Salicylaldehydes, 6-substituted, synthesis

A structurally related tetrameric macroheterocycle is compound 13 that is prepared in a one-pot synthesis (yield 64%) from salicylaldehyde and (3-aminophenyl)boronic acid in methanol (Fig. 4). Due to its insolubility it has been characterized only by mass spectrometry. If a substitutent is introduced at the imine function (R = Me, Ph), trimeric structures (14 and 15) are... 

A further example of the utility of the cyclobuta[ >]chroman system in synthesis (see 6.4.1.3) is provided by the conversion of the cyclobutenedione derivatives (19) into substituted xanthones. Compounds (19) are obtained in high yield from salicylaldehydes and squarate esters and their reaction with alkenyl, aryl and heteroaryl li compounds is both facile and high yielding <96JA12473>. 

Although thiosalicylaldehyde 46a (R2 = H) was first synthesized by Friedlander and Lenk (Scheme 23),95 it is an unstable intermediate and should be stored in solution below 0°C. Alternate synthetic procedures utilizing o-chlorobenzaldehyde or salicylaldehyde, as starting materials, are shown in Scheme 24.96 The preferred method for the synthesis of substituted thiosalicylaldehydes 46 is via salicylaldehyde. 

One method of solving the kinetics dilemma is well known in coordination chemistry that is, start with a labile metal ion and render it inert during the course of the synthetic reaction. We have accomplished this in the case of zirconium(IV) by starting with tetrakis(salicylaldehydo)zirconium(IV), which is quite labile, and polymerization with 1,2,4,5-tetraaminobenzene in a Schiff-base condensation reaction in situ (6). The polymeric product contains a "double-headed" quadridentate ligand, which is much more inert to substitution. However, 1,2,4,5-tetraaminobenzene has become very expensive. Therefore, the synthesis of a zirconium polymer with 3,3, 4,4 -tetraaminobiphenyl (commercially 3,3 -diami nobenzidine) with zirconium salicylaldehyde, Zr(sal)4 (7) has been undertaken as shown below ... 

Condensation of salicylaldehyde and its derivatives with a variety of esters of chlo-roacetic acids in the presence of TBAB led to the synthesis of benzo[fo]furans by means of a solid-liquid PTC reaction under the action of microwave irradiation [33], This was a modification of one of the most popular routes to substituted benzo[fo]fu-... 

I2 vapor is extremely corrosive while scandium compounds are moisture-sensitive and very expensive. In addition, these reactions are carried out in an environmentally unfriendly solvent, CH2CI2. We have reported the bismuth triflate-catalyzed synthesis of substituted dihydro-2//-1-benzopyrans by the condensation of substituted salicylaldehydes with 2,2-dimethoxypropane (Scheme 3) [22]. 

There are a number of examples of the synthesis of chromans using o-quinone methides as the heterodiene in a hDA reaction. Both pyrano[3 -c]-benzopyrans and cyclopenta[c][l]benzopyrans result from an intramolecular cycloaddition of a substituted o-quinonemethide generated under mild conditions. In the former case, salicylaldehyde and an unsaturated alcohol yield the rra/is-fused tetrahydropyranobenzopyran (Scheme 10) <99JOC9507>. However, the latter synthesis (Scheme 11) is less selective <99BCJ73>. 

The formylation of phenols with the electron-rich olefin to give imidazolidin-2-yl-phenols is very selective and avoids mixtures of o- and p-isomers which are frequently obtained by methods commonly employed for the synthesis of phenolaldehydes. Para substitution of the cyclic aminal group in the phenol is preferred. If the p-position is blocked or sterically hindered, the reaction proceeds via the ortho- aminals to salicylaldehydes. Incorporation of more than one aldehyde group in the benzene nucleus is often achieved with hydroxy- and aminophenols. 

The template synthesis of mixed nitrogen and oxygen donor macrocycles are mainly based on substituted salicylaldehydes or salicyl-aldehyde-metal complexes (82), e.g.,... 

Nitrobenzofurans (21) have been obtained by the condensation of substituted salicylaldehydes with bromonitromethane,18,19 a versatile reagent useful for the synthesis of various other nitro-heterocycles. The yields however, are variable (5-52%) [Eq. (3)]. 

Another possibility that may lead us to chiral dendrimers lies in the axial chirality of substituted [2.2]p-cyclophanes. The salicylaldehyde-containing cyclophane (80) of this type was presented by Belokon et al.28 In contrast to the experiments mentioned above, we tried to bring elements of chirality into the periphery of the molecule by connecting it through an imine bridge (Section IV.A.). The synthesis of 4-hydroxy [2.2]p-cyclophane (79), via the bromide29 and the final formyla-... 

The solvent-free MW-assisted synthesis of 2-amino-substituted isoflav-3-enes has been reported it ean be aehieved in one pot via the in situ generation of enamines and their subsequent reaetions with salicylaldehydes (Scheme 8.22). This environmentally friendly procedure does not require azeotropic removal of water using large excess of aromatic hydrocarbon solvents for the generation of enamines. 

The Perkin reaction involves the condensation of a carboxylic acid anhydride and an aldehyde in the presence of a weak base, often the sodium or potassium salt of the acid or triethylamine, to give unsaturated carboxylic acids (equation 1). The first example of this reaction was described by Perkin in 1868 and involves a synthesis of coumarin by heating the sodium salt of salicylaldehyde with acetic anhydride (equation 2). The reaction is generally applicable only to aromatic aldehydes and is particularly useful for the preparation of substituted cinnamic acids, as illustrated by equation (3). ... 

Coumarins. - There is interest in the synthesis of 3-substituted coumarins cyclization of substituted salicylaldehydes with cyanoacetamide, followed by treatment with phosphoryl chloride in DMF, has given coumarin-3-carbonitriles. High yields of 3-phenylcoumarins were obtained when ortho-hydroxy-aldehydes or -ketones were treated with phenylacetyl chloride-potassium carbonate.When cyclohexane-1,3-diones (187) were condensed with triethyl orthoformate and either urea and thiourea and the initial product (188) was allowed to condense with nitriles, the 3-carboxamide (189) was obtained in good yield.The antibacterial activity of some sulphones has prompted the synthesis of 3-arylsulphonyl-coumarins by oxidation of sulphides. ... 

The most promising procedure so far was introduced by Jacobsen and coworkers in 1990 [20] and has been reviewed [19]. The method uses chiral, C2-symmetric (salen)Mn complexes, such as shown in Scheme 8.6. Such materials are very easily prepared by the condensation of a chiral diamine with a substituted salicylaldehyde, followed by coordination of the metal. The ready availability of both components and the swift synthesis of the target complexes permits easy access to a great many catalyst variations, which facilitates reaction optimization. The starting Mn(III) complex is subjected to in situ oxidation with the stoichiometric oxidant, usually NaOCl (bleach ). The use of this inexpensive and relatively safe oxidant is another virtue of this system. 

A radical cation is involved in the direct synthesis of chromans by an intramolecular oxidative cyclisation of 3-arylpropanols 32 brought about by a hypervalent iodine(III) reagent <04TL2293> and iodonium species catalyse the intramolecular arylation of alkenes which yields iodo-substituted chromans 33 <04JA3416>. 3-Allenylchroman-4-ols result from a one-pot reaction between salicylaldehydes and 1,4-dibromobut-2-yne in which the intramolecular cyclisation of the intermediate ether is mediated by In metal <04SL45>... 

A one-pot synthesis of isoflav-3-enes 52 was achieved by the reaction of substituted salicylaldehydes 50 with enamines 51 in the presence of a catalytic amount of ammonium acetate under MWI for 2-6 min in 71-88% yields. The reaction of 50 with 51 in benzene under an inert atmosphere produced 52 in 45-55% yields (Scheme 10) (98JOC8038). 

The condensation of salicylaldehyde or its derivatives with various derivatives of ethyl acetate in the presence of piperidine led to the synthesis of coumarins 95 in 55-94% yields under solvent-free conditions using MWI. Similarly, the benzo analogs 96 were prepared in 75-82% yields from 2-hydroxy-1-naphthaldehyde within 3-lOmin (Scheme 19) (98JCR(S)468). However, naphtho[2,l-Z ]pyran-3-ones 96 were prepared in 58-67% yields from the same aldehyde and substituted acetic acids under MWI for 6-8 min but in the presence of DCC and using DMSO as a solvent (Scheme 19) (97JCR(S)178). 

The synthesis of the non-symmetric ligands is based on the Bimolecular Aromatic Mannich reaction. Non-symmetric ligands can be obtained via two different routes. The first route comprises a sequential Mannich reaction on a phenol using two different secondary amines. An alternative route is a Mannich reaction using a secondary amine and a substituted salicylaldehyde followed by either condensation of the aldehyde functionality with a primary amine and subsequent reduction or reductive amination with a secondary amine. 

In addition, the salicylaldehyde derivative 5 has been reacted with 1,2-diaminoethane to divinylsalenes which were afterwards copolymerized with styrene to cross-linked polymers in which Co(II) was introduced [21]. Also divinyl-substituted Mn(II salen complexes have been successfully copolymerized [22,23]. The aim of this interesting research is the synthesis of heterogeneous catalysts for the asymmetric epoxidation of olefins using chiral Mn(III)-salen complexes [24]. 

A dual catalyst system piperidine-iodine was used in the synthesis of 3-substituted coumarins through a one-pot three-component reaction of salicylaldehyde derivatives, P-keto esters, and l-(2-aminophenyl)pyrrole in DMF at room temperature (14T2048) and through a four-component reaction of salicylaldehyde derivatives, P-keto esters, ammonium acetate, and isatoic anhydride in DMF at 60°C (Scheme 55) (14SL1596). 

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