Anhydrides acylation

It is estimated that mote than 25 x 10 different potentially toxic OP esters can be made using Schrader s classic (27) formula for effective phosphorylating agents, (39), where R and are short-chain alkyl, alkoxy, alkylthio, or alkylamino groups, and X is a displaceable moiety with a high energy P-bond such as E or acyl anhydride, and the pentavalent phosphoms atom is bonded to oxygen or sulfur. 

One of the simplest ways to prepare a chitin gel is to treat chitosan acetate salt solution with carbodiimide to restore acetamido groups. Thermally not reversible gels are obtained by AT-acylation of chitosans N-acetyl-, N-propionyl- and N-butyryl-chitosan gels are prepared using 10% aqueous acefic, propionic and bufyric acid as solvents for treatment with appropriate acyl anhydride. Both N- and 0-acylation are found, but the gelation also occurs by selective AT-acylation in the presence of organic solvents. 

Hydrosilylation of imine compounds was also an efficient method to prepare amines. The hydrosilylation product TV-silylamines can readily be desilylated upon methanol or water treatment, yielding the corresponding amines. The amines can be converted to their corresponding amides by subsequent acyl anhydride treatment. The first attempt to hydrogenate prochiral imines with Rh(I) chiral phosphine catalysts was made by Kagan102 and others. These catalysts exhibited low catalytic activity, and only moderate ee was obtained. 

The C2-symmetrical chiral amine tran.v-(2/ ,6y )-2,6-bis(benzyloxymethyl)piperidine (1), prepared15 from commercially available (S)-2-(benzyloxymethyl)oxirane, has been used in diastereoselective amide alkylations. Thus, the chiral amine of 76% ee is acylated [anhydride or mixed trimethylacetic acid anhydride, 1.2 equivalents of triethylamine and 0.05 equivalents of 4-(dimethylamino)pyridine] and the resulting amide 2 treated with 2.1 equivalents of lithium diisopropylamide at —78 CC to give the enolate. This is then alkylated to give high diastereo-meric ratios (>94 6) of alkylation products 3 in 60-93% yield16. 

Compds of the general structure RC(0)N(N02)A.CH2.C(N02)2CH2.Ar N(N02)-C(0)R where R is alkyl and A is alkalene, were also patented by Frankel Sc Klager (Ref 4) for use as HE chges or proplnt additives. These nitramides are prepd by heating the appropriate dinitrodi-amines with acyl anhydrides and treating the product with HNO - Thus, the following N-nitro nitramides were prepd cited ... 

At the 2,3-positions reactions of 2-substituted pyridinium salts with acyl anhydrides... 

Thenaldehyde (thiophene-2-carbaldehyde) is readily available via the Vilsmeier-Haack reaction of DMF with thiophene catalyzed by phosphorus oxychloride. The Sommelet reaction with 2-chloromethylthiophene also gives reasonable yields (63AHC(l)l). Likewise, thiophene is readily acylated with acyl anhydrides or acid chlorides (equation 14), using mild Friedel-Crafts catalysts, such as tin(IV) chloride, zinc chloride, boron trifluoride, titanium tetrachloride, mercury(II) chloride, iodine and even silica-alumina gels or low-calcium-content montmorillonite clays (52HC(3)l). 

Co(III)] complexes. For example, the coupling of 3-halocholestanes (333) and Michael acceptors affords epimeric mixtures of the 3-homologated steroids (334). The electrochemical nucleophilic acylation of a, 3-unsaturated aldehydes, a,3-unsaturated ketones and a,(3-unsaturated nitriles with acyl anhydrides affords adducts (335) in moderate yields.226a-b Similarly, the reduction of N-methyloxazolinium salts (336) affords die A, O-acetal intermediates (337) which are readily hydrolyzed (Scheme 102).226c... 

Perfluoro)acyl anhydrides Common silylation reagents Other derivatizing agents Reaction tubes for GC-derivatization... 

Like acid chlorides, anhydrides are activated acid derivatives, and they are often used for the same types of acylations. Anhydrides are not as reactive as acid chlorides, and they are occasionally found in nature. For example, cantharidin is a toxic ingredient of Spanish fly, which is used as a vesicant ( causing burning and blistering ) to destroy warts on the skin. 

IAA conjugates identified from plants can be esters or acyl anhydrides with simple sugars or cyclitols, esters with larger molecular weight polysaccharides, or polysaccharide moieties of glycoproteins. IAA can also be found conjugated by amide linkage to amino acids such as aspartate or to peptides or proteins. 

The role of trifluoroacetic anhydride in these acylations was indicated by the diminished yield of acylation product obtained when the ratio of trifluoroacetic anhydride to hydroxy compound lay below unity, optimum conditions requiring a slight excess of this reagent. A catalytic function was, therefore, excluded, and the view was advanced that trifluoroacetic anhydride serves the purpose of converting the added carboxylic acid into the corresponding acyl trifluoroacetate. Later work on the nature of the equilibria between acyl anhydrides and acids in the presence of trifluoroacetic anhydride showed that the acylating capacity of a mixture of a carboxylic acid and trifluoroacetic anhydride is enhanced by the trifluoroacetic acid liberated when the unsymmetrical anhydride is formed. Further, cryo-scopic studies on solutions in acetic acid of the pure, unsymmetrical anhydride, acetyl trifluoroacetate, have shown that, contrary to an earlier conclusion that acetic anhydride is not formed to any appreciable extent, acetyl trifluoroacetate is, in fact, almost completely converted into acetic anhydride in excess acetic acid. In carrying out an acylation with trifluoroacetic anhydride and a carboxylic acid, it is, therefore, important to avoid an excess of the acid, so that the maximum concentration of the unsymmetrical anhydride is present in the equilibrium system. Extensive studies made on the action of acyl trifluoroacetates on hydroxy compounds under different conditions, with the simultaneous formation of the acyl and trifluoroacetyl derivatives, will be discussed later. 

The present methods for the preparation of N acyl a arylenamides include (i) reductive acylation of ketoximes with iron metal [2] or phosphines [3] in the presence of acyl chlorides or acyl anhydrides (Method A) (ii) metal catalyzed coupling of vinyl halides [4], triflates [5], or tosylates [6] with amides (Method B) (iii) reaction of imine intermediates derived from nitriles with acyl chlorides or anhydrides (Method C) [7] and(iv) Pd catalyzed coupling ofaryl tosylates with N acyl vinylamines (MethodD) [8]. 

Acyl Halides (CO-X) > Acyl Anhydrides (-CO-O-OCR) > Acyl Thioester (-CO-SR) > Acyl Esters (-CO-OR) > Acyl Amides (-CO-NR2)... 

Phosphation can occur simultaneously with acylation. Such reaction of starch in a mixture of 87% phosphoric acid and acetic acid with acyl anhydrides produced a gummy substance, which transformed into an amorphous solid upon purification.1593... 

Anhydrides of unsaturated acids could react in pyridine, as shown in the preparation of methacrylic esters.1908 1909 As with acetic anhydride, higher aliphatic acyl anhydrides produced triesters,1910 but benzoic anhydride produced only a diester. Subsequent acylation with benzoic and acetic anhydrides provided a mixed acetyldibenzoyl starch.1911... 

The reactivity of acyl chlorides determines the selectivity of the reaction.1938 Benzoyl chloride provided disubstituted products rather than triesters,1946-1948 but maltodextrins formed triesters. However, by adjusting the reaction conditions, mono- and di-esters of fatty acids could also be prepared.1949 On the other hand, acetylation usually led to the triacetate.1438 Chlorides of unsaturated acids, when treated with pregelatinized starch, did not require any solvent other than water. In this case, dissolved alkali played the role of catalyst. Mixed esters were also formed when mixtures of acyl chlorides1950-1953 or acyl anhydrides were used.1954 1955... 

Bartoli, G., Bosco, M., Marcantoni, E., Massaccesi, M., Rinaldi, S., and Sambri, L. 2002. LiG104-acyl anhydrides complexes as powerful acylating reagents of aromatic compounds in solvent free conditions. Tetrahedron Lett. 43 6331-6333. 

Various acyl derivatives (31)-(35) of schumannificine (28) detailed in Table 6 have been prepared by standard methods using the appropriate acyl anhydride or chloride [41,43]. Schumannificine has also been methylated at C-7 and C-5 by treatment with trimethylanilinium hydroxide in methanol to yield (36),(37) [43]. 

Acylation of hydroxyl groups by treatment with an acyl anhydride, such as acetyl anhydride, can be a useful derivatization step. Dry conditions are essential for derivatization of the sample with the acyl anhydride in dichloromethane or pyridine at 60-80°C for ca. 60 min. Acyl derivatives are stable and after evaporation of the reagents they can, if necessary, be purified before GC-MS analysis. 

Since A -acyl-1,2,4-triazinium salts are very unstable, all attempts to register their formation in solutions by NMR have failed. Nevertheless, these reactive species are undoubtedly formed on treatment of 1,2,4-triazines with acyl anhydrides or acyl halogenides, and N-acylation has proved to be a very effective procedure for activation of... 

The addition of aromatic or heteroaromatic C-nucleophiles at C-6 of l,2,4-triazin-5-ones 34 proceeds rather smoothly when the reactions are carried out in such solvents as acyl anhydrides or formic acid. There are two reasons (1) the formation of A -acyl-l,2,4-triazinium salts 34 facilitates nucleophilic addition reactions (2) the (j -adducts 37 are stabilized by the A -acyl group, as illustrated by the formation of adducts 37 with phenols, arylamines, pyrroles, and indoles (Scheme 22 Table 8) <1997JHC573, 1997JHC1013,1998RJ0297,1998RJ0452, 2001MC77, 2004RCB1351>. 

Interaction of 3-phenyl-l,2,4-triazin-5-one 34 with L-menthol in the presence of acyl anhydrides gives rise to a mixture of l-acyl-6-[(Ti, 3 i, 4 3 )-menthyl-3 ]-3-phenyl-(63 )-l,6-dihydro-l,2,4-triazin-5(4//)-ones 69 and l-acyl-6-[(1 i ,3 i, 4 3 )-menthyl-3 ]-3-phenyl-(6i )-l,6-dihydro-l,2,4-triazin-5(47/)-ones 70. The reaction proceeds stereo-selectively with predominant formation of (63 )-isomers (Scheme 34) <2001TL2393, 2004RCB1290>. The diastereomeric excess can be enhanced when a substituent located in the vicinity of the reactive center is able to hinder sterically the formation of one of the isomers. Indeed, for compounds with R =CH3, the ratio of stereoisomers 69 and 70 proved to be 60 40, 20% de, while in the case R = / -C3H7 the ratio was 85 15, and 70% de. 

There is dispute over the role of the active site Glu-270 one theory advocates a general base mechanism, while the other advocates a nucleophilic mechanism. If a nucleophilic attack on the substrate carbonyl by Glu-270 occurs, an acyl anhydride intermediate covalently bound to the enzyme is generated. If the general base is the real mechanism, no such intermediate intervenes. The putative... 

A new mechanism is proposed here to illustrate the Nencki reaction from acyl anhydride, with the preference of para-acylation and the requirement of at least one equivalent of ZnCl2. 

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