotriazines. The key step relied on the microwave-promoted substitution of the chlorine atom in monochlorotriazines (Scheme 12.7) [35]. Whereas the conventional procedure required relatively harsh conditions such as 80 °C for 5 h or very long reaction times (4 days), all substitution reactions were found to proceed within 6 min, with both amines and solutions of cesium salts of phenols, and use of microwave irradiation in a domestic oven under atmospheric reaction conditions. The reactions were conducted by applying a SPOT-synthesis technique [36] on 18 x 26 cm cellulose membranes leading to a spatially addressed parallel assembly of the desired triazines after cleavage with TFA vapor. This concept was later also extended to other halogenated heterocycles, such as 2,4,6-trichloropyrimidine, 4,6-dichloro-5-nitropyrimidine, and 2,6,8-trichloro-7-methylpurine, and applied to the synthesis of macrocyclic peptidomimetics [37]. 

The synthesis of the polycyclic 5-5-6-5 derivative 81 was realized by nucleophilic substitution of the 5,6-dichloro[ 1,2,5]oxadiazolo[5,4-7]pyrazine 79 with 5-aminotetrazole 80 (Scheme 17). This conversion took place at room temperature and the product 81 was isolated in moderate 36% yield. Many other heterocyclizations with N,N, N,0-, /V,.Y-bidentate nucleophiles gave the corresponding reaction in up to 93% yield <1997CHE1352>. 

In 2,6-disubstituted 1,3-diazaazulenes, such as 14a-c (Scheme 5 62BCJ1188), nucleophilic substitution occurs preferentially at C-6, rather than at C-2. Attack at C-2, if possible at all, demands harsher conditions. In 2,8-dichloro-l-azaazulenes only chlorine atoms at position 8 are susceptible to hydrolysis (61YZ1799 62YZ418 77BCJ1184), and in 2-ethoxy-l,3-diazaazulenes 17 and 18 only the substituents at C-6 are attacked (68CPB1308). The reason is that the electron densities at the seven-membered-ring positions 6 and 8 are lower than at C-2. 

The dichloro compounds 65 derived from l,4-oxathiane-3-carboxanilides 64 yield bicyclic P-lactams on treatment with base through an intramolecular nucleophilic substitution facilitated by the neighbouring sulfur atom <99H(50)713>. 

The reaction of 2,6-dichloro-3-methyl-5-nitropyrimidine 163 with dithizone 164 resulted in the formation of the 6-chloropyrimido[4,5-< ]-l,3,4-thiadiazine 43 shown in Equation (26) which, as discussed in Section 10.20.5.4 (Equation 7), is a useful substrate for subsequent nucleophilic substitution <2005PS2477, 2004HC0335, 1997IJG223>. 

Of relevance to the results just described is the observation93 of the formation of significant proportions of 6,6 -dichloro-6,6 -di-deoxysucrose hexabenzoate and a monochloro-monodeoxy-mono-O-p-tolylsulfonylsucrose hexabenzoate, on treatment of 6,6 -di-0-p-tolylsulfonylsucrose with benzoyl chloride in pyridine at room temperature. These products arise by nucleophilic substitution of the p-tolylsulfonyloxy groups by the chloride ion of pyridinium chloride the isolation of a monochloro-monodeoxysucrose derivative indicated a difference in reactivity of the p-tolylsulfonyloxy groups at C-6 and C-6. ... 

Cyclodipnict(III)azanes may exist as cis or trans isomers, cf. cyclodipho-sph(III)azanes (Section 11.4.1). The solid-state structures of the dichloro derivatives [ClE( i-N Bu)]2 (E = As, Sb ) reveal a cis configuration however, the derivatives [XSb(p-N Bu)]2 (X = N3, O Bu), prepared by nucleophilic substitution reactions, are isolated as trans isomers. In general, there is a trend towards the preferential formation of trans isomers in the solid state for the heavier pnictogens.In solution, however, NMR data indicate the existence of cis and trans isomers for some derivatives. In the case of the bisamido derivative [DippN(H)Sb()i-N Bu)]2, both the cis and trans isomers have been structurally characterised (Figure 11.23). ... 

The 5- and 7-positions of the l,2,4-triazolo[l,5-a]pyrimidine ring are very reactive toward nucleophilic substitution, the 7-position being the more reactive. Thus, the 7-substituted and 5,7-disubstituted triazolo[l,5-a]pyrim-idines 185 and 186 were prepared by the reaction of 5,7-dichloro-l,2,4-triazolo[l,5-a]pyrimidine (184) with amines or hydrazines [81KFZ31 88IJC(B)825 91PHA184] (Scheme 35). 

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