Dimethoxycinnamic Acid

Preparation by demethylation of 2,3-dimethoxy-acetophenone [2277-2281], (73%) [2278], (50%) [2280], itself obtained by oxidation of 2,3-dimethoxyphenyl methyl carbinol [2277,2279-2281], This carbinol was prepared either from 2,3-dimethoxybenzaldehyde by an oiganomagnesium synthesis [2277,2279,2280] or from 2,3-dimethoxycinnamic acid by Posner s method [2280,2281],... 

This procedure has been used by the submitters and others to prepare the following cinnamic acids from substituted benzal-dehydes o-nitrocinnamic acid (70%),2 -nitrocinnamic acid (77%),2 w-cyanocinnamic acid (71%),3 o-chlorocinnamic acid (82%),4 m-chlorocinnamic acid (53%),4 -chlorocinnamic acid (73%),4 2,4-dichlorocinnamic acid (70%),4 3,4-dichlorocinnamic acid (81%),4 w-bromocinnamic acid (31%),4 -methoxycinnamic acid (60%),4 and 3,4-dimethoxycinnamic acid (77%).4... 

The most common hydroxycinnamic acid derivatives are p-coumaric (4-hydroxy-cinnamic), caffeic (3,4-dyhydroxycinnamic), ferulic (4-hydroxy-3-methoxycinnamic), and sinapic (4-hydroxy-3,5-dimethoxycinnamic) acids, which frequently occur in foods as simple esters with quinic acid or glucose (Mattila and Kumpulainen 2002). 

An alternative route from (11) to (V) involves adding (II) and diethylmethylmalonate to prepare dimethyl-3,5-dimethoxyhydro-cinnamic acid as described for the preparation of (III). Then dehydrate and hydrolyze to dimethyl-3,5-dimethoxycinnamic acid which is hydrogenated to the alcohol and converted in several steps to (V). 

The medicinal chemistry of Alzheimers is complicated by the fact that the etiology of this disease is still far from clear. Evidence points to an association with decreased levels of acetyl choline in the brain. Many of the drugs that have been introduced to date for treating this disease thus comprise agents intended to raise the deficient levels of that neurotransmitter by inhibiting the loss of existing acetylcholine due to the action of cholinesterase. A compound based on an indene that, perhaps surprisingly, inhibits that enzyme has been proposed for the treatment of Alzheimer s. Aldol condensation of piperidine aldehyde (4-2) with the indanone (4-1) from cyclization of 3,4-dimethoxycinnamic acid leads to the olefin (4-3). Catalytic reduction removes the double bond to afford donepezil (4-4) [3]. 

Naphthalene- and anthracene-derived phenols did, however, almost uniformly precipitate (Table VI). In natural materials (not grapes or wines) which contain them they would be included in the formaldehyde precipitable group. Several primary amines capable of SchifFs base formation reacted with formaldehyde to lose their F-C oxidizability, but only the resorcinol analog, 3-aminophenol, precipitated (Table VIII). Sulfite also reacted but did not precipitate with formaldehyde, and the F-C oxidizability was suppressed (Table IX). The resorcinol derivative, 2,4-dimethoxycinnamic acid, formed a precipitate with formaldehyde, but it did not react appreciably in the F-C assay. 

Dimethoxycinnamic acid is a good source of 6-hydroxycoumarin and the preparation illustrates the value of boron tribromide in the cleavage of ethers (69MI22401). 

Dimethoxycinnamic acid Methyl anthranilate Benzene sulfonyl chloride Sodium hydroxide... 

The structure of these bases has been elucidated by spectroscopic and chemical methods. A basic hydrolysis of both subcosine-I and subcosine-II resulted in 3,4-dimethoxycinnamic acid as well as lasubine-I for 69 and lasubine-II for alkaloid 67. 

A more complex pathway was proposed by Funk and Brodelius (1990a,b, 1992), where caffeic acid was first methylated at the 4-posi-tion, followed by the 3-position to produce 3,4-dimethoxycinnamic acid, which was then demethylated at the 4-position, prior to a glucosylation step. Side-chain cleavage was proposed to occur at a late stage to produce vanillic acid (or its /Tn-glucoside), which was then reduced to vanillin (Fig. 15.3). 

A different access to the resorcarene skeleton was found in the Lewis acid (BF3 Et20) catalysed tetramerization of 2,4-dimethoxycinnamic acid esters or amides (Scheme 9). 2,6-Dimethoxy derivatives rearrange during the reaction and may be also used. A mixture of stereoisomers of 29 is usually obtained in yields of 65-80%, the composition of which depends on R and on the reaction conditions . 

Cinnamic acid derivatives 960—see also 2,4-Dimethoxycinnamic acid esters Cinnamic acids—see Hydroxycinnamic adds, tratts-4-Hydroxy-a-cyanocinnamic acid Circular dichroism 992 Claisen condensation,... 

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