Dihydroquinoline derivatives

This is an example of the Doebner synthesis of quinoline-4-carboxylic acids (cinchoninic acids) the reaction consists in the condensation of an aromatic amine with pyruvic acid and an aldehj de. The mechanism is probably similar to that given for the Doebner-Miller sj nthesis of quinaldiiie (Section V,2), involving the intermediate formation of a dihydroquinoline derivative, which is subsequently dehydrogenated by the Schiff s base derived from the aromatic amine and aldehyde. 

Interestingly, a reverse isomerization (1,4-dihydro 1,2-dihydro) was observed when a 1,4-dihydroquinoline derivative was obtained by the reaction of lithiated l-ethoxycarbonyl-l,2-dihydroquinoline-2-phosphonate 36 with benzyl bromide... 

Dihydroquinoline derivatives offer moderate antioxidant and flex cracking activity with excellent metal poison protection. 

The a-methoxylated products are highly useful building blocks for the construction of a carbon-carbon bond a to the trifluoromethyl and diflu-oromethyl groups, which is difficult to obtain by other methods, as shown in Scheme 6.15. Thus, a-tri and a-difluoromethylated a-aminonitriles, which are precursors to the corresponding fluorinated a-amino acids, have been prepared in good yields, and flourinated homoallyanilines have been also successfully prepared [44]. in addition, tri- and difluoromethylated tetra- and dihydroquinoline derivatives can be prepared by cationic polar cycloaddition in high yields [45]. 

Various intermediates (uracil, thymine, pyrazoline, /S-carboline, and dihydroquinoline derivatives) have been prepared in this way [142-147]. 

Dihydroquinoline derivatives are known to exhibit a wide spectrum of biological activities such as antimalarial, antibacterial, and anti-inflammatory behavior [69-71]. In addition, substrates possessing the dihydroquinoline moiety... 

Dihydroquinoline derivatives are synthesized in intramolecular hetero Diels-Alder reaction from -(alkynylsiloxy)aldimines in triflic acid702 [Eq. (5.255)]. 

The indolenine 17 and the 3,4-dihydroquinoline derivative 18 have been prepared and comparative studies made. In the case of compound 18, there is hydrogen bonding between the hydroxyl and the carbonyl groups but this does not occur in compound 17 <1998J(P1)1193, 1998J(P 1)1203>. 

The ever-present problem as to whether nucleophilic addition has occurred a or y to the heteroatom in a six-atom aromatic ring is best solved via PMR spectral analysis, considering both chemical shift and coupling constant data. In particular, the 1,2- and 1,4-dihydroquinoline derivatives, 3 and 4, which are potential methoxide adducts from quinolinium cations are readily... 

Aminoalkyl-3, 4-dihydroquinoline derivatives, (VII), prepared by Jaroch (8) were effective as nitric oxide synthase inhibitors and used as anti-inflammatory agents. 

Estrogen antagonists consisting of 4-fluoroalkyl-2H-benzopyrans, (IV), and 3,4-dihydroquinoline derivatives were prepared by Kuenzer (5) and Wallace (6), respectively, for use as antiuterus growth agents. 

Amuilations of pyridinium- and quinolinium-salts however have not been reported so far. From the addition reactions of C-nucIeophiles like Grignard, organozinc and organotin reagents to pyridinium- and quinolinium-salts have been reported to be valuable methods for the construction of substituted dihydropyridine [4a-4d] and dihydroquinoline-derivatives [4d-4e] results of our studies in the field of benzothiopyrylium-salts [5] we concluded that the sequential intermolecular 1,2-addition/intramolecular 1,4-addition of 4-silyloxyquinolinium-salts 1 with 2-silyloxy-l,3-butadienes 2 might be useful for the diastereoselective preparation of annulated quinolones 3. 

Heterocycles can also be prepared by cyclization reactions under Barbier conditions. An unexpected dihydroquinoline derivative is isolated from the reaction of a haloalkylaniline with an aldehyde [Eq. (25) 61]. 

Reissert reaction. Formation of l-acyl-2-cya-no-l,2-dihydroquinoline derivatives (Reissert compounds) by reaction of acid chlorides with quinoline and potassium cyanide hydrolysis of these compounds yields aldehydes and quinaldic acid. 

A novel one-pot domino process was developed to synthesize substituted 1,2-dihydroquinoline derivatives 102 with high regioselectivity using a silver catalyst <05OL2675>. Scheme 29 shows the proposed pathway, which starts with the hydroamination of alkyne 103 and aniline 104. This is followed by C-H addition with another alkyne 103 and C-H addition cyclization to give intermediate 105. The final step is another C-H addition with alkyne 103 yielding the desired product 102. The scope and mechanism of this one-pot process is still under investigation. 

Cyclised chloroacetanilides, such as 2,3-dihydroindole and 1,2-dihydroquinoline derivatives, are completely inactive. 

An organobase including guanidine is often used as co-catalyst (or base) in palladium coupling reactions [84]. The 2-methylenepropane-l,3-diol diacetate reacts with 7,8-dihydroquinoline derivative in the presence of palladium acetate [Pd(OAc)2], TMG (1) and triphenylphosphine (PPhs) to give the methylene bridged compound in 92% yield, which can be converted to a diamino analogue of huperzine A, an inhibitor of acetylcholine esterase [84a](Scheme 4.32). 

On the other hand, bit-electrocyclization reaction of enolizable vinyl quinine mono- and di-imide substrates provides a high-yielding process to access dihydroquinolines derivatives." ... 

This reaction was initially reported by Reissert in 1905 and extended by Grosheintz and Fischer in 1941 It is the synthesis of aldehyde involving the formation of 1 -acyl-2-cyano-1,2-dihydroquinoline derivatives from acyl chlorides, quinoline, and potassium cyanide and the subsequent hydrolysis of said dihydroquinoline derivatives under acidic conditions to produce quinaldic acid and aldehydes. The original procedure occurs smoothly for aroyl or cinnamoyl chloride in liquid SO2 but not in benzonitrile, ether, dioxane, acetone, or CHCb. However, the modification from Grosheintz and Fischer using hydrogen cyanide and 2 eq. quinoline in absolute benzene is also adaptable for aliphatic acid chlorides. This is one of the methods that converts acyl chlorides into aldehydes and is found to be superior to the normal Rosenmund Reduction. For example, o-nitrobenzoyl chloride has been converted into o-nitrobenzaldehyde in 60% yield by the current reaction, whereas the Rosenmund Reduction is not suitable for such conversion. Therefore, this reaction is referred to as the Grosheintz-Fischer-Reissert aldehyde synthesis or Reissert aldehyde synthesis. ... 

Dihydroquinoline derivative p-phenylene-diamine derivative Sulfonamide accelerator Zinc oxide Sulfur... 

The SnCl2-reduction system has also been apphed in the reduetion of S 2 nucleophilic substitution products 583, alfording more functional quinolines, 4-(substituted vinyl)-quinolines 584, in moderate yields, with several exclusions of the formation of dihydroquinoline derivative 585 (Scheme 4.174). However, using compounds 586 as substrates without a ketone moiety, the ester group can also participate in the intramolecular cychzation, but the subsequent dehydrogenation does not occur and, therefore, tetrahydroquinolin-2-ones 587 were obtained in 51-62% yields (frans form only). From this study, the preference of the activated carbonyl group COR for cychzation has the order R = Me > Ph > O-alkyl. 

A series of poly-functionaUzed dihydroquinoline derivatives 91 (26 examples) were synthesized by a three-component domino reaction of aldehydes 69 (1 equiv) and 1-arylethylidenemalononitriles 90 (2 equiv) in ethylene glycol using NaOH as a base promoter under microwave irradiation within 8-20min (Scheme 12.34) [55]. In this process, the concomitant formation of two new cycles was readily achieved. 

Scheme 12.34 Three-component synthesis of dihydroquinoline derivatives.

Ohno et al. (1985) attempted to examine the hypothesis by means of the redox interconversion between a 1,4-dihydroquinoline derivative and the corresponding quinolinium cation. It was found that the 2,4-dimethyl-3-carbamoylquinoline derivative with a secondary amine... 

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