Benzaldehyde dimethyl acetal

The second group of reactions is called vicinal difunctionalization. They embrace the C2 and C3 positions of the furan ring simultaneously. Thus, complex 3 (X = O, R = R = R = H) reacts with benzaldehyde dimethyl acetal to give 4H-furanium cation (the product of electrophile addition at C4), which experiences further attack by the methoxide group with formation of the acetal 8 (950M2861). This reaction is possible in the presence of the Lewis acid (BF3—OEt2). Reaction with methyl vinyl ketone in methanol, when run in identical conditions. 

KetalizatUm under aproric conditions benzaldehyde dimethyl acetal (14)... 

A solution of 1-trimethylsilyloxycyclohex-l-ene (5.12 mmol) and benzaldehyde dimethyl acetal (5.47 mmol) in dichloromethane (15 ml) was cooled to —78°C, and to this was added TMSOTf (0.05 mmol) in dichloromethane (0.5 ml). The mixture was stirred at -78°C for 8h, and then quenched by the addition of water at —78 °C. Dichloromethane (50 ml) was added, and the mixture was washed with saturated sodium hydrogen carbonate solution and brine, and dried. Concentration provided a crude oil consisting of a 93 7 mixture of erythro- and r/jreo-2-(methoxyphenyl-methyl)cyclohexanone. Chromatography on silica gel (20g, eluant petroleum ether ether 10 1) gave the pure erythro (82%) and threo (6.7%) isomers as oils. 

To a stirred solution of TMSOTf (0.1 mmol) in dichloromethane (1ml). cooled to -78°C, were added successively methoxytrimethylsilane (20 mmol) and benzaldehyde (10 mmol). The mixture was stirred at — 78 °C for 3h, and then quenched by the addition of pyridine (0.2ml) at — 78°C. The mixture was poured on to saturated sodium hydrogen carbonate solution (15 ml), and extracted with ether (3x15 ml). The combined organic extracts were dried over sodium carbonate/sodium sulphate (1 1), filtered, concentrated and distilled, to give benzaldehyde dimethyl acetal (9.4mmol, 94%), b.p. 125-135°C/51 ramHg. 

Benzaldehyde, 43, 73, 123 Benzaldehyde diethyl acetal, 108, 110,122—3 Benzaldehyde dimethyl acetal, 34, 111 Benzenesulphonylhydrazonc, 13 Benzophenone, 137 Benzophenone cyanohydrin, 137 p-Benzoquinone, 137... 

Dimethyl acetals of aldehydes and ketones, for example benzaldehyde dimethyl acetal 121, and hemiacetals, react with allyltrimethylsilane 82 at -78 °C in CH2CI2, in the presence of TMSOTf 20 [169], trimethyhodosilane TIS 17 [159, 170],... 

Benzaldehyde dimethyl acetal 121 reacts, for example, with the silylated allylic alcohol 645, in the presence of SnCl2-MeCOCl, via an intermediate analogous to 641, to the 3-methylenetetrahydrofuran 646 and methoxytrimethylsilane 13 a [182], whereas benzaldehyde dimethyl acetal 121 reacts with the silylated homoallylalco-hol 640 in the presence of TMSOTf 20 to afford exclusively the ds 4-vinyltetrahy-drofuran 647 and 13 a [183]. A related cyclization of an a-acetoxy urethane 648 containing an allyltrimethylsilane moiety gives the 3-vinylpyrrohdine 649 in 88% yield and trimethylsilyl acetate 142 [184, 185]. Likewise, methyl 2-formylamido-2-trimethylsilyloxypropionate reacts with allyltrimethylsilane 82 or other allyltri-methylsilanes to give methyl 2-formamido-2-aUyl-propionate and some d -unsatu-rated amino acid esters and HMDSO 7 [186] (Scheme 5.56). 

Acetals of aldehydes such as benzaldehyde dimethyl acetal 121 are readily reduced by trimethylsilane 84a [213] or triethylsilane 84b in the presence of TMSOTf 20... 

A solution of TMSOTf 20 (3 pL, 0.017 mmol) in 1 mL acetonitrile is added at -20 °C under an argon atmosphere to a solution of benzaldehyde dimethyl acetal 121 (0.34 mmol, 51.7 mg) and (Z)-(5-trimethylsilyloxy-2-pentenyl)trimethylsilane 640 (94.9 mg, 0.412 mmol) in 3 mL acetonitrile. After 20 min at 20 °C the reaction is quenched with phosphate buffer (pH 7). The combined CH2CI2 extracts are washed with brine and dried (Na2S04) to give, after evaporation, 59.2 mg (99%) 647 [183] (Scheme 5.93). 

Acetalization or ketalization with silylated glycols or 1,3-propanediols and the formation of thioketals by use of silylated 1,2-ethylenedithiols and silylated 2-mer-captoethylamines have already been discussed in Sections 5.1.1 and 5.1.5. For cyclizations of ketones such as cyclohexanone or of benzaldehyde dimethyl acetal 121 with co-silyl oxyallyltrimethylsilanes 640 to form unsaturated spiro ethers 642 and substituted tetrahydrofurans such as 647, see also Section 5.1.4. (cf. also the reaction of 654 to give 655 in Section 5.2) Likewise, Sila-Pummerer cyclizations have been discussed in Chapter 8 (Schemes 8.17-8.20). 

Benzyl Bromide [Reductive Bromination of an Acetal].506 To a suspension of tin(II) bromide (5.1 mg, 0.02 mmol) and benzaldehyde dimethyl acetal (54.8 mg, 0.36 mmol) in CH2C12 (2.5 mL) were added successively Et3SiH (65.0 mg, 0.56 mmol) and acetyl bromide (96.8 mg, 0.79 mmol) in CH2C12 (1 mL) at room temperature under an argon atmosphere. The mixture was stirred for 3 hours at room temperature and quenched with a phosphate buffer (pH 7). 

The product possesses a homoallylic stannane moiety, which can be utilized as a useful synthon for cyclopropane formation (Scheme 68). Upon treatment of the homoallylstannane with HI, destannative cyclization takes place to give cyclopropylmethylsilane.271,272 A Lewis acid-catalyzed reaction with benzaldehyde dimethyl acetal affords vinylcyclopropane.273... 

Chiral hydroxy benzimidazole 267 was dialkylated with dibromomethane or benzaldehyde dimethyl acetal to form benzo[4,5]imidazo[l,2-f]oxazoles 268 and 269 (Equation 118) C1997TA1491, 1998TA2245>. After removal of the BOC group and formylation of the liberated amine, formylaminomethylthiazole cyclized in phosphoryl chloride to... 

Reaction of 1 with benzaldehyde and zinc chloride gave a diastereomeric mixture (6) of R- and 5-2,3-O-benzylidene derivatives (4a and 4b). The former (4a) would be identical to the acetal described by Zinner et al. (3) as 2,4-O-benzylidene-D-ribono-1,5-lactone. This structure was further established as 4a, by chemical and physical studies of the product obtained on reaction of 1 with benzaldehyde dimethyl acetal (7). The 2,3-O-benzylidene derivative, obtained by Garegg et al. (8) on reaction of 1 with a,a-dichlorotoluene in pyridine, has the same properties as compound 4a, which would indicate the -configuration for the acetal carbon. 

Table 9.37 Addition of benzaldehyde dimethyl acetal to allenylsilanes.

Cyclodextrins slow the rate of hydrolysis of benzaldehyde dimethyl acetal, PhCH(OMe)2, in aqueous acid as the substrate binds in the cyclodextrin s cavity, producing a less reactive complex. Added alternative guests compete for the binding site, displacing the acetal and boosting hydrolysis. 

Acetals of aldehydes are usually stable to lithium aluminum hydride but are reduced to ethers with alane prepared in situ from lithium aluminum hydride and aluminum chloride in ether. Butyraldehyde diethyl acetal gave 47% yield of butyl ethyl ether, and benzaldehyde dimethyl acetal and diethyl acetal afforded benzyl methyl ether and benzyl ethyl ether in 88% and 73% yields, respectively [792]. 

Uranium(VI) fluoride in l,l,2-trichloro-l,2,2-trifluoroethane at 0°C oxidizes12 aldehydes to acid fluorides in moderate yields (e.g., heptanoyl fluoride from heptaldehyde in 47% yield, benzoyl fluoride from benzaldehyde in 40% yield) benzaldehyde gives methyl benzoate and benzaldehyde dimethyl acetal when the reaction mixture is worked up by quenching with methanol.13... 

Homo-Reformatsky reaction.1 The reaction of 1-ethoxy-1-trimethylsilyloxy-cyclopropane (1) with an aldehyde in the presence of ZnCl2 results in y-silyloxy esters via a zinc homoenolate (a) of ethyl propionate (equation I). Znl2 is the preferred catalyst in the case of reactions with acetophenone and benzaldehyde dimethyl acetal and in reactions of l-isopropoxy-l-(t-butyldimethylsilyl-oxy)cyclopropane with aromatic aldehydes. 

To avoid stannyl reagents, there is the possibility to synthesize the same building block in one more step. First step is the formation of the benzylidene acetal 38 at the positions C-4 and C-6 of the glucal 10. The acetal formation at C-4 / C-6 is favored because you can get a six-membered instead of a five-membered ring at the position C-3 / C-4. To form 38 benzaldehyde dimethyl acetal 39 can be used with catalytic amounts of para-toluenesulfonic acid. 

Step 3 Selective /nmy-acetalization of the 1,3-diol with benzaldehyde dimethyl acetal. 

If the acetic acid is replaced by methanol in the electrolyte, the electrochemical oxidation yields the corresponding benzaldehyde dimethyl acetals in excellent yields. This reaction which was discovered by BASF181), can also be used for the industrial synthesis of aromatic aldehydes. 

Toluene itself cannot be oxidized to benzaldehyde dimethyl acetal under similar conditions (Rhone-Poulenc 189)) ... 

Propose a mechanism for the acid-catalyzed reaction of benzaldehyde with methanol to give benzaldehyde dimethyl acetal. 

TTie most common methods generally used to prepare benzylidene acetals involve (a) reaction of a diol with benzaldehyde in the presence of p-toluenesul-fonic acid or a Lewis acid (usually zinc chloride)144 145 — a reaction that is accelerated by ultrasonication146 — or (b) reaction of the diol with benzaldehyde dimethyl acetal (a,a-dimethoxytoluene) in the presence of camphorsuifonic acid or p-toluenesulfonic acid as shown in Scheme 3.79.147 Both 1,3-dioxolanes or 1,3-dioxanes can be formed under these conditions. Yields may be improved by running the reactions under reduced pressure to remove the methanol as it is formed.88-148... 

Benzylidenation of (/ )-butane-1,2,4-triol using either benzaldehyde (with azeotropic removal of water) or acetal exchange with benzaldehyde dimethyl acetal gave essentially the same result a mixture of three acetals in the ratio 90 5 5. 

Although (13) gives benzaldehyde dimethyl acetal (63%) upon further anodic oxidation, 3-methoxy-cycloheptatriene (14) (3-MCHT) and l>meAoxycycloheptatriene (15) (1-MCHT) afford 7,7-dimethoxy cycloheptatriene (16), which is a good precursor of tropone (equation 19). 

A solvent effect on diastereoselectivity was also observed with other substrates (Table XVIII). Generally, when aromatic aldehydes (benzaldehyde, furfural, 2-thiophenecarbaldehyde) and benzaldehyde dimethyl acetal were used, the ratio of threo to erythro products increased in the following order... 

Treatment of methyl a-D-glucopyranoside with benzaldehyde dimethyl acetal in the presence of camphorsulfonic acid (CSA) gives methyl 4,6-0-benzylidene-a-D-glucopyranoside. ... 

Step 2. Reductive cleavage of the acetal and reduction of the ester groups Step 3. Selective transacetalization of the 1,3-diol with benzaldehyde dimethyl acetal... 

---