Carbonylation, carboxylic acids

By in situ MAS NMR spectroscopy, the Koch reaction was also observed upon co-adsorption of butyl alcohols (tert-butyl, isobutyl, and -butyl) and carbon monoxide or of olefins (Ao-butylene and 1-octene), carbon monoxide, and water on HZSM-5 (Ksi/ Ai — 49) under mild conditions (87,88). Under the same conditions, but in the absence of water (89), it was shown that ethylene, isobutylene, and 1-octene undergo the Friedel-Crafts acylation (90) to form unsaturated ketones and stable cyclic five-membered ring carboxonium ions instead of carboxylic acids. Carbonylation of benzene by the direct reaction of benzene and carbon monoxide on solid catalysts was reported by Clingenpeel et al. (91,92). By C MAS NMR spectroscopy, the formation of benzoic acid (178 ppm) and benzaldehyde (206 ppm) was observed on zeolite HY (91), AlC -doped HY (91), and sulfated zirconia (SZA) (92). 

This chapter deals with the carboxylic acids, carbonyl halides, carboxylic esters, carbonitriles, carbaldehydes, and ketone of 1,8-naphthyridine. 

As in all of these more complex syntheses, other routes to the target compound are possible. This route was chosen because the Grignard reaction introduces a double bond without removing functionality at carbon 3. Dehydration occurs in the desired direction to produce a double bond conjugated with the carboxylic acid carbonyl group. 

This reaction requires high temperatures because the intermediate amide is a poor nucleophile and the carboxylic acid carbonyl group is unreactive. 

The precursor to an amino acid prepared by enantioselective hydrogenation has a Z double bond conjugated with a carboxylic acid carbonyl group. 

Because it is easier to protonate an aldehyde than a carboxylic acid (compare benzoic acid and benzaldehyde in Appendix C), the ring closure would be written best as protonation of the aldehyde oxygen followed by nucleophilic reaction of the carboxylic acid carbonyl oxygen. The carbonyl oxygen acts as the nucelophile because a resonance-stabilized cation is produced. If the hydroxyl oxygen acts as a nucleophile, the cation is not resonance-stabilized. 

The carboxylic acid carbonyl frequency is shifted to lower frequency by 1 to 6 percent in carboxylic acid dimers, which is much less than the relative shifts of The mechanical splitting of the symmetric and antisymmetric carbonyl stretching modes is evident in the difference between the Raman and IR spectra of formic acid. Of course the average of these two is of interest, but often only one is measured. 

Carboxylic acids. Carbonyl compounds undergo a-cleavage on exposure to NaOCl under microwave conditions. 

A MW-assisted protocol for the synthesis of azides, thiocyanates, and sulfones has been developed (Scheme 12) that has proved to be a useful alternative, as the use of environmentally deterimental volatile chlorinated hydrocarbons is avoided.All the reactions with these readily available halides or tosylates have shown significant increase in reactivity, thus reducing the reaction times with substantial improvement in the yields. Various functional groups such as ester, carboxylic acid, carbonyl, and hydroxyl were unaffected under the mild reaction conditions employed. This method involves simple experimental procedures and product isolation which avoids the use of phase-transfer catalysts, and is expected to contribute to the development of greener strategy for the preparation of various azides, thiocyanates, sulfones, and other useful compounds. 

This MW-assisted synthesis of azides, thiocyanates and sulfones proved to be a useful alternative that avoids the use of environmentally detrimental volatile chlorinated hydrocarbons. Various functional groups such as ester, carboxylic acid, carbonyl and hydroxyl were unalTected under the mild reaction conditions employed. ... 

With certain reactants isocyanides undergo three-component condensation and with others four-component condensation.32 1 Three-component addition occurs when isocyanides react with the combinations carboxylic acid-carbonyl compound, hydrogen, azide-carbonyl compound, tropylium salt-water, or two molecules of hydrogen thiocyanate. 

Figure 11.20 shows the dose-dependent absorbance profiles of the carboxylic OH stretch (3100-3500 cm ) and the ester C-O-C stretch (around 1150 cm of a poly(CBN-co-NBCA) exposed to 248-nm radiation and baked afterward at 120, 130, 140, and 150°C. The carboxylic acid OH stretch and the carboxylic acid carbonyl (C O) stretch (1695-1705 cm ) both increase, while the ester carbonyl (C O) stretch (1730-1735 cm ) decreases with increasing dose of exposure (0-50 mJ/cm ), which allows us to follow the deprotection of the t-butyl ester group and the consequent conversion to a carboxylic acid group. The C-O-C (1150 cm ) stretch of the ester also decreases with dose of exposure, indicating the loss of the isobutylene group from the resist polymer. ... 

The position of the carbonyl peak, however, does not depend entirely on inductive effects. In esters, the overlap of the lone pair of electrons on X with the C=0 bond reduces the double bond character of the C=0 bond, so the ester carbonyl group absorbs in the range 1755-1735 cm . Aldehydes and ketones come next at 1740-1700cm , then the carboxylic acid carbonyl absorbs at 1725-1700 cm , which is lower than might have been expected, but its position is affected by the dimeric nature of the carboxylic acid group in solution. 

The complexings of D-glucose, D-fructose, and maltose with borate anions have been studied by polarimetric, conductivity, and pH measurements, and circular dichroism methods have been used to investigate the complexing of cuprammonium ions with carbohydrate diols and amino-alcohols. An examination of the c.d. spectra of fifteen methyl 3-acetamido-3,6-dideoxyhexopyranoside derivatives measured in methanol, 2,2,2-trifluoroethanol, and acetonitrile su ests that the amide group is not completely planar and may show chirality. The n it transition of the carboxylic acid carbonyl groups at... 

Oxygen is known to occur in several different forms in coal, including phenolic hydroxyl, carboxylic acid, carbonyl, ether linkages, and heterocyclic oxygen (Chapter 10). 

The dianhydride VII was used to graft cellulose samples in the presence of 4-dimethylaminopyridine as the catalyst [36, 37]. FTIR spectroscopy revealed the presence of peaks at 1852, 1785, 1730 and 1645 cm" associated, respectively, with anhydride, ester and carboxylic acid carbonyl functions, proving that only one anhydride group had reacted with the substrate, leaving the other available for further modification e.g. its participation in the growth of a polyester matrix). 

Snapshots of the distribution of the 12 water molecules present in the simulated IMC assembly, represeutiug a concentration of 0.6% w/w, indicated that most, but not all, of the water molecules were monomeric with occasional dimer formation also detected. More than 90% of the water molecules were hydrogen bonded. Of these, 36 13% were involved in a single HB, while 28 7% and 29 10% participated in two or three HBs, respectively. When water was the hydrogen donor, 39 8% of its HBs were formed with the benzamide carbonyl, 37 12% were with an IMC carboxylic acid carbonyl, 12 6% were with the —OCH3 group, and 12 9% were with other water molecules. 

Some of the more innovative and creative aspects of peptide chemistry have centered around the peptide bond-forming reaction. Because of the asymmetric center adjacent to the carboxylic acid carbonyl group, the superficially simple operation of amide formation has required study, unparalleled in detail, to avoid racemization. While racemization can usually be limited to less than 1% there is still no universally infallible reaction technique and the advantages of having several good methods at one s disposal is well known to every peptide organic chemist. Presently, in our laboratory, we prefer to first use the MCA method employing isobutyl chloroformate with one equivalent of a relatively weak base such as N-methylmorpholine in tetrahydrofuran. If this proves unsatisfactory we then resort to a method from one of the series A, DCCl-HOBT, ED Cl, WRK, or one of the active ester methods such as OSU, OPCP, or ONP. Soon, we may find it appropriate to add the BBDQ, NCA, SPY, and DPPA methods to this list for reasons outlined below. 

Besides carboxylic acids, carbonylation can give their derivatives or ketones if other nucleophiles were used to cleave the acylpalladium complex. Thus, esters and amides are formed with alcohols and amines, while ketones can be obtained in the presence of such carbanion synthons as organometallic compounds. Certainly, these processes leave a small margin for the intervention of water in any form, as in the presence of water the competition between the different nucleophiles would lower the selectivity, as, for example, in the... 

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