Catechol, synthesis

Genetically engineered microbes have been used by Draths and Frost (1998a, b) to synthesize common but important chemicals such as adipic acid and catechol (see Fig. 3.23). The noteworthy aspect of this work is that the starting materials were renewable feedstock. The principles of green chemistry state that "a raw material of feedstock should be renewable rather than depleting wherever technically and economically practicable" (Anastas and Warner, 1998). This reaction addresses this principle and more, as it can be seen. Classical catechol synthesis beginning with benzene (obtained from petroleum, a nonrenewable feedstock) involves a multistep process (see Fig. 3.22). 

Catechol Derivatives. An elegant synthesis of trimethoxybenzaldehyde [86-81-7] (4) starting from quaiacol [90-05-1] (5) and formaldehyde (75) has been developed. The reaction sequence is as follows ... 

Catechol is produced by coproduction with hydroquinone starting from phenol. Other techniques such as coal extraction remain marginal. The installed capacities (- 25,000 t/yr) are now sufficient to cover the demand. Catechol is mainly used for synthesis in food, pharmaceutical, or agrochemical ingredients. A specific appHcation of / fZ-butylcatechol is as a polymerisation inhibitor. 

Dopamine. Dopamine (DA) (2) is an intermediate in the synthesis of NE and Epi from tyrosine. DA is localized to the basal ganglia of the brain and is involved in the regulation of motor activity and pituitary hormone release. The actions of DA are terminated by conversion to dihydroxyphenylacetic acid (DOPAC) by monoamine oxidase-A and -B (MAO-A and -B) in the neuron following reuptake, or conversion to homovanillic acid (HVA) through the sequential actions of catechol-0-methyl transferase (COMT) and MAO-A and -B in the synaptic cleft. 

The original commercial source of E was extraction from bovine adrenal glands (5). This was replaced by a synthetic route for E and NE (Eig. 1) similar to the original pubHshed route of synthesis (6). Eriedel-Crafts acylation of catechol [120-80-9] with chloroacetyl chloride yields chloroacetocatechol [99-40-1]. Displacement of the chlorine by methylamine yields the methylamine derivative, adrenalone [99-45-6] which on catalytic reduction yields (+)-epinephrine [329-65-7]. Substitution of ammonia for methylamine in the sequence yields the amino derivative noradrenalone [499-61-6] which on reduction yields (+)-norepinephrine [138-65-8]. The racemic compounds were resolved with (+)-tartaric acid to give the physiologically active (—)-enantiomers. The commercial synthesis of E and related compounds has been reviewed (27). The synthetic route for L-3,4-dihydroxyphenylalanine [59-92-7] (l-DOPA) has been described (28). 

The more traditional methods of phenazine synthesis falling into the type A synthesis are altogether less satisfactory than the application of the Beirut reaction. Traditionally, Ris prepared phenazine in low yield by heating o-phenylenediamine and catechol in a sealed tube at 200 °C (1886CB2206) however, the method appears to be unsatisfactory at best and gives, in addition to phenazine, 5,10-dihydrophenazine in varying amounts (Scheme 53). Several variants of this procedure exist o-benzoquinone has been used in condensation with 0-phenylenediamine and yields as high as 35% have been reported, and 1,2,3,4-tetrahydrophenazine has been prepared by condensation of o-phenylenediamine with cyclohexane- 1,2-dione. 

The first method is shown in Eq. (3.1). This corresponds to the so-called one plus one synthesis of crowns. The notion is that a single diol unit is allowed to react with a single polyethylene glycol having leaving groups at each end. An example of this would be the synthesis of benzo-15-crown-5 from catechol and tetraethylene glycol dichloride. Note that the stoichiometry of this method is identical to that of method X which is shown below in Eq. (3.3). 

The ortho-xylyl unit may be considered as the synthetic complement of the catechol unit so often used in crown synthesis. This is especially so for the 1,2-bromomethyl compounds which may be used as electrophiles. These units have been incorporated in numerous crowns over the years and the syntheses are all quite similar. 

The principal variations on the normal crown synthesis methods were applied in preparing mixed crowns such as those shown in Eq. (3.55) and in forming isomers of the dibinaphthyl-22-crown-6 systems. The latter has been discussed in Sect. 3.5 (see Eq. 3.21) . The binaphthyl unit was prepared to receive a non-naphthyl unit as shown in Eq. (3.57). Binaphthol was allowed to react with the tetrahydropyranyl ether or 2-chloroethoxyethanol. Cleavage of the THP protecting group followed by tosyla-tion of the free hydroxyl afforded a two-armed binaphthyl unit which could serve as an electrophile in the cyclization with catechol. Obviously, the reaction could be accomplished in the opposite direction, beginning with catechol". ... 

Ik 1 onstitution has been deteimined by its synthesis from catechol in presence of concentiated... 

In the 3-adrenergic blocking drug pyrroxan (48), the catechol moiety is masked in a doxane ring. The synthesis begins by alkylation of phenyl acetonitrile by 2-chloroethanol to produce alcohol Recuction converts this to amino alcohol which... 

Azaloxan (12) is an antidepressant agent. Its synthesis can be accomplished starting with the reaction of catechol (7) and 3,4-dibromobutyronitrile (obtained by addition of bromine to the olefin) to give l,4-benzodioxan-2-ylacetonitrile (8). A series of functional group transformations ensues [hydrolysis to the acid (9), reduction to the alcohol (10) and conversion to a tosylate (11)] culminating in an SN-2 displacement reaction on tosylate 11 with l-(4-piperidinyl)-2-imidazolidi-none to give azaloxan (12) [3]. 

Safrole, a substance isolated from oil of sassafras, is used as a perfumery agent. Propose a synthesis of safrole from catechol (1,2-benzenediol). 

Metabolic pathways containing dioxygenases in wild-type strains are usually related to detoxification processes upon conversion of aromatic xenobiotics to phenols and catechols, which are more readily excreted. Within such pathways, the intermediate chiral cis-diol is rearomatized by a dihydrodiol-dehydrogenase. While this mild route to catechols is also exploited synthetically [221], the chirality is lost. In the context of asymmetric synthesis, such further biotransformations have to be prevented, which was initially realized by using mutant strains deficient in enzymes responsible for the rearomatization. Today, several dioxygenases with complementary substrate profiles are available, as outlined in Table 9.6. Considering the delicate architecture of these enzyme complexes, recombinant whole-cell-mediated biotransformations are the only option for such conversions. E. coli is preferably used as host and fermentation protocols have been optimized [222,223]. 

The piperonal synthesis (p T 9) is an example where the two ortho oxygen substituents would be very difficult to set up. We therefore (guideline 7) start with available catechol ( o-dihydroxybenzene),... 

Just as the synthesis of DA and NA is similar so is their metabolism. They are both substrates for monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT). In the brain MAO is found in, or attached to, the membrane of the intraneuronal mitochondria. Thus it is only able to deaminate DA which has been taken up into nerve endings and blockade of DA uptake leads to a marked reduction in the level of its deaminated metabolites and in particular DOPAC. The final metabolite, homovanillic... 

The reason why synthesis of natural urushiols involves multistep, tedious procedures is that the reactive unsaturated group cannot be directly introduced on the catechol moiety protection and deprotection of the catechol moiety are... 

Alkylcatechols are important as chemicals and chemical intermediates in the fine chemistry industry for the synthesis of flavouring agents, agricultural chemicals and pharmaceuticals [1]. 3-methyl catechol has a special value from the industrial point of view. Previously y-alumina was found to be an effective catalyst for the gas-phase methylation of catechol with methanol [2]. The process can be schematically presented as ... 

Goss, C.H.A., Henderson, W., Wilkins, A.L. and Evans, C. (2003) Synthesis, characterisation and biological activity of gold(lll) catecholate and related complexes. Journal of Organometallic Chemistry, 679, 194. 

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