Amino Anhydrides

The subsequent fast intramolecular rearrangement of the amino anhydride [197, 198]... 

The polymerization reaction followed second-order kinetics which was rationalized by assuming that the bimolecular rearrangement involving two monomer molecules was the rate determining step. It has been assumed that the isomerization results in the formation of the amino anhydride (XXXIV) or its dimer (XXXV), viz. 

The polymerization of the carboxy-lactam (XXXIII) proceeded with a distinct induction period [247] (tj) which was taken into account in the evaluation of the conversion data. The monomer is consumed in the isomerization reaction (152) with the formation of the amino anhydride (S) the rate being... 

N-carboxy-a-amino anhydride (2), presumably through the acid chloride. Anhy-drides of type (2) are useful starting materials for the synthesis of polypeptides.21 21D. Konopihska and I. Z. Siemion,/) Chem. internal. Ed., 6,248 (1967)... 

Some Fmoc-amino adds are not readily soluble in DCM and will require the addition of DMF to assist complete dissolution. Many Fmoc-amino anhydrides are also poorly soluble in DCM and will precipitate from the reaction mixture as they are formed. However, this is not a problem, since they re-dissolve in... 

Phthalyl derivatives. Many amino acids condense with phthalic anhydride at 180-185° to yield crystaUine phthalyl derivatives ... 

Place 0-5 g. of the amino acid and 1 0 g. of phthalic anhdride in a Pyrex test-tube and immerse the lower part of the tube in an oil bath, which has previously been heated to 180-185°. Stir the mixture occasionally during the first 10 minutes and push down the phthalic anhydride which sublimes on the walls into the reaction mixture with a glass rod. Leave the mixture undisturbed for 5 minutes. After 15 minutes, remove the test-tube from the bath when the liquid mass solidifies, invert the test-tube and scrape out the excess of phthalic anhydride on the walls. RecrystaUise the residue from 10 per cent ethanol or from water. 

Acetates may also be prepared by adding acetic anhydride to somewhat dilute solutions of compounds containing hydroxyl (or amino) groups in aqueous caustic alkahs. The amount of alkali used should suffice to leave the hquid shghtly basic at the end of the operation, so much ice should be added that a little remains unmelted, and the acetic anhydride should be added quickly. 

Hydrolysis of the azlactone leads to the acylaminooinnamic acid the latter may be be reduced catal3rtlcally (Adams PtOj catalyst 40 lb. p.s.i.) and then hydrolysed by hydrochloric acid to the amino acid. Alternatively, the azlactone (say, of a-benzylaminocinnamic acid) may undergo reduction and cleavage with phosphorus, hydriodic acid and acetic anhydride directly to the a-amino acid (d/ p phenylalanine). 

Phenacetin may be conveniently prepared in the laboratory from p-amino-phenol. The latter is readily acetylated with acetic anhydride to give p-acetyl-aminophenol this Is ethylated in the form of the sodio derivative to yield acetyl p-phenetidine (phenacetin) ... 

Other substituents which belong with this group have already been discussed. These include phenol, anisole and compounds related to it ( 5.3.4 the only kinetic data for anisole are for nitration at the encounter rate in sulphuric acid, and with acetyl nitrate in acetic anhydride see 2.5 and 5.3.3, respectively), and acetanilide ( 5.3.4). The cations PhSMe2+, PhSeMe2+, and PhaO+ have also been discussed ( 9.1.2). Amino groups are prevented from showing their character ( — 7 +717) in nitration because conditions enforce reaction through the protonated forms ( 9.1.2). 

Maleic anhydride condenses with 2-aminothiazole-4-carboxylic acid giving the raaleimide 107 (269) another report claims, however, that the reaction of 2-amino-4-methylthiazole with this anhydride gives the N-substituted maleamic acid (108) (Scheme 73) (270). 

Acetylation of 2-phenyl-4-amino-5-benzoylthiazole takes place on the exocyclic nitrogen (49). This exocyclic nitrogen remains the reactive center even with 2-imino-3-aryl-4-amino-5-carboxamido-4-thiazoline (111). Its acetylation with acetic anhydride gives the 4-acetamido derivative (112), which reacts further on heating to yield 2-(acetylimino)-(3H)-3-aryl-5-methylthiazolo[4,5-d]pvrimidin-7-(6H)-one (113) (Scheme 76) (276). 

The general pattern of alkylation of 2-acylaininothiazoles parallels that of 2-aminothia2ole itself (see Section III.l). In neutral medium attack occurs on the ring nitrogen, and in alkaline medium a mixture of N-ring and N-amino alkylation takes place (40, 43, 161. 163). In acidic medium unusual behavior has been reported (477) 2-acetamido-4-substituted thiazoles react with acetic anhydride in the presence of sulfuric acid to yield 2-acetylimino-3-acetyl-4-phenyl-4-thiazolines (255) when R = Ph. but when R4 = Me or H no acetylation occurs (Scheme 151). The explanation rests perhaps in an acid-catalyzed heterocyclization with an acetylation on the open-chain compound (253), this compound being stabilized... 

The most suitable synthetic method for these products is the heterocyc-lization reaction of N-thioacyl derivatives of amino acids (202) with phosphorus tribromide (378, 442-450, 559, 560) or anhydrous trifluoroacetic acid (448, 449, 451, 452) (Scheme 103). Treatment of N-thioacyl amino acids with acetic anhydride leads directly to the thiazolylacetate without isolation of an intermediate thiazolinone (365. 452). 2-Alkoxy-derivatives of A-2-thiazoline-5-one, however, can be obtained without acetylation by this method (453, 454). 

Another procedure for obtaining a-aminoketones is by reduction of a-nitrosoketones in the presence of the required carboxylic acid. Acylaminoketones are prepared either by reacting acids with the chlorhydrate of a-aminoketones according to the method of Pictet and Gauss (41) or by the action of acid anhydrides upon a-amino acids (550). 

Substituted 5-hydroxythiazoles (267b), Rj = alkylmercapto, acyl-amino, and sec-amino, are prepared by cydization of N-thioacyl-amino acids (266) with phosphorus tribromide or acetic anhydride (Scheme 137) (317, 350). i en the cydization of 266, R2 = H, is carried out with acetic anhydride in the presence of benzaldehyde (317, 325) or ethylformate (317), the benzylidene (268), R2=Ph, Rj = SR or CH2Ph, or 4-ethoxymethylene (268), Rj = SR and R2 = OEt, derivative is obtained directly (Scheme 138). 

For uniformity with the stmctures given in the Colourindex the ammonium radical (9) is used for the amino-substituted xanthenes and the keto form for the hydroxy derivatives. The xanthene dyes may be classified into two main groups diphenylmethane derivatives, called pyronines, and triphenylmethane derivatives (eg, (4)), which are mainly phthaleins made from phthaUc anhydride condensations. A third much smaller group of rosamines (9-phenylxanthenes) is prepared from substituted ben2aldehydes. The phthaleins may be further subdivided into the following fluoresceins (hydroxy-substituted) rhodamines (amino-substituted), eg, (6) and mixed hydroxy/amino-substituted. 

Similarly, A[-carboxy-a-amino acid anhydrides react with aromatics such as toluene, xylenes, and mesitylene to give a-amino acylated products ia moderate yields with almost complete retention of configuration of the a-amino acid. 

The A/-carboxyl group is lost duting the reaction, and no additional deprotection step is requited (104). Benzene reacts with A/-carboxyglyciae anhydride to give aminomethyl phenyl ketone however, it does not react with other A/-carboxy-a-amino acid anhydrides (105). 

Other Reactions of Phospholipids. The unsaturated fatty acid groups in soybean lecithin can be halogenated. Acetic anhydride combined with the amino group of phosphatidylethanolamine forms acetylated compounds. PhosphoHpids form addition compounds with salts of heavy metals. Phosphatidylethanolamine and phosphatidjhnositol have affinities for calcium and magnesium ions that are related to interaction with their polar groups. 

There are numerous further appHcations for which maleic anhydride serves as a raw material. These appHcations prove the versatiHty of this molecule. The popular artificial sweetener aspartame [22839-47-0] is a dipeptide with one amino acid (l-aspartic acid [56-84-8]) which is produced from maleic anhydride as the starting material. Processes have been reported for production of poly(aspartic acid) [26063-13-8] (184—186) with appHcations for this biodegradable polymer aimed at detergent builders, water treatment, and poly(acryHc acid) [9003-01-4] replacement (184,187,188) (see Detergency). 

Monomer Reactivity. The poly(amic acid) groups are formed by nucleophilic substitution by an amino group at a carbonyl carbon of an anhydride group. Therefore, the electrophilicity of the dianhydride is expected to be one of the most important parameters used to determine the reaction rate. There is a close relationship between the reaction rates and the electron affinities, of dianhydrides (12). These were independendy deterrnined by polarography. Stmctures and electron affinities of various dianhydrides are shown in Table 1. 

This scheme eliminates the process of converting bis(etherimide)s to bis(ether anhydride)s. When polyetherimides are fusible the polymerization is performed in the melt, allowing the monamine to distill off. It is advantageous if the amino groups of diamines are more basic or nucleophilic than the by-product monoamine. Bisimides derived from heteroaromatic amines such as 2-arninopyridine are readily exchanged by common aromatic diamines (68,69). High molecular weight polyetherimides have been synthesized from various N,lSf -bis(heteroaryl)bis(etherimide)s. 

Conversion of aniline to acetanilide [103-84-4] by reaction with acetic anhydride, is a convenient method for protecting the amino group. The acetyl group can later be removed by acid or base hydrolysis. 

MDA reacts with acid anhydrides to form amides. In the reaction with maleic anhydride both of the amino hydrogens are replaced to form the imide, A[,Ar-(methylenedi-/)-phenylene) dimaleimide [1367-54-5]... 

Anhydride Formation. The carboxyl group ia A/-protected amino acids is converted iato the symmetrical anhydride on treatment with the carbodiimide (84). 

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