Acyl halides relative reactivity

There are alternatives to the addition-elimination mechanism for nucleophilic substitution of acyl chlorides. Certain acyl chlorides are known to react with alcohols by a dissociative mechanism in which acylium ions are intermediates. This mechanism is observed with aroyl halides having electron-releasing substituents. Other acyl halides show reactivity indicative of mixed or borderline mechanisms. The existence of the SnI-like dissociative mechanism reflects the relative stability of acylium ions. 

Dehalogenation.1 DMBI effects dehalogenation of a-halo carbonyl compounds in a variety of ethereal solvents with formation of DMBI+X in generally high yield. The order of relative reactivity is Br > Cl > F (halides) and primary > secondary > tertiary (for the a-substituted position). In combination with HO Ac (1 equiv.) the reagent also reduces acyl chlorides to aldehydes (70-90% yield). 

All acid derivatives hydrolyze to give carboxylic acids. In most cases, hydrolysis occurs under either acidic or basic conditions. The reactivity of acid derivatives toward hydrolysis varies from highly reactive acyl halides to relatively unreactive amides. 

Just as the comparatively weak metal-metal bonds pose problems for the synthesis of the difunctional dimers, they cause similar problems in the synthesis of the polymers. The relative weakness of the metal-metal bonds makes them more reactive than the bonds found in standard organic polymers thus, under many standard polymerization reaction conditions, metal-metal bond cleavage would result. For example, metal-metal bonds react with acyl halides to form metal-hahde complexes. Therefore, the synthesis of polyamides using metal-metal bonded diamines and diacyl chlorides would simply lead to metal-metal bond cleavage rather than polymerization. Likewise, metal-metal bonded complexes are incompatible with many Lewis... 

Kinetic studies of acylation reactions are somewhat limited by the insolubility of the acyl halide-Lewis acid complexes in many of the solvent systems that are used. However, useful results have been obtained and, as far as we are concerned, relative rates of reactions are of greater importance than absolute values. In any case it is not possible to distinguish between the two mechanistic extremes on the basis of the observed kinetics." Friedel-Crafts acylations are generally characterized by high substrate selectivity and frequently by high positional selectivity. Relative rate data show, as expected, that toluene is more reactive than benzene and that /n-xylene is the most reactive of the dimethylbenzenes. Values, relative to benzene, for benzoylation catalyzed by aluminum chloride were r-butylbenzene (72), toluene (1.1 X 10 ), p-xylene (1.4 x 10 ), o-xylene (1.12 x 10 ), and m-xylene (3.94 x 10- ). Competition data for the trifluoroacetylation of a number of heterocycles using trifluoroacetic anhydride at 75 "C gave the relative rates thiophene (1.0), furan (1.4 x lO ), 2-methylfuran (1.2 x 10 ) and pyrrole (5.3 x 10 ). ... 

Metal triflates can be easily prepared from metal halides and triflic acid at -78 C. They show several unique properties compared with the corresponding metal halides. In an early study, Olah reported the use of boron-, aluminum-, and gallium triflates [M(OTf)J as effective Friedel-Crafts catalysts. In the benzoylation and acetylation of toluene and benzene with acyl chlorides, the relative reactivity is boron triflate > gallium triflate > aluminum triflate, in agreement with the relative acidity strength. 

In the book, Condensation Polymers By Interfacial and Solution Methods, by P.W. Morgan,67 interfacial polyamide formation is stated to occur in the organic phase, that is, on the organic solvent side of the interface. Several proofs are presented in support of this statement. For instance, monofunctional acyl halides added to the difunctional acyl halide in the organic phase always lowered polymer molecular weights. However, monofunctional amines added to the difunctional amines in the aqueous layer did not always show this effect. In this latter case, partition coefficients became a factor, particularly when relative reactivities of the amines were comparable. Mass transfer rate of diamine across the interface into the organic phase was noted to be the rate-controlling step at all concentrations of diamine. 

A carboxyhc acid derivative will undergo a nucleophilic acyl substitution reaction provided that the newly added group in the tetrahedral intermediate is not a much weaker base than the group that was attached to the acyl group in the reactant. The weaker the base attached to the acyl group, the easier it is for both steps of the nucleophilic acyl substitution reaction to take place. The relative reactivities toward nucleo-phihc acyl substitution acyl halides > acid anhydrides > carboxylic acids and esters > amides > carboxylate ions. 

Consequently, aldehydes and ketones are not as reactive as carbonyl compounds in which Y is a very weak base (acyl halides and acid anhydrides), but are more reactive than carbonyl compounds in which Y is a relatively strong base (carboxylic acids, esters, and amides). A molecular orbital explanation of why resonance electron donation decreases the reactivity of the carbonyl group is given in Section 17.15. 

Notes 1. Acyl halides are very reactive, but included for comparison. 2. Other relatively inert groups, such as NO2 and C=N, may not be readily placed on the scale. 

The four carboxylic acid derivatives that are the focus of this chapter have the relative reactivity toward nucleophilic acyl substitution as follows. The differences in this trend are dramatic. For example, at common ambient temperatures and neutral pH, acid halides will react with water within seconds to minutes, while anhydrides will do so over minutes to hours. Esters, however, do not... 

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