Methylbenzaldehydes

In the Gatteinicin-Koch reaction, a formyl group (-CHO) is introduced directly onto a benzene ring. For example, reaction of toluene wjfh CO and HCJ in the presence of mixed CUCI/AICI3 gives p-methylbenzaldehyde. Propose a mechanism. 

The mass spectrum of 2-methylbenzaldehyde suggests an aromatic compound because of the intensity of the molecular ion and peaks at m/z 39, 51, and 65 (see Figure 6.2). The loss of hydrogen atoms and loss of 29 Daltons from the molecular ion indicate that this is an aromatic aldehyde. Looking up m/z 91 in Part III suggests the following structure ... 

The cycloaddition of photoenol of o-methylbenzaldehyde 66 with 5-alkyli-dene-l,3-dioxane-4,6-dione derivatives 67 is an example of a photo-induced Diels Alder reaction in which one component, the diene in this case, is generated by irradiation [48]. The yields of some cycloadducts 68, generated by photo-irradiation of a benzene solution of 66 and 67 at room temperature, are reported in Table 4.14. The first step of the reaction is the formation of (E)-enol 69 and (Z)-enol 70 (Equation 4.7) by an intramolecular hydrogen abstraction of 66 followed by a stereo- and regioselective cycloaddition with... 

Dieis-Aider reactions of photoenoi of 2-methylbenzaldehyde with 5-alkylidene-1,3-dioxane-4,6-dione derivatives [48]... 

Benzenediamine (352) and 4-p-chlorobenzyl-3-hydroxy-5-p-tolyl-2,5-dihy-dro-2-furanone (353) gave 3-(p-chlorophenethyl)-2(177)-quinoxahnone (354) with loss of p-methylbenzaldehyde (isolated as its phenyUiydrazone) (EtOH,... 

Unsymmetric compartmental ligands that allow for the controlled synthesis of unsymmetric Ni2 or heterobimetallic NiM complexes have received particular attention.1876,1892 A wide range of such ligands derived particularly from 2-hydroxy-3-hydroxymethyl-5-methylbenzaldehyde and 2-hydroxy-3-hydroxymethyl-bromo-benzaldehyde has now been prepared and used for Ni com-plexation. These ligands have monopodal iminic pendent arms and either mono- or dipodal aminic pendent arms and the terminal donors of the pendent arms can be provided by pyridine, imidazole, and tertiary amino groups.1893-1897 Complexes are usually prepared by reaction of the requisite Ni11 salts with the preformed ligand. 

Compound 39a reacts with N-methylbenzaldehyde imine as cycloaddend under the conditions metioned above — quite expectedly — to give a mixture of stereoisomeric 1 -oxa-3-aza-4Xs-phosphorins 37). 

To a solution of red phosphorus (3.1 g, 0.1 mol) in DMSO (6 ml) the following was added successively potassium hydroxide (0.95 g, 17 mmol) in water (50 mmol) and aldehyde, 4-methylbenzaldehyde (0.90 g, 7.5 mmol). The reaction mixture was sonicated for 10 min, after which it was filtered to remove excess phosphorus. The filtrate was then acidified to pH = 2-3 with 37% aqueous HC1 and extracted with chloroform. The aqueous portion was concentrated to dryness, and the residue dissolved in a minimum of acetic acid. The supernatant layer was separated from the solid and concentrated to dryness to give the product a-hydroxy-p-methylbenzylphosphonous acid in 30% yield. 

The generation of phenylcarbene (512) and p-tolylcarbene at 250 °C/40Torr in the gas phase brought about only the ring expansion to give 5 and 10, respectively and their dimerization yielding 522 and 557 (Scheme 6.113). The co-thermolysis of the sodium salts of benzaldehyde and p-methylbenzaldehyde tosylhydrazone also gave rise to the mixed heptafulvalene 556. With a ratio of 1 2 1, the amounts of 522, 556 and 557 verified the expectation based on statistics [212]. 

Scheme 6.113 Formation of heptafulvalene (522), its methyl derivative 556 and its dimethyl derivatives 557 on co-thermolysis of the sodium salts of benzaldehyde and p-methylbenzaldehyde tosylhydrazones.

Biological. A proposed microbial degradation mechanism is as follows 4-hydroxy-3-methylbenzyl alcohol to 4-hydroxy-3-methylbenzaldehyde to 3-methyl-4-hydroxybenzoic acid to 4-hydroxyisophthalic acid to protocatechuic acid to p ketoadipic acid (Chapman, 1972). In anaerobic sludge, diethyl phthalate degraded as follows monoethyl phthalate to phthalic acid to protocatechuic acid followed by ring cleavage and mineralization (Shelton et al, 1984). 

Chemical/Physical. Under atmospheric conditions, the gas-phase reaction of o-xylene with OH radicals and nitrogen oxides resulted in the formation of o-tolualdehyde, o-methylbenzyl nitrate, nitro-o-xylenes, 2,3-and 3,4-dimethylphenol (Atkinson, 1990). Kanno et al. (1982) studied the aqueous reaction of o-xylene and other aromatic hydrocarbons (benzene, toluene, w and p-xylene, and naphthalene) with hypochlorous acid in the presence of ammonium ion. They reported that the aromatic ring was not chlorinated as expected but was cleaved by chloramine forming cyanogen chloride. The amount of cyanogen chloride formed increased at lower pHs (Kanno et al., 1982). In the gas phase, o-xylene reacted with nitrate radicals in purified air forming the following products 5-nitro-2-methyltoluene and 6-nitro-2-methyltoluene, o-methylbenzaldehyde, and an aryl nitrate (Chiodini et ah, 1993). 

A //-hexane solution containing ///-xylene and spread as a thin film (4 mm) on cold water (10 °C) was irradiated by a mercury medium pressure lamp. In 3 h, 25% of the ///-xylene photooxidized into ///-methylbenzaldehyde, ///-benzyl alcohol, ///-benzoic acid, and m methylacetophenone (Moza and Feicht, 1989). 

Photolytic. A n-hexane solution containing /n-xylene and spread as a thin film (4 mm) on cold water (10 °C) was irradiated by a mercury medium pressure lamp. In 3 h, 18.5% of the p-xylene photooxidized into p-methylbenzaldehyde, p-benzyl alcohol, p-benzoic acid, and p-methylacetophenone (Moza and Feicht, 1989). Glyoxal and methylglyoxal were produced from the photooxidation of p-xylene by OH radicals in air at 25 °C (Tuazon et al., 1986a). The rate constant for the reaction of p-xylene and OH radicals at room temperature was 1.22 x lO " cmVmolecule-sec (Hansen et al., 1975). A rate constant of 7.45 x 10 L/molecule-sec was reported for the reaction of p-xylene with OH radicals in the gas phase (Darnall et al, 1976). Similarly, a room temperature rate constant of 1.41 x 10 " cm /molecule-sec was reported for the vapor-phase reaction of p-xylene with OH radicals (Atkinson, 1985). At 25 °C, a rate constant of 1.29 x lO " cmVmolecule-sec was reported for the same reaction (Ohta and Ohyama, 1985). 

In the gas phase, p-xylene reacted with nitrate radicals in purified air forming 3,6-dimethylnitrobenzene, 4-methylbenzaldehyde, and an aryl nitrate (Chiodini et al, 1993). 

Arnett and coworkers later examined the reaction of lithium pinacolone enoiate with substituted benzaldehydes in THE at 25 °C. The determination of the heat of reaction indicated that the Hammett p value for the process is 331. Although the aldol reaction was instantaneous in THF at 25 °C, the reaction with o- or p-methylbenzaldehyde could be followed using a rapid injection NMR method in methylcyclohexane solvent at —80 °C. Application of Eberson s criterion based on the Marcus equation, which relates the free energy of ET determined electrochemically and the free energy of activation determined by kinetics, revealed that the barriers for the ET mechanism should be unacceptably high. They concluded that the reaction proceeds via the polar mechanism . Consistent with the polar mechanism, cyclizable probe experiments were negative . The mechanistic discrepancy between the reactions of benzaldehyde and benzophenone was later solved by carbon kinetic isotope effect study vide infraf. ... 

Meclizine Meclizine, l-[(4-chlorphenyl)methyl]-4-[(3-methylphenyl)phenyl]piperazine (16.1.16), is synthesized by reductive amination of a mixture of 3-methylbenzaldehyde with l-(4-chlorbenzhydryl)piperazine using hydrogen over Raney nickel [27-29]. 

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