Primary amines protection

A primary amine, protected by reaction of the amine with cyclopentadiene and formaldehyde (H2O, rt, 3 h), is cleaved by trapping cyclopentadiene with A -methylmaleimide (H2O, 2.5 h, 23-50°, 61-97% yield), CUSO4 (EtOH or MeOH, 70°, 74-99%), or Bio-Rad AG 50W-X2 acid ion-exchange resin, 82-98% yield. ... 

A variety of cleavage conditions have been reported for the release of amines from a solid support. Triazene linker 52 prepared from Merrifield resin in three steps was used for the solid-phase synthesis of aliphatic amines (Scheme 22) [61]. The triazenes were stable to basic conditions and the amino products were released in high yields upon treatment with mild acids. Alternatively, base labile linker 53 synthesized from a-bromo-p-toluic acid in two steps was used to anchor amino functions (Scheme 23) [62]. Cleavage was accomplished by oxidation of the thioether to the sulfone with m-chloroperbenzoic acid followed by 13-elimination with a 10% solution of NH4OH in 2,2,2-trifluoroethanol. A linker based on l-(4,4 -dimethyl-2,6-dioxocyclohexylidene)ethyl (Dde) primary amine protecting group was developed for attaching amino functions (Scheme 24) [65]. Linker 54 was stable to both acidic and basic conditions and the final products were cleaved from the resin by treatment with hydrazine or transamination with ra-propylamine. 

The procedure has been extended to the synthesis of 7V,7V -substituted diamines 166 from the diazides 164 and dichloroboranes 165177. Primary amines protected by the t-butoxycarbonyl group are obtained by the action of trialkylboranes R3B (R = Bu, s-Bu, CsHn or cyclohexyl) on the lithium or potassium salt of t-butyl 7V-(tosyloxy)carbamate (equation 62)178. 

Primary amine protection Imides of the type derived from this anhydride are stable to conventional conditions for deacetylation, benzylation, benzylidenation, and... 

In early studies into the use of the dithiasuccinoyl (Dts) primary amine protecting group, the desired (V-alkylated derivatives (6) were prepared from the reaction between O-ethyl-AAalkyl (or aryl) thiocarbamates (9) and cblorocarbonylsulfenyl chloride (5) (eq9). ... 

Mono-substitution products of primary amines cannot easUy be prepared by direct action of the appropriate reagent for example, bromination of aniline yields largely the 2 4 6-tribomo derivative and nitration results in much oxidation. If, however, the amino group is protected as in acetanilide, smooth substitution occurs. Thus with bromine, />-bromoacetanilide is the main product the small quantity of the ortlio isomeride simultaneously formed can be easily eliminated by crystallisation. Hydrolysis of p-bromoacetanilide gives/ -bromoaniline ... 

This reaction can also be utili2ed to prepare functionali2ed initiators by reaction of butyUithium with a substituted 1,1-diphenylethylene derivative. For example, polymers end functionali2ed with primary amine, tertiary amine, phenol, and bis(phenol) groups have been prepared in essentiaUy quantitative yield by using the reaction of butyUithium with the corresponding substituted (or protected) 1,1-diphenylethylene (87). 

Cyclohexylamine is miscible with water, with which it forms an azeotrope (55.8% H2O) at 96.4°C, making it especially suitable for low pressure steam systems in which it acts as a protective film-former in addition to being a neutralizing amine. Nearly two-thirds of 1989 U.S. production of 5000 —6000 t/yr cyclohexylamine serviced this appHcation (69). Carbon dioxide corrosion is inhibited by deposition of nonwettable film on metal (70). In high pressure systems CHA is chemically more stable than morpholine [110-91-8] (71). A primary amine, CHA does not directiy generate nitrosamine upon nitrite exposure as does morpholine. CHA is used for corrosion inhibitor radiator alcohol solutions, also in paper- and metal-coating industries for moisture and oxidation protection. 

PhCH20CO-imidazolyl, 4-dimethylaminopyridine, 16 h, it, 76% yield. Two primary amines were protected in the presence of a secondary amine. 

Phthalimide-NC02Et, aq. Na2C03, 25°, 10-15 min, 85-95% yield. This reagent can be used to protect selectively primary amines in the presence of secondary amines. ... 

The formation of vinylogous amides from primary amines and -dicarbonyl compounds gives rise to hydrolyzable amine derivatives with greatly decreased nucleophilicity of the nitrogen function. Thus these derivatives have found some use as protecting groups in peptide syntheses 617-619). 

N02C6H40C02Bn, Pyr, DMF, 26°, 24 h, 74% yield. Primary amines are selectively protected over secondary amines, but anilines are insufficiently nucleophilic to react with this reagent. ... 

The primary amine of an amino acid as its tosylate salt can be protected by coordination with a crown ether. The protection scheme was sufficient to allow the HOBt/DDC coupling of amino acids. The crown is removed by treatment with diisopropylethylamine or KCl solution. 

A trifluoromethylsulfonamide can be prepared from a primary amine to allow monoalkylation of that amine. The triflamide is not stable to strong base, which causes elimination to an imine, but when used to protect an indole, it is cleaved with K2CO3 in refluxing methanol. ... 

---