Reactive amines

Aromatic amines (anilines) may become activated in vivo to form reactive amines. These are nucleophiles and may attack DNA, forming covalent modifications. Aromatic nitro compounds can be metabolised to also form reactive amines. A-nitroso compounds result in the alkylation of oxygen sites in DNA bases (0-6 in guanine and 0-4 in thymidine) [8,10]. 

These compounds are able to intercalate between the coils of the DNA double helix. 

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All lene Oxides and Aziridines. Alkyleneamines react readily with epoxides, such as ethylene oxide [75-21-8] (EO) or propylene oxide [75-56-9] (PO), to form mixtures of hydroxyalkyl derivatives. Product distribution is controlled by the amine to epoxide mole ratio. If EDA, which has four reactive amine hydrogens, reacts at an EDA to EO mole ratio which is greater than 1 4, a mixture of mono-, di-, tri,-, and tetrahydroxyethyl derivatives of EDA are formed. A 10 1 EDA EO feed mole ratio gives predominandy 2-hydroxyethylethylenediamine [111-41-1], the remainder is a mixture of bis-(2-hydroxyethyl)ethylenediamines (7). If the reactive NH to epoxide feed mole ratio is less than one and, additionally, a strong basic catalyst is used, then oxyalkyl derivatives, like those shown for EDA and excess PO result (8,9). 

Step-growth polymerization processes must be carefully designed in order to avoid reaction conditions that promote deleterious side reactions that may result in the loss of monomer functionality or the volatilization of monomers. For example, initial transesterification between DMT and EG is conducted in the presence of Lewis acid catalysts at temperatures (200°C) that do not result in the premature volatilization of EG (neat EG boiling point 197°C). In addition, polyurethane formation requires the absence of protic impurities such as water to avoid the premature formation of carbamic acids followed by decarboxylation and formation of the reactive amine.50 Thus, reaction conditions must be carefully chosen to avoid undesirable consumption of the functional groups, and 1 1 stoichiometry must be maintained throughout the polymerization process. 

Addihon of primary and secondary amines to 1,3-butadiene and isoprene at 0 to 180°C over solid bases such as MgO, CaO, SrO, LajOj, Th02, and ZrOj has also been studied. CaO exhibits the highest achvity, while ZrOj is inachve. MejNH is the most reactive amine, giving primarily the 1,4-addihon product which undergoes iso-merizahon to the enamine N,N-dimethyl-l-butenylamine. It has been proposed that addihon of amines to 1,3-dienes on basic catalysts proceeds via aminoallyl carban-ion intermediates which result from addihon of amide ions to the dienes [169, 170]. 

Anchored amine materials can be prepared through a number of synthetic methodologies. Because of the potential importance of these materials to organic synthesis, a ninhydrin assay was developed as a rapid laboratory determination of available surface amines. The assay agreed well with expected values for aminopropyltriethoxysilane grafted onto commercial silica. The assay also distinguished between reactive amines and protonated or poisoned surface amines on co-condensed SBA-15 materials. 

At the second stage of chlorine substitution in the tetramers there is a greater statistical probability for the incoming nucleophile to attack the phosphorus adjacent to =P(C1)(NHR), viz. P4 or P8, rather than the remote phosphorus, viz. P6 (Fig. 9). However, this statistical effect is countered by the electron releasing effect of the substituent already present on P2, which tends to deactivate P2 as well as P4 and P8 towards further nucleophilic substitution. It is observed that reactive amines such as dimethylamine (94) or ethylamine (95) react with N4P4C18 and... 

Electrophilic site for Schiff base formation with reactive amines such as a-amino acids. Corresponding transaminated species, pyridoxamine, reacts with electrophilic carbonyl compounds... 

The first designed catalyst where there was some understanding of the relationship between structure and function was oxaldie 1, a 14-residue peptide that folds in solution to form helical bundles [11] (Fig. 12). Oxaldie 1 was designed to catalyze the decarboxylation of oxaloacetate, the a-keto acid of aspartic acid, via a mechanism where a primary amine reacts with the ketone carbonyl group to form a carbinolamine that is decarboxylated to form pyruvate. The reaction is piCj dependent and proceeds faster the lower the piC of the primary amine if the reaction is carried out at a pH that is lower than the piCj, of the reactive amine. The sequence contains five lysine residues that in the folded state form... 

The curing sequence and kinetics of this adhesive system prevent the NTMP from Inhibiting the reactive amines until the curing reaction Is well under way. In contrast, the epoxypolyamide primer contains free amino groups at room temperature and may be inhibited by the electrophilic NTMP species prior to curing. (Equation 3)... 

In 2004, Rayner and coworkers reported a dynamic system for stabilizing nucleic acid duplexes by covalently appending small molecules [34]. These experiments started with a system in which 2-amino-2 -deoxyuridine (U-NH ) was site-specifically incorporated into nucleic acid strands via chemical synthesis. In the first example, U-NH was incorporated at the 3 end of the self-complementary U(-NH2)GCGCA DNA. This reactive amine-functionalized uridine was then allowed to undergo imine formation with a series of aldehydes (Ra-Rc), and aldehyde appendages that stabilize the DNA preferentially formed in the dynamic system. Upon equilibration and analysis, it was found that the double-stranded DNA modified with nalidixic aldehyde Rc at both U-NH positions was amplified 34% at the expense of Ra and Rb (Fig. 3.16). The Rc-appended DNA stabilizing modification corresponded to a 33% increase in (melting temperature). Furthermore, imine reduction of the stabilized DNA complex with NaCNBH, resulted in a 57% increase in T. ... 

The triflate 125 is formed from the hydroxy precursor (Equation 131) and undergoes a variety of nucleophilic substitution processes <2006TL4437>, including Suzuki and Stille couplings (Equations 132 and 133, respectively). Amination of 125 with aliphatic amines occurs under thermal conditions, using either conventional or microwave heating (Equation 134), but the reactions of 125 with less reactive amines require palladium catalysis (Equation 135). 

The subsequent explosion of array technologies has been sparked by two key inno-vations. The first is the use of non-porous solid support, such as glass, which has facilitated the miniaturization of the array and the development of fluorescence-hybridization detection (16, 17, 18). The second critical iimovation has been the development of methods for high-density spatial synthesis of oligonucleotides, which allows the analysis of thousands of genes at the same time. Because DNA cannot bind directly to the glass, the surface is first treated with silane to covalently attach reactive amine, aldehyde, or epoxies groups that allow stable attachment of DNA, proteins, and other molecules. 

Primary amines can be dehydrogenated under mild conditions and in high yields to nitriles at the nickel hydroxide electrode (Eq. (9)). Short chain and reactive amines are already oxidized at 5 °C, whilst long chain amines need somewhat higher temperatures. Diamines are converted smoothly to dinitriles (Table 13). 

The following reagents and techniques can be used to transform directly car-boxylates or sulfhydryl groups into reactive amine functional groups. In addition, sugars, polysaccharides, or carbohydrate-containing macromolecules may be modified to contain amines after mild periodate activation to form aldehyde groups. 

In lieu of 19F NMR spectroscopy, a second method for determining loading involves the reaction of an accurately weighed sample of resin with a known quantity of a reactive amine, e.g., 2-methylbenzylamine. The reaction product is evaluated by 1H NMR and LC/MS. Loading is determined by integration and comparison of the aromatic methyl protons and the o-methylene protons of the product amide relative to the starting amine. 

The extent to which the rate coefficients in Tables 3 and 4 approach that expected for a diffusion-controlled process is illustrated in Fig. 1. For the less reactive amines, nitrosyl chloride reacts significantly faster than nitrosyl... 

Carbazole, like most aromatic amines, oxidizes readily via electron transfer. We recognized early that electron transfer may be an important initiation process for polymerizing the N-vinyl derivative. Some years ago we showed (29) that cycloheptatrienyl cation could act as an efficient one-electron transfer reagent, producing the appropriate cation radicals from reactive amines such as phenothiazine and tetramethyl-p-phenylene-diamine. It was also suggested that the product of the reaction between cycloheptatrientyl cation and carbazole itself was the carbazole cation radical. However, our recent work (21) has demonstrated that one-electron oxidation of carbazole leads directly to the 3,3-dicarbazoyl cation radical (VII). 

This in no way detracts from the proved ability of the cyclohepta-trienyl cation to oxidize reactive amines, and consequently there is always doubt as to the true nature of the reaction mechanism when tropylium ion initiates polymerization of N-vinylcarbazole. We have made a detailed kinetic study of this polymerization (34), using an adiabatic calorimetric technique. Some typical data are shown in Table VII. Initiation is instantaneous and complete, there is no termination, and kp is evaluated readily as 4.6 X 10+5M-1 sec. 1 at 0°C. with Ea = 6 kcal./mole. By comparing data for the ion pair dissociation constant of C7HT"SbCl 6 (Table I) with the catalyst concentrations employed (Table VII) it is apparent that free tropylium ions are the dominant initiating speices. It... 

What are the alternatives There are two main ones, and both involve functional group interconversion, with the reactive amine being converted to a less reactive derivative before disconnection. The first solution is to convert the amine to an amide and then disconnect that. The reduction of amide to amine is quite reliable, so the FGI is a reasonable one. 

Enamines derived from relatively reactive amines, such as pyrrolidine and sterically unhindered cyclic ketones, are formed rapidly either with or without acid catalysis35,42. In the case of 2-substituted cyclic ketones (2-methylcyclohexanone,l-tetralone), cyclo-heptanone and higher cyclic ketones on the one hand, and with weakly basic (e.g. morpholine) or hindered amines on the other, the use of toluene solvent and a catalytic amount of p-toluenesulphonic acid affords good yields and shortens the reaction time. 

Finally, the Mannich reaction may be applied to the. synthesis of reactive amines used as crosslinking agents of epoxy resins. The process requires the availability of molecules possessing more than two NH groups, which are obtained by reaction of polyfunctional substrates with polyfunctional primary amines (oligomeric polyalkyle-ncamines, diamino cyclohexane, etc.) - (see also 422, Chap. Ill, C). 

With very reactive amines, and at low acidity where protonation is not extensive, it has been found possible to achieve the inequality kjLArNHMe] > k i for Scheme 1, for the reaction of N-methylaniline in 2 X 10 M HCIO4... 

Many peptides contain reasonably reactive amines, as well as an occasional free guanidine function. By the same token, the sugars that... 

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