Amine generation

Thermolysis of 4-methyl(4-phenyl)isoxazolin-5-one produced a-cyanophenylacetic acid <67JHC533). The pyrolysis of 3-methylisoxazoline-4,5-dione 4-oxime generated fulminic acid, which was trapped in a liquid N2 cooled condenser for further study. Pyrolysis of metal salts such as Ag or Na produced the corresponding highly explosive salts of fulminic acid 79AG503). Treatment of the oxime with amines generated bis-a,/3-oximinopropionamides (Scheme 65) <68AC(R)189). 

Scheme 2.12 shows some representative Mannich reactions. Entries 1 and 2 show the preparation of typical Mannich bases from a ketone, formaldehyde, and a dialkylamine following the classical procedure. Alternatively, formaldehyde equivalents may be used, such as l>is-(di methyl ami no)methane in Entry 3. On treatment with trifluoroacetic acid, this aminal generates the iminium trifluoroacetate as a reactive electrophile. lV,A-(Dimethyl)methylene ammonium iodide is commercially available and is known as Eschenmoser s salt.192 This compound is sufficiently electrophilic to react directly with silyl enol ethers in neutral solution.183 The reagent can be added to a solution of an enolate or enolate precursor, which permits the reaction to be carried out under nonacidic conditions. Entries 4 and 5 illustrate the preparation of Mannich bases using Eschenmoser s salt in reactions with preformed enolates. 

Anionic polymerization techniques were also critical for the synthesis of a model cyclic triblock terpolymer [cyclic(S-fo-I-fr-MMA)] [196]. The linear cctw-amino acid precursor S-fr-I-fr-MMA was synthesized by the sequential anionic polymerization of St, I and MMA with 2,2,5,5-tetramethyl-l-(3-lithiopropyl)-l-aza-2,5-disilacyclopentane as the initiator and amine generator, and 4-bromo-l,l,l-trimethoxybutane as a terminator and carboxylic acid generator. Characterization studies of the intermediate materials as well as of the final cyclic terpolymer revealed high molecular and compositional homogeneity. Additional proof for the formation of the cyclic structure was provided by the lower intrinsic viscosity found for the cyclic terpolymer compared to that of the precursor. 

Scheme 9. (A) Different dendrimers as macromolecular scaffolds for MRI contrast agents ethylenediamine cored polyamido amine, generation 4 (PAMAM G4), top hyperbranched, ethylenediamine cored polyethylene imine (HB-PEI), bottom left hyperbranched, amino functionalized polyglycerol (HB-PG), bottom right. (B) Different moieties attached to the respective dendrimers via amide or thiourea bonds.

Sulfur atom as internal nucleophile. In this area, it has been shown that the reaction of 8-bromo-l,3-dimethyl-7-(2,3-epithiopropyl)xanthine 147 with a range of aliphatic and aromatic amines generates efficiently 2-amino-substituted 2,3-dihydro-thiazolo[2,3-/]xanthine derivatives 148. The process involves a sequential amine-induced thiirane ring opening followed by thiolate z/MYi-substitution of chlorine atom (Equation 66) <1994PCJ647>. 

In a variation of this procedure [19], a small amount of acid is added to a suspension of a sulphonated amine in sodium nitrite solution the sulphonic acid group on the amine generates nitrous acid and diazotisation proceeds to completion. 

A large number of nitramine-based explosives have been synthesized via Mannich-type condensation reactions (Section 5.13.2). The amines generated from these reactions often have the powerful electron-withdrawing trinitromethyl or fluorodinitromethyl groups positioned on the carbon a to the amino group. This reduces amine basicity to an extent that A-nitration becomes facile. The energetic nitramines (17), (19) and (21) have been synthesized from the condensation of ethylenediamine with 2,2,2-trinitroethanol, 2-fluoro-2,2-dinitroethanol with ethanolamine, and 2-fluoro-2,2-dinitroethylamine with 2,2-dinitro-l,3-propanediol respectively, followed by A-nitration of the resulting amine bases (16), (18) and (20), respectively. 

Entries 1 and 2 in Scheme 2.11 show the preparation of Mannich bases from a ketone, formaldehyde, and a dialkylamine following the classical procedure. Alternatively, formaldehyde equivalents may be used, such as bis(dimethylamino)methane in entry 3. On treatment with trifluoroacetic acid, this aminal generates the iminium trifluoroacetate as a reactive electrophile. 

Introduce bulky substituent(s) ortho to the amine/amine-generating group(s) so as to provide steric hindrance to inhibit bioactivation. 

R NCIO system also makes the medium acidic, however the strength of the EGA is much weaker than that of a CH Clj—LiClO system due to neutralization of EGA with trialkyl amine produced by cathodic reduction of the ammonium cation Therefore, an EGA-catalyzed reaction can be performed even in a CH Cl — —R NCIO or MeCN—R NCIO system when a divided cell is employed. Presumably, amines generated in the cathode compartment diffuse slowly into the anode compartment where the EGA reaction occurs. 

Attack of the tertiary amine generates the enolate which will attack the aldehyde. 

These complexes are very reactive electrophiles, and reactions with alcohols, a thiol, or amines generate new functionally substituted cluster compounds ... 

Nucleophilic attack at a carbocationic carbon, similar to that observed in metal -carbynes, has been observed from CNBu additions to the //2-t/2-ace-tylide in the complex Fe2(CO)6(C=CPh)PPh2 (427). The ligand dipole, indicated from the X-ray structural determination of the product 96, makes it susceptible to additions of primary amines, generating the carbene 97. 

Exhaustive alkylation of aminonaphthols, such as 2-amino-7-naphthol, and coupling with diazotized aromatic amines generates yellow, orange, red, and brown cationic azo dyes. Compound 5 dyes human hair and polyacrylonitrile in brown shades [26],... 

The synthesis of aza-C-glycosides has been reported (Equation 190) <2005T11716>. The primary amine generated undertakes a conjugate addition to an enone intermediate. 

Whereas the T1 linker involves immobilization of a diazonium salt on an amine resin, the T2 linker is the reversal of this concept. An immobilized diazonium salt 73 was prepared from Merrifield resin 70 in two steps subsequent addition of primary and secondary amines generated triazenes 74. Attachment of hydroxylamine, hydrazines, sulfoximines, and phenols (to give azo coupling products) proceeds equally well (Scheme 6.1.16). 

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