Carbonates, amino functionalization

Acylation. Reaction conditions employed to acylate an aminophenol (using acetic anhydride in alkaU or pyridine, acetyl chloride and pyridine in toluene, or ketene in ethanol) usually lead to involvement of the amino function. If an excess of reagent is used, however, especially with 2-aminophenol, 0,A/-diacylated products are formed. Aminophenol carboxylates (0-acylated aminophenols) normally are prepared by the reduction of the corresponding nitrophenyl carboxylates, which is of particular importance with the 4-aminophenol derivatives. A migration of the acyl group from the O to the N position is known to occur for some 2- and 4-aminophenol acylated products. Whereas ethyl 4-aminophenyl carbonate is relatively stable in dilute acid, the 2-derivative has been shown to rearrange slowly to give ethyl 2-hydroxyphenyl carbamate [35580-89-3] (26). 

The amino functional group is not commonly encountered in steroid synthesis except perhaps in steroidal alkaloids. However, certain elimination reactions have been shown to have theoretical and limited preparative importance, largely due to the efforts of McKenna and co-workers. The Hofmann rule for 2 elimination predicts that alkaline elimination of quaternary ammonium salts will occur towards the carbon carrying the most hydrogen atoms cf. the converse Saytzeff orientation, above). In cyclohexyl systems, the requirement for diaxial elimination appears to be important, as in other 2 eliminations, and the Hofmann rule frequently is not obeyed [e.g., (116) (117)]. 

In the next step, the best candidate from the series 2-oxo-4-(9-phenanthryl)-dihy-dropyrimidine 22 was prepared and isolated in enantiomerically pure form, then attached to a macroporous polymer support. To attach the isolated selector to the amino functionalized macroporous polymethacrylate support, a suitable reactive handle had to be introduced into the dihydropyrimidine. We chose to functionalize the methyl group at the C6 carbon atom by a simple bromination to afford (-)-22. Coupling of this compound to the amino functionalized support then gave the desired chiral stationary phase CSP 12 (Scheme 3-6) containing 0.20 mmol g of the selector. 

A second strategy is to attach a linker (also referred to as a handle or anchor) to the resin followed by assembly of the molecule. A linker is bifunctional spacer that serves to link the initial synthetic unit to the support in two discrete steps (Fig. 3). To attach a linker to a chloromethyl-PS resin, a phenol functionality such as handle 4 is used to form an ether bond (Fig. 4). To attach the same handle to an amino-functionalized support, acetoxy function 5 or a longer methylene spacer of the corresponding phenol is applied to form an amide bond. Both of these resins perform similarly and only differ in their initial starting resin [4], An alternative approach is to prepare a preformed handle in which the first building block is prederivatized to the linker and this moiety is attached to the resin. For peptide synthesis, this practice is common for the preparation of C-terminal peptide acids in order to reduce the amount of racemization of the a-carbon at the anchoring position [5],... 

Not all drugs contain functional groups that lend themselves readily to prodrug derivatization. A case in point is the carbonic anhydrase inhibitors such as acetazolamide, ethoxzolamide, and methazolamide. Although the amino functional group of their sulfonamide moiety can be methylated, the resulting analogs... 

A P-amino function also shields the CF3 carbon (Scheme 5.20). 

The effect which amino functionality has on the thermal and impact sensitivity of polyni-troarylenes (Section 4.8.1.4) makes amination by VNS a method with much future potential for energetic materials synthesis. Other carbon, nitrogen, oxygen and sulfur nucleophiles can displace aromatic hydrogen examples with 1,3-dinitrobenzene and 1,3,5-trinitrobenzene are extensive. 

Due to the synthetic and biological importance of amines and a-aminoketones, acids and esters, the introduction of amino functionality into carbon nucleophiles provides a convenient and practical route for their synthesis "In addition, a number of electrophilic amination methodologies have been developed for the asymmetric synthesis of amines and a-aminocarbonyl compounds " ". 

Cyclohexane can be partially oxidized by just attacking one C-C bond to open the ring with functional groups on each end of the six-carbon chain to produce the six-carbon amino acid or adipic acid. Sketch the intermediates to these products starting with cyclohexanone. 

The reactivity of amino functions on diazotization and condensation with dimethylformamide dimethyl acetal has been discussed in CHEC-II <1996CHEC-II(7)431>. The diamine 220 is readily converted into a variety of tricyclic pyrazolo[3,4-r/ pyrimidines under a variety of conditions <2004T5093>. Thus with chloroacetyl chloride the chlor-oacetyl derivative 221 was formed. This could not be further cyclized into 222. Refluxing 220 with diethyl oxalate afforded 223 while 224 was formed when the reaction was conducted at 40 °C. Treatment of 224 with POCI3 afforded 223. Reacting 220 with carbon disulfide afforded 225 (Scheme 14) <2004T5093>. 

The procedure reported here provides a convenient method for the a-hydroxylation of ketones which form enolates under the reaction conditions. The reaction has been applied successfully to a series of para-substituted acetophenones, 1-phenyl-1-propanone, 3-pentanone, cyclopentanone, cyclohexanone, cycloheptanone, cyclododecanone, 2-methyl cyclohexanone, 2-norbornanone and benzalacetone. In the case of a steroidal example it was shown that a carbon-carbon double bond and a secondary hydroxyl group are not oxidized. A primary amino function, as in the case of p-aminoacetophenone, is not affected.5 Similarly, a tertiary amino ketone such as tropinone undergoes the a-hydroxy at ion reaction.5... 

Two anomalies are distinctly observable in the recovery data. The first feature involves CA, which was not well-retained by the polyurethane-carbon adsorbent either from its individual solution or when mixed with the other five compounds. The effluent from the column contained more CA than was found sorbed onto the adsorbent. Although it is tempting to attribute this lack of sorption to the amino functionality, basicity cannot be the entire reason because DCB with two amino groups behaved normally. Perhaps water solubility could also be a contributing factor. In any event, this result indicates some ineffectiveness of the polyurethane-carbon mixed adsorbent system and shows the need for further investigations of various parameters affecting the recovery of CA or other similar compounds. 

The 3-benzyloxyisoxazole system has functioned as a storable /3-keto amide unit in the construction of tetracyclines (78JA3609). Michael addition of the anion of the 3-benzyloxyisoxazole (442) to the dienolone (441) followed by deesterification-decarboxylation gave rise to (443) in 80% yield. Dehydration of this material and sodium hydride-induced cyclization afforded (445). Hydrogenolysis over palladium on carbon produced the desired ( )-dedimethylamino-12a-deoxyanhydrotetracycline (446 Scheme 99). This isoxazole route has also been extended to the preparation of a tetracycline having the usual amino function in the A ring. 

The reaction is carried out by mixing the peptide and l-fluoro-2,4-dinitrobenzene in the presence of a weak base such as sodium carbonate. In the first step the base abstracts a proton from the terminal H3N group to give a free amino function. The nucleophilic amino group attacks l-fluoro-2,4-dinitrobenzene, displacing fluoride. 

In a-branched amines, however, protonation induces considerable deshieldings a to the amino function, as demonstrated in the series t-butyl-, di-iso-propyl-, and t-butyl-dimethylamine, while shieldings are found for fi carbons as usual [338]. 

This reaction takes place because diimides, —N=C=N—, have reactive cumulated double-bond systems like those of ketenes, C=C=0 isocyanates, —N=C=0 and isothiocyanates, —N=C=S and are susceptible to nucleophilic attack at the central carbon. In the first step of the diimide-coupling reaction, the carboxyl function adds to the imide to give an acyl intermediate, 9. This intermediate is an activated carboxyl derivative RCO—X and is much more reactive toward an amino function than is the parent acid. The second step therefore is the aminolysis of 9 to give the coupled product and yV,N -dicyclohexylurea ... 

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