Fluorination secondary amines

Primary and secondary amines, when added to fluorine-containing alkynes, yield secondary or tertiary fluoroalkylenamines For example, 1-hydroperfluoro 1 decyne reacts with secondary amines in a variety of solvents at 5 °C to give A / f-dialkyl-Ul-dihydroperfluoro 1 decenamines as products The configuration of the double bond is probably E [9]... 

The fluoride [NS(0)F]3 is more stable thermally and towards nucleophilic reagents than the corresponding chloride. For example, 8.15a is hydrolyzed by water to NH(S02NH2)2, whereas sulfanuric fluoride is unaffected by cold water. In warm water, however, hydrolysis occurs to give the [N3S304F2] anion. All three fluorine atoms in [NS(0)F]3 can be replaced by primary or secondary amines at 80-90°C in the absence of a solvent. Mono- or diphenyl derivatives can be prepared by treatment of [NS(0)F]3 with PhLi in diethyl ether at -70°C, while the Friedel-Crafts reaction with benzene at reflux in the presence of AICI3 gives two isomers of [NS(0)Ph]3. ... 

Displacement of Vinyl fluorine or chloride by secondary amines has given some unusual enamines as illustrated for the preparation of 1,1-difluoro-2-piperidino-3-phenyl-2-cyclobutene (151) (US), l,l-difluoro-2,4-dipiperidino-3-phenyl-2-cyclobutene (152) (114), and 2-phenyl-3-(l -aziridinyl)-2-cyclohexenone (153) (115). 

Nitrogen- or Fluorine-Containing Phosphonates In N-containing phosphoric acid esters an >NH or >NR group is used instead of the bivalent >0. A typical reaction is the transformation of POCl3 with primary or secondary amines to the corresponding amides see Eq. (73) ... 

Treatment with sodium hypochlorite or hypobromite converts primary amines into N-halo- or N,N-dihaloamines. Secondary amines can be converted to N-halo secondary amines. Similar reactions can be carried out on unsubstituted and N-substituted amides and on sulfonamides. With unsubstituted amides the N-halo-gen product is seldom isolated but usually rearranges (see 18-13) however, N-halo-N-alkyl amides and N-halo imides are quite stable. The important reagent NBS is made in this manner. N-Halogenation has also been accomplished with other reagents, (e.g., sodium bromite NaBr02) benzyltrimethylammonium tribromide (PhCH2NMe3 Br3"), and NCS. The mechanisms of these reactions involve attack by a positive halogen and are probably similar to those of 12-47 and 12-49.N-Fluorination can be accomplished by direct treatment of amines °° or... 

Reid KA, JTG Hamilton, RD Bowden, DO Hagan, L Dasaradhi, MR Amin, DB Harper (1995) Biosynthesis of fluorinated secondary metabolites by Streptomyces cattleya. Microbiology (UK) 141 1385-1393. 

Selective nucleophilic displacement of the C-10 fluorine atom of 158 was achieved with secondary amines iV-methylpiperazine, 4-methylpiperidine, or 1,2,3,4-tetrahydroisoquinoline affording the product 159 in low to moderate yield <2000JHC297>. 

Combination of the Hantzsch ester mediated transfer hydrogenation together with chlorine (116) or fluorine (117) electrophiles allows for the formal addition of HCl or HF aaoss a double bond in a catalytic asymmetric manner (Scheme 48) [178], Within this paper the reactions were further refined by the use of two cycle-specific secondary amines which effectively operated independently within the same reaction mixture. Impressively, this allowed access to either diastereoisomer of the product depending upon the absolute configuration of the catalyst used in the second step of the sequence. 

In the reaction of 1-naphthol with 3-nitro-4-fluorobenzalmalononitrile in ethanol, catalyzed by secondary amines, nucleophilic displacement of fluorine competes with pyran ring closure. Application of a tertiary amine (N-methylmorpholine) leads to the selective formation of the corresponding aminochromene (94H(38)399). 2,3-, 1,8-Dihydrooxynaphthalenes 148 and 149 react with 1 or 2 equiv. of aromatic aldehyde 28 and MN 27a to yield naphthopyrans 150 and 151 or dipyrans 152 and 153 (90IJB885, 02RCB2238) (Scheme 53). 

Hydrogen atoms bonded to nitrogen, as well as those attached to carbon, are replaced by fluorine upon perfluorination of primary and secondary amines (Fig. 37) [101, 102]. Perfluorinated tertiary amines have also been prepared (Figs. 38 and 39) [78,103]. 

Furin et al. [90] have conducted the electrochemical fluorination of a series of amines, tripropylamine, tributylamine and triamylamine, and a series of enamines formed by the reaction of hexafluoropropene, its dimers and trimers with the secondary amines dipropylamine, dibutylamine and dial-lylamine. As well as the anticipated saturated perfluoroanalogues of the starting materials by-products resulting from structural breakdown were also produced. 

While aromatic amines are discussed in Section 5.2.14., various data for aliphatic amines are listed in Table 20. It is worthwhile remembering that tertiary perfluorinated amines, such as perfluorotributylamine. are completely stable, inert and nontoxic compounds, while some partially fluorinated tertiary amines tend to be unstable, eliminating hydrogen fluoride even at low temperature and are therefore toxie. Primary and secondary aliphatic fluorinated amines carrying CF,N groups have not, so far, been isolated due to their instability. 

One example has been reported in which fluorine is replaced by an N-nuclcophilc with the intermediacy of a carbene species. Thus, when 3-fluoro-3-phenyl-3//-diazirine (2) is irradiated in the presence of a secondary amine, a diaminophenylmcthanc derivative 3 is formed.19... 

Primary and secondary amines, when added to fluorine-containing alkynes,... 

Ref 46a Two benzylic alcohols are selectively oxidized with active M11O2 in the presence of two secondary amines. In a similar compound, possessing two methoxy substituents in the place of the two fluorine atoms, the corresponding oxidation provides a modest 34% yield of the desired dialdehyde. This happens because the methoxy substituents render the amines more oxidation-sensitive. ... 

Reid KA, Hamilton JT, Bowden RD, O Hagan D, Dasaradhi L, Amin MR, Harper DB (1995) Biosynthesis of Fluorinated Secondary Metabolites by Streptomyces cattleya. Microbiology 141 1385... 

Direct enantioselective catalytic a-fluorination of aldehydes has been carried out using jV-fluorobenzenesulfonimide [F-N-(02SPh)2] and a chiral secondary amine (an imidazolidinone) to provide enamine organocatalysis.295... 

SAR studies have shown that a weakly basic imidazole or 1,2,4-triazole rings substituted only at the N-l position are essential for activity. The substituent must be lipophilic in character and usually contains one or more five or six membered ring systems, some of which may be attached by an ether, secondary amine or thioether group to the carbon chain. The more potent compounds have two or three aromatic substituents, which are singly or multiply chlorinated or fluorinated at positions 2, 4 and 6. These nonpolar structures give the compounds a high degree of lipophilicity, and hence membrane solubility. 

Amines. The synthesis of fluorinated ethyl amines has been accomplished 96 by heating CHF2CH2I to 130° in a sealed tube with concentrated aqueous ammonia a mixture of the primary amine, CHF2CH2NH2, secondary amine, (CHF2CH2)2NH, and tertiary amine, (CHF2CH2)3N, is obtained. 

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. ... 

When functional groups are present, the products can be quite complex. Primary and secondary amines give NF2 and NF compounds respectively and fluorination of sulphur compounds gives products in which the sulphur has been oxidised to its maximum valency state of six [149] (Table 2.4). Hydroxy compounds can give fluoroalkyl hypo-fluorites (fluoroxy compounds) (see also Chapter 3, Section IIIB), the corresponding alkyl derivatives not being stable [150, 151] bisfluoroxy derivatives have also been isolated [152-154] (Figure 2.27). 

Class II Other liquids composed of molecules containing both active hydrogen atoms and donor atoms (oxygen, nitrogen, and fluorine)—e.g., alcohols, acids, phenols, primary and secondary amines, oximes, nitro compounds with alpha-hydrogen atoms, nitriles with alpha hydrogen atoms, ammonia, hydrazine, HF, HCN (plus nitromethane, acetonitrile even though these form 3-dimensional networks they have weaker bonds than —OH and —NH bonds in class I)... 

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