Bromination secondary amines

Bromination of the methyl group of (249) with A -bromosuccinimide, followed by reaction with excess secondary amine gave (250) which shows combined analgesic and antitussive properties. The Reformatsky reaction has also been used for the preparation of 2-amino-ethyl 3,3-diaryl-3-hydroxypropanates (251) as well as their dehydration products. The propene amides (252) have also been prepared for pharmacological evaluation. In l-methyl-3-bis (2-thienyl)-... 

Finally the aminoquinoline bearing a primary amine at the terminal carbon atom of the side chain is itself an effective antimalarial drug. Ring opening of 2-methyltetrahydrofuran by bromine gives the dibromide, 99. The primary halide is sufficiently less hindered so that reaction with potassium phthalimide affords exclusively the product of displacement of that halogen (100). Alkylation of the aminoquinoline with lOO affords the secondary amine, 101. Removal of the phthalimide group by means of hydrazine yields primaquine (102). ... 

In recent studies, we found that primary and secondary amines, alone or somehow faster in the presence of the soft Lewis acid Ag+ (refs. 7-9) substitute the bromine in (S)-2-bromopropanamides, in an organic solvent, at room temperature, and yield N-alkyl-, and N,N -dialky 1-aminopropanamides, with inversion of configuration and high enantiomeric excess. Conversely, in the presence of silver oxide (Ag20), much faster reactions occur with retention of configuration, giving... 

Benzotriazol-l-yl)methyl]triphenylphosphonium chloride 848 reacts with BunLi and aldehydes to give l-(alken-l-yl)benzotriazoles 849. Addition of bromine to the double bond of derivatives 849 followed by a reaction with amines furnishes amides 850. A variety of primary or secondary amines can be used. This way aldehydes are conveniently homologated and converted to amides with a one-atom longer chain (Scheme 136) <2004ARK(ix)44. 

Dipolar cycloaddition reactions, of nitrones to olefins, 46, 97 of 3-phenylsydnone, 46, 98 Dispiro[5.1.5.1]tetradecane-7,14-dione, photolysis to cyclohexylidene-cyclohexane, 47, 34 preparation from cyclohexanecarbonyl chloride and triethylamine, 47, 34 Displacement of bromine from 1-bromo-2-fluoroheptane to give 2-fluoro-heptyl acetate, 46, 37 N,N -Disubstituted formamidines from triethyl orthoformate and primary amines, 46, 41 N,N-Disubstituted thioureas from secondary amines and silicon tetra-isothiocyanate, 45, 69 N,N-Disubstituted ureas from secondary amines and silicon tetraiso-cyanate, 45, 69... 

A second method is due to J. von Braun and consists in the addition of cyanogen bromide to tertiary cyclic bases.1 In the unstable addition product a C—N-linkage is broken and at the same time the bromine wanders to a new position. A brominated derivative of cyanamide is produced and this, on hydrolysis, yields a secondary amine which can be broken down further, e.g. 

Bis(bromomethyl)quinoxaline (126) is better prepared by the condensation of o-phenylenediamine and l,4-dibromobutane-2,3-dione than by side-chain bromination of 2,3-dimethylquinoxaline. It reacts with secondary amines, forming quinoxalino[2,3-c]pyrrolidine salts, e.g. (127).134 Reaction with thiols yields 2,3-bis(thiomethyl)quinoxalines,135... 

The normal reactions of benzo[6]thiophene 1,1-dioxides have been reviewed (70AHC(11)177). Electrophilic substitution (nitration, bromination) takes place at position 6. 3-Halo derivatives undergo normal nucleophilic displacement reactions, but 2-bromobenzo[6]thiophene dioxide gives the 3-ethoxy derivative in ethanolic NaOH. The reaction of 3-methoxy derivatives with secondary amines can give rise either to enamines... 

An alternative approach to synthesis of this ring system involves insertion of CO into the brominated secondary base (43), by treatment with carbon monoxide, lead tetra-acetate, and triphenylphosphine in tributylamine, the product being the amide (44), reduction of which affords the amine.81 Govadine (42 R1 = R4 = OMe, R2 = R5 = OH, R3 = H) has been synthesized by the conventional ring-closure, with formaldehyde, of the diphenolic base (45), or of its dibenzyl ether, in acid solution.82 Tetrahydroberberines, together with N-benzyltetrahydroisoquinolines, have also been obtained by the electrolytic reduction of 3,4-dihydroisoquinolines of structure (46).83... 

Pentamethinestreptocymine Dyes are formed by reaction of bromine cyanide, chlorine cyanide, or 2,4-dinitrochlorobenzene with pyridine and cleavage of the resultant compounds with primary or secondary amines. The tetraacetal of gluta-conaldehyde is also used to form the methine chain [2], The dyes can be used to dye paper. 

Vinylic substitution of bromine by noncyclic primary and secondary amines in 3-bromo-4,4-dimethoxy-2-butenoates and corresponding nitriles occurs in a stereocontrolled fashion. Regardless of the starting stereochemistry, the product possesses trans amino and ester (or nitrile) groups (equation 20)174. Also, displacement of bromine from 5-bro-mouracils, by cyclic amines, has been used as a preparation of novel pyrimidine inhibitor intermediates1. This reaction has been shown to be assisted by the presence of fluoride ion... 

The electron-withdrawing S=0 group helps the nucleophilic substitution of bromide with sodium phenolate in 3-bromobenzoMthiophene 1-oxide (Scheme 26). Nucleophilic substitution of bromine could also be carried out using secondary amines such as piperidine and morpholine <2005JOC3569>. 

Methods for the chlorination of secondary amines, secondary amides and imides have been reviewed. Secondary alkylamines can be chlorinated by r-butyl hypochlorite at low temperature, or by sodium hypochlorite or iV-chlorosuccinimide. A(-Bromination and A(-iodination can be brought about using the appropriate halogen, but these N-halodialkylamines are unstable and are rarely isolated. A(-Flu-oroamines and Mfluoroamides are also rare. The A(-fluoroimide (CP3S02)2NF, has, however, been prepared by direct fluorination widi fluorine. It is a stable liquid which shows promise as a fluorinating agent for aromatic compounds. ... 

A variety of piperidines are formed by intramolecular cyclization of y-aminoolefins via bromination of the double bond. Chiral secondary amines provide diastereoselectivity <03CC1918>. 

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