Chlorinations quinoline

The photopolymerization of methyl methacrylate using a quinoline-chlorine charge-transfer complex has been investigated. Bulk polymerization was found to follow normal free-radical kinetics, whereas in solution variable monomer exponents were observed depending on the nature of the solvent. The kinetic nonideality in solution was attributed to retardation and initiator termination via degradative chain-transfer involving solvent-modified initiating complexes and chain radicals. 

This coupling works best when the halogen at the 7-position is bromine rather than chlorine or fluorine. This represents the first appUcation of this coupling reaction to the intact quinoline nucleus and thus represents an important advance in quinolone chemistry. 

Reaction of 1-ethoxycyclohexene (34) with dichlorocarbene gives 1-ethoxy-7,7-dichloronorcarane (35) in 87 % yield. Rearrangement of dichlorocyclo-propane (35) in hot quinoline results in loss of both chlorine atoms to give l-ethoxycyclohepta-l,3,5-triene (37) in 37% yield. Hydrolysis of enol ether (37) with a very small quantity of hydrochloric acid in methanol produces cyclohepta-3,5-dienone (38) in 91 % yield. ... 

Because of the similarity of the substituent effects in s-triazine and quinoline derivatives, it seems probable that in the former sequence hydrogen falls between the chlorine atom and the methoxy group. 

The usual order found with halogenonitrobenzenes is F > Cl Br I, the order of Cl and Br being variable, just as in heteroaromatic reactivity. The position of fluorine is of interest the available data indicate that it is usually the same as for nitrobenzene derivatives. Thus, in acid hydrolysis the order F > Cl for 2-halogeno-quinolines can be deduced beyond doubt since the fluoro derivative appears to react in the non-protonated form and the chloro derivative to resist hydrolytic attack even in the protonated form under appropriate conditions (Section II,D, l,d). Furthermore, in the benzo-thiazole ring, fluorine is displaced by the CHgO reagent at a rate 10 times that for chlorine. ... 

The first thiazoloquinolines, namely angularly annelated 2-methyl-thiazolo [4,5-/]quinoline 19 and linearly annelated 2-methyl-thiazolo[4,5-g]quinoline 20, were prepared in 1937 in poor yield using the Skraup reaction and exploiting the blockage of position 4 in 5-amino-2-methylbenzothiazole with a chlorine atom, as shown in Scheme 10 (37LA60). 

Acetylation of 6-amino-7-chloro-5,8-quinolinedione and subsequent replacement of the chlorine atom to a -SH and then a -SMe group gave the final linear 2-methyl-4,9-dioxo-4,9-dihydrothiazolo[4,5-g]quinoline 40 (59LA108). 

When reacted with dimethyl acetylenedicarboxylate, the amines produced ben-zotriazolylaminobutendioates 188 accompanied by A-benzotriazolyl substituted 2-pyridones only in the case of 5-amino-2-methyl-2//-benzotriazole, the triazolo-9,10-dihydrobenzo[d]azepine and an unusual cyclization product, triazolo-2-oxindole (convertible into 2-methyltriazolo[4,5-/]carbostyril-9-carboxylate) were formed. The quinolones 189 were aromatized to chloroesters 190 these in turn were hydrolyzed to chloroacids 191 and decarboxylated to 9-chlorotriazolo[4, 5-/]quinolines 192 (Scheme 58) (93H259). The chlorine atom could be replaced with 17 various secondary amines to give the corresponding 9-aminoalkyl(aryl) derivatives 193, some of which exhibit both cell selectivity and tumor growth inhibition activity at concentrations between 10 and 10 " M (95FA47). 

Chlorination. Electrophilic chlorination of quinoline (66) in neutral medium showed a positional selectivity order of 3 > 6 > 8. The 5- and 8-positions should be sterically hindered to some extent. Hammett cr+ values predict an order for electrophilic substitution of 5 > 8 = 6 > 3. Treatment with chlorine at 160-190°C converted quinoline into a mixture of 3-chloro-, 3,4-dichloro-, 3,4,6- and 3,4,8-trichloro-, 3,4,6,8-tetrachloro-, and 3,4,6,7,8-pentachloro-quinolines. At lower temperatures ( 100°C) the major product was 3-chloroquinoline, albeit in low yield. The 4-substituted species may have arisen from an addition-elimination or radical process (70JHC171). 

Polychlorination processes have included exhaustive chlorination in the presence of antimony pentachloride, which destroyed the molecule (1882JCS412). Chlorine in carbon tetrachloride gave 3,4,6,8-tetrachlo-roquinoline chlorine dissolved in thionyl chloride gave the 4,5,7,8-isomer, whereas thionyl chloride alone produced a mixture of 3,4,5,6,7,8-hexachloro- (57%) and 3,4,6,8-tetrachloro- (37%) quinolines (73YZ73 74S356, 74URP432143). 

In the Meisenheimer reaction of quinoline 1-oxides chlorine atoms usually enter the 2-and 4-positions, but not exclusively. 2,4-Dibromoquinoline 1-oxide was 6-chlorinated (57MI1), and the 5- and 6-nitroquinoline 1-oxides were 3-chlorinated to some extent (44JOC302). This reaction with phosphoryl chloride-phosphorus pentachloride has also been used in the preparation of chlorinated phenanthrolines (88YZ1148). 

Sometimes lateral chlorination can occur on a methyl or alkylthio substituent, especially when phosphorus pentachloride or its mixtures with phosphoryl chloride are used (91JHC1549). Reactions of 2-methyl-4(I//)-quinoline (67) exemplify this behavior (81CPB1069) (Scheme 31) 2-chloro-3- and -4-methyquinolines are also subject to methyl chlorinations by similar reagents (91JHC1549). Sulfuryl chloride and NCS are also likely to induce a proportion of lateral chlorination (83KFZ1055 86S835). 

Variable results have been reported for the halogenation of thieno[2,3-6]quinoline (123). Initial attack was mainly at the 3-position, but it was difficult to avoid the formation of 2,3-dihalogenated products, even when only 1 mol of halogen was used (predictions are for 2- and 3-substitution [77ZN(B)1331]). Bromine buffered in chloroform gave the 3-monobromo derivative, but analogous chlorination gave a mixture that included some... 

Reduction of the heterocyclic ring and incorporation of a nitro function affords a compound with antischistosomal activity, oxamniquine (60). Its synthesis begins with chlorination of 2,6-dimethyl-quinoline, which proceeds regiospecifically on the methyl group adjacent to the ring nitrogen (56). 

Quinoline Salicylic acid Silicon Dinitrogen tetroxide, linseed oil, maleic anhydride, thionyl chloride Iodine, iron salts, lead acetate Alkali carbonates, calcium, chlorine, cobalt(II) fluoride, manganese trifluoride, oxidants, silver fluoride, sodium-potassium alloy... 

These protocols were applied to pyridines, quinolines, and naphthyridines. They are compatible with other functional groups, for instance, acid derivatives. Dehydration can be effected by a chemical process (chlorinating agents), or simply by heating. Method A3 generally required harsh conditions, since in most examples no base was added for HC1 consumption, therefore lowering the reactivity of the pyridine nitrogen, present as its hydrochloride salt. 

Two papers concerning the reduction of chlorinated quinolines have been published [116, 117]. Electrolysis of 3,4,5,6-tetrachloro-2-picolinic acid at a silver... 

Chloroquinolines are reactive groupings due to electron-deficient carbon to which the halogen is attached. This carbon is electron-deficient due to the combined electron-withdrawing effects of the chlorine substituent and the quinoline nitrogen. The electrophilic carbon is thus able to react readily with nucleophiles present in the body. The impact of this grouping on a molecule is illustrated by 6-chloro-4-oxo-10-propyl-4H-pyrano[3,2-g]quinoline-2,8-dicarboxylate (Figure 8.28). In contrast to many related compounds (chromone-carboxylates) lacking the chloroquinoline, 6-chloro-4-oxo-10-propyl-4H-pyrano[3,2-g]quinoline-2,8-dicarboxylate is excreted as a... 

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