P-Chlorobenzaldehyde

All these routes use known reactions and are about the same length. Do you notice that no less than three have the unsaturated acid 353A as an intermediate. If we need to try out new reactions it is best to choose a route with a common intermediate (353A here) so that if one route fails we can use the same intermediate for another. We can then choose between the three routes on cost. The 1977 prices of the starting materials are p-chlorobenzaldehyde 9.80/500g diethyl rnalonate 2.80/500g... 

Cost per mole is the relevant figure p-chlorobenzaldehyde, MW 140.5, costs 2.75 per mole. 

A is common to all the routes we are considering but it is obviously cheaper to use a mole of cyanide or nitromethane rather than another mole of rnalonate. In fact, though, these contribute relatively httle to the cost, the main part being p-chlorobenzaldehyde. So, use whichever route you hke ... 

In a variation on this approach, p-chlorobenzaldehyde is rst condensed with 2-aminopyridine. Reduction of the resulting iff base (62) affords the corresponding secondary amine. Alkyl-ion with the usual side chain affords the antihistamine, chlor-ramine (64). ... 

Condensation of p-chlorobenzaldehyde with 3-mercaptopropionic acid in the presence of ammonium carbonate leads to the thiazi-none, 179. The reaction very probably proceeds by the intermediacy of the carbonyl addition product, I7S lactamization completes formation of the observed product. Oxidation of 179 to the sulfone by means of potassium permanganate in acetic acid gives chlormezanone (180), a minor tranquilizer with muscle-relaxant properties. 

Reduction of carbonyl groups Terpene and aromatic aldehydes (lOOppm) were reduced by microalgae. In a series of chlorinated benzaldehyde, m - or p-chlorobenzaldehyde reacted faster than the o-derivative. Due to toxicity, the substrate concentrations are difficult to increase. Asymmetric reductions of ketones by microalgae were reported. Thus, aliphatic " and aromatic " ketones were reduced. 

The Claisen-Schmidt condensation of 2 -hydroxyacetophenone and different chlorinated benzaldehydes over MgO has been investigated through kinetic and FTIR spectroscopic studies. The results indicate that the position of the chlorine atom on the aromatic ring of the benzaldehyde substantially affects the rate of this reaction. In particular, the rate increases in the following order p-chlorobenzaldehyde < m-chlorobenzaldehyde < o-chlorobenzaldehyde. The difference between the meta and para-substituted benzaldehyde can be attributed to electronic effects due to the difference in the Hammett constants for these two positions. Steric effects were found to be responsible for the higher rate observed with the o-chlorobenzaldehyde. 

Additional adsorption studies were also carried out using para- and ortho-chlorobenzaldehydes (Figure 4). The results obtained with p-chlorobenzaldehyde are very similar to the ones obtained with m-clilorobenzaldehyde and were omitted from this paper for brevity. In contrast, substantial differences are observed in the spectra of adsorbed o-chlorobenzaldehyde. In particular, in this case the 1620 cm"1 band characteristic... 

In addition to the ionic liquid-mediated procedure in solution (see Scheme 6.112), Leadbeater and coworkers also presented a solid-phase protocol for a one-pot Mannich reaction employing the above mentioned chlorotrityl linker [67]. In this approach, p-chlorobenzaldehyde and phenylacetylene were condensed with readily prepared immobilized piperazines (Scheme 7.56). 

Cations, cyclopropenyl, 54, 97 o-Chlorobenzaldehyde, by reduction of o-chlorobenzonitrile with Raney nickel alloy in formic acid, 51, 23 p-Chlorobenzaldehyde, by redaction of p-chlorobenzonitflle with Raney nickel alloy,1 51, 22... 

Reaction of telluronium salts/n-BuLi with carbonyl compounds synthesis of alcohols with telluronium salt (a2) (typical procedure) A solution of n-BuLi (1.1 mmol) in hexane is added to a solution of the telluronium salt (0.459 g, 1.2 mmol) in THF (6 mL) at -78°C under N2. The mixture is warmed at -60°C and stirred for 10 min. After cooling again at -78°C, p-chlorobenzaldehyde (0.140 g, 1.0 mmol) in THF (2 mL) is added. The mixture is then allowed to warm at room temperature. After the reaction is complete (monitored by TLC), the usual work-up and flash chromatography yield pure p-chlorophenyl(phenyl)carbinol. 

This procedure is to be avoided with steam-volatile aldehydes (e.g., p-chlorobenzaldehyde) in which case the reduction product is isolated by solvent extraction.4... 

Our first results in this field were published in 1999 [13], when we reported that ferrocene 9 was capable of catalyzing the enantioselective addition of diphe-nylzinc to aromatic aldehydes, affording diaryl methanols with good to high enantioselectivities. For example, from the reaction between p-chlorobenzaldehyde 37a and diphenylzinc 7 in the presence of 5 mol% ferrocene 9 (at 0 °C), product 27a was obtained with 82% ee (Scheme 2.1.2.6). 

Fig. 2.1.2.1 Reaction profile of the phenylzinc addition to p-chlorobenzaldehyde 37a, as determined by FT-IR. Curve A ZnPh2 (0.65 equiv), ZnEt2 (1.3 equiv), toluene, rt. Curve B ZnPh2 (1.50 equiv), toluene, rt.

Problem 15.18 Prepare the following compounds from benzene, toluene, and alcohols of four or fewer C s (a) 2-methylpropanal (isobutyraldehyde), (b) p-chlorobenzaldehyde, (c) p-nitrobenzophenone (p-NOjCftH4COC,.H,), (d) benzyl methyl ketone, (e) p-methylbenzaldehyde. ... 

Problem 15.21 For the Cannizzaro reaction, indicate (a) why the reaction cannot be used with aldehydes having an a H, —CHCHO (b) the role of OH and OD (Problem 15.20) (c) the reaction product with ethanedial, 0==CH—CH==0 (d) the reaction products of a crossed-Cannizzaro reaction between (i) formaldehyde and benzaldehyde, (ii) benzaldehyde and p-chlorobenzaldehyde. ... 

The initially patented synthesis of cetirizine (4) by UBC S. A. in Belgium was an extension of the hydroxyzine (41) synthesis.Gngnard addition to p-chlorobenzaldehyde gave (4-chloro-phenyl)-phenyl-methanol, which was easily brominated using PBrs in benzene to give 4-chlorodiphenylmethyl bromide (42). Sn2... 

Condensation of 2-hydrazinopyrimidine (384) with an aromatic aldehyde formed the Schiff bases (386), which then cyclized with bromine to 6-bromo-l,2,4-triazolo[4,3-a]pyrimidine (383) and with carbon disulfide to 387 (92PS145). A similar cyclization was effected also on 384 to give 388 (68T2839 85FRP2549834), but the cyclization of 384 or 385 with carbon disulfide afforded 3-thiolo-l,2,4-triazolo[4,3-a]pyrimidin-7-ones 389 and 390, respectively. A small amount of the isomeric 3-thiolo-l, 2,4-triazolo[4,3-a]pyrimidin-5-one was isolated in the former case (68T2839). Reaction of 385 with benzaldehyde [67JCS(C)498] or p-chlorobenzaldehyde (90MI3) followed by oxidation with LTA in benzene afforded 391 (Scheme 73). 

An interesting variation in reactivity has also been shown20 in the carbocyclic series on reaction of Schiff s base derived from aniline and p-chlorobenzaldehyde with a number of isomeric dichlorotoluenes. 2,4-Dichlorotoluene yields only the expected stilbene 2,5-dichloro-toluene, according to reaction conditions and molar ratios, gives either the stilbene or 1,2,3-triarylpropane, whereas 2,6-dichlorotoluene yields only the addition product 24. 

A mixture of p-chlorobenzaldehyde If (0.7 g, 5 mmol), aniline 2f (0.455 g, 5 mmol) and montmorillonite K-10 clay (0.1 g) contained in a 25-mL beaker was placed in an alumina bath inside the microwave oven and irradiated for 2 min. The in situ generated Schiff s base was mixed thoroughly with freshly prepared NaBH4-clay (5.0 mmol of NaBH4 on 1.72 g of reagent) and water (1 mL). The reaction mixture was again irradiated for 30 s (65 °C). Upon completion of the reaction, monitored on TLC, the product was extracted into methylene chloride (3x 15 mL). The removal of solvent under reduced pressure provided pure /V-phe-nyl-p-chlorobenzylamine 4f in 90% yield. The identity of the product was confirmed by formation of the hydrochloride salt, mp 209-211 °C. 

---