Electron aromatic aldehydes

The phenylacetic acid derivative 469 is produced by the carbonylation of the aromatic aldehyde 468 having electron-donating groups[jl26]. The reaction proceeds at 110 C under 50-100 atm of CO with the catalytic system Pd-Ph3P-HCl. The reaction is explained by the successive dicarbonylation of the benzylic chlorides 470 and 471 formed in situ by the addition of HCl to aldehyde to form the malonate 472, followed by decarboxylation. As supporting evidence, mandelic acid is converted into phenylacetic acid under the same reaction conditions[327]. 

The cation—radical intermediate loses a proton to become, in this case, a benzyl radical. The relative rate of attack (via electron transfer) on an aromatic aldehyde with respect to a corresponding methylarene is a function of the ionization potentials (8.8 eV for toluene, 9.5 eV for benzaldehyde) it is much... 

By using an aromatic aldehyde carrying an electron-releasing group the intermediate cation can be stabilized. This is the basis of the widely-used Ehrlich colour reaction for pyrroles, indoles and furans which have a free reactive nuclear position (Scheme 21). 

AC2O, PCI3, 20°, 1-24 h, 30-90% yield. Aromatic aldehydes bearing electron-withdrawing groups tend to give low yields under these conditions. 

For cyclopentanone, cyclohexanone, and cycloheptanone, the K values for addition are 48, 1000, and 8 M , respectively. For aromatic aldehydes, the equilibria are affected by the electronic nature of the aryl substituent. Electron donors disfavor addition by stabilizing the aldehyde whereas electron-accepting substituents have the opposite effect. 

Both aromatic and aliphatic acids work, though aromatic aldehydes are far more common. Increasing electron density of the aromatic aldehyde lowers the yield. Formaldehyde can also be used."... 

The reaction of electron-rich aromatic compounds with yV,A -dimethylformamide 2 and phosphorus oxychloride to yield an aromatic aldehyde—e.g. 3 from the substituted benzene 1—is called the Vilsmeier reaction or sometimes the Vilsmeier-Haack reaction. It belongs to a class of formylation reactions that are each of limited scope (see also Gattermann reaction). 

One further comparison aromatic aldehydes, such as benzaldehyde, are less reactive in nucleophilic addition reactions than aliphatic aldehydes because the electron-donating resonance effect of the aromatic ring makes the carbonyl group less electrophilic. Comparing electrostatic potential maps of formaldehyde and benzaldehyde, for example, shows that the carbonyl carbon atom is less positive (less blue) in the aromatic aldehyde. 

Similarly, Dakka and Sasson (ref. 26) showed that benzylic alcohols could be selectively oxidized to the corresponding aromatic aldehydes using HBr/H202 as the oxidant (Fig. 23). The reaction was not successful with electron-rich aromatics which underwent competing nuclear bromination. 

Many known color reactions involve electrophilic substitution at an electron-rich aromatic or heteroaromatic (cf. 4-(dimethylamino)-benzaldehyde - acid reagents and vanillin reagents ). Here aliphatic or aromatic aldehydes react in acid medium to yield polymethyne cations which are intensely colored di- or triarylcarbenium ions [4, 10]. 

With para-substituted aromatic aldehydes, electronic factors had little effect on the ee (52-64%), and similar ee s were obtained for the other substrates [25]. 

Samarium diiodide is another powerful one-electron reducing agent that can effect carbon-carbon bond formation under appropriate conditions.257 Aromatic aldehydes and aliphatic aldehydes and ketones undergo pinacol-type coupling with Sml2 or SmBr2. 

Bieber reported that the reaction of bromoacetates is greatly enhanced by catalytic amounts of benzoyl peroxide or peracids and gives satisfactory yields with aromatic aldehydes. A radical chain mechanism, initiated by electron abstraction from the organometallic Reformatsky reagent, is proposed (Scheme 8.27).233 However, an alternative process of reacting aldehydes with 2,3-dichloro-l-propene and indium in water followed by ozonolysis provided the Reformatsky product in practical yields.234 An electrochemical Reformatsky reaction in an aqueous medium and in the absence of metal mediator has also been reported.235... 

This method is particularly useful for electron-deficient aromatic aldehydes, but it is not efficient with aliphatic aldehydes, probably a consequence of competitive aldol reaction. 

The criss-cross addition of azines of aromatic aldehydes with various electron-deficient olefins in which the double bond is terminal, for example, methyl acrylate, acrylonitrile, or in which allylic substituents do not sterically hinder the reaction, for example, maleic anhydride, is well known and was duly covered in CHEC-II(1996)<1996CHEC-II(8)747>, as well as in a review <1997ALD97>. Recently, the reaction has been used for the preparation of hyperbranched polymers <1998MI2655, 2002MAC712>. 

Tandem reaction of aromatic aldehydes with electron-deficient acetylenes and dialkyl acetylenedicarboxylates in the presence of I it iN led to the formation of fully substituted furans in moderate yields. One appropriate example is shown below <06EJOC5174>. 

Yokomatsu, T., Yamagishi, T., and Shibuya, S., Enantioselectivity for hydro-phosphonylation of aromatic aldehydes catalyzed by lanthanum binaphthol complex. Remarkable electronic effect of aromatic substituents, Tetrahedron Asymm., 4, 1783, 1993. 

The Bulfington group [17] at Johnson and Johnson Pharmaceutical have also developed a very efficient and concise synthesis (Scheme 5) of the Furst-ner intermediate (6) to lukianol A. The synthesis relies on the condensation of benzyl nitriles with aromatic aldehydes under basic conditions to give the corresponding electron deficient alkenes (23). 

The mechanism proposed for the aldehyde dehydrogenases includes an enzyme-bound hemiacetal intermediate, possibly via a thioester bond with a cysteine (100). The specificity of the enzyme for aldehydes is quite broad. Apparent Km values for many aliphatic and aromatic aldehydes are in the micromolar range, with the highest reaction velocities observed for aldehydes with electron-with-drawing substituents on the a carbon for aliphatic aldehydes and in the para position for aromatics (99). 

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