Synthesis from aromatic aldehydes

The Willgerodt reaction allows amide synthesis from aromatic aldehydes or ketones, using a secondary amine and a thiating agent. The mechanism of the more convenient Kindler modification, employing sulfur and morpholine, has been reviewed.281... 

Isoquinoline synthesis from aromatic aldehydes or benzyl halides and aminoacetal (Pomeranz-Fritsch) or from benzylamines and glyoxal acetal (Schlitter-Muller) (see 1st edition). 

Arylidene-2-phenyl-5(47/)-oxazolones (azlactones) 121 were prepared via Erlenmeyer synthesis from aromatic aldehydes 119 and hippuric acid 120 employing calcium acetate under solvent-free conditions with microwaves irradiation <04TL425>. 

BORSCHE - BEECH Aromatic Aldehyde Synthesis Synthesis of aromatic aldehydes and of akyl aryl ketones from aldoximes or semcaibazones and aromatic dlazonum salts... 

Isequinoline synthesis Irom aromatic aldehydes and an aminoacetal (Pomeranz-Frttsch) or from phenethylamines and glyonal acetal (Schlitter-Muller). 

Bismuth(III) acetate catalyzes the synthesis of azlactones (17) from aromatic aldehydes in moderate to good yields via the Erlenmeyer synthesis. While the standard procedure for azlactone synthesis consists of using a stoichiometric amount of fused anhydrous sodium acetate, 10 mol% of Bi(OAc)3 is sufficient to catalyze the reaction and the crude product is found to be > 98% pure. 

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1 J-difluoroolefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a 1,3-dichloro-2-propanol derivative and ethyl-... 

Another example of a microwave-assisted 1,3-dipolar cycloaddition using azomethine ylides and a dipolarophile was the intramolecular reaction reported for the synthesis of hexahydrochromeno[4,3-fo]pyrrolidine 105 [70]. It was the first example of a solvent-free microwave-assisted intramoleciflar 1,3-dipolar cycloaddition of azomethine ylides, obtained from aromatic aldehyde 102 and IM-substituted glycinate 103 (Scheme 36). The dipole was generated in situ (independently from the presence of a base like TEA) and reacted directly with the dipolarophile present within the same molecifle. The intramolecu-... 

Nitroalkenes prepared from aromatic aldehydes are especially useful for natural product synthesis. For example, the products are directly converted into ketones via the Nef reaction (Section 6.1) or indoles (Section 10.2) via the reduction to phenylethylamines (Section 6.3.2). The application of these transformations are discussed later here, some examples are presented to emphasize their utility. Schemes 3.3 and 3.4 present a synthesis of 5,6-dihydroxyindole66 and asperidophytine indole alkaloid,67 respectively. 

Dipolar addition to nitroalkenes provides a useful strategy for synthesis of various heterocycles. The [3+2] reaction of azomethine ylides and alkenes is one of the most useful methods for the preparation of pyrolines. Stereocontrolled synthesis of highly substituted proline esters via [3+2] cycloaddition between IV-methylated azomethine ylides and nitroalkenes has been reported.147 The stereochemistry of 1,3-dipolar cycloaddition of azomethine ylides derived from aromatic aldehydes and L-proline alkyl esters with various nitroalkenes has been reported. Cyclic and acyclic nitroalkenes add to the anti form of the ylide in a highly regioselective manner to give pyrrolizidine derivatives.148... 

I.2. Oxidation of Amines Oxidation of primary amines is often viewed as a particularly convenient way to prepare hydroxylamines. However, their direct oxidation usually leads to complex mixtures containing nitroso and nitro compounds and oximes. However, oxidation to nitrones can be performed after their conversion into secondary amines or imines. Sometimes, oxidation of secondary amines rather than direct imine oxidation seems to provide a more useful and convenient way of producing nitrones. In many cases, imines are first reduced to secondary amines which are then treated with oxidants (26). This approach is used as a basis for a one-pot synthesis of asymmetrical acyclic nitrones starting from aromatic aldehydes (Scheme 2.5) (27a) and 3,4-dihydroisoquinoline-2-oxides (27b). 

In addition, iodine snccessfnlly catalyzed the electrophilic snbstitntion reaction of indoles with aldehydes and ketones to bis(indonyl)methanes [225], the deprotection of aromatic acetates [226], esterifications [227], transesterifications [227], the chemoselective thioacetalization of carbon functions [228], the addition of mercaptans to a,P-nnsatnrated carboxylic acids [229], the imino-Diels-Alder reaction [230], the synthesis of iV-Boc protected amines [231], the preparation of alkynyl sngars from D-glycals [232], the preparation of methyl bisnlfate [233], and the synthesis of P-acetamido ketones from aromatic aldehydes, enolizable ketones or ketoesters and acetonitrile [234],... 

Carrigan MC, Eash KJ, Oswald MC, Mohan RS (2001) An efficient method for the chemoselective synthesis of acylals from aromatic aldehydes using bismuth triflate. Tetrahedron Lett 42 8133-8135... 

Aggen DH, Arnold JN, Hayes PD, Smoter NJ, Mohan RS (2004) Bismuth compounds in organic synthesis. Bismuth nitrate catalyzed chemoselective synthesis of acylals from aromatic aldehydes. Tetrahedron 60 3675-3679... 

The nucleophilic addition of organometallic reagents to imines provides an attractive route to amines [4]. Recendy, however, some completely different approaches to the synthesis of a-aryl amine were reported. Hayashi and Ishigeda-ni found a new catalytic system for the asymmetric addition of arylstannanes to imines derived from aromatic aldehydes (Scheme 11) [20]. 

Several procedures for the synthesis of aromatic aldehydes are available which involve the selective oxidation of a methyl group attached to an aromatic ring. A useful general reagent is a solution of chromium trioxide in acetic anhydride and acetic acid. The aldehyde is converted into the gem-diacetate as it is formed and is thus protected from further oxidation. The aldehyde is liberated from the diacetate by hydrolysis under acid conditions the yields, however, are frequently only moderate (e.g. p-nitrobenzaldehyde, Expt 6.117). 

The Stacker reaction has been employed on an industrial scale for the synthesis of racemic a-amino acids, and asymmetric variants are known. However, most of the reported catalytic asymmetric Stacker-type reactions are indirect and utilize preformed imines, usually prepared from aromatic aldehydes [24]. A review highlights the most important developments in this area [25]. Kobayashi and coworkers [26] discovered an efficient and highly enantioselective direct catalytic asymmetric Stacker reaction of aldehydes, amines, and hydrogen cyanide using a chiral zirconium catalyst prepared from 2 equivalents of Zr(Ot-Bu)4, 2 equivalents of (R)-6,6 -dibromo-1, l -bi-2-naphthol, (R)-6-Br-BINOL], 1 equivalent of (R)-3,3 -dibromo-l,l -bi-2-naphthol, [(R)-3-Br-BINOL, and 3 equivalents of N-methylimida-zole (Scheme 9.17). This protocol is effective for aromatic aldehydes as well as branched and unbranched aliphatic aldehydes. 

Catalysis by TEMPO has the advantage of being general for oxidation of both benzylic or non benzylic alcohols to aldehydes, whereas catalysis by PINO, although limited to the synthesis of aromatic aldehydes, has the advantage that the radical is generated in situ from the less expensive N-hydroxyphthalimide, which can be more easily recovered and recycled. 

The Hantzsch pyridine synthesis is an old discovery (1882) which sprang into prominence in the 1980s with the discovery that the dihydropyridine intermediates prepared from aromatic aldehydes are calcium channel blocking agents and therefore valuable drugs for heart disease with useful effects on angina and hypertension. 

One-pot synthesis of ( )-alkenes has been directly performed from nitromethane by a radical process (Liu and Yao, 2001). In fact, the strategy is to react P-nitrostirene (3) as shown in Figure 2.1, in situ prepared from aromatic aldehydes (1) with nitromethane (2) in the acetic acid solution with a catalytic amount of ammonium acetate at 70-100°C, with triethylborane in the biphase of diethyl ether and aqueous solution in the presence of oxygen in air as radical initiator, to generate (4). 

Aryl -a-aminopropionic acids are obtained by reduction of azlactones with phosphorus and 50% aqueous hydriodic acid in glacial acetic acid. Many other reducing agents have been used. Reviews of this synthesis and related reactions have been made. The azlactones are conveniently prepared in good yields from aromatic aldehydes and N-acyl derivatives of glycine. Potassium carbonate has been found to be a superior catalyst for this condensation. Ketones cannot be substituted for the aromatic aldehydes. ... 

Synthesis From Alcohols.— The general methods of synthesis of aromatic aldehydes and ketones are several. The aldehydes may be prepared by the direct oxidation of the corresponding primary alcohol, usually with dilute nitric acid, e.g.. 

Improved Synthesis of Aromatic Aldehydes from Ozonolysis of Olefins... 

Pomeranz-Fritsch reaction Synthesis of isoquinolines from aromatic aldehydes and 2,2-dialkoxvethylamine. 358... 

Phase-transfer catalysis is a useful procedure for a variety of interesting metal-catalyzed reactions. - However, only one example of this approach has been reported for the synthesis of diynes by the sp-sp carbon coupling reaction. Thus vinylic dibromides derived from aromatic aldehydes have been shown to react with carbon monoxide, in the presence of zerovalent palladium compounds as the metal catalyst, and under phase-transfer conditions in a two-phase system (benzene, 5 M NaOH), to give the corresponding diynes in reasonable yields (equations 21 and 22). ... 

Condensations. Alumina promotes the formation of a-hydroxyphosphonate esters from aromatic aldehydes and dialkyl phosphonates, and the adducts are converted to a-aminophosphonate esters on reaction with ammonia. A solvent-free synthesis of a-nitro ketones comprises mixing nitroalkanes, aldehydes, and neutral alumina and oxidizing the adducts with wet, alumina-supported CrOj (15 examples, 68-86%). The Knoevenagel reaction, the Michael addition of nitromethane to gcm-diactivated alkenes, and the formation of iminothiazolines from thioureas and a-halo ketones are readily effected with alumina under microwave irradiation. 

Bao W, Wang Z (2006) An effective synthesis of bromoesters from aromatic aldehydes using tribromide ionic liquid based on f prolinol as reagent and reaction medium under mild conditions. Green Chem 8 1028-1033... 

Base catalyzed synthesis of a-hydroxyphosphonates from aromatic aldehydes and diethyl phosphite... 

An interesting route to a-carboxy-8-lactones (81) and a-methylenelactones (80), based on hydrolysis of Knoevenagel products (79) of Meldrum s acid with cyclic aliphatic ketones (78), has been developed (Scheme 14). Reduction of 5-methylene derivatives of Meldrum s acid has been performed catalyti-caiiyi30 or by use of LAH. Imidoylation reaction of Meldrum s acid and subsequent solvolysis of the resulting (82) yields -enamino esters (83) in good yields.Flash vacuum pyrolysis of alkylidene derivatives of Meldrum s acid can be used to prepare methylene ketenes (84), a class of compounds difficult to prepare by conventional methods. By this procedure, methylene ketenes are obtained from aromatic aldehydes and ketones and from aliphatic ketones in only two steps. Intramolecular trapping of the methylene ketene obtained from the ketone (85) has been used successfully in the synthesis of the naphthol (86). ... 

A new, mild and general method for the synthesis of aryl-substituted-1,3,5-triazines from aromatic aldehydes and ammonia has been found. Treatment of a 1 1 pyridine, concentrated ammonia solution of aromatic aldehyde with excess of Fremy s salt at room temperature gave a readily separable mixture of a primary amide and 1,3,5-triazine (189). A,A-Dibenzylidenephenyl-methanediamine (190) on similar treatment produced almost identical results (Scheme 56) <85S95>. Extension of the reaction to aliphatic aldehydes does not appear to be possible as attempts to oxidize 2,4,6-trimethyl-hexahydro-1,3,5-triazine with Fremy s salt gave rise to complex mixtures, in low yield. 

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