Reactions aromatic amidation

It was found inadvisable to use more than four molecules of form-amide [ (47) when R = H] per molecule of anthranilic acid and the condensation produces best results when the mixture is heated at 120 -130°C for 2 hr followed by further heating at 170°-180 C for 2 hr. Other variants of this reaction involve the use of ammonium o-acylaminobenzoates, anthranilic acid in the presence of nitriles and acetic anhydride, o-acetamidonitrile with acetic anhydride or hydrogen peroxide, anthranilic esters and aliphatic or aromatic amides or amidines, isatoic anhydride with amides or amidines, and anthranilic esters with aryl iminochlorides in acetoned The mechanism proposed by Bogert and Gotthelf has had experimental supporR and is represented in Scheme 12. 

Application of the Bischler-Napieralski reaction to amides of tryptophan has been investigated. The cyclodehydration of acetyltrypto-phan under conventional conditions proved unsuccessful. Attempted ring closure of acetyltryptophan or its ethyl ester was accompanied by decarboxylation and aromatization, yielding... 

The N-bromination of amides with bromine and alkali has been extensively researched as the first step of the Hofmann degradation. However, it is difficult to isolate the N-bromoamides because of their subsequent reaction to produce amines, which proceeds very readily under excessive alkaline conditions. Now, the reaction of amides with a stoichiometric amount of BTMA Br3 and sodium hydroxide in ice-water gave N-bromoamides in fairly good yields. Our method can be applied to various types of aliphatic, aromatic, and heterocyclic amides (Fig. 31) (ref. 39). 

The nucleophile assisted ring-opening reactions of phosphonate bearing phthahmide 13 has been utihzed in the synthesis of mixed primary phosphine-phosphonate and aromatic amide functionahzed primary bisphosphines as out-hned in Scheme 6 [50],... 

Based on the char yield after correction, we found that all the additives improved the char yield of PMI. ZnCl2 was 40% higher than that of pure PMI. The ZnCl2 probably catalyzes the reaction of cyano groups with itself or with aromatic amide rings, but we have not experimentally studied this. 

The aromatic amides have attracted considerable interest from the photochemical point of view. However, anilides are less prone to photochemical rearrangements than the analogous phenyl esters. For this reason, the side reactions involving other parts of the molecule may compete favorably with PFR. Shizuka started the study of anilides in the 1960, and thereafter a number of papers have appeared dealing with the PFR of A -acyl anilines, carbazoles, indoles, and so forth. 

The a-hydroxyamino intermediates from reduction of aromatic amides in acetonitrile can be trapped in the presence of chlorotrimethylsUane and subsequent work-up yields the aromatic aldehyde in good yields. This reaction has been car-... 

In a systematic study of the chemistry of A-sulfinylamines (R—N=SO), Kresze and his co-workers33 demonstrated the outstanding reactivity of the closely related A-sulfinylsulfonamides (RS02N=S0). Their initial sulfinylating action [e.g. on alcohols and amines, Eqs. (1) and (2)] may be followed by immediate further reaction. Thus, amides yield nitriles [Eq. (3)], while both aromatic and aliphatic thioamides are converted into 3,5-disubstituted 1,2,4-thia-diazoles [Eq. (4)] in satisfactory yields. 

IV.192. REACTIONS AND CHARACTERISATION OF SUBSTITUTED AROMATIC AMIDES (AROMATIC ACYLATED BASES)... 

Reaction XCVII. Hydrolysis of Amides, Acid Chlorides and Acid Anhydrides. (A., 188, 73 B., 26, R 773 28, R., 917, 32, 1118.)—All these compounds on hydrolysis yield acids. The anhydrides are hydrolysed by treatment with water or dilute alkali, the acid chlorides are usually very rapidly hydrolysed by water, but in the aromatic series 10% caustic alkali is sometimes necessary. The amides are boiled with caustic alkali solution (10%) or with cone, hydrochloric or sulphuric acid. They are, especially the substituted aromatic amides, very resistant to the action of acids, so that the former method is the best. Another method is to dissolve the amide in cone, sulphuric acid, and add sodium nitrite in the cold, afterwards gently warming. Sometimes dilute sulphuric acid and addition of the nitrite in the warm gives better results. 

By treatment of an amide with sodium hypobromite or sodium hypochlorite solution (or with halogen admixed with aqueous alkali), a primary amine having one less carbon atom is produced. Good yields are obtained when the reaction is applied to most aliphatic and aromatic amides. Examples are provided by the preparation of anthranilic acid and 3-aminopyridine (Expt 6.53). 

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... 

When the crystal of 59c was irradiated at 0°C, a single regioisomer of 60c was obtained quantitatively. The photoproduct 60c showed an ee of 42%. Furthermore, a higher ee value of 60c (87% ee) was obtained in the reaction at -50°C. The radical mechanism has been confirmed in the photo-Fries rearrangement of aromatic amides. 

Palladium-catalyzed carbonylation reactions with aryl halides are powerful methods of generating aromatic amides, hydrazides, esters and carboxylic acids [25]. We have previously reported the exploitation of Mo(CO)6 as a robust carbon monoxide-releasing reagent in palladium-catalyzed carbonylation reactions [26-29]. This stable and inexpensive solid delivers a fixed amount of carbon monoxide upon heating or by the addition of a competing molybdenum coordinating ligand (for example DBU). This allows for direct liberation of carbon monoxide in the reaction mixture without the need for external devices. 

One of our initial forays into Mo(CO)6-promoted carbonylations included the investigation of intermolecular reactions using amines as nucleophiles to form secondary and tertiary aromatic amides from aryl bromides and iodides [27]. Subsequent work using the activating preligand f-Bu3PHBF4 has allowed for the extension of this chemistry into examples using aryl chlorides as substrates (Scheme 1) [30]. 

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