Di-tert-butyl Dicarbonate and 4-(Dimethylamino)pyridine Revisited. Their Reactions with Amines and Alcohols¹

Abstract

The reaction of BOC2O in the presence and absence of DMAP was examined with some amines, alcohols, diols, amino alcohols, and aminothiols. Often, unusual products were observed depending on the ratio of reagents, reaction time, polarity of solvent, pKa of alcohols, or type of amine (primary or secondary). In reactions of aliphatic alcohols with BOC2O/DMAP, we isolated for the first time carbonic-carbonic anhydride intermediates; this helps explain the formation of symmetrical carbonates in addition to the O-BOC products. In the case of secondary amines, we succeeded to isolate unstable carbamic-carbonic anhydride intermediates that in the presence of DMAP led to the final N-BOC product. The effect of N-methylimidazole in place of DMAP was also examined.

A simple and eco-sustainable method for theO-Boc protection/deprotection of various phenolic structures under water-mediated/catalyst-free conditions

“…Various phenols were converted to the O-tert-Boc derivatives in excellent yield after 30Á 120 min, proving the advantage of this procedure. No side product was formed as previously cited [8]. The All reactions were carried out in depressurized systems under argon atmosphere; 1 mmol of substrate was dissolved in 10 mL of freshly bidistilled water.…”

“…The introduction of Boc moiety into phenols is generally achieved by the reaction of (Boc) 2 O in the presence of a phase transfer catalyst [7], 4-dimethylaminopyridine (DMAP) as catalyst [8] and using Lewis acids such as BiCl 3 [9], Zn(OAc) 2 [10], 1-tertbutoxy-2-tert-butoxycarbonyl-1,2-dihydroisoquinoline (BBDI) [3,4] and NaTiO 4 [11], or using 6,7-dimethoxyisoquinoline [12] as an organocatalyst.…”

“…More recently, Procopio et al [16] described a new method for the protection/deprotection of the O-tertbutoxy carbonates of alcohols and phenols using mesoporous silica-supported (Er III -MCM-41). However, these conditions are not chemoselective, require harsh conditions, long reaction time, and nucleophilic organocatalysts used sometimes involve the generation of side products in significant quantities such as symmetrical carbonates, cyclic carbonates, and carbonicÁcarbonic anhydrides [8].…”

A facile procedure for tert-butoxycarbonylation of amines promoted by yttria-zirconia based strong Lewis acid catalyst

“…11 However, the same reaction in the presence of yttria-zirconia based Lewis acid catalyst under the reaction condition employed did not lead to any side products. In this connection, our methodology for NBoc protection is noteworthy.…”

Organocatalysis: Fundamentals and Comparisons to Metal and Enzyme Catalysis

“…and Alexanian [81] proposed a room-temperature direct esterification of carboxylic acids with alcohols catalyzed by DMAP or better, by 4-pyrrolidinopyridine (PYP) in the presence of N,Nʹ-dicyclohexylcarbodiimide (DCC: drying agent) (Scheme 6). DMAP and other 4-aminopyridines have been used to catalyze acyl or sulfonyl transfer reactions, including the reactions of (t-BuO)2CO (Boc2O) with amines, alcohols, diols, aminoalcohols, and aminothiols [82] and the chemoselective trifluoroacetylation of anilines using ethyl trifluoroacetate [83]. The catalytical effect of DMAP and analogous 4-aminopyridines results from their high nucleophilicity, favoring a fast addition/elimination process that generates the N-acylpyridinium intermediates 5.…”