Amine masked

FC McKay, NF Albertson. New amine-masking groups for peptide synthesis. J Am Chem Soc 79, 4686, 1957. 

L.A. Carpino, Oxidative reactions of hydrazine, II. Isophthalimides. New protective groups on nitrogen. J. Amer. Chem. Soc. 79 98-101 (1957) F.C. McKay, N.F. Albertson, New amine-masking groups for peptide synthesis, J. Amer. Chem. Soc. 79 4686-4690 (1957)... 

Acetylene is also protected as propargyl alcohol (300)[2H], which is depro-tected by hydrolysis with a base, or oxidation with MnOi and alkaline hydrolysis. Sometimes, propargyl alcohols are isomerized to enals. Propargyl alcohol (300) reacts with 3-chloropyridazine (301) and EtiNH to give 3-diethylami-noindolizine (303) in one step via the enal 302[2I2]. Similarly, propargyl alcohol reacts with 2-halopyridines and secondary amines. 2-Methyl-3-butyn-2-ol (304) is another masked acetylene, and is unmasked by treatment with KOH or NaOH in butanol[205,206,213-2l5] or in situ with a phase-transfer cata-lyst[2l6]. 

Reductive alkylations have been carried out successfully with compounds that are not carbonyls or amines, but which are transformed during the hydrogenation to suitable functions. Azides, azo, hydrazo, nitro and nitroso compounds, oximes, pyridines, and hydroxylamines serve as amines phenols, acetals, ketals, or hydrazones serve as carbonyls 6,7,8,9,12,17,24,41,42,58). Alkylations using masked functions have been successful at times when use of unmasked functions have failed (2). In a synthesis leading to methoxatin, a key... 

In contrast, A, JV-diethyl-3-(methylsulfanyl)-5-phenyl-3//-azepin-2-amine (22) on treatment with methyl or benzyl halides and potassium amide in liquid ammonia undergoes alkylation solely at the masked benzylic 5-position to yield 4,4-disubstituted 4//-azepines, e.g. 23.224... 

The parent dibenzotriazepine behaves as a masked diazonium salt hydriodic acid, for example, yields 2 -iodobiphenyl-2-amine (1 a) and hydrobromic acid in the presence of copper powder gives the corresponding bromo compound lb.331... 

A-Acido imines (R R"C = N —X=0) like /V-acyl (X = CR) /V-sulfonyl [X = S(R)=0]2-7 or /V-diphenylphosphinoylimines [X = P(C6H5)2]3 are masked inline derivatives of ammonia. Compared to the imines themselves these activated derivatives are better electrophiles showing less tendency to undergo undesired deprotonation rather than addition of organometal-lics1812 The apparent advantages of these compounds have been exploited for asymmetric syntheses of amines, amides, amino acids and /J-lactams1-8 I6. 

Addition of organometallics to hydrazones provides hydrazines1, which can be converted to the corresponding amines by hydrogenolysis. Hydrazones can therefore be regarded as masked imine derivatives of ammonia. This methodology has been utilized successfully for numerous stereoselective syntheses of amines and amine derivatives2-23. 

This fully aromatic amide, based oil the amino acid p-aminobenzoic acid, can be spontaneously synthesized from p-aminobenzoic chloride.7 9 72 To prevent this occurring at an unwanted moment, the amine group is masked by forming the hydrochloric acid salt with hydrochloric acid. 

For the addition of an organometailic compound to an imine to give a primary amine, R in RCH=NR would have to be H, and such compounds are seldom stable. However, the conversion has been done, for R = aryl, by the use of the masked reagents (ArCH=N)2S02 [prepared from an aldehyde RCHO and sulfamide (NH2)2S02]. Addition of R"MgX or R"Li to these compounds gives ArCHR"NH2 after hydrolysis. ... 

Piperidines bearing a masked aldehyde function in the e-position are easily transformed into quinolizidine compounds through intramolecular reductive amination after deprotection (acetal precursors) or oxidative cleavage (tv e-diols). Some examples are given below. 

An enantioselective synthesis of (—)-lupinine 6 was based on a similar reductive amination process. In this case, (k)-phcnylglycinol was used to obtain a chiral nonracemic oxazololactam which was cyclized after reduction of N-C and O-C bonds and subsequent hydrolysis of the masked aldehyde <2004T5433>. 

A common choice of crosslinker for this type of reaction is sulfo-SMCC, which has been used extensively for antibody conjugation (Chapter 20, Section 1.1). A better option for dendrimer conjugation is to use a similar crosslinker design, but one that contains a hydrophilic PEG spacer arm to promote dendrimer hydrophilicity after modification. Derivatization of an amine-dendrimer with a NHS-PEG-maleimide can create an intermediate that is coated with water-soluble PEG spacers. This modification helps to mask any potential for nonspecific interactions that the PAMAM surface may have, while providing terminal thiol-reactive maleimides for coupling ligands (Figure 7.10). 

Add a quantity of NHS-salicylic acid methyl ester reagent dissolved in coupling buffer to the slide surface to provide at least a 2-fold molar excess of crosslinker over the quantity of amines present on the surface. The surface of the slide may be coated with a minimum solution volume of the crosslinker by layering the solution over the surface. Slide masks or gaskets may be used to isolate only certain regions for modification. Alternatively, the slide may be immersed in the crosslinker solution. The NHS-salicylic acid methyl ester may be first dissolved in DMF as a concentrated stock solution and then an aliquot... 

The susceptibility of the sydnone ring to acid-catalyzed hydrolysis at elevated temperature is exploited for the preparation of hydrazines <2000MI227>. Primary amines are first converted to sydnones, which are then hydrolyzed to give hydrazines that may be isolated or reacted further without isolation <1996CHEC-II(4)165>. As masked hydrazines, 3-arylsydnones are firstly subjected to acid-catalyzed ring opening and then allowed to react further in situ with 2-(4-chlorophenyl)hydrazono-3-oxo-butyric acid to form substituted pyrazolidinones (Equation 2) <2005SC2169>. 

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