Primary alkyl amines

Bis(bromomethyl)-5//-dibenz[/), / ]azepines, e.g. 12, prepared by free-radical bromination of the 10,11-dimethyl compound with yV-bromosuccinimide, on treatment with a primary alkyl-amine followed by alkaline hydrolysis, yield l,2,3,8-tetrahydrodibenzo[. /]pyrrolo[3,4-<7]-azepines, e.g. 13, which possess useful pharmacological properties.91,163... 

Primary alkyl amines RNHi can be convertedto alkyl halides by (1) conversion to RNTs2 (p. 447) and treatment of this with I or Br in DMF, or to N(Ts)—NH2 derivatives followed by treatment with NBS under photolysis conditions, (2) diazotization with terr-butyl nitrite and a metal halide such as TiCU in DMF, or (3) the Katritzky pyrylium-pyridinium method (pp. 447,489). Alkyl groups can be cleaved from secondary and tertiary aromatic amines by concentrated HBr in a reaction similar to 10-71, for example,... 

All in aqueous solution at 25°C unless otherwise noted equilibrium constants have dimensions of M. Various alkane thiols, of similar equilibrium reactivity. Methylamine or a primary alkyl amine of similar reactivity. Dimethylamine or a secondary alkyl amine of similar reactivity °Reference 30. Reference 14. RSH is mercaptoethanol. Reference 31. Reference 32. Reference 33. Reference 21. RSH is ethanethiol " Reference 34. Reference 35. Reference 36. Reference 37. RSH is 2-methoxyethanethiol. Reference 38. Reference 39. Reference 40. Reference 23. Reference 41. Reference 31. Reference 42. Reference 5. Reference 43. In ethanol. Reference 44. Reference 45. Reference 46. RNKj is n-butylamine. "Reference 47. 

With the exception of intramolecular amination reactions, all of the early aryl halide aminations were catalyzed by palladium complexes containing the sterically hindered P(o-tol)3. In papers published back-to-back in 1996, amination chemistry catalyzed by palladium complexes of DPPF and BINAP was reported.36,37 These catalysts allowed for the coupling of aryl bromides and iodides with primary alkyl amines, cyclic secondary amines, and anilines. 

Chang et al. reported a mild tandem intramolecular hydroamination of yne amines to form an endo-adduct intermediate, which reacts with electron-deficient azides to produce cyclic amidines <06JA12366>. Selected examples of an interesting synthetic route to tropene derivatives 165 via a dual hydroamination strategy is shown below. This one-step reaction makes use of a palladium catalyst and takes place by sequential intermolecular hydroamination of cycloheptatriene with aryl, heteroaryl, and primary alkyl amines to generate intermediate 166, followed by transannular intramolecular hydroamination <06JA8134>. 

Simple unactivated Immonlum salts generated In situ from formaldehyde and primary alkyl amines undergo a facile aza Diels-Alder reaction with cyclopentadlene at ambient temperature to afford novel N-alkylated 2-azanorbornenes. The procedure described above Is general and can be applied to a number of primary alkyl amines. Yields of N-alkyl substituted 2-azanorbornenes are good to excellent. Use of ammonium chloride and... 

The dyes may be prepared by treatment of l,4-diamino-2,3-dicyanoanthraquinone with sulfuric acid followed by alkylation of the imide by primary alkyl amine exchange. Alternatively, the sulfuric acid treatment may be carried out in the presence of a secondary alcohol (Scheme 11). 

Due to the failure of ammonia in this reaction, a variety of alternative strategies to prepare primary alkyl amines utilizing Pd catalysis have been investigated.196-198-200 4,4 -Dimethoxybenzhydrylamine (DMB 8) reacts with allyl acetates under Pd° catalysis and can be debenzylated with formic acid to yield a primary amine (equation 57).200 Similarly, p-toluenesulfonamides196-197 and azides can be conveniently converted to amines following their participation in the Pd-catalyzed alkylation. 

We found that the color yielded for primary alkyl amine positive tests is strongly influenced by the presence of other functional groups. Specifically we could not establish a clear positive for arginine, asparagine, and cysteine when their lateral chains were deprotected. A similar effect was observed in the case of secondary amines or sterically hindered amines such as Aib. 

Fig. 6.20. Mechanism of the second step of the Gabriel synthesis of primary alkyl amines.

It is well-known that organoboranes can be utilized to yield primary amines by treating them with chloramine or hydroxylamine-O-sulfonic acid Recently Kabalka et al. reported a convenient synthesis of primary alkyl amines via the reaction of organoboranes with ammonium hydroxide in the presence of sodium hypochlorite (Eq. 13) The reaction presumably proceeds through the in situ formation of chloramine. 

The phosphoramidite derivative of N-nitrothymidine (44) has been synthesised and found suitable for oligonucleotide synthesis using a standard phosphite triester solid phase approach. The N-nitrothymidine residues could be converted into a range of N -modified thymidines by reaction with primary alkyl amines. Phosphoramidite derivatives of 4-nitroindazole N and N -(2 -deoxy-p-D-ribofuranosides) (45, 46) have been synthesised, their base pairing properties investigated and found to show ambiguous base pairing. Seela has also reported the syntheses of the phosphoramidite derivatives of 8-aza-7-adenine... 

With nitrous acid. The reaction of the aromatic primary amines with nitrous acid is different from that of the aliphatic primary amines with the same reagent, and serves to distinguish the two groups of compounds. When a primary alkyl amine is treated with nitrous acid the hydroxyl compound of the radical is formed and all of the nitrogen of the amine is given off as free nitrogen. The reaction is as follows ... 

Primary alkyl amines RNH2 can be converted to alkyl halides by (i) conversion to RNTs2 (p. 498) and treatment of this with P or Br in DMF, or to N(Ts)—NH2 derivatives followed by treatment with A-bromosuccinimide under... 

Subbaiah, G., Sethuram, B., Mahadevan, E. G., Rao, T. N. Kinetics of methylation of primary alkyl amine hydrochlorides with formaldehyde... 

Later, a range of anionic O -donor ligands (66-79) were screened to improve the /V-arylalion of primary alkyl amines using aryl bromides as substrates (Scheme 9)265. 

SCHEME 9. Anionic 0-donors screened for W-aiylation of primary alkyl amines... 

The labile alkoxy group of an alkoxyquinone is displaced by a primary alkyl-amine at ambient temperature, and a side-chain keto group reacts with the amino function to form this ring. Reviews of the chemistry of heterocyclic quinones are available [2947, 3650). 

Nitrous acid serves to differentiate sharply primary alkyl amines from primary aryl amines. The salts of the former are converted into alcohols by this reagent. The reaction in the case of methylamine is expressed by the equation,—... 

Simple unactivated fmmonlun salts generated in situ from formaldehyde and primary alkyl amines undergo a facile aza Diels-Alder reaction with... 

Primary alkyl amines. a-Alkoxy azides are reduced to primary amines by lithium aluminum hydride in ether. A side reaction noted occasionally, reduction to an ether, can be suppressed by addition of TMEDA. Sodium bis(2-methoxy-ethoxy)aluminum hydride cannot replace lithium aluminum hydride in this reductive amination. The a-alkoxy azides are available by reaction of aldehydes with azidotrimethylsilane, by addition of hydrazoic acid to an enol ether, or by reaction of ketals with the l8-crown-6 complex of sodium azide. 

---