Acyl compounds

Ring enlargement of A-acyl compounds, generally observed with oxaziridines, is observed only occasionally with diaziridines. Under more forced conditions of acylation with acetic anhydride, oxadiazolines like (139) were obtained (76MIP50800). A 4-nitrobenzoyl derivative rearranged at room temperature (76JOC3229). 

There has been recent interest in naphtho-fused dithiepines as chiral acyl anion equivalents, particularly since the starting dithiol 128 can be obtained in enan-tiomerically pure form (89TL2575). This is transformed using standard methods into the dithiepine 129, but showed only moderate diastereoselectivity in its addition to carbonyl compounds. On the other hand, as we have seen previously for other systems, formation of the 2-acyl compound 130 and reduction or addition of a Grignard reagent gave the products 131 with much better stereoselectivity (91JOC4467). 

Electronically, we find that strongly polarized acyl compounds react more readily than less polar ones. Thus, acid chlorides are the most reactive because the electronegative chlorine atom withdraws electrons from the carbonyl carbon, whereas amides are the least reactive. Although subtle, electrostatic potential maps of various carboxylic add derivatives indicate the differences by the relative blueness on the C-O carbons. Acyl phosphates are hard to place on this scale because they are not used in the laboratory, but in biological systems they appear to be somewhat more reactive than thioesters. 

The pharmacologically active and commercially important 5//-dibenz[/>,/]azepines 40 are available by base-catalyzed dehydrobromination of their 5-acyl- 10-bromo-l 0.11-dihydro derivatives 38,118 followed by hydrolysis of the isolable tV-acyl compounds 39 29.119-121... 

During the final coupling reaction between free amine 36 and oxadiazole 2 unse-lective acylation of the phenolic OH occurs to give the bis-acylated compound 43. 

C(l)-Acylation of the l,4-dihydro-277-pyrazino[2,TA]quinazoline-3,6-diones 57 (R4 = Me, Rz = Bn, CH2-C6H4-MeO-/>) by treatment with LHDMS at — 78 °C followed by addition of acyl chlorides resulted in the as- 1-acyl derivatives with de > 95% in good yield. Formation of the air-product was explained by equilibration through the anion formed by deprotonation at C-l. The 1-acyl compounds were unstable and easily retransformed into the starting 57 <1998TA249>. 

Azolo[l,8]naphthyridines. The reactions of the chloronaphthyridine 229 with o-phenylenediamine at 200 °C and with sodium azide in acetic acid give the fused-ring products 230 and 231, respectively (Scheme 54) <2003IJB192>. Amino acid-substituted naphthyridines can be cyclized to the fused imidazolones 232 upon treatment with phosphorus oxychloride and under microwave irradiation (Equation 62) <2002SC857>. Acylation of 2-hydrazino-naphthyridines followed by heating gives W-acyl compounds which are cyclized intramolecularly to the [l,2,4]tri-azolo[4,3- ][l,8]naphthyridines 233 (Scheme 55) <1996IJB106>. The same compounds may also be obtained from... 

If the R group of Cp2TiR was not electron-withdrawing, reaction with CO resulted in the formation of an acyl compound. However, isolation of the initially formed CO adduct, Cp2Ti(CO)(R), was unsuccessful in these cases. 

Condensation of aromatic acyl compounds with N,N-dimethylformamide diethyl acetal in a pressure tube under the action of microwave irradiation affords easy access to l-aryl-3-dimethylaminoprop-2-enones in almost quantitative yield after 6 min. These intermediates can then be reacted with hydrazine hydrate under conventional reflux in ethanol to form the corresponding 3-substituted pyrazoles [95] (Scheme 8.69). 

Acylium ions are formed by the departure of a negative ion or group from an acyl compound. Just as in the case of other carbonium... 

The depressed reactivity of the CO bond in metal carbonyls relative to organic carbonyls is not apparent in the case of BH3 and A1H3. For example, Masters and coworkers have observed that I B THF reduces metal acyl compounds to the corresponding alkyls, eq. 16. Although no mechanistic studies have been reported, it... 

C>2-Tosyl diazeniumdiolates are quite stable and are the most studied derivatives [164]. Solvolysis in sodium methoxide solution generates the alkylated C-diazenium-diolate (Scheme 3.16), while under more neutral conditions a reaction analogous to that of the acyl compounds occurs. The added stability of the tosylates has enabled labeling studies, which have shown that these reactions are probably initiated by migration of the acyl and tosyl groups to Oi. 

Carboxylic acids, being weaker acids, react with la-a with inversion of configuration at the anomeric center to yield /2-0-acyl compounds (1,53). This mild and convenient method for 1 -0-acylation of carbohydrates is also useful for pharmacological drug modification (54) or for the resolution of carboxylic acids (53). 

Lewis acid-catalyzed ene reactions proceed between allenyl sulfides, e.g. 330, and aldehydes 329 to afford cis-trans mixtures of 1,3-butadienes 331 (Scheme 8.90) [168, 175b], Similar ene reactions observed with imines such as 332 provide the corresponding allylamines [168,177]. It was also found that the ene reaction of 1-silylated allenyl sulfide 333 with various aldehydes (or acetals) furnishes a,/l-unsaturatcd acyl compounds such as 334 and 335 under BF3-etherate catalysis [175b]. 

O-alkyl and O-acyl compounds do not undergo rearrangement to form C-derivatives under the conditions in which the latter are prepared, as above described (cf. p. 245). This change takes place, however, at least in the case of the O-acyl derivatives, as the result of the catalytic action of solid potassium carbonate in indifferent solvents (Claisen), e.g. 

In the presence of a large excess of olefin, most of the HCo(CO)4 is quickly converted to the acyl compound and none is available for acyl cleavage to the final products hence, under these conditions aldehyde yield is very low and a 1 1 ratio of absorbed CO HCo(CO)4 is approached. On the other hand, in the absence of a large excess of olefin, the rate of acyl formation is slower, and sufficient HCo(CO)4 is available to cleave the... 

The described imidoylation of a-acyl radicals deserves great interest since a-acyl compounds are not only versatile building blocks but also exhibit several biological activities. ... 

Coenzyme A is another adenine nucleotide derivative, with its primary functional group, a thiol, some distance away from the nucleotide end of the molecule. This thiol plays an important role in biochemistry via its ability to form thioesters with suitable acyl compounds (see Box 7.18). We have seen how thioesters are considerably more reactive than oxygen esters, with particular attention being paid to their improved ability to form enolate anions, coupled with thiolates being excellent leaving groups (see Box 10.8). 

On the basis of the CO dependence of the transformation of the P-chelates into the carbonyl acyl compounds, it was proposed that the rate-limiting step in the overall conversion of the P-chelates to carbonyl acyl complexes is related to the opening of the metallacycle by CO (steps a and b in Scheme 7.13) rather than to the following migratory insertion of the alkyl carbonyl complex that is independent of the CO pressure (step c). 

The sequence in Figure 12-32 not only represents the general reactivity of carboxylic acid derivatives but also gives information on the ease of synthesis. The more reactive a species is, the more difficult it is to prepare it (and vice versa). From this series, you can see that synthesizing a less reactive acyl compound from a more reactive acyl compound is always possible. 

The organic esters have a greater order of stability, but it is difficult to prepare completely acylated compounds without concurrently anhy-drizing the hexitol unless one uses acid anhydrides or chlorides. Early attempts to prepare higher aliphatic esters of D-mannitol resulted in the formation of mixtures of mannitans and mannides. It is for this reason that caution must be exercised in interpreting some of the work in the literature. The analytical values of the pure compounds and the mixtures are such that one cannot differentiate between them. 

When an enarnine reacts with an acyl halide or acid anyhydrides the product is the C-acylated compound. The iminium ion that forms hydrolyzes when water is added, and overall reaction provides a synthesis of b-diketones. 

On heating to 140°C in the absence of a solvent, the Al-acyl compounds 18 rearrange quantitatively to the isomeric structures 17. " The rate of reaction is increased by bulky ring substituents, being immeasurably slow when R = R = R = Me it also depends on the nature of R Crossing experiments have shown the migration to be intermolecular. ... 

Dibenzothiophene carbamate 396 was converted to the corresponding l,3-oxazin-2-one derivatives 397 in a two-step, one-pot procedure. Lithiation of 396 gave a bis-anion intermediate, treatment of which with ketones led to cyclization to tetracyclic l,3-oxazin-2-ones 397 (Equation 43). In the similar reaction of the analogous dibenzofuran carbamate, a hydroxymethyl-substituted acylic compound was formed <1998J(P1)457>. 

Cobalt hydrocarbonyl reacts rapidly with conjugated dienes, initially forming 2-butenylcobalt tetracarbonyl derivatives. These compounds lose carbon monoxide at 0°C. or above, forming derivatives of the relatively stable l-methyl-ir-allyl-cobalt tricarbonyl. As with normal alkylcobalt tetracarbonyls, the 2-butenyl derivatives will absorb carbon monoxide, forming the acyl compounds but these acyl compounds also slowly lose carbon monoxide at 0°C. or above, forming 7r-allyl complexes. The acyl compounds can be isolated as the monotriphenylphosphine derivatives (47). 

If the formation of formate esters under hydroformylation conditions involves the carbonylation of an alkoxycobalt carbonyl as suggested previously (90), this would be evidence that cobalt hydrocarbonyl adds the reverse way to acyl groups. Since the formation of formate esters can be explained as well by a CO insertion into a cobalt-hydrogen group followed by alcoholysis, however, the data would be explained best if a cobalt-carbon bond was formed in the hydride reduction of acyl compounds. 

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