Methoxy ether derivatives

Alternatively the cyclization of the amine i to the methoxy ether derivative ii can be performed by the following reaction sequence. 

A popular method is to analyse the total fatty acid methyl esters by CjC after reaction with silver nitrate/anhydrous methanol for 2 h at 30°C (Bianchini, Ralaimanarivo and Gaydou, 1981 Eisele et aL, 1974 Gaydou, Bianchini and Ralaimanarivo, 1983 Ralaimanarivo, Gaydou and Bianchini, 1982). Most fatty esters remain unchanged, but cyclopropene esters are converted to later-eluting methoxy ether derivatives and small amounts of ketone derivatives. Two partially resolved peaks, those from sterculic acid eluting later, are observed for each type of derivative from each cyclopropene acid and can be quantified and used to determine the proportion of sterculic and malvalic acids in the untreated oil. Verification of the identities of the acids can be determined from GC-MS of the methyl esters of the products (Ahmad et al., 1979 Eisele et ai, 1974) but prominent allylic ions in the mass spectra of the DMOX derivatives of the methoxy ethers are more readily interpretable to reveal the positions of the cyclopropene rings (Spitzer, 1995). 

Similar treatment of resibufoaenin and lAx vrtebufogenin resulted ultimately in C-21 methoxy ether derivatives. °... 

A remarkable feature of the Birch reduction of estradiol 3-methyl ether derivatives, as well as of other metal-ammonia reductions, is the extreme rapidity of reaction. Sodium and -butyl alcohol, a metal-alcohol combination having a comparatively slow rate of reduction, effects the reduction of estradiol 3-methyl ether to the extent of 96% in 5 minutes at —33° lithium also effects complete reduction under the same conditions as is to be expected. Shorter reaction times were not studied. At —70°, reduction with sodium occurs to the extent of 56 % in 5 minutes, although reduction with lithium is virtually complete (96%) in the same time. (The slow rates of reduction of compounds of the 5-methoxytetralin type is exemplified by 5-methoxy-tetralin itself with sodium and f-butyl alcohol reduction occurs to the extent of only 50% in 6 hours vs. 99+% with lithium.) The iron catalyzed reaction of sodium with alcohols must be very fast since it competes so well with the rapid Birch reduction. One cannot compensate for the presence of iron in a Birch reduction mixture containing sodium by adding additional metal to extend the reaction time. The iron catalyzed sodium-alcohol reaction is sufficiently rapid that the aromatic steroid still remains largely unreduced. 

Two approaches for the synthesis of allyl(alkyl)- and allyl(aryl)tin halides are thermolysis of halo(alkyl)tin ethers derived from tertiary homoallylic alcohols, and transmetalation of other allylstannanes. For example, dibutyl(-2-propenyl)tin chloride has been prepared by healing dibutyl(di-2-propenyl)stannane with dibutyltin dichloride42, and by thermolysis of mixtures of 2,3-dimethyl-5-hexen-3-ol or 2-methyl-4-penten-2-ol and tetrabutyl-l,3-dichlorodistannox-ane39. Alternatively dibutyltin dichloride and (dibutyl)(dimethoxy)tin were mixed to provide (dibutyl)(methoxy)tin chloride which was heated with 2,2,3-trimethyl-5-hexen-3-ol40. 

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. 

Catalyst performance was far superior to the corresponding BINAP or Me-Du-Phos systems, with both conversions and selectivities being higher. The hydrogenation of enol ethers using Rh-PennPhos catalysts has been reported in a patent by Zhang [67d]. Under mild conditions, high enantioselectivities were obtained (73-94% ee) for 1-aryl-l-methoxy-ethene derivatives 121, compared to Me-DuPhos (40-73% ee) and BINAP (46-48% ee). 

The derived enthalpies of formation of the n-propyl and ec-butyl lithiated methoxy ethers are —260 and —275 kJmon, respectively, from equation 16, the enthalpies of protodelithiation, the enthalpy of formation of n-butyl lithium from Table 1 and of liquid n-butane, and the measured enthalpies of formation of methyl n-propyl ether (Iq, —266.0 ... 

In 1989 Cutler et al.1 reported the isolation of 3,7-dimethyl-8-hydroxy-6-methoxyisochro-man (1) from Penicillium corylophilum and demonstrated that it inhibited etiolated wheat coleoptiles at 10-3 and 1(T4M, as did the acetoxy (2) and methoxy (3) derivatives (Figure 5.1).2 The Parent compound had originally been isolated from moldy millet hay implicated in the death of cattle,3 but the metabolite had not been tested in plants. Because of the encouraging results obtained in the wheat coleoptile bioassay, isochromans 1,2, and 3 were assayed on greenhouse-grown bean, com, and tobacco plants. The methyl ether exhibited the greatest herbicidal activity in all the plants treated, while the parent and its acetoxy derivative were active only on corn. 

Since the acetoxy and methoxy synthetic derivatives exhibited herbicidal activity, we were curious whether this also occurred with other esters and ether derivatives of 1 and its isomer, 3,7-dimethyl-6-hydroxy-8-methoxyisochroman (4). We reasoned that 3,7-dimethyl-6,8-dimethoxyisochroman (3) represents a logical precursor for the systematic preparation of the desired ester and ether analogs of isochromans 1 and 4. To test this conjecture, we needed both an efficient synthesis of bis-ether 3 and a practical way to demethylate the C(6) or C(8) ethers selectively. 

A 1,2-hydride shift has been invoked399 to account for the formation of p-methoxyphenylbutyraldehyde derivatives (337) during the treatment of />methoxy-benzyl-protected allylic alcohols (336) with zeolites. A similar C-glycosidation procedure involving Lewis acid-catalysed anomeric oxygen to carbon rearrangement of tetrahydropyranyl ether derivatives has been reported400 (see Scheme 82). It has been... 

The above iodides have been used as 1 -labelled building blocks in the preparations of [3-nC]tyrosine, (9-methyl[3-nC]tyrosine, /7-chloro[3-nC]phenylalanine and / -fluoro[3-JlC]phenylalanine by alkylations of glycine derivatives241. The [nC]ethyl ether derivatives (using sodium ethoxide as nucleophile) and 3-nitrophenyl-4-methoxy[(Z-nC]benzyl ether (using sodium 3-nitrophenolate) have been synthesized also, employing 4-methoxy(ar-14C)benzyl iodide 18324. ... 

RSeCJIi — ROCHi. Oxidation of an alkyl phenyl selenide with m-chloroperben-zoic acid (2-5 equiv.) in methanol affords the corresponding alkyl methyl ethers in high yield. Oxidation of selenides with a vicinal phenyl group is accompanied by rearrangement of the phenyl group. vtc-Methoxy selenides derived from cycloalkenes are oxidized under these conditions to dimethyl acetals of ring-contracted aldehydes. 

Disposition in the Body. Slowly but completely absorbed following oral administration. It appears to undergo significant first-pass metabolism bioavailability about 70%. After intravenous administration, about 57% of a dose is excreted in the urine and 30% in the faeces over a period of 21 days less than 10% of the dose is excreted as unchanged drug. The principal metabolite is the desmethyl derivative, which has been shown to be active in animals, but hydroxylation also occurs to form phenolic derivatives which may be further converted to aromatic methoxy ethers or excreted as glucuronide conjugates A -oxidation also occurs and maprotiline A -oxide has been reported to be active numerous minor metabolites have been identified in urine. 

Mukaiyama aldol reactions of various silyl enol ethers or ketene silyl acetals with aldehydes or other electrophiles proceed smoothly in the presence of 2 mol % B(CgF5)3 [151a,c]. The following characteristic features should be noted (i) the products can be isolated as j8-trimethylsilyloxy ketones when crude adducts are worked-up without exposure to acid (ii) this reaction can be conducted in aqueous media, so that the reaction of the silyl enol ether derived from propiophenone with a commercial aqueous solution of formaldehyde does not present any problems (iii) the rate of an aldol reaction is markedly increased by use of an anhydrous solution of B(C6Fs)3 in toluene under an argon atmosphere and (iv) silyl enol ethers can be reacted with chloromethyl methyl ether or trimethylorthoformate hydroxymethyl, methoxy-methyl, or dimethoxymethyl Cl groups can be introduced at the position a to the carbonyl group. These aldol-type reactions do not proceed when triphenylborane is used (Eq. 92). 

Vanillin.—Two very important essential oil constituents are ether derivatives. One of these is vanillin, the chief constituent of vaniUa beans from which vanilla extract is made, and the other is heliotropin, also known as piperonal, which has the odor of heliotrope flowers. Vanillin is the mono-methyl ether of protocatechuic aldehyde, the methoxy... 

Replacement of the methoxy group with a hydroxyethyl ether function was found to largely overcome this limitation of the chemistry, affording the corresponding cyclic quinol ether ketals (LXXXVII) in good yield [Eq. (44)]. Mild acidic hydrolysis of the cyclic ketals to the quinol ether derivatives was nearly quantitative except when R = t-Bu [Eq. (44)], wherein loss of /-butyl led to reduction during the hydrolysis [98,99]. 

The simple ether derivatives, 2-methoxy-naphthalene [CAS no. 93-04-9], nerolin, and 2-ethoxy-naphthalene [CAS no. 93-18-5] now are made easily by methylation (using dimethyl sulfate) or ethylation (using di-ethylsulfate) for use in perfume formulation and more recently as drugs intermediates. 

In order to reverse the diastereoselectivity in the aldol reaction, the Lewis acid-catalyzed silyl enol ether addition (73) (Mukaiyama aldol reaction) was examined. Since the Mukaiyama aldol reaction is assumed to be proceeded via an acyclic transition state, a chelation controled aldol reaction of the a-alkoxy aldehyde should be possible (74). In the presence of TiCU, the silyl enol ether derived from 14 was reacted with aldehyde 13, followed by desilylation to afford the desired anti-Felkin product 122a as a single adduct (Scheme 21). Based on precedents for chelation-controlled Mukaiyama aldol reaction (74), the exceptional high selectivity in this reaction would be accounted for by chelation of TiCl4 with the C23-methoxy group of the aldehyde 13 (eq. 13). On the other hand, when the lithium enolate derived from 14 was treated with the aldehyde 13, followed by desilylation, it gave a 1 4 ratio of the two epimers in favour of the undesired (22S)-aldol product... 

The methoxy ethers of the amino alcohols obtained from the addition of methyl-, ethyl-, or phenylmagnesium halide to 7V-benzylproline methyl esters can be converted to the corresponding, /V-amino derivatives by exactly the same procedures as described for SAMP10. The products [e.g., SADP, (S)-27, the a,a-dimethyl product] form azaenolates with carbonyl compounds which are used in enantioselective a-oxidations (Section D.4.I.). 

A closely related methodology (route c) involves the dianion from a diketone (R = Me) with the anion of dimethyl malonate (R = Me) (ref.25). The bis-trimethylsilyl ether from methyl acetoacetate has been interacted with the ketalised acid chloride shown (R = CgH ) to furnish the methoxy carbonyl derivative of olivetol (route d) (ref.26). It was also found that pentane-2,4-dione with dimethyl malonate in the presence of sodium hydride afforded methyl orsellinate (ref.26). In a biomimetic approach (route e) a tetraketone has been enzymically cyclised to give the corresponding orsellinic acid (R=H, R = alkyl) (ref. 27). 

An obvious question is how could such a group participate in electron-transfer or coupling reactions A few experimental observations for the terminal i.e., C12--C13) double bonds may be relevant to this question. This terminal bond undergoes certain addition reactions much more readily than do either of the two inner double bonds. For example, in dilute solutions of sulfuric acid in methanol, a dimethyl ester, dimethyl ether derivative (Figure 18) can be prepared without evidence of other products with methoxy groups at C5 or C9. We were surprised to find that as a consequence of this addition reaction at C13, a shift of 3 nm... 

---