Acyl chlorides synthesis using

An acyl chloride was used in the synthesis of the spermidine alkaloid cannabisativine (162) by Natsume and coworkers [92]. As shown in Scheme 53, the precursor 160 was hydrolyzed with Ba(OH)2 and the resulting amino acid was directly converted to acyl chloride HCl salt, a cold solution of which was added dropwise to a potassium carbonate suspension in acetonitrile to achieve the lactam closure. Deprotection of the methoxymethyl groups with acid afforded macrolactam 161 in 43% yield from 160. 

Having streamlined the synthesis of acyl chloride 54, the indirect preparation of methyl enol ester 51a was addressed. As previously discussed, attempts to synthesize 53a from formyl Meldrum s acid 58 had proven unsuccessful. However, Cossy and coworkers have reported the preparation of 53a via the ozonolysis of alkene 82 and subsequent use of the crude aldehyde in the total synthesis of octalactin. Thus, methyl vinyl acetate (82) was subjected to ozonolysis at —78 °C, followed by a reductive quench to provide formyl acetate 53a (Scheme 24). The crude methyl formyl acetate was acylated with acyl chloride 54, using the previously optimized conditions, to afford methyl enol ester 51a in 74% yield over two steps. This modification to the synthesis removes a further two reactions from the sequence with a formal synthesis of (—)-7-deoxyloganin (24) now achieved in 10 steps, a length more in keeping with the complexity of this target. 

Other approach for the synthesis of ketones is the acylation of het-eroarenes discovered by Kakiuchi and further developed hy Frost. Kakiuchi presented the acylation of benzo[ft]quinoline and 2-phenyl-pyridine with aromatic and vinylic acyl chlorides using [RuCl2(PPh3)3] in toluene at 120 °C (Scheme 21). ° Later, Frost extended this transformation to the reaction of 1-arylpyrazoles and aliphatic acyl chlorides by using [RuCl2(p-cymene)]2 and PCya (Scheme 21). Interestingly, higher yields of the acylation products were obtained for the more sterically... 

Subsequently, this version of Claisen rearrangement was extended to tertiary allyl amines and acyl chlorides [87], Using Lewis acid catalyst, excellent stereoselectivity of the product was found. For example, 3,3-disubstituted aUyl morpholine 125 with propionyl chloride in the presence of TiCLt gives highly stereoselective syn product 126 [87]. This method is useful for the synthesis of... 

A -methylglucamine synthesis in the second reaction step in the first step, A -methyllactitolamine was obtained from lactose in a reductive amination reaction similar to that shown in Fig. 2a. Long-chain acyl chlorides were used for the amidation of the A -methyllactitolamine (XVII, Fig. 5) and the reaction was conducted in dimethylformamide (DMF) using triethylamine as catalyst at 5-10°C for 2 h. The yield of pure products XVIII, for which the... 

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. 

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%. 

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... 

Acyl hydrazides are useful precursors for the synthesis of 1,2,4-triazoles. Reaction of acyl hydrazides 149 with imidoylbenzotriazoles 148 in the presence of catalytic amounts of acetic acid under microwave irradiation afforded 3,4,5-trisubstituted triazoles 150 <06JOC9051>. Treatment of A-substituted acetamides with oxalyl chloride generated imidoyl chlorides, which reacted readily with aryl hydrazides to give 3-aryl-5-methyl-4-substituted[ 1,2,4]triazoles <06SC2217>. 5-Methyl triazoles could be further functionalized through a-lithiation and subsequent reaction with electrophiles. ( )-A -(Ethoxymethylene)hydrazinecarboxylic acid methyl ester 152 was applied to the one-pot synthesis of 4-substituted-2,4-dihydro-3//-1,2,4-triazolin-3-ones 153 from readily available primary alkyl and aryl amines 151 <06TL6743>. An efficient synthesis of substituted 1,2,4-triazoles involved condensation of benzoylhydrazides with thioamides under microwave irradiation <06JCR293>. 

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). 

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... 

The reagents and methods employed for coupling in solid-phase synthesis are the same as for synthesis in solution, but a few are excluded because they are unsuitable. The mixed-anhydride method (see Section 2.6) and l-ethoxycarbonyl-2-ethoxy-l,2-dihydroquinoline (see Section 2.15) are not used because there is no way to eliminate aminolysis at the wrong carbonyl of the anhydride. Acyl azides (see Section 2.13) are too laborious to make and too slow to react. The preparation of acyl chlorides (see Section 2.14) is too complicated for their routine use this may be rectified, however, by the availability of triphosgene (see Section 7.13). That leaves the following choices, bearing in mind that a two to three times molar excess of protected amino acid is always employed. 

Bis-acyl sulphides are obtained in only low yield by the standard reaction of sodium sulphide with an acyl chloride, but the addition of Adogen results in their viable synthesis with yields >70%. Examples using quaternary phosphonium salts provide the optimum yields (> 90%) [63]. Similarly, thiophenols have been benzoylated using benzoyl chloride under basic conditions in the presence of ammonium salts [12]. 

The use of ethylene adduct lb is particularly important when the species added to activate catalyst la is incompatible with one of the reaction components. Iridium-catalyzed monoallylation of ammonia requires high concentrations of ammonia, but these conditions are not compatible with the additive [Ir(COD)Cl]2 because this complex reacts with ammonia [102]. Thus, a reaction between ammonia and ethyl ciimamyl carbonate catalyzed by ethylene adduct lb produces the monoallylation product in higher yield than the same reaction catalyzed by la and [Ir(COD)Cl]2 (Scheme 27). Ammonia reacts with a range of allylic carbonates in the presence of lb to form branched primary allylic amines in good yield and high enantioselectivity (Scheme 28). Quenching these reactions with acyl chlorides or anhydrides leads to a one-pot synthesis of branched allylic amides that are not yet directly accessible by metal-catalyzed allylation of amides. 

Both above mentioned complex hydrides have been successfully used for the preparation of unsaturated aldehydes from unsaturated acyl chlorides (yields 48-71%) [1011] and for the synthesis ofp-nitrobenzaldehyde from p-nitroben-zoyl chloride [775, 7077], a reduction which could hardly be achieved by applying catalytic hydrogenation. 

Although the simplest route to prepare hydroxamic acid derivatives remains the reaction of hydroxylamine with acid chlorides, this last method cannot be apphed to all Af-protected-a-amino acids. The synthesis of Fmoc-protected amino acid hydroxamates represents the only exception to this rule . In fact, Fmoc-amino acid hydroxamates 98 can be synthesized by the acylation of hydroxylamine using Fmoc-amino acid chlorides 97 in the presence of MgO (Scheme 52). The route is simple, efficient, and affords good yields of products. 

The alkynyl ketones 840 can be prepared by the reaction of acyl chlorides with terminal alkynes. Cul in the presence of Et3N is the cocatalyst[719]. (1-Alkynyl)tributylstannanes are also used for the alkynyl ketone synthesis[720]. The a, 9-alkynic dithio and thiono esters 842 can be prepared by the reaction of the corresponding acid chloride 841 with terminal alkynes[721,722],... 

It is a useful starting material for organic synthesis. It reacts readily with alkenes (such as methyl vinyl ketone, styrene, methyl acrylate, etc.), carbon monoxyde, isocyanides, and acyl chlorides to afford good yields of organic products by selective formation of carbon-carbon bonds.8... 

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