Aldehydes acyl chlorides

Variations of this reaction have been applied over the years, typically involving the condensation of 2-aminothiophenols with substituted carboxylic acids, acyl chlorides, aldehydes, and nitriles. Initially, the reaction involves the formation of an imine that cyclizes spontaneously and then oxidation to form benzothiazole. An application of this chemistry has been showcased in the synthesis of 2-(4-aminophenyl)benzothiazoles and the evaluation of their in vitro and in vivo activities against breast cancer cell lines, with compound a exhibiting the most potent growth inhibition. Unfortunately, there are limitations due to the difficulties met during the syntheses of readily oxidizable o-aminothiophenol-bearing substituents. 

Unlike acyl chlorides, aldehydes and ketones do not undergo nucleophilic acyl substitution. Explain. 

The Pd-catalyzed hydrogenoiysis of acyl chlorides with hydrogen to give aldehydes is called the Rosenmund reduction. Rosenmund reduction catalyzed by supported Pd is explained by the formation of an acylpalladium complex and its hydrogenolysis[744]. Aldehydes can be obtained using other hydrides. For example, the Pd-catalyzed reaction of acyl halides with tin hydride gives aldehydes[745]. This is the tin Form of Rosenmund reduction. Aldehydes are i ormed by the reaction of the thio esters 873 with hydrosilanes[746,747]. 

The reduction of acyl halides with hydrogen to form aldehydes using Pd catalyst is well known as the Rosenmund reduction[756]. Some acyl chlorides give decarbonyiation products rather than aldehydes under Rosenmund conditions. The diene 890 was obtained by decarbonyiation in an attempted Rosenmund reduction of acetyloleanolic acid chloride (889)[757], Rosenmund reduction of sterically hindered acyl chlorides such as diphenyl- and tnpheny-lacetyl chloride (891) gives the decarbonylated products 892[758],... 

Many compounds contain more than one functional group Prostaglandin Ei a hormone that regulates the relaxation of smooth muscles con tains two different kinds of carbonyl groups Classify each one (aldehyde ketone carboxylic acid ester amide acyl chloride or acid anhydride) Identify the most acidic proton in prostaglandin Ei and use Table 1 7 to estimate its pK ... 

The chemistry of the carbonyl group is probably the single most important aspect of organic chemical reactivity Classes of compounds that contain the carbonyl group include many derived from carboxylic acids (acyl chlorides acid anhydrides esters and amides) as well as the two related classes discussed m this chapter aldehydes and ketones... 

The peroxycarboxyhc acid can be generated m situ by autoxidation of aldehydes, either in the presence of anhydrides or an acyl chloride and a base, eg, sodium carbonate, or basic ion-exchange resins (44,187,188,210) ... 

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. 

H-Bond Acceptor (HBA) Acyl chlorides Acyl fluorides Hetero nitrogen aromatics Hetero oj gen aromatics Tertiary amides Tertiary amines Other nitriles Other nitros Isocyanates Peroxides Aldehydes Anhydrides Cyclo ketones Ahphatic ketones Esters Ethers Aromatic esters Aromatic nitriles Aromatic ethers Sulfones Sulfolanes... 

ROSENMUNO < SAITZEW ReAldehyde Hydrogenation of acyl chlorides to aldehydes b) the presence of poisoned Pd catalyst. 

More recently the acylation of aldehyde enamines has been reinvestigated (75) and shown to proceed normally when the enamine is added to the acid chloride. The morpholine enamine of isobutyraldehyde (98), on being added to an ether solution of acetyl chloride, afforded the iminium salt (99), from which the ketoaldehyde (100) was obtained in 66% yield by hydrolysis (75). 

The name Rosenmund reduction is used for the catalytic hydrogenation of an acyl chloride 1 to yield an aldehyde 2. 

The Rosenmund reduction is usually applied for the conversion of a carboxylic acid into the corresponding aldehyde via the acyl chloride. Alternatively a carboxylic acid may be reduced with lithium aluminum hydride to the alcohol, which in turn may then be oxidized to the aldehyde. Both routes require the preparation of an intermediate product and each route may have its advantages over the other, depending on substrate structure. 

Anhydrides are reduced with relative ease. McAlees and McCrindle 20) established the following increasing order of difficulty for various carbonyls acid chlorides > aldehydes, ketones > anhydrides > esters > carboxylic acids > amides. Reduction may proceed by 1,2-addilion of hydrogen or by cleavage of an oxygen-carbonyl bond. If 1,2-addition to the carbonyl occurs, as in the presence of strong protic acids over palladium, 1,1-diesters are formed by acylation 26). 

The sequential treatment of triazine derivative 990 with acyl chlorides and acetic anhydride and perchloric acid afforded (86H1031) thiadi-azolo[l, 2,4]triazinium perchlorates 991. On the other hand, cyclocondensation of 992 with organic acids gave 993 [82JHC1577 83JAP(K)58/180492] and 994 with aromatic aldehydes (84JIC552) (Scheme 183). 

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%. 

Aldehydes can be directly converted to acyl chlorides by treatment with chlorine however, the reaction operates only when the aldehyde does not contain an a hydrogen and even then it is not very useful. When there is an a hydrogen, a halogenation (12-4) occurs instead. Other sources of chlorine have also been used, among them S02Cl2 and r-BuOCl. The mechanisms are probably of the free-radical type. V-Bromosuccinimide, with AIBN (p. 912) as a catalyst, has been used to convert aldehydes to acyl bromides. 

Aldehydes and ketones can be converted to ethers by treatment with an alcohol and triethylsilane in the presence of a strong acid or by hydrogenation in alcoholic acid in the presence of platinum oxide. The process can formally be regarded as addition of ROH to give a hemiacetal RR C(OH)OR", followed by reduction of the OH. In this respect, it is similar to 16-14. In a similar reaction, ketones can be converted to carboxylic esters (reductive acylation of ketones) by treatment with an acyl chloride and triphenyltin hydride. " ... 

Many aldehydes and ketones have been converted to g m-difluoro compounds with sulfur tetrafluoride (SF4), " including quinones, which give 1,1,4,4-tetra-fluorocyclohexadiene derivatives. With ketones, yields can be raised and the reaction temperature lowered, by the addition of anhydrous HF. Carboxylic acids, acyl chlorides, and amides react with SF4 to give 1,1,1-trifluorides. In these cases the first product is the acyl fluoride, which then undergoes the ge i-difluorination reaction ... 

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