Erlenmeyer synthesis

Azlactones — see also l,3-Oxazolin-5-ones Erlenmeyer synthesis, 6, 202 hydrolysis, S, 64, 101 tautomerism, 6, 186 unsaturated... 

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. 

The now readily available 2-thenaldehydes were utilized for the preparation of azlactones involving the Erlenmeyer synthesis ... 

Erlenmeyer synthesis org chem Preparation of cyclic ethers by the condensation of an aldehyde with an a-acylamino acid in the presence of acetic anhydride and sodium acetate. 3r-l3n,mT-3r sin-th3-s3s erucic acid org chem C22H42O2 A monoethenoid acid that is the cis isomer of bras-sidic acid and makes up 40 to 50% of the total fatty acid in rapeseed, wallflower seed, and mustard seed crystallizes as needles from alcohol solution, insoluble in water, soluble in ethanol and methanol. o rus ik as ad erythrite See erythritol. er o.thrTt ... 

The first procedure to prepare unsaturated 5(4//)-oxazolones was the Erlenmeyer synthesis" " that was described more than one hundred years ago and is still used extensively with some variations in the experimental conditions. In general, the reaction employs an acylamino acid, for example, A-acetyl- or A-benzoylglycine are the most common, and a carbonyl compound, usually an aldehyde, in the presence of a cyclodehydrating agent such as acetic anhydride (Scheme 7.114). Hundreds of unsaturated oxazolones 363 have been obtained via this procedure and these compounds are valuable intermediates for the synthesis of many interesting organic compounds. 

The Erlenmeyer synthesis usually proceeds with a very high degree of stereoselectivity to favor the thermodynamically more stable (Z) isomer that is easily isolated by recrystallization. In some cases, the (Z) isomer is the only product obtained. This general methodology has been used extensively to prepare of a wide variety of unsamrated oxazolones. 

The classical experimental conditions of the Erlenmeyer synthesis use anhydrous sodium acetate and acetic anhydride to effect cyclodehydration. However, many other reagent combinations have been used to improve the yield and the stereoselectivity of the reaction. With these aims in mind, zinc acetate,... 

Bis-4-arylidene-5(4//)-oxazolones are easily obtained from aromatic dialdehydes by the Erlenmeyer synthesis. Such bis(oxazolones) react with a,co-diamines to provide a convenient approach to macrolactams.Tandem Erlenmeyer condensation-macrolactamization (TECM) has been used to prepare analogues of naturally occurring, biologically active cyclic peptides such as bastadin-5. 

Condensation of A -acylglycines with carbonyl compounds, the Erlenmeyer synthesis, continues to be exploited to prepare of a wide variety of unsaturated-5(47/)-oxazolones. The reaction is performed in the presence of a cyclodehydrating agent and recently bismuth(lll) acetate has been evaluated in this capacity. Alternatively, unsaturated 5(47/)-oxazolones can be obtained from hippuric acid and a carbonyl compound or from the appropriate dehydroamino acid derivative using 3-(aIkoxycarbonyl)benzotriazole-l-oxides as the cyclodehydrating agent. 

L-Dopa was produced industrially by Hoffrnann-LaRoche, using a modification of the Erlenmeyer synthesis for amino acids. In the 1960s, research at Monsanto focused on increasing the L-Dopa form rather than producing the racemic mixture. A team led by William S. Knowles (1917—) was successful in producing a rhodium-diphosphine catalyst called DiPamp that resulted in a 97.5% yield of L-Dopa when used in the Hoffrnann-LaRoche process. Knowles s work produced the first industrial asymmetric synthesis of a compound. Knowles was awarded the 2001 Nobel Prize in chemistry for his work. Work in the last decade has led to green chemistry synthesis processes of L-Dopa using benzene and catechol. 

Oxazolones are attacked by a variety of electrophiles at C(4) these reactions, which require the presence of bases, proceed through the enolate anions (197). This type of anion adds to carbonyl compounds, a key step in the Erlenmeyer synthesis of unsaturated azlactones (equation 35) (see Section 4.18.4.3.4). The anions are intermediates in the formation of the amides (198) when oxazolones are treated with enamines (Scheme 15) (71JCS(C)598>. 

An extension of the Erlenmeyer synthesis is the condensation of acylamino acids with triethyl orthoformate which leads to the ethoxymethylene derivatives (297). These can be hydrolyzed to the corresponding enols, which in turn can be converted into chloromethylene compounds, e.g. (298). The lability of the chlorine atom in this compound (see arrows) can be put to good account reaction with organometallic compounds or with benzene and its derivatives under Friedel-Crafts conditions yields unsaturated lactones (298 aryl or heteroaryl in place of Cl). The method is especially valuable in cases where the aldehyde is not readily available. 

Acylaminocarboxylic acids 288 are converted into 5(4//)-oxazolinones 289 by acid anhydrides (Scheme 140). In an extension of this reaction, A-acyl derivatives of glycine 290 react with aldehydes with concomitant cyclization to give azlactones 291 (Scheme 141) this is the basis of the Erlenmeyer synthesis of amino acids. Treatment of amino acid derivatives 292 with PBr3 affords the thiazolidine-2,5-dione 293 (Scheme 142) <1971CB3146>. 

Mogilaiah, K., Prashanthi, M., Reddy, C. S. Solid support Erlenmeyer synthesis of aziactones using microwaves. Indian J. Chem., Sect. B 2003, 42B, 2126-2128. 

In a manner related to the Erlenmeyer synthesis, hippuric acid (34) is converted to the oxazole (35) by the action of IV-methylformanilide and... 

Bids and Bi(OTf)3 catalyze the carbonyl-ene reaction [181] and Diels-Alder reaction [182] without diene polymerization (Scheme 14.89). The tandem [4-+2] cycloaddition reaction (Scheme 14.90) [183] and the Erlenmeyer synthesis of azalactones (Scheme 14.91) [184] are catalyzed by BiCl3 and by Bi(OAc)3, respectively. 

Two syntheses of cyclopenin have been fully described. " One involved the preparation of a penultimate intermediate (21) as a mixture of two double bond isomers which were separated and transformed by epoxidation with meta-chloroperbenzoic acid into cyclopenin (18) and isocyclopenin respectively. In the other, the same intermediate (21) was prepared by two stereospecific routes starting with hippuric acid derivatives (23)." The Erlenmeyer synthesis on (23) produced the ester (22) which gave the benzodiazepine (21) in two steps. An extension of this approach led to the synthesis of cyclopenol [(18), m-HOC6H4 for Ph]. 

The Erlenmeyer azalactone synthesis generally affords predominantly, and often exclusively, (Z) isomers (32). However, a simple method for the synthesis of ( ) isomers (33), obtained previously by separation of isomeric mixtures or isomerization procedures, has been reported. Aromatic aldehydes condense with hippuric acid when heated in polyphosphoric acid (PPA) to afford (33) in 80-90% yields (equation 17 Table 4). Alternatively, the (Z) isomers may be heated in PPA to afford the corresponding ( ) isomers in excellent yield. The authors note that hippuric acid is not converted to (26) in PPA, the generally accepted intermediate in the Erlenmeyer synthesis. Furthermore, both isomers of 2-(benzamid-oyl)cinnamic acid, (34) and (35), obtained by the alkaline hydrolysis of (32 R = H, Ar = Ph) and (33 R = H, Ar = Ph), respectively are converted to (33 R = H, Ar = Ph) in PPA (Scheme 9). The authors therefore suggest a mechanism involving condensation, first of the aldehyde and hippuric acid followed by... 

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>. 

While the classical Erlenmeyer synthesis of azlactones (condensation of aldehydes with hippuric or aceturic acid in the presence of acetic... 

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