Amine-based inhibitors

Boilers and steam systems Steel steam lines can be inhibited by the use of a volatile amine-based inhibitor such as ammonia, morpholine or cyclohexylamine introduced with the feedwater. It passes through the boiler and into the steam system, where it neutralizes the acidic conditions in pipework. The inhibitor is chemically consumed and lost by physical means. Film-forming inhibitors such as heterocyclic amines and alkyl sulphonates must be present at levels sufficient to cover the entire steel surface, otherwise localized corrosion will occur on the bare steel. Inhibitor selection must take into account the presence of other materials in the system. Some amine products cause corrosion of copper. If copper is present and at risk of corrosion it can be inhibited by the addition of benzotriazole or tolutriazole at a level appropriate to the system (see also Section 53.3.2). 

Also, no specific amine-based inhibitor is generally provided to protect LP steam condensate pipework against the ravages of carbonic acid (H2C03)-induced condensate line corrosion. 

In stimulation fluids containing concentrated HCl, the partial substitution of water by alcohols such as methanol, ethanol, and glycerol increases the corrosivity of the acid fluids and reduces the efficiency of the corrosion inhibitors [1148]. This effect is especially important for fatty amine-based inhibitors. For products containing acetylenic-type inhibitors the detrimental effect is less important and a weight loss may be maintained within acceptable limits using slightly higher, but still reasonable, levels of inhibitor. 

Amine-based inhibitors can lose some of their inhibitive qualities in low-pH environments. 

The performance of amine-base inhibitors can be substantially improved by metal halides, especially Cul. Urotropine was used for years in mixtures with Sb and/or Cu + salts or Kl (the Soviet inhibitors SU, SUM, U-1, and UM series). Walker discovered that a mixture of an acetylenic alcohol, an aromatic nitrogen salt (quaternary ammonium compound), an aromatic hydrocarbon, and an antimony salt are very effective on ferrous metals in 15% HCI, at 500 psig (where 1 psi = 6.895 kPa), at 325°F (163°C) he claims this mixture will work well up to 500°F (260°C). 

G. M. Graham, S. J. Dyer, and P. Shone. Potential application of amine methylene phosphonate based inhibitor species in HP/HT (high pres-sure/high temperature) environments for improved carbonate scale... 

The biogenic amines are the preferred substrates of MAO. The enzyme comes in two flavors, MAO-A and MAO-B, both of which, like FMO, rely on the redox properties of FAD for their oxidative machinery. The two isoforms share a sequence homology of approximately 70% (81) and are found in the outer mitochondrial membrane, but they differ in substrate selectivity and tissue distribution. In mammalian tissues MAO-A is located primarily in the placenta, gut, and liver, while MAO-B is predominant in the brain, liver, and platelets. MAO-A is selective for serotonin and norepinephrine and is selectively inhibited by the mechanism-based inhibitor clorgyline (82). MAO-B is selective for /1-phcncthylaminc and tryptamine, and it is selectively inhibited by the mechanism-based inhibitors, deprenyl and pargyline (82) (Fig. 4.32). Recently, both MAO-A (83) and MAO-B (84) were structurally characterized by x-ray crystallography. 

Propargylic, cyclopropyl, and fluoroallyl amines are powerful and irreversible mechanism-based inhibitors of MAOs. Oxidation by the enzyme affords a very active entity onto which a nucleophile of the enzyme, or of the cofactor, can be added (Figure 7.53). 

Certain compounds which have the ability to film or adsorb onto a metal surface are effective at improving fuel lubricity performance. These compounds include modified fatty acids, modified fatty amines, and other amine=based compounds. For years, the lubricity performance of jet fuel has been improved by treatment with organic acid based corrosion inhibitors. 

Reaction Between an Amine-Based Filmer or Neutralizer and the Carboxylic Acid Based Corrosion Inhibitor... 

This problem is not common and is not expected. However, in a situation of gross overtreatment with an amine-based processing aid, interaction with a carboxylic acid based corrosion inhibitor is possible. In dilute solution within the fuel, it is unlikely that these compounds will react since only low levels, <5 ppm, of filmer or neutralizer will typically carry over into finished fuel. If the two do react, the product formed will provide corrosion protection, but not as effectively as the unreacted carboxylic acid based inhibitor. 

Structural studies of complexes between aspartyl proteases and statine-based inhibitors indicate that the hydroxy group of statine displaces a water molecule present at the active site, and forms hydrogen bonds with the two aspartic carbonyl groups which are essential to the mechanism of hydrolysis. 2 The replacement of this hydroxy moiety by an amine (Scheme 19) has been investigated in order to increase the binding strength by electrostatic interac-... 

Mechanism-based inhibitors or suicide substrates seem to be particularly prevalent with CYP3A4. Such compounds are substrates for the enzyme, but metabolism is believed to form products that deactivate the enzyme. Several macrolide antibiotics, generally involving a tertiary amine function, are able to inhibit CYP3A4 in this manner (147,148). Erythromycin is one of the most widely used examples of this type of interaction, although there are other commonly prescribed agents that inactivate CYP3A4 (149-151), and a consideration of this phenomenon partially explains a number of interactions that are not readily explained by the conventional in vitro data (152). 

Schering-Plough uses (S)-4-phenyl-2-oxazolidinone in the large-scale production of their cholesterol absorption inhibitor Zetia (ezetimibe) (11) (Scheme 23.l).40 2 Condensation of the alcohol 12 with imine 13 in the presence of a Lewis acid such as TiCl4 and tertiary amine base yields compound 14. Silylation followed by intramolecular cyclization with tetrabutylammonium fluoride (TBAF) yields the protected ezetimibe 15. Removal of the protecting groups is carried out with weak acid to afford Ezetimibe (11). 

Several hundreds of irreversible MAO inhibitors have been prepared, exemplified by the MAO A-selective clorgyline (134) and the MAO-B selective deprenyl (135). The search for selective MAO B inhibitors has produced a series of mechanism-based inhibitors containing a 3-fluoroallylamine as a critical structural unit (figure 17). The proposed mechanism of inactivation involves nucleophilic addition of the cofactor or of an active site nucleophile to the double bond. Activation of the double bond occurs through M AO-mediated oxidation of the ally lie amine to the electron-deficient iminium species225-227. 

Another approach to the suppression of catalytic activity has been taken by workers at the University of Waterloo.26,42-44 After conducting extensive laboratory trials on flyash obtained from a variety of combustion plants, an amine-based destroyer/inhibitor mixture was formulated. This reactant was injected into the boiler of a MSW incinerator in an amount that represented 7-10% of the flyash loading in the flue gas the destroyer in the temperature window 590 + 50°C, and the inhibitor in the temperature window 375 + 50°C. Overall reductions in PCDD/F formation of 80-94% were claimed. This approach has yet to be made commercially available. 

The mechanism by which amines are oxidised by flavoproteins has been an issue of considerable debate in recent years. The debate has been particularly heated in the case of the enzyme monoamine oxidase (Silver-man, 1995). Through the use of a variety of mechanism-based inhibitors and based on studies of nonenzymic mechanisms of amine oxidation, a mechanism for monoamine oxidase in which substrate is initially oxidized by single electron transfer to the enzyme flavin to give an aminium cation... 

In this chapter, we discuss the synthetic methodologies used to prepare fluoroolefins and present examples of mechanism-based inhibitors of amine oxidases, r-aminobutyric acid transaminase and S-adenosylhomocysteine hydrolase which incorporate this structural functionality. Ve have restricted our discussion to the syntheses of terminal mono-, di- and trifluoroolefins, omitting the large body of synthetic endeavour directed towards other fluoro olefins (4). 

After the initial discovery that 0-fluoromethylene-substituted amines (e.g., 184, Table 1) were potent, mechanism-based inhibitors of monoamine oxidase (MAO) (41), the concept was successfully broadened to include most of the common amine oxidases (Table 1). This approach was also used to design inhibitors of y-aminobutyric acid transaminase both the a- and 0- substituted amino acids 189 and 190 were found to inactivate this enzyme. Recently, applica-tion of this concept to the design of inhibitors of S-adenosyl-homocysteine hydrolase (SAH) has led to the discovery of very potent inhibitors of this enzyme (e.g., 176, Table 1). 

Maillard MC, Flom RK, Benson TE, Moon JB, Mamo S, Bienkowski M, Tomasselli AG, Woods DD, Prince DB, Paddock DJ, Emmons TL, Tucker JA, Dappen MS, Brogley L, Thorsett ED, Jewett N, Sinha S, Varghese J (2007) Design, synthesis, and crystal structure of hydroxyethyl secondary amine-based peptidomimetic inhibitors of human beta -secretase. J Med Chem 50 776-781... 

Drewamine. [Drew Ind. Div.] Amine based corrosion inhibitor for boiler water treatment... 

BUTENO-p-LACTONE (674-82-8) Forms explosive mixture with air (flash point 91°F/33°C). Violent reaction with water, oxidizers. Violent polymerization or explosion caused by elevated temperatures, acids, amines, bases, or sodium acetate. Incompatible with alcohols, halons. A storage hazard can decompose causing explosion add inhibitor. 

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