Pentylamines

The adaptation of the Bischler-Napieralski reaction to solid-phase synthesis has been described independently by two different groups. Meutermans reported the transformation of Merrifield resin-bound phenylalanine derivatives 32 to dihydroisoquinolines 33 in the presence of POCI3. The products 34 were liberated from the support using mixtures of HF/p-cresol. In contrast, Kunzer conducted solid-phase Bischler-Napieralski reactions on a 2-hydroxyethyl polystyrene support using the aromatic ring of the substrate 35 as a point of attachment to the resin. The cyclized products 36 were cleaved from the support by reaction with i-butylamine or n-pentylamine to afford 37. 

The 1-(N-ethyl-N-2-hydroxyethylamino)-4-pentanone from above (284.2 grams) was dissolved in 300 grams of 28% ammoniacal methanol and reduced catalytically with Raney nickel (at an initial pressure of 1,000 pounds) at room temperature. After 24 hours the catalyst was filtered off and the product distilled in vacuo through a column, yielding 254 grams of a fraction distilling at 88.5° to 96°C at 0.3 mm and comprising mainly 5-(N-ethyl-N-2-hydroxyethylamino)-2-pentylamine. An analytical sample of this fraction distilled at 93°C at 0.6 mm. 

Amines are converted into alkenes by a two-step process called the Iiofnunn elimination. SN2 reaction of the amine with an excess of CH3I in the first stej yields an intermediate that undergoes E2 reaction when treated with silvei oxide as base. Pentylamine, for example, yields 1-pentene. Propose a structim for the intermediate, and explain why it undergoes ready elimination. 

The inhibiting effect of DHQ and its NH3 product was studied on the final step in the network of Fig. 2, the alkene hydrogenation. To avoid confusion with the PCHE olefin formed from DHQ, cyclohexene (CHE) was used as the reactant, and pentylamine (PA) was used as the source of NH3. When the hydrogenation of CHE is performed in the presence of NH3, we have... 

The Derivative, 5-(biotinamido)pentylamine, contains a 5-carbon cadaverine spacer group attached to the valeric acid side chain of biotin (Thermo Fisher). The compound can be used in a carbodi-imide reaction process to label carboxylate groups in proteins and other molecules, forming amide bond linkages (Chapter 3, Section 1). However, the main use of this biotinylation reagent is in the determination of factor XHIa or transglutaminase enzymes in plasma, cell, or tissue extracts. 

Figure 11.13 5-(Biotinamido)pentylamine can be used to label glutamine residues in proteins by enzymatic action of transglutaminase.

Lee, K.N., Maxwell, M.D., Patterson Jr., M.K., Birckbichler, P.J., and Conway, E. (1992) Identification of transglutaminase substrates in HT29 colon cancer cells Use of 5-(bio-tinamido)pentylamine as a transglutaminase-specific probe. Biochim. Biophys. Acta 1136, 12-16. 

Slaughter, T.F., Achyuthan, K.E., Lai, T.-S., and Greenberg, C.S. (1992) A microtiter plate transglutaminase assay utilizing 5-(biotinamido)pentylamine as substrate. Anal. Biochem. 205, 1-6. 

FIGURE 3. The NMR spectra of the two racemic diastereomers of lV-(4-methyl-2-pentyl)-a-methoxy-a-trifluoromethylphenylacetamide prepared from racemic a-methoxy-a-(trifluoromethyl)phenylacetic acid [MTPA, ( )-83] and racemic 4-methyl-2-pentylamine [( )-84] (A) 60-MHz proton spectrum in chloroform-4 with tetramethylsilane (TMS) as the internal standard (B) 94.1-MHz fluorine-19 spectrum in chloroform-4 with trifluoroacetic acid as the internal standard. Reprinted with permission from Reference 76. Copyright (1969) American Chemical Society... 

The most important example of alkene elimination is found for ionized 1-pentylamine, for which propene loss is the dominant fragmentation of metastable ions. However, this channel is not of general importance metastable ionized 1-butylamine eliminates a much smaller proportion (15%) of ethylene and higher homologues of metastable ionized n-pentylamine rarely expel alkenes to any appreciable extent44. Nevertheless, [M — C H2 ]+ ions do appear in LELT spectra of long-chain primary alkylamines (e.g. at m/z 31, 45, 59, 73, 87 and 101 for 1-octylamine, Figure 2)113. 

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