Methoxybenzaldehyde derivatives

Mercaptoethanol reagent 380 Mercury cations 144,311 Mercury lamps 20, 22 ff emission lines 23, 24 -, high pressure 22 ff -, technical data 23 Mercury(I) nitrate reagent 337 Mercury(II) salt reagent 340 Mesaconic acid 61 Mesoporphyrin 101, 102 Metal cations 310—312,398 Metal complexes 248, 398 Methanol, dipole moment 97 Methine dyestuffs 360 4-Methoxyaniline see Anisidine 4-Methoxybenzaldehyde see Anisaldehyde Methoxybenzaldehyde derivatives 72 Methoxycinnamic acid 277... 

In the lactonic alkaloid molecule one can find three synthons pelle-tierine, a 4-methoxybenzaldehyde derivative, and p-hydroxycinnamic acid. In all published syntheses of lactonic Lythraceae alkaloids they are the building blocks. 

A first set of experiments, the study of the protonation of enolates obtained from benzaldehyde Schiff bases and Lithium Diisopropylamide, showed that the asymmetric induction was not significantly affected by the size of the R moiety of the amino acid (R = Me, Et, i-Pr, n-Bu, f-Bu, Ph ee = 44-56%). The two main factors improving the enantioselection were the Ar substituent of the Schiff base and the lithium amide used for the deprotonation. The following results (Table 1) indicate clearly that the enantioselectivity increases with the electron-donating power of substituents para to the Schiff base (eq 3), leading to 70% ee with the Schiff base of p-methoxybenzaldehyde derived from phenylglycine. ... 

The latter combination is very selective. Thus, even with methoxybenzaldehyde derivatives only small quantities of the Dakin product (see Dakin reactions, under Section 9.2.2.2) are formed [130]. This reaction has also been performed in a triphasic system using a perfluorinated selenium catalyst [132]. 

Anhalonine and Lophophorine. Spath and Gangl showed that each of these alkaloids contains a methylenedioxy group and that the quarternary iodide prepared from dZ-anhalonine is identical with lophophorine methiodide so that lophophorine must be N-methylanhalonine. Anhalonine was synthesised from 3 4-methylenedioxy-5-methoxybenzaldehyde by condensation with nitromethane, reduction of the product to the corresponding -ethylamine, the acetyl derivative (VII) of which, on treatment with phosphoric anhydride, condensed to 6-methoxy-7 8-methylenedioxy-l-methyl-3 4-dihydrofsoquinoline, m.p. 60-2°. This, on reduction, furnished the corresponding tetrahydrofsoquinoline, which proved to be anhalonine (VIII), and on conversion to the quaternary methiodide the latter was found to be lophophorine (IX) methiodide. The possible alternative, 8-methoxy-6 7-methylenedioxy-l 2-dimethyl-l 2 3 4-tetrahydrofsoquinoline, was prepared by Freund s method and the methiodide shown not to be identical with lophophorine methiodide. 

The adduct derived from (a-benzyloxyacetaldehyde (97 % ee) is an important intermediate en route to compactin and mevinolin [76]. In contrast, modest enantioselectivity was attained when the cycloadditions were catalyzed by a chiral BINOL-ytterbium-derived catalyst [77]. Pyridines were used as additives, and the best enantioselection (93% ee) was attained only in the case of p-methoxybenzaldehyde using 2,6-lutidine. 

The electrosynthesis of 4-methoxybenzaldehyde (anisaldehyde) from 4-methoxy-toluene by means of direct anodic oxidation is performed on an industrial scale [69]. Via an intermediate methyl ether derivative, the corresponding diacetal is obtained, which can be hydrolyzed to the target product. The different types of products - ether, diacetal, aldehyde - correspond to three distinct single oxidation steps. 

The aprotic diazotisation of tetrachloroanthranilic acid in the presence of benzaldehyde or />-methoxybenzaldehyde results in the formation of the 1,3-benzodioxan derivatives (131, R = Ph) and (131, R = >-C gH 4-OMe) respectively 155). The absence of products analogous to (129) in these reactions suggests that the formation of the compounds (131) do involve tetrachlorobenzyne. Some indication of the mechanism of these reactions was given by the fact that no analogous adduct has been isolated in attempted reactions of tetrachlorobenzyne with p-nitrobenzaldehyde. However, in the presence of acetone we obtained a low yield of the compound (132). 

The synthesis of 3-H-oxazol-2-ones was described by Nam et al. [69]. The substituted benzoin 89 was formed from the coupling of 3,4,5-trimethoxy-benzaldehyde 18 with 3-nitro-4-methoxybenzaldehyde, Scheme 22. Reaction with PMB-isocyanate and subsequent cyclization gave the protected oxazolone derivative 90. The PMB group was removed by reflux in TFA and reduction of the nitro-group was performed using Zn to give the combretoxazolone-aniline 91. 

The reaction of thiocarboxamidocinnamonitrile derivative 389 with 2-hydrazinothiazoM(5//)-one in absolute ethanol containing a catalytic amount of triethylamine affords 5-oxopyrano[2,3-z/]thiazolc 390. It has been found that the reaction of compound 390 with chloroacetic acid gives the 5-oxopyrano[ 2,3-z/]thiazole 391. The structure of this compound has been confirmed by its reaction with 4-methoxybenzaldehyde in acetic acid to give the 6-oxopyr-ano[2, 3 4,5]thiazolo[2,3-c][l,2,4]triazole derivative 84 (Scheme 44) <1999ZN(B)1589>. 

Qualitative spot tests for aldehydes, in the presence of ketones, are generally only reliable for water-soluble compounds. This problem can be overcome by the use of 4-amino-3-hydrazino-5-mercapto-1,2,4-triazole (Purpald , Aldrich Chemical Company) in the presence of Aliquat (Scheme 5.27). Under aerial oxidation, the initially formed colourless cyclic adduct changes colour through red to purple. The colourless cyclic aminal can also be formed by ketones, but only the adducts derived from the aldehydes are oxidized to the purple bicyclic aromatic system [28]. Weakly electrophilic aldehydes, e.g., 4-methoxybenzaldehyde, reacts slowly, but will give the positive coloration upon gentle heating to ca. 70°C for one or two minutes. 

The benzenesulfonyl substituent has also been used in conjunction with the lithiation of an azaindole derivative (86FRP2574406 89FRP26274931), and thus 1-benzenesulfonyl-1//-pyrrolo[3,2-c ]pyridine was able to be successfully lithiated and alkylated with p-methoxybenzaldehyde, although reaction with more hindered ketones could not be achieved (Scheme 19)[91JCS(P1)3I73]. 

Aryl alkyl amines gave hydroxylamine 0-arylsulfonates when reacted with arylsul-fonyl peroxide. The products were later decomposed to azomethine and further hydrolysis results in the corresponding amine with one less carbon atom. Thus when p-methoxy-benzylamine was treated with p-nitrophenylsulfonyl peroxide at —78 °C in ethyl acetate, p-methoxybenzaldehyde and p-methoxyaniline were obtained . Cyclic amines with p-nitrophenylsulfonyl peroxide were converted to the Al-(p-nitrophenylsulfonyloxy)amine derivatives, which further rearranged to ring-expanded cyclic imines in good yields (equation 9 f. ... 

Several cases warrant special mention. As an example, ring opening, hydrogenation, and subsequent transformations of the 5(47/)-oxazolone 459 derived from 2,3-dihydroxy-4-methoxybenzaldehyde affords a biomimetic synthesis of racemic stizolobinic acid 463 as shown in Scheme 7.151. ... 

Polyethers and polyesters having methoxybenzalazine units with various alkylene groups (C4, C6 and Cg) in the main chain were synthesized from vanillin (7,8). The condensation reaction of 4,4 -alkylenedioxybis (3-methoxybenzaldehyde) [VI] with hydrazine monohydrate was applied to the synthesis of polyethers [VII] (Mn, 7.4 x 103 for C4, 7.3 x 103 for C6 and 4.1 x 103 for Cg derivatives), as shown in Scheme 3. Polyesters [IX] (77jnh, 0.35 dl/g for C4, 0.38 dl/g for C6 and 0.43 dl/g for Cg derivatives) were synthesized from 4,4 -dihydroxy-3,3 -dimethoxybenzalazine [VIII] and di-carboxylic acid chlorides by conventional low temperature solution polycondensation, as shown in Scheme 4. 

A mixture of 205 g POCl, and 228 g N-methylformanilide was allowed to incubate at room temperature until there was the development of a deep claret color with some spontaneous heating. To this, there was added 70.8 g 2,3-dimethyl-anisole, and the dark reaction mixture heated on the steam bath for 2.5 h. The product was then poured into 1.7 L H20, and stirred until there was a spontaneous crystallization. These solids were removed by filtration, H20 washed and air dried to give 77.7 g of crude benzaldehyde as brown crystals. This was distilled at 70-90 °C at 0.4 mm/Hg to give 64.8 g of 2,3-dimethyl-4-methoxybenzaldehyde as a white crystalline product with a mp of 51 -52 °C. Recrystallization from MeOH produced ananalyticalsamplcwithampof55-55.5°C. Anal.(C 0H12O2)C,H. Themalononitrile derivative (from the aldehyde and malononitrile in EtOH with a drop of triethylamine) had a mp of 133-133.5 °C from EtOH. Anal. (C Hl2N20) C,H,N. Recently, this aldehyde has become commercially available. 

A low amount (1 mol%) of triflic acid is sufficient to carry out the hetero Diels-Alder reaction of aromatic aldehydes with simple dienes to furnish 3,6-dihyro-2/7-pyran derivatives in moderate to good yields692 [Eq. (5.248)]. The strongly deactivated para-methoxybenzaldehyde and pentanal gave the products in very low yields. 

Quinazolines are of great interest in the pharmaceutical industry as protein tyrosine kinase inhibitors. Dener et al 8 described a synthesis starting from 2-methoxybenzaldehyde, Wang, or Rink resins. With the aldehyde resin reductive aminations were undertaken to yield polymer-bound secondary amines (Fig. 7). The latter were subjected to 2,4-dichloro-6,7-dimethoxyquinazoline to give the 4-amino-substituted derivatives. These were then allowed to react with primary or secondary amines at 135-140° in the presence of DBU in DMA. As a result of a detailed scope and limitation study, Dener et al,28 note that some bifunctional amines, such as piperazine, give to some extent dimeric derivatives. 

Irradiation of lactone 131 with ( )-anethole in benzene gave cyclobutane 132 together withp-methoxybenzaldehyde [215] (Scheme 43). Similar irradiation of lactone 133 gave both cyclobutane 134 and an olefin 136 derived from an oxe-tane precursor 135. 

Working across the preceding pages from left to right, we may derive from the four aldehydes at least one of the chemical names for each of the remaining products. (These are only shown when commonly used.) Anisaldehyde, for example, is sometimes referred to as para-methoxy benzaldehyde, and vanillin can be referred to aspara-hydroxy-/raeta-methoxy benzaldehyde, or 4-hydroxy-3-methoxybenzaldehyde. (Not surprisingly the common name is the one preferred.)... 

Fig. 4-1. Examples of classical methods indicating a phenylpropanoid structure of lignin. (A) Permanganate oxidation (methylated spruce lignin) affords veratric acid (3,4-dimethoxybenzoic acid) (1) in a yield of 8% and minor amounts of isohemipinic (4,5-dimethoxyisophtalic acid) (2) and dehydrodiveratric (3) acids. The formation of isohemipinic acid supports the occurrence of condensed structures (e.g., /3-5 or y-5). (B) Nitrobenzene oxidation of softwoods in alkali results in the formation of vanillin (4-hydroxy-3-methoxybenzaldehyde) (4) (about 25% of lignin). Oxidation of hardwoods and grasses results, respectively, in syringaldehyde (3,5-dimethoxy-4-hydroxybenzaldehyde) (5) and p-hydroxybenzaldehyde (6). (C) Hydrogenolysis yields pro-pylcyclohexane derivatives (7). (D) Ethanolysis yields so-called Hibbert ketones (8,9,10, and 11).

Antiseptic plant-derived phenols include phenol (Phe-OH, hydroxybenzene, carbolic acid), />-cresol (4-methylphenol), catechol (1,2-dihydroxybenzene), resorcinol (1,3-dihydroxybenzene) and pyrogallol (1,2,3-trihydroxybenzene). Other simple phenols with antimicrobial properties include some related to benzoic acid (benzenecarboxylic acid), namely salicylic acid (2-hydroxybenzoic acid), ginkgoic acid (2-hydroxy-6-(pentadec-8-enyl)benzoic acid), gentisic acid (2,5-dihydroxybenzoic acid), pyrocatechuic acid (3,4-dihydroxybenzoic acid) and gallic acid (3,4,5-trihydroxybenzoic acid). Other plant-derived phenol-related compounds include 4-methylcatechol, 1,3-dihydroxy-5-(heptadec-12-enyl)benzene, hydroquinone (1,4-dihy-droxybenzene), 1,4-dihydroxy-2-geranyl (di-isoprenyl)benzene and 4-methoxybenzaldehyde (/>-anisealdehyde). 

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