Quinoline reaction with sodium

Acetyl chloride, reaction with sodium formate, 50, 1 with propylene, aluminum chloride, and quinoline to give trans-3-pentene-2-one,... 

As would be expected, the weaker reducing agent, sodium boro-hydride, has received little attention for the reduction of quinolines. The reaction of 2-chloro-3,7-dicarbomethoxy-5,6-benzoquinoline (80) has been reported by Walker to yield 3,7-dicarbomethoxy-5,6-benzo-1,4-dihydroquinoline (81) on reaction with sodium borohydride.96 The success of this reaction may depend upon the electron-withdrawing properties of the carbomethoxy groups. 

Pyridine is an aromatic 6n electron heterocycle, which is isoelectronic with benzene, but electron deficient. Nucleophiles thus add almost invariably to carbon C2 of the imine-like C=N double bond. Perhaps the best known nucleophilic addition is the Chichibabin reaction with sodium amide in liquid ammonia, giving 2-aminopyr-idine. Reactions of the quinoline moiety of cinchona alkaloids can be more complex. Although expected 2 -addition can be achieved easily with organolithium reagents to yield 13 (Scheme 12.6) [9], LiAlH4, for example, has been shown to attack C4 en route to quincorine and quincoridine (Schemes 12.4 and 12.5). C4 selectivity is due to chelation of aluminum by the C9 OH oxygen. 

A useful method for the conversion of quinoline-2- and -4- and isoquinoline-1-chlorides into iodides utilizes the hydrochloride salt of the heterocycle in reaction with sodium iodide in hot acetonitrile presumably it is the A-protonated species that is attacked by the iodide. ... 

Aminolysis of benzopyran 301 with ammonium acetate afforded the quinoline 302, which upon reaction with DMF diethyl acetal (DMFDEA) produced a mixture of the respective N- and O-alkylated derivatives 303 and 304. The latter compound was also prepared by chlorination of 302 with PCI5 followed by reaction with sodium ethoxide. Further treatment of 303 and 304 with DMFDEA in toluene at 180-200 °C resulted in C-alkylation to give 305 and 307, respectively. Column chromatography on silica gel resulted in the formation of 306 and 308, respectively with the recovery of the starting material 303 (91KGS86) (Scheme 57). 

The reactions between 2-alkyl-quinolines and dimethyl acetylenedicarboxy-late have been further investigated, and a mechanism for the formation of the cyclobutapyrroloquinoline (143) from 2-methylquinoline has been proposed. The reaction of the 2-(benzylsulphonyl)quinoline (144) with sodium methoxide unexpectedly gives the 2-methoxylated benzyl ketone (145) via the intermediate formation of a thiophen SS-dioxide. " ort/io-Lithiation of 2-,3-,5-,6-, and 7-fluoroquinolines has been achieved by the reaction at a low temperature (—60°C) with lithium di-isopropylamide in THF, this system obviating the problem of addition reactions.A variety of... 

Treatment of quinoline with cyanogen bromide, the von Braun reaction (17), in methanol with sodium bicarbonate produces a high yield of l-cyano-2-methoxy-l,2-dihydroquinoline [880-95-5] (5) (18). Compound (5) is quantitatively converted to 3-bromoquinoline [5332-24-1], through the intermediate (6) [66438-70-8]. These conversions are accompHshed by sequential treatment with bromine in methanol, sodium carbonate, or concentrated hydrochloric acid in methanol. Similar conditions provide high yields of 3-bromomethylquinoHnes. 

Reduction. Quinoline may be reduced rather selectively, depending on the reaction conditions. Raney nickel at 70—100°C and 6—7 MPa (60—70 atm) results in a 70% yield of 1,2,3,4-tetrahydroquinoline (32). Temperatures of 210—270°C produce only a slightly lower yield of decahydroquinoline [2051-28-7]. Catalytic reduction with platinum oxide in strongly acidic solution at ambient temperature and moderate pressure also gives a 70% yield of 5,6,7,8-tetrahydroquinoline [10500-57-9] (33). Further reduction of this material with sodium—ethanol produces 90% of /ra/ j -decahydroquinoline [767-92-0] (34). Reductions of the quinoline heterocycHc ring accompanied by alkylation have been reported (35). Yields vary widely sodium borohydride—acetic acid gives 17% of l,2,3,4-tetrahydro-l-(trifluoromethyl)quinoline [57928-03-7] and 79% of 1,2,3,4-tetrahydro-l-isopropylquinoline [21863-25-2]. This latter compound is obtained in the presence of acetone the use of cyanoborohydride reduces the pyridine ring without alkylation. 

The use of sodium tribromoacetate as the dibromocarbene precursor has been investigated and found to provide the Ciamician-Dennstedt product in higher yield than the traditional alkoxide/alcohol reaction conditions. Deprotonation of bromoform with sodium ethoxide in ethanol and reaction of the resultant carbene with 6 provides quinoline 9 in 9% yield thermolysis of sodium tribromoacetate in the presence of 6 furnishes 9 in 20% yield (Scheme 8.3.3). 

An interesting use of the Camps quinoline synthesis is in the ring contraction of macrocycles. Treatment of 9 member ring 24 with sodium hydroxide in water furnished quinolin-4-ol 25, while 26 furnishes exclusively quinolin-2-ol 27 under the same reaction conditions (no yield was given for either reaction). The reaction does not work with smaller macrocycles. The authors rationalize the difference in reactivity based upon ground state conformation differences, but do not elaborate. 

Reaction of 2,4,7-trichloroquinoline with sodium methoxide (65°, 30 min) yielded an equal mixture of 2,7-dichloro-4-methoxy- (40%) and 4,7-dichloro-2-methoxy-derivatives (31%). The activating effect of the chloro groups is evident from the inertness of 4-chloro-quinoUne to methoxide ion at 65°. Alteration of the relative reactivity by cationization of the azine ring is again noted here in the acid-catalyzed hydrolysis (dilute HCl, 100°, 1.5 hr) of the trichloro compound to give 72% of the 2-hydroxylation product.Similarly, acid-hydrolysis of the alkoxy group proceeds much more readily in 2-ethoxy-4-chloro- than in 4-ethoxy-2-chloro-quinoline. ... 

The palladium-catalyzed reaction of o-iodoanilides with terminal acetylenic carbinols provides a facile route to the synthesis of quinolines using readily available starting materials (93TL1625). When o-iodoanilide 126 was stirred with acetylenic carbinol 127 in the presence of bis-triphenyl phosphine palladium(ll) chloride in triethylamine at room temperature for 24 h, the substituted alkynol 128 was obtained in 65% yield. On cyclization of 128 with sodium ethoxide in ethanol, 2-substituted quinoline 129 was obtained in excellent yield. 

An interesting reaction of dimsyl anion 88 is the methylation of polyaromatic compounds. Thus naphthalene, anthracene, phenanthrene, acridine, quinoline, isoquinoline and phenanthridine were regiospecifically methylated upon treatment with potassium t-butoxide and DMSO in digyme or with sodium hydride in DMSO123-125. Since ca. 50% of D was found to remain in the monomethyl derivative 93 derived from 9-deuteriophenanthrene 92, the mechanistic route shown in Scheme 2 was suggested125. 

Like the corresponding methylpyridines, 2- and 4-methylquinolines can be deprotonated by a base, such as sodium methoxide, forming resonance-stabilized anions (Scheme 3.9). The latter are useful in synthesis, providing nucleophilic reagents that allow extension of quinoline side chains through reactions with appropriate electrophiles. Activation of the 2-methyl group can also be achieved by the use of acetic anhydride (the same type of process occurs with 2-methylpyridine, Section 2.7.1, Worked Problem 2.3). 

By reacting quinoline first with benzoyl chloride and then with aqueous potassium cyanide, the corresponding Reissert compound is obtained. The reaction is normally carried out in one operation using a two-phase system plus a phase transfer catalyst. The N-benzoy group can then be removed by heating with sodium hydroxide solution, and the reaction is continued to hydrolyse the nitrile function to the acid ... 

Pyridine reacts with sodium hydrazide in the presence of hydrazine to yield 2-hydrazinopyridine in the absence of free hydrazine a hydrazo compound is formed (Scheme 88) (64AG(E)342). A difference between hydrazination and amination is the formation of 1,4-adducts which cannot be rearomatized even on heating. This is reflected in the behaviour of quinoline, which gives only a 0.5% yield of a -hydrazino product, whereas 4-methylquino-line is hydrazinated in 76% yield (64AG(E)342). Acridine behaves differently with sodium hydrazide/hydrazine, 9,10-dihydroacridine is formed almost quantitatively, but reaction in the absence of hydrazine yields 9-aminoacridine (65%). An even higher yield of 9-amino-acridine is obtained when sodium Af.AC-dimethylhydrazide is used (Scheme 89). Good evidence for intermediacy of (151) comes from the isolation of (152) on hydrolysis of (151). 

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