Amine precursor

In Diels-Alder reactions a nitroolefin may function as an electron-deficient ene com-onent or a 1,2-dihydropyridine derivative may be used as a diene component. Both types of iactants often yield cyclic amine precursors in highly stereoselective manner (R.K. Hill, 1962 i. BOchi, 1965, 1966A). 

Preparation from Amines. The most common method of preparing isocyanates, even on a commercial scale, involves the reaction of phosgene [75-44-5] and aromatic or aUphatic amine precursors. The initial reaction step, the formation of N-substituted carbamoyl chloride (1), is highly exothermic and is succeeded by hydrogen chloride elimination which takes place at elevated temperatures. 

Aliphatic Isocyanates. Aflphatic diisocyanates have traditionally commanded a premium price because the aflphatic amine precursors ate mote expensive than aromatic diamines. They ate most commonly used in appHcafions which support the added cost or where the long-term performance of aromatic isocyanates is unacceptable. Monofuncfional aflphatic isocyanates, such as methyl and -butyl isocyanate, ate used as intermediates in the production of carbamate-based and urea-based insecticides and fungicides (see Fungicides, agricultural Insectcontroltechnology). 

Neoprene Type TW was shown to have low oral toxicity in rats. The LD q was found to be in excess of 20,000 mg/kg. Human patch tests with Types GN, W, WRT, and WHV showed no skin reactions (169). The FDA status of Du Pont Neoprene polymers is described (172). Although polychloroprene itself has not been shown to have potential health problems, it should be understood that many mbber chemicals that may be used with CR can be dangerous if not handled properly. This is particularly tme of ethylenethiourea curatives and, perhaps, secondary amine precursors often contained in sulfur modified polychloroprene types. Material safety data sheets should be consulted for specific information on products to be handled. 

The formation of an enamine from an a,a-disubstituted cyclopentanone and its reaction with methyl acrylate was used in a synthesis of clovene (JOS). In a synthetic route to aspidospermine, a cyclic enamine reacted with methyl acrylate to form an imonium salt, which regenerated a new cyclic enamine and allowed a subsequent internal enamine acylation reaction (309,310). The required cyclic enamine could not be obtained in this instance by base isomerization of the allylic amine precursor, but was obtained by mercuric acetate oxidation of its reduction product. Condensation of a dihydronaphthalene carboxylic ester with an enamine has also been reported (311). 

Cyclohexanones may serve as precursors to aromatic amines in a reductive alkylation, the source of hydrogen being aromatization of the cyclohexanone (66). In a variation, an aromatic nitro compound acts as both an amine precursor and a hydrogen acceptor (64). 

The early recognition of the role of stable nitroxyl free radicals, e.g., 2,2,6,6-tetramethyl-4-oxopiperidine, and their hindered amine precursors, in polymer stabilization soon led to the development of the hindered amine light stabilizer (HALS) class of photoantioxidants. The first HALS, Tinuvin 770, AO-33, (commercialized in 1974) proved to offer much higher UV-stabil-ity to polymers than any conventional UV-stabilizer available at the time such as UV-absorbers, nickel compounds and benzoates. Table 3). 

Research on the formation of NDMA in beer has centered on three possible sources of amine precursors (74). N-Nitros-amine formation from amines such as hordenine, famine and methyltyramine which are formed endogenously in the germination of barley has been discussed elsewhere in this symposium (75). The Brewers Association of Canada (74) investigated the... 

Prevent the nitrosating reaction with amine precursors. 

Reactions of A-(/>-methoxyphenyl)imines 223a and 223b with diorganozincs result in the formation of chiral arylalkyl secondary amines 227, Scheme 130). Upon alkylation of three other types of imines 224b-226b, valuable amine precursors are obtained, which can be transformed in one step to the corresponding primary amines with a chiral center in the a-position. 

Another frequently used multicomponent reaction is the Kindler thioamide synthesis (the condensation of an aldehyde, an amine, and sulfur). The Kappe group has described a microwave-assisted protocol utilizing a diverse selection of 13 aldehyde and 12 amine precursors in the construction of a representative 34-member library of substituted thioamides (Scheme 6.114) [226]. The three-component con-... 

The same group recently disclosed a related free radical process, namely an efficient one-pot sequence comprising a homolytic aromatic substitution followed by an ionic Homer-Wadsworth-Emmons olefination, for the production of a small library of a,/3-unsaturated oxindoles (Scheme 6.164) [311]. Suitable TEMPO-derived alkoxy-amine precursors were exposed to microwave irradiation in N,N-dimethylformam-ide for 2 min to generate an oxindole intermediate via a radical reaction pathway (intramolecular homolytic aromatic substitution). After the addition of potassium tert-butoxide base (1.2 equivalents) and a suitable aromatic aldehyde (10-20 equivalents), the mixture was further exposed to microwave irradiation at 180 °C for 6 min to provide the a,jS-unsaturated oxindoles in moderate to high overall yields. A number of related oxindoles were also prepared via the same one-pot radical/ionic pathway (Scheme 6.164). 

Reductive amination of an aldehyde with excess primary amine, using a support-bound borohy-dride, provides the desired secondary amine contaminated with the primary amine precursor. Covalent capture of the primary amine with a support-bound aldehyde provides the pure secondary amine. Treatment with excess isocyanate yields the final urea product, which is purified by reaction with a support-bound amine to remove unreacted isocyanate. For the full potential of this method to be realized, further development of support-bound reagents and scavengers for most of the important chemical transformations will be necessary. Al-... 

Another potent peripheral vasodilator with hypotensive activity is minoxidil (U-10,858, XXXI). The drug was developed at the Upjohn Corporation, apparently as a follow-up of a previous clinical candidate, diallylmelamine -N-oxide (U-20,388, XXXII). The amine precursor, diallylmelamine (U-7720, XXXIII), is active in rats and dogs but not in man because the active... 

Volatile nitroso compounds were determined in hams processed in elastic rubber nettings by SPE and GC-CLD577. By a similar method A-n i tro sodi ben zy lamine (278b), a semivolatile nitrosamine, was determined in these products by SPE followed by GC interfaced to a nitrosamine-specific TEA-CLD detector the coefficient of variation was 10.6% at the 2.1 ppb level578. The nitrosamines detected in ham most likely originate from the amine precursors in rubber and from the nitrite commonly used in the meat curing process. 

Migration of nitrosamines into consumer products can occur via direct contact of materials such as waxed containers, elastic and rubber etc.81. Morpholine is used extensively as an industrial solvent for wax formulations. The wax formulations are used for coating fruits and vegetables to prevent moisture loss and increase shelf-life of the products. Paper and cardboard packed with morpholine was also found to give rise to NDMA, as these packaging materials were found to be contaminated with NDMA as well. Besides this, rubber products also provided a migratory source for both nitrosamines and nitros-able amine precursors, as trace levels of NDEA and TV-nitrosodibutylamine (NDBA) have been reported in cured meats with amine-based accelerators in the rubber nettings82. 

Carr, R.H. Jackson, A.T. PreUminary MALDI-TOF and Field Desorption Mass Spectrometric Analyses of Polymeric Methylene Diphenylene Diisocyanate, Its Amine Precursor and a Model Polyedier Prepolymer. Rapid Commun. Mass Spectrom. 1998, 72,2047-2050. 

Predictable interactions occur between the MAOIs and any amine precursors, or directly or indirectly acting sympathomimetic amines (e.g. the amphetamines, phenylephrine and tyramine). Such interactions can cause pronounced hypertension and, in extreme cases, stroke. 

Honomer Properties (Table I). The amide/acetal 1 (R=He or Et) and Its amine precursor are Ames negative. Compound 1 shows a very high LD50 and low skin or eye Irritation. A low vapor pressure, Its liquid form and Infinite miscibility with water and common solvents are additional pluses. 

By analogy with the biogenesis of oximes via oxidation of amino acids or biogenic amines, the biosynthetic pathway for insertion of the ketoxime function into the antibiotic, nocardicin A (18), was shown to be dependent on the oxidation of the corresponding primary amine precursor of 18 by cytochrome PTSO ". Similarly, the formation of the ketoxime bond of verongamine (17) is attributed to the oxidation of a primary amine precursor . 

The commercial availability of basic pyridine derivatives has encouraged a tremendous amount of research into pharmaceutically active compounds. Two reviews in particular list a large number of medicinal compounds (B-80MI20900,77CZ389) based on the pyridine ring. Likewise, the occurrence of benzopyridine natural products with chemotherapeutic activity has stimulated the production of synthetic materials from aromatic amine precursors. Some important examples are presented below. 

At all levels of theory, the N-acetyl group of N-acetyl-N-arylnitrenium ions is rotated out of the plane of the aromatic ring, although to different extents." The N-acetyl group destabilizes the ion by ca. 20 kcal/mol relative to an N-methyl substituent in comparison with the neutral amide and amine precursors. This destabilization was attributed by Ford and Herman to loss of resonance in the amide precursor on going to the nitrenium ion, not to inductive destabilization of the ion by the acyl group. 

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