Anisaldehyde, synthesis

Hydroxybenzaldehyde has an agreeable aromatic odor, but is not itself a fragrance. It is, however, a useful intermediate in the synthesis of fragrances. The methyl ether of -hydroxybenzaldehyde, ie, -anisaldehyde, is a commercially important fragrance. Anisaldehyde can be made in a simple one-step synthesis from hydroxybenzaldehyde and methyl chloride. Another important fragrance, 4-(p-hydroxyphenyl)butanone, commonly referred to as raspberry ketone, can be prepared from the reaction of -hydroxybenzaldehyde and acetone, followed by reduction (see Flavors and spices). 

Cyanohydrin trimethylsilyl ethers are generally useful as precursors of ctir-bonyl anion equivalents and as protected forms of aldehydes. Direct conversion of p-anisaldehyde into 0-TRIMETHYLSILYL-4-METH0XYMANDEL0-NITRILE employs a convenient in situ generation of trimethylsilyl cyanide from chlorotnmethylsilane A general synthesis of allemc esters is a variant of the Wittig reaction. Ethyl (triphenylphosphoranylidene)acetate converts pro-pionyl chloride into ETHYL 2,3-PENTADlENOATE. 

Electrochemical techniques, proposed for the synthesis of naphthaquinone, anisaldehyde, and benzaldehyde (Walsh and Mills, 1993). 

Additionally, the influence of the life time of the micro-structured devices as well as the expenditure of the peripheral equipment was estimated in order to obtain insight into the ecological hot-spots of the system. A conventional macro-scaled semi-continuously operated batch process was chosen as a reference process. The comparison of both technological systems was performed by means of the two-step synthesis of m-anisaldehyde serving as model reaction. 

The synthesis of m-anisaldehyde [3] is a very exothermic lithium-organic reaction (Scheme 7.1). In a macro-scaled batch reactor, this synthesis can only be carried out under extensive safety precautions and with high energetic effort for operating the cooling system. 

Scheme 7.1 Synthesis of m-anisaldehyde, model reaction of case study 1.

Combining, in tandem, the nitro-aldol reaction with the Michael addition using thiophenol is a good method for the preparation of P-nitro sulfides as shown in Eqs. 4.2 and 4.3. This reaction is applied to a total synthesis of tuberine. Tuberine is a simple enamide isolated from Streptomyces amakusaensis and has some structural resemblance to erbastatin, an enamide which has received much attention in recent years as an inhibitor of tyrosine-specific kinases. The reaction of p-anisaldehyde and nitromethane in the presence of thiophenol yields the requisite P-nitro sulfide, which is converted into tuberine via reduction, formylation, oxidation, and thermal elimination of... 

TABLE 16. Synthesis of a-substituted ketones (208) from p-anisaldehyde, 1-chlorobutyl p-tolyl sulfoxide and electrophiles... 

Carbonyl alkylation and condensation reactions are always of great value in synthesis, and the formation of o-ANISALDEHYDE via 4,4-dimethyl-2-oxazoline, 2,2-DIMETHYL-3-PHENYLPROPION-ALDEHYDE via alkylation of the magnesio-enamine salt and threo-4-HYDROXY-3-PHENYL-2-HEPTANONE via a directed aldol... 

Solid-Phase Synthesis Terminated by Tetramic Acid Cyclative Cleavage (Scheme 2). The Fmoc-L-Val resin (loading 0.7 mmol/g) is first deprotected with 20% piperidine in DMF for 20 min, and the resin washed and dried. The resin ( 0.3 g, 0.67 mmol/g) is shaken with p-anisaldehyde (0.25 ml, 10 molar equiv.) and sodium triacetoxyborohydride (0.65 g, 15 molar equiv.) in 10 ml CH2C12 for 8 h, followed by washing and drying to give resin 4. 

SodaKoryo 176)claims a special electrolyte (fm.-butanol-HO Ac—Et4 NX—Cu(OAc)2) for the same synthesis, but the yields (77%) are lower. UOP 177) has developed a laboratory process for anisaldehyde based on this method. 

Berthelette et al. [143] reported a detailed study on the stereochemistry of vinyl halide (chlorides and bromides) synthesis by the Julia-Kocienski method. In the model experiments using chloromethyl PT sulfone and anisaldehyde (Scheme 109), the isomer ratio depends on the countercation. 

Columbia. The preparation of the reagent from 2-amino-2-methyl-l-propanol and formic acid is described in a note to a procedure for the synthesis of o-anisaldehyde ... 

Hydrotalcite-derived materials also show good performances in analogous reactions, such as the Claisen-Schmidt condensation of substituted 2-hydroxyacetophe-nones with substituted benzaldehydes, the synthetic route to flavonoids and the condensation of 2,4-dimethoxyacetophenone with p-anisaldehyde to synthesize Vesidryl, a diuretic drug [270]. Another similar class of reactions in which HT-based materials give good results are Knoevenagel condensations [271]. An example is the synthesis of citronitrile, a perfumery compound with a citrus-like odor, which can be prepared by HT-catalyzed condensation of benzylacetone with ethyl cyanoacetate, followed by hydrolysis and decarboxylation (Figure 2.42b) [272]. 

The Knoevenagel reaction has also been used in the synthesis of alkaloids. In a preparation of yohim-bane derivatives, 2-cyano-4 -methoxycinnamic acid, the Knoevenagel product of p-anisaldehyde and... 

The Midland reduction has also been used in the large-scale synthesis of chiral glycines. Deuterium labeled anisaldehyde was reduced with 3 to provide deuteriated arylmethyl alcohol 21 in 82% ee.13 This alcohol was then converted in 4 steps to JV-Boc-glycine (22). 

The synthesis starts from the A-Boc-tyrosine methyl ester, which was O-benzylated, since the prenyl ether required in the target compound is not compatible with the conditions required for the preparation of the hydoxylamine or the hydrogenation of the isoxazolidine intermediate (Scheme 40). Following cleavage of the A-Boc, the resulting primary amine was treated with anisaldehyde, and after oxidation with m-CPBA... 

The synthesis of an analogue, a pyranochalcone isolated from a related species Millettia pachycarpa, which is described (ref.84) as an insect anti-feedant, commenced with the prenylation of 2,4-dihydroxyacetophenone with prenyl bromide in a basic medium to afford several products but primarily 2,4-dihydroxy-3-C-prenylacetophenone in 50% yield. Formic acid cyclisation gave a pyrone which was condensed with anisaldehyde. The resulting chalcone was oxidised in which reaction the non hydrogen-bonded hydroxyl group participated to obtain the final product. This was also be derived by the alternative of chalcone formation from 2,4-dihydroxyacetophenone followed by prenylation (non-specific) and finally DDQ oxidation. 

The preparation of this reagent and the use for synthesis of o-anisaldehyde have been published. ... 

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