Synthesis acyl chlorides

Unusual Friedel-Crafts reactions, IX. One-step ortho-acylation of phenols with a,(3-unsaturated acyl chlorides. Synthesis of 2 -hydroxychalcones and sorbicillin analogues. Tetrahedron 40 4081-4084. 

Cooley JH, Evain EJ (1989) Amine dealkylations with acyl chlorides. Synthesis-Stuttgart 1-7... 

The Pd-catalyzed coupling of an acyl chloride with benzyl chloride to form the benzyl ketone 854 proceeds in the presence of an excess of Zn. In this reaction, benzyl chloride reacts with Zn to form benzylzinc, which undergoes transmetallation with acylpaliadium complex[729]. The reaction has been applied to the synthesis of riccardin B (855)[730]. 

The customary method for the laboratory synthesis of acid anhydrides is the reac tion of acyl chlorides with carboxylic acids (Table 20 1)... 

Synthesis. Symmetrical diacyl peroxides (20, R = R = alkyl or aryl) are prepared by the reaction of an acyl chloride or anhydride with sodium peroxide or hydrogen peroxide and a base ... 

The synthesis of pyrazolines and pyrazoles of the [CCNN + C] type with the creation of two bonds, N(2)-C(3) + C(3)-C(4) (or N(l)-C(5) + C(5)-C(4)), has been studied by several groups. Beam and coworkers have published a series of papers on the synthetic utility of lithiated hydrazones. Thus, the methylhydrazone of acetophenone (598) is converted by butyllithium into the dianion (599), which in turn reacts with methyl benzoate to afford the pyrazole (600) (76SC5). In earlier publications Beam et al. have used aldehydes and acyl chlorides to obtain pyrazolines and pyrazoles by the same method. 

The most important method for the synthesis of aromatic ketones 3 is the Friedel-Crafts acylation. An aromatic substrate 1 is treated with an acyl chloride 2 in the presence of a Lewis-acid catalyst, to yield an acylated aromatic compound. Closely related reactions are methods for the formylation, as well as an alkylation procedure for aromatic compounds, which is also named after Friedel and Crafts. 

Hydrazides (RCONHNH2) are highly useful starting materials and intermediates in the synthesis of heterocyclic molecules.2 They can be synthesized by hydrazinolysis of amides, esters and thioesters.3 The reaction of hydrazine with acyl chlorides or anhydrides is also well known,4 but it is complicated by the formation of 1,2-diacylhydrazines, and often requires the use of anhydrous hydrazine which presents a high thermal hazard. Diacylation products predominate when hydrazine reacts with low molecular weight aliphatic acyl chlorides, which makes the reaction impractical for preparatory purposes.5... 

Microwave irradiation has been used to accelerate the Gewald reaction for the one-pot synthesis of N-acyl aminothiophenes on solid support [67]. A suspension of cyanoacetic acid Wang resin 35, elemental sulfur, DBU and an aldehyde or ketone 36 in toluene was irradiated for 20 min at 120 °C in a single-mode microwave synthesizer (Scheme 13). Acyl chloride 37 was added, followed by DIPEA, and the mixture was irradiated for 10 min at 100 °C. After cooling to room temperature, the washed resin was treated with a TEA solution to give M-acylated thiophenes 38 in 81-99% yield and purities ranging from 46-99%. 

A strategy involving sequential 1,3-dipolar cycloadditions has been reported for the synthesis of novel bis-isoxazolo substituted piperidines 192a and 192b (Eqs. 18 and 19) [53]. It consists of the Michael addition of an unsaturated alkox-ide 185 to )3-nitrostyrene 184 followed by an INOC or ISOC reaction to provide isoxazolines 187-189 (Eq. 18 and Table 18). A polymer supported acyl chloride... 

Other than energy considerations, on which there is little comparative data, the most important green role for photochemistry is in improving atom economy. Although only a preliminary research result, an excellent example of this is the avoidance of the need for stoichiometric amounts of Lewis acid catalysts in the synthesis of some acylated aromatic compounds. Benzoquinone can be reacted with an aldehyde under a sunlamp to yield an acylhydroquinone in up to 88% yield. The alternative procedure would involve reaction of an acyl chloride with hydroquinone and a... 

Previous syntheses An example of this point can be recognized by examination of one known synthesis of thienobenzazepines (Scheme 6.1). This synthetic route involves a key palladinm-catalyzed cross-conpling of stannyl intermediate 3, prepared by method of Gronowitz et al., with 2-nitrobenzyl bromide. Acetal deprotection and reductive cyclization afforded the desired thienobenzazepine tricycle 4. In support of structure activity relationship studies, this intermediate was conveniently acylated with varions acyl chlorides to yield several biologically active componnds of structure type 5. While this synthetic approach does access intermediate 4 in relatively few synthetic transformations for stractnre activity relationship studies, this route is seemingly nnattractive for preparative scale requiring stoichiometric amounts of potentially toxic metals that are generally difficult to remove and present costly purification problems at the end of the synthesis. 

As noted in the preceding section, one of the most general methods of synthesis of esters is by reaction of alcohols with an acyl chloride or other activated carboxylic acid derivative. Section 3.2.5 dealt with two other important methods, namely, reactions with diazoalkanes and reactions of carboxylate salts with alkyl halides or sulfonate esters. There is also the acid-catalyzed reaction of carboxylic acids with alcohols, which is called the Fischer esterification. 

The best yields are obtained when the ketene has an electronegative substituent, such as halogen. Simple ketenes are not very stable and must usually be generated in situ. The most common method for generating ketenes for synthesis is by dehydrohalo-genation of acyl chlorides. This is usually done with an amine such as triethylamine.167 Other activated carboxylic acid derivatives, such as acyloxypyridinium ions, have also been used as ketene precursors.168 Ketene itself and certain alkyl derivatives can be generated by pyrolysis of carboxylic anhydrides.169... 

Scheme 8.13. Synthesis of Ketones from Acyl Chlorides and Stannanes...

Several new methods for the synthesis of the oxazole nucleus were published. A new consecutive three-component oxazole synthesis by an amidation-coupling-cycloisomerisation sequence was developed. The synthesis started from propargylamine 92 and acyl chlorides. To extend this process, a four component sequence involving a carbonylative arylation by substitution of one acyl chloride with an aryl iodide and a CO atmosphere was also performed <06CC4817>. 

In 1991 Bose described the synthesis of ot-vinyl /1-lactams by reaction of ,/l-unsa-turated acyl chlorides with a Schiff base in chlorobenzene under microwave irradiation (an example of the eco-friendly MORE chemistry, in which only a limited amount of solvent is used) [20b]. Under these conditions, a-vinyl /1-lactam formation can be achieved in 65-70% in approximately 5 min (classical conditions require several hours and lead only to modest yields). 

Heavy ketones have been synthesized by several synthetic methods shown in Scheme 19 (i) the reaction of divalent group 14 element species with chalcogen sources, (ii) the reaction of dihydrometallanes with chalcogen sources, (iii) the dechalcogenation of metal polychalcogenides, (iv) the reaction of dilithiomet-allanes with dihalochalcogenides, and (v) substitution of the chloro group of heavy acyl chlorides. The methods used for the synthesis of heavy ketones are summarized in Tables 3-5. 

The method (i) can be applied to the synthesis of almost all heavy ketones (Tables 3-5). Silanethiones and a silaneselone stabilized by the coordination of a nitrogen group have been synthesized by the method (ii) (Table 4). The method (iii) is effective to the synthesis of kinetically stabilized tricoordinate heavy ketones, although it cannot be applied to the synthesis of double-bond compounds between heavier group 14 elements and tellurium due to the instability of polytellurides (Table 3). The method (iv) can be used only when the unique dilithiometallanes can be generated (Table 3). The synthesis of heavy ketones by the method (v) demands the isolation of the corresponding heavy acyl chlorides as stable compounds (Table 5). 

Although the synthesis of 3-isoxazolols from P-keto esters and hydroxylamine suffers from the formation of 5-isoxazolones as major products, treatment of acyl chlorides with Meldrum s acid 4 followed by aminolysis gave rise to p-keto hydroxamic acids 6 that cyclised to the corresponding 5-substituted 3-isoxazolols 7 without formation of any byproduct <00JOC1003>. Cyclisation of N-substituted salicylhydroxamic acids 9 under... 

Darensbourg et al. found that HCr(CO)5 converts acyl chlorides to aldehydes rapidly at 25 °C (Eq. (26)) [26]. Yields >90% were detected by gas chromatography (GC) for preparation of CH3CHO, n-BuCHO, PhCHO, and PhCH2CHO. Since CH3OD converts HCr(CO)5 to DCr(CO)] , the reaction of [HCr(CO)5] with PhCOCl in the presence of CH3OD provided a convenient synthesis of the deuterated aldehyde, PhCDO. 

Isoquinoline alkaloids. The regioselective allylation of N-acyl heterocycles (13, 10) can be used for synthesis of isoquinoline alkaloids. Thus simultaneous reaction of the dihydroisoquinoline (1) with a diunsaturated acyl chloride (2) and allyltributyltin affords the 1,2-adduct (3), which undergoes a Diels-Alder cyclization... 

---