Carboxylic acid amide aldehydes

The presence of the good leaving group (chloride) attached directly to the carbon-oxygen double bond makes all manner of addition-elimination reactions possible for acid chlorides. The acid chloride can be used to make anhydrides, esters, carboxylic acids, amides, aldehydes, ketones, and alcohols. 

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). 

Alkylation of Aldehydes, Esters, Carboxylic Acids, Amides, and Nitriles... 

Addition of HCN to acetone to form the cyanohydrin is still the main route to methyl methacrylate. Hydrocyanins can be converted to amino acids as well. The nitrile group can be easily converted to amines, carboxylic acids, amides, etc. Addition to aldehydes and activated alkenes can be done with simple base, but addition to unactivated alkenes requires a transition metal catalyst. The methods of HCN addition have been discussed by Brown [2],... 

Carbonyl carbons, such as those in esters, carboxylic acids, amides, ketones and aldehydes, in which the sp carbon is bonded by a ir-bond to the highly electronegative O, have a characteristic chemical shift of S 160-220 (Box 4.13). Within this range, the sp carbon atoms of aldehydes and ketones are most deshielded and usually resonate at 8 185-220, while those of carboxylic acids and their derivatives resonate about 160-180. 

Amides of this type are also used to transform carboxylic acids into aldehydes. 

Reduction of carboxylic acids to aldehydes. 2 3-Acyllhiazolidine-2-thiones (2) can be prepared by reaction of l,3-thiazolidine-2-thione (1) with carboxylic acids directly (using 2-chloro-l-methylpyridinium iodide, 8, 95-96) or with acid chlorides (triethylamine or DCC). They can also be prepared from reaction of the thallium salt of 1 with an acid chloride. Yields by all four methods are 70-95%. The amides are reduced to aldehydes by either DIBAH or, generally in higher yield, by NaBH4 (90-98% yield). 

This latter thought has an important consequence if compounds with C=0 double bonds are sorted in decreasing order of resonance stabilization of their C=0 group they are at the same time sorted according to their increasing propensity to enolization. So as the resonance stabilization of the C=0 double bond decreases from 22 kcal/mol to somewhere near zero in the order carboxylic acid amide > carboxylic acid ester/carboxylic acid > ketone > aldehyde > carboxylic acid chloride/-bromide, the enol content increases in this same order (Figure 12.2). These circumstances immediately explain why no enol reactions whatsoever are known of carboxylic acid amides, virtually none of normal carboxylic acid esters/carboxylic acids, but are commonly encountered with ketones, aldehydes and carboxylic acid halides. 

Another route to carboxylic acids from aldehyde products (once again, generally produced via hydroformylation catalysis) was discovered by Wakamatsu and coworkers. They reported the carbonylation of aldehydes and primary organic amides to produce A-acylamino acids (equation 16). The reaction is efficiently catalyzed by HCo(CO)4 at 100 °C and 140 bar of 3 2 H2/CO (hydrogen is needed to help stabilize HCo(CO)4). Yields of over 90% of the appropriate... 

For C=0 stretching vibrations of acid chlorides, acid anhydrides, carboxylic acids, esters, aldehydes, ketones, amides and salts, see tables 2.4 and 2.5. 

Cyanoborohydride and its modified reagents have been used for reductive dehalogenations. Thus, the combination of sodium or tetrabutylammonium cyanoborohydride, sodium or potassium 9-cyano-9-hydro-9-borabicyclo[3.3.1]nonanate [9-BBNCN] (2) or polymeric cyanoborane (3) in HMPA furnishes an efficient and mild system for the reduction of alkyl halides. The reagents are selective in that other functional groups, including ester, carboxylic acid, amide, cyano, alkene, nitro, sulfone, ketone, aldehyde and epoxide, are essentially inert under the reduction conditions thus, the reduction procedure is attractive for synthetic schemes which demand minimum damage to sensitive portions of the molecule. 

Adsorption TLC selection of the mobile phase is conditioned by sample and stationary-phase polarities. The following polarity scale is valid for various compound classes in NPTLC in decreasing order of K values carboxylic acids>amides>amines>alcohols>aldehydes > ketones > esthers > nitro compounds > ethers > hal-ogenated compounds > aromatics >olefins > saturated hydrocarbons > fluorocarbons. For example, retention on silica gel is controlled by the number and functional groups present in the sample and their spatial locations. Proton donor/acceptor functional groups show the greatest retention, followed by dipolar molecules, and, finally, nonpolar groups. 

In analogy to the synthesis of iminium salts (Section 4.2.2.1.), acyiiminium ions (60) can be obtained from carbonyl precursors (1), such as ketones or aldehydes, and carboxylic acid amides (62 Scheme 30). In addition, other amides can be used, such as p-toluenesulfonamides, which lead to the corresponding N-tosylated iminium salts. ... 

The preparation of acyliminium ions is not restricted to aldehyde or ketone derivatives as starting materials, but can also use the more highly oxidized carboxylic acid amides as precursors, e.g. reduction of imides (66) affords (67 Scheme 33). For constitutionally unsymmetrical imides, regiocontrol can be achieved in many cases by the choice of the appropriate hydride-transfer reagent. ... 

Functional Groups aldehydes ketones alcohols alkyl groups and rings carboxylic and phosphoric acids and esters amines carboxylic acids amides carbohydrate heterocyclic bases phosphate esters... 

Reactivity of various carboxyl derivatives decreases in the order, acid chlorides > (aldehydes, ketones) > anhydrides > esters > carboxylic acids > amides. Carboxylic acids are reduced to alcohols under vigorous conditions. High P (35 X 10 to 70 X 10 kPa) and elevated T (up to 230°C) are required to effect conversion in high yields. 

Given a Lewis structure, a condensed formula, or a line drawing for an organic compound, identify it as representing an alkane, alkene, alkyne, arene (aromatic), alcohol, carboxylic acid, ether, aldehyde, ketone, ester, amine, or amide. 

Aromatic and aliphatic A,iV-dialkyl carboxylic acid amides, carboxylic esters, and free carboxylic acids are converted into aldehydes by diisobutyl-alane if reduction is carried out at low temperatures (0°C or — 70°C) 269, 279, 280, 286) ... 

Amines and aldehydes from carboxylic acid amides... 

Carboxylic acids can be prepared by the oxidation of primary alcohols or aldehydes, the hydrolysis of nitriles, or the hydrolysis of esters which can be used as protecting groups for carboxylic acids. Amides can also be hydrolysed to carboxylic acids. However, drastic reaction conditions are needed due to the lower reactivity of amides and so amides are less useful as carboxylic acid protecting groups. 

Within the last two decades, a number of chemical structures have been proposed as metal deactivators for polyolefins. These include carboxylic acid amides of aromatic mono- and di-carboxylic acids and N-substituted derivatives such as N,N -diphenyloxamide, cyclic amides such as barbituric acid, hydrazones and bishydrazones of aromatic aldehydes such as benzaldehyde and salicylaldehyde or of o-hydroxy-arylketones, hydrazides of aliphatic and aromatic mono- and di-carboxylic acids as well as N-acylated derivatives thereof, bisacylated hydrazine derivatives, polyhydrazides, and phosphorus acid ester of a thiobisphenol. An index of trade names and suppliers of a few commercial metal deactivators is given in Appendix A4. 

It is not necessary to use phosphorus oxychloride complexes of formamides, because Roh and Kochendorfer in 1937 demonstrated that the iminium chlorides themselves react similarly and Bosshard and Zollinger have shown that comparable yields can be obtained using chlorodimethylformiminium chloride as the reagent. However, in the synthesis of diarylketones good yields are only obtained when the phosphorus oxychloride complex of the corresponding arylcarboxylic acid amide has been used The synthesis of ketones from carboxylic acid amides, phosphorus oxychloride and suitable substrates predates the aldehyde synthesis by approximately 40 years but it is of only limited usefulness because side reactions are very often encountered... 

Carboxylic acid amides from aldehydes and alcohols... 

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