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-c and 1,2,4,5-benzene tetracarboxylic-1,2:4,5-dianhydride produced bis-diazo compounds 10a-c and dimide 11 respectively. All new compounds were tested for their protective activity against DNA damage induced by bleomycin-iron complex. Compound 2 showed the greatest protection against DNA damage, thus diminishing chromogen formation between the damaged DNA and thiobarbituric acid.

This review summarizes the synthetic methods, reactions and biological applications of 2-chloroquinoline-3-carbaldehydes during the period from 1999 to 2011. The reactions are subdivided in groups that cover reactions at the chloro or aldehyde substituent and reactions which involve both groups. Most reaction types have been successfully applied and used in the production of biological active compounds.Keywords: Vilsmeier-Haack reaction, quinolines, aldehydes IntroductionInteresting pharmacological properties have been associated with 2-chloroquinoline-3-carbaldehydes and their derivatives.1,2 These compounds have shown antimicrobial, [1][2][3] antimalarial, 4,5 anti-inflammatory, 6-9 antitumor, 10,11 and anti-parasitic activity. 12 Despite this versatile importance, and in connection to our previous review articles about biologically active heterocyclic systems, 13 2-chloroquinoline-3-carbaldehydes have not been previously reviewed.The main objective of the present survey is to provide the synthesis, reactions, and biological applications of 2-chloroquinoline-3-carbaldehydes from 1999 to the end of 2011 and provide useful and up-to-date data for organic and medicinal chemists. Synthetic MethodsThere have been a number of practically important routes to synthesise of 2-chloroquinoline-3-carbaldehydes, e.g. (i) Vilsmeier-Haack reaction of acetanilides, (ii) oxidation of the corresponding alcohols. Vilsmeier-Haack reaction2-Chloroquinoline-3-carbaldehydes 2 were synthesized from acetanilides 1 via a VilsmeierHaack reaction either by traditional methods [14][15][16][17][18][19][20][21][22][23] or by microwave, 24 or ultrasonic irradiation (Scheme 1). 25Scheme 1 Reviews and Accounts ARKIVOC 2012 (i) 211-276Page 213 © ARKAT-USA, Inc. Oxidation of the corresponding alcohols(2-Chloroquinolin-3-yl)methanol 3 was oxidized to aldehyde 2 using a combination of diethyl diazene-1,2-dicarboxylate (DEAD) and catalytic ZnBr 2 in refluxing toluene (Scheme 2). 26Scheme 2 3 Chemical Reactions Substitution reactionsTreatment of 2-chloroquinoline-3-carbaldehydes 2 with prenyl thiolate or prenyl alcoholate 4 in the presence of sodium hydroxide or potassium t-butoxide, furnished S/O-prenyl aldehydes 5 in 72-84% yield, respectively. S/O-prenyl aldehyde 5, underwent imino Diels-Alder reactions with various substituted anilines in the presence of InCl 3 in acetonitrile resulting in the formation mixture of cis and trans products 7 and 8 in 55-71% yields by intramolecular cycloaddition reaction of the imine 6 generated in situ in the one pot-reaction (Scheme 3). 14 Scheme 3Knoevenagel hetero Diels-Alder reaction of 5 (X = O) with N,N'-dimethylbarbituric acid in water was carried out in the presence of piperidine at room temperature. The intermediate Knoevenagel adduct 9 was not isolated and allowed to cyclise at room temperature after 3 h stirring gave the cis-fused pentacyclic pyrano [2,3-b]quinoline derivatives 10 with high yield (80%) and diastereoselectivity (> 99%) (Scheme 4). 27 Scheme 4Recently, tetrahydrocyclopenta[c]acri...

Review: 183 refs.

Treatment of heterocyclic β‐ketonitriles 1a,b with hydrazine hydrate and phenylhydrazine afforded the hydrazine derivatives 2a‐d which cyclized in PPA into pyrrolo[3,4‐c]pyrazoles 3a‐d. Reaction of 1a,b with cyanoacetohydrazide furnished the cyanoacetyl pyrrolo[3,4‐c]pyrazoles 4a,b. The hydrazine 2c reacted with β‐diketone and β‐ketoesters to afford pyrazolyl‐pyrrolines 5‐7. Also the later hydrazine reacted with some D‐aldoses and aceteophenone to give the corresponding hydrazones 10‐12 and hydrazine carboxamide derivatives 15a,b respectively.