Heterocyclic amine

As noted in Section 15.5 in connection with a discussion of aromaticity, a cyclic organic compound that contains atoms of two or more elements in its ring is a called a heterocycle. Heterocyclic amines are particularly common, and 

Most heterocycles have the same chemistry as their open-chain coimter-parts. Lactones and acyclic esters behave similarly, lactams and acyclic amides behave similarly, and cyclic and acyclic ethers behave similarly. In certain cases, however, particularly when the ring is unsaturated, heterocycles have imlque and interesting properties. 

Pyrrole, the simplest five-membered unsaturated heterocyclic amine, is obtained commercially by treatment of furan with ammonia over an alumina catalyst at 400 °C. Furan, the oxygen-containing analog of pyrrole, is obtained by acid-catalyzed dehydration of the five-carbon sugars found in oat hulls and corncobs. 

Although pyrrole appears to be both an amine and a conjugated diene, its chemical properties are not consistent with either of these structural features. Unlike most other amines, pyrrole is not basic—the pK of the pyrrolinium ion is 0.4 unlike most other conjugated dienes, pyrrole undergoes electrophilic substitution reactions rather than additions. The reason for both these properties, as noted in Section 15.5 is that pyrrole has six 77 electrons and is aromatic. 

Each of the four carbons contributes one ir electron, and the s/7 -hybridized nitrogen contributes two more from its lone pair. 

Propose a synthesis of the drug sulfathiazole from benzene and any necessary amine. 

Propose syntheses of the following compounds from benzene  

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Imidazole can be A -allylated. The A -glycosylimidazole 299 is prepared by regiospecific amination at the anomeric center with retention of configuration. Phenoxy is a good leaving group in this reaction[181]. Heterocyclic amines such as the purine base 300 are easily allylatedfl 82]. 

Butler recently reviewed the diazotization of heterocyclic amines (317). Reactions with nitrous acid yield in most cases N-exocyclic compounds. Since tertiary amines are usually regarded as inen to nitrosation, this... 

Heterocoagulation Heterocyclic Heterocyclic amines Heterocyclic azo dyes Heterocyclic compounds Heterocyclic dyes Heterocyclic polymers Heterocyclic thiophenes Heteroepitaxy Heterogeneous catalysis Heterogemte Heteroglycan Heterojunction... 

Aminopyrazines and 2-aminoquinoxalines, like their pyridine analogs, react with nitrous acid under aqueous conditions to give the 2(l//)-pyrazinones and 2(l//)-quinoxalinones. 2-Aminoquinoxalines are more readily hydrolyzed than typical heterocyclic amines and 2-amino-3-methylquinoxaline, for example, undergoes hydrolysis on heating at 100 °C with dilute sodium hydroxide (59JCS1132). 

The activating effect of a trichloromethyl group is seen in the 2-dechlorination reactions of 2-chloro-4,6-bis(trichloromethyl)-s-tria-zine (175) with arylsulfonylhydrazides (24 hr) and heterocyclic amines (3 hr) at 20° and with unbasifled primary and secondary alcohols (65°, 30 min). The 4,6-diphenyl or 4,6-bis(4-chlorophenyl) analogs do not react in this manner. ... 

Synthesis of heterocyclic amines by hydrogenative amination of aldehydes and ketones 99MI29. 

Transition metal-catalyzed synthesis of hetarylamines and hetaryl ethers from triflates and aryl/hetaryl halides or heterocyclic amines 98AG(E)2046. 

Methoxybutenone with heterocyclic amines, e.g. 257, condenses in either a 2 1 ratio (adduct 258) or a 1 2 ratio (adduct 259) (67CB1680). 

Certain amine oxides, especially those derived from six-membered heterocyclic amines e.g. N-methylpiperidine oxide, that cannot go through a planar, five-membered transition state, do not undergo the Cope elimination reaction. 

Acylation of thiosemicarbazide with propionyl chloride, interestingly, does not stop at the acylated product (124). Instead, this intermediate cyclizes to the thiadiazole, 125, under the reaction conditions. Hydrolysis then affords the heterocyclic amine, 126. Acylation by 88 followed by removal qf the acetyl group affords sulfaethidole (116) variation of thle acid chloride used in the preparation of the heterocycle leads to 117 and 118. 

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). 

Pyrimidine and imidazole rings are particularly important in biological chemistry. Pyrimidine, for instance, is the parent ring system in cytosine, thymine, and uracil, three of the five heterocyclic amine bases found in nucleic acids An aromatic imidazole ring is present in histidine, one of the twenty amino acids found in proteins. 

Heterocyclic amines—compounds in which the nitrogen atom occurs as part of a ring—are also common, and each different heterocyclic ring system has its own parent name. The heterocyclic nitrogen atom is always numbered as position 1. 

Table 24.1 lists pXa values of some ammonium ions and indicates that there is a substantial range of amine basicities. Most simple alkylainines are similar in their base strength, with p/q/s for their ammonium ions in the narrow range 10 to 11. Aiylctmines, however, are considerably less basic than alkylamines, as are the heterocyclic amines pyridine and pyurole. 

Problem 24.15 What product would you expect from Hofmann elimination of a heterocyclic amine such as piperidine Write all the steps,... 

Other common five-membered heterocyclic amines include imidazole and thiazole. Imidazole, a constituent of the amino acid histidine, has two nitrogens, only one of which is basic. Thiazole, the five-membered ring system on which the structure of thiamin (vitamin Bt) is based, also contains a basic nitrogen that is alkylated in thiamin to form a quaternary ammonium ion. 

Heterocyclic amines are compounds that contain one or more nitrogen atoms as part of a ring. Saturated heterocyclic amines usually have the same chemistry as their open-chain analogs, but unsaturated heterocycles such as pyrrole, imidazole, pyridine, and pyrimidine are aromatic. All four are unusually stable, and all undergo aromatic substitution on reaction with electrophiles. Pyrrole is nonbasic because its nitrogen lone-pair electrons are part of the aromatic it system. Fused-ring heterocycles such as quinoline, isoquinoline, indole, and purine are also commonly found in biological molecules. 

Compounds which correspond to 1,2-quinone diazides can also be obtained by diazotization of aromatic and nonaromatic heterocyclic amines with a hydroxy group in the ortho position. Examples include 3,4-quinolinequinone-3-diazide (2.35, Sus et al., 1953 Sus and Moller, 1955) and 3-diazochromane-2,4-dione (2.36, Arndt et al., 1951). Syntheses of more complex heterocyclic quinone diazides have been tabulated by Ershov et al. (1981, p. 105). More recent publications are cited in a paper by Tisler s group (Klotzer et al., 1984). 

A novel application of a phenyl aryldiazosulfone was found by Kessler et al. (1990). l-[4-(7V-Chlorocarbonyl-7V-methylamino)phenyl]-2-(phenylsulfonyl)diazene (6.18) is an acid chloride with a potential diazonio group. The above authors showed that in organic solvents (THF, etc.) this compound reacts easily, as expected, with nucleophiles (HNu), e.g., with aliphatic, aromatic, or heterocyclic amines, with cystine dimethyl ester, or with 4-methoxyphenol at the carbonyl function, yielding... 

N-Glycosyl derivatives are conveniently named as glycosylamines. In the case of complex heterocyclic amines, such as nucleosides, the same approach is used. 

Bicychc pyrazinones foimd in several natural products were synthesized via Michael addition of heterocyclic amines to nitro olefin followed by reduction/cyclization of the nitro group of the adduct [20] (Scheme 5). Further elaboration of the C-6 methoxycarbonyl group in pyrazinone to the n-propyl guanidine group could result in the synthesis of indoloperamine. 

If an aliphatic amino group is to a COOR, CN, CHO, COR, and so on, and has an a hydrogen, treatment with nitrous acid gives not a diazonium salt, but a diazo compound Such diazo compounds can also be prepared, often more conveniently, by treatment of the substrate with isoamyl nitrite and a small amount of acid. Certain heterocyclic amines also give diazo compounds rather than diazonium salts. ... 

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