Amino-derivatives

Amino-derivatives.—Thermodynamic aspects of the synthesis of phospham from ammonia and red phosphorus  

The aminophosphazenes are still of interest as fertilizers with a high PN content 106 107 and they impart improved flame resistance to cellulosic materials108 and phenol-formaldehyde resins109 (see also Section 7). Other aspects of their chemistry have been reviewed.110 

Cyclization at a geminal diamino-group can be effected111 by the dichlorosilane, MeHSiCla to give (46). A closely related geminal-diamino-compound is the precursor of a bisphosphazenyl-derivative 13 

Chlorocyclophosphazenes are not particularly reactive towards silicon-nitrogen compounds, but the spirocyclic compounds (47) have been prepared.112 

An interesting development in the chemistry of aminocyclotetraphosphazenes is the formation of bicyclic structures. In the first example113 the phosphazene ring is 

Amino-derivatives.— The cyclophosphazene N3Pa(NH2)6 undergoes a rapid reaction with formaldehyde (80) was identified by its n.m.r. spectrum, but its isolation was 

Kobayashi, Chem. Letters, 1976, 479 Bull. Chem. Soc. Japan, 1976, 49, 3524. 

Brief information on the formation of anilino-derivatives from NaPsClg and HaNCeHjR-p (R=H, NO2, NH2, etc.) in pyridine solution, and on the preparation of structurally related compounds (84), which have applications as scorch inhibitors 

Monophosphazenyl derivatives (87) of N3P3CI8 and NsPgFe were prepared by the reaction shown. In the fluoride series (X=F), further substitution is limited to 

The cwi-diamino-compounds (88) are the precursors of new spiro-compounds (89). The compounds (89) can be protonated on the nitrogen atoms of the original 

5 Amino Derivatives. - An improved procedure for making 6 -alkylamino and 6 -arylamino-6 -deoxy derivatives of p-CD via the tosylate has been reported Mono-6 -amino-6 -deoxy-p- and y-CD have been amide linked to peptides including substance P. Antibodies to CDs and to substance P recognized the corresponding portions of the peptidyl-CDs  

As part of a study of the cleavage of DNA by ribose-containing biopolymers various derivatives of 5-amino-5-deoxyribose were iV-bonded to C-6 of p-CD via the monotosylate to give model enzymes. They showed catalytic activity in hydrolysing phosphodiesters (nuclease activity) as well as phosphatase and ligase activities. The vicinal cis-diol of the ribofuranose was required for expression of these activities.  

The aldehyde formed by oxidation of one of the primary hydroxyl groups of P-CD on reductive animation with sodium cyanoborohydride in the presence of the porphyrin with three p-sulfonophenyl and one p-aminophenyl substituent groups gave the 6-linked CD-porphyrin compound. This has a propensity to dimerize by inclusion of the aromatic macrocycle in the CD ring.  

NsP3(NH2)6,H20. Further examples of the use of aminocyclophosphazenes, [NP(NH2)]3,4, as fertilizers for cereal crops have appeared.  

An extensive series of amino-, N3P3F5 NR R (R = H, R = Et Ri = R2 = Et, Pr , or Bu ), andhydrazino-derivatives, N3P3Fb NH NR R (R = R = H or Me R = H, R = Me) has been obtained by direct reactions of amines and hydrazines with N3P3F6. With derivatives of primary amines, reactions with silylamines occur at the amino-group rather than at the phosphorus atoms  

The physical properties of these derivatives measured included the P-N-P coupling constants, which were all within the relatively narrow range 109—115 Hz. Geometrical isomers of the non-geminal bisdimethylaminoderivative NgP3F4(NMe2)2 have been separated by g.l.c. and identified by dipole moment measurements. 

Ondracek, K. Haas, and W. Wanek, Z. Pflanzenernaehr. Dueng. Bodenk., 1971, 

Niecke, H. Thamm, and D. Bohler, Inorg. Nuclear Chem. Letters, 1972, 8, 261. 

The appearance of virtual coupling effects in the n.m.r. spectra of the two dimethylamino-derivatives N4P4Cle(NMe2)2 and N4P4Cl2(NMea)g has been used for structural assignments, which are in agreement with X-ray crystallographic studies (see also refs. 86, 115, and 116), 

A study of the Faraday effect of some dimethylamino-, isopropylamino-, and t-butylamino-derivatives of NgPgCle shows that molecular magnetic rotations (of polarized light) increase with increasing degree of aminolysis. 

The electrical conductivity of a series of amino-derivatives of NaPsCIe is greater than that of N3P3CI6 itself.  

The tetrachloro-derivative N3P3Cl4(NC4H80)(NC)2H4), a product of the reaction of the monomorpholino-derivative N8P8Cl6(NC4H80) with aziridine, has a non-geminal structure.  

A novel cyclophosphazene-substituted tin-nitrogen ring compound (33) has been identified from the reaction  

4(5)-Nitroimidazoles are readily made by nitration of imidazole or 1-substituted imidazoles in concentrated sulfuric acid (see Section 7.2.1). It is much more difficult to make 2-nitroimidazoles since direct nitration is seldom observed in the 2-position. Although electrophilic nitrodehalogenation reactions, too, occur mainly at C-4(5) [1], Katritzky has recently selectively nitrodeiodinated 2,4,5-triiodoimidazole to prepare 2,4(5)-dinitro-5(4)-iodo-and 2,4,5-triiiitroimidazoles, albeit in poor yield [2], Other routes to 2-nitroimidazoles include those which react a diazonium fluoroborate with the nitrite ion, and methods which oxidize 2-amino derivatives, themselves often only available by laborious sequences. The most appealing routes to 2-nitroimidazoles are the methods which make the 2-lithio derivative and treat it with a source of nitronium ion (e.g. n-propyl nitrate or N2O4) [3-5] (see Section 7.2.2). 

Biological oxidation of a 2-aminoimidazole gives poor yields ( 38%), and none at all with l-alkyl-2-aminoimidazoles. Nor will oxidation with peroxy-trifluoroacetic acid work It is, however, satisfactory for the oxidation of 4-aminoiniidazoles (which are usually rather unstable compounds). ITie most common way of making 2-nitroi midazoles is from the diazonium fluoro-borates subjected to the Gattermann reaction (see Section 7.3). Yields vary from 20 to 50% [6, 7], and again are dependent on the availability of the 2-aminoimidazoles (see Section 8.2.2). 

TAlkyl-5- and l-alkyl-4-nitroimidazoles can be made with a good degree of regiospecificity by alkylation of 4(5)-nitroimidazole in neutral and basic media, respectively (see Section 7.1.1 and Table 7.1.1). See also the cine nucleophilic substitutions of 1,4-dinilroimidazoles (Section 7.3.1). 

Attention here focuses on the synthesis of primary amino derivatives, especially 2-aminoimidazoles and -benzimidazoles. 4(5)-aminoimidazoles are often quite unstable compounds which may be difficult to isolate [8]. The 

4(5)-amino-5(4)-cyaiioimidazoles are, however, now well known and are of special interest because they can be converted into purines. 

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Other chlorinated naphthalenes. The other monochloronaphthalene (2-), the ten theoretically possible dichloronaphthalenes, and the fourteen trichloronaphthalenes have all been prepared, generally from the corresponding amino-derivatives by diazotization and treatment with CuCl. They are of little industrial importance. 

The most noteworthy reaction of azo-compounds is their behaviour on reduction. Prolonged reduction first saturates the azo group, giving the hydrazo derivative (C NH-NH C), and then breaks the NH NH linkage, with the formation of two primary amine molecules. If method (1) has been employed to prepare the azo-compound, these two primary amines will therefore be respectively (a) the original amine from which the diazonium salt was prepared, and (6) the amino derivative of the amine or phenol with which the diazonium salt was coupled. For example, amino-azobenzene on complete reduction gives one equivalent of aniline, and one of p-phenylene diamine, NHaCeH NH benzene-azo-2-naphthoI similarly gives one equivalent of aniline and one of... 

Anthraquinone is of great technical importance, as many of its derivatives form valuable dyes notable among these are the hydroxy-derivatives (alizarin, etc.)y the amino-derivatives (indanthrene, etc.) and the sulphonic acids. 

Anthranilic acid. This substance, the ortho amino derivative of benzoic acid, may be conveniently prepared by the action of sodium hypobromite (or sodium hypochlorite) solution upon phthalimide in alkaline solution at 80°. The ring in phthalimide is opened by hydrolysis to phthalamidic acid and the latter undergoes the Hofmann reaction (compare Section 111,116) ... 

The reactivity of the amino radical has not yet been investigated. Alkaline hypochlorite oxidation, known in the pyridine series to yield azo derivatives (155,156). and photolysis of N,N-dichloro derivatives, which may be obtained by action of sodium hypochlorite on amino derivatives in acidic medium (157). should provide interesting insight on this reactivitv. 

Recent results for the quantitative nitration of 2-alkylthiazoles (386) suggest that a reinvestigation of the nitration of amino derivatives would be worthwhile. 

An interesting class of 2-imino-3-amino-4-thiazolines (408) has been described (578, 701, 726). These 3-amino derivatives of 4-thiazoiine may also be prepared from 2,3-diaminothiazolium salts (406) in basic medium (101) or through the acid-catalyzed rearrangement of 2-acylaminoimino-3-phenyl-4-phenyl-4-thiazolines (407) (Scheme 233) (99, 724). 

According to the position of nitrogen, the leaving substituent may be brought either by ketometbylene (5-ethoxymethylene) (method A) reacting on an aminothiazoHum or by an amino derivative of this ketometbylene reacting on a 2-methylthiazolium (method B) (Scheme 57). 

This aspect of electrophOic reactivity has been studied with several alkylthiazoles, and it is noteworthy that reduction of 4-(5-) nitrothia-zoles yields the amino derivatives that are good starting compounds for synthesis. Reaction takes place at the 5-position or at the 4-position if the 5-position is blocked, on the 4- and 5-positions at the same time but with poorer yields, if the 2-position is substituted (228, 231. 235-239, 244). 

Rifamycin S also undergoes conjugate addition reactions to the quinone ring by a variety of nucleophiles including ammonia, primary and secondary amines, mercaptans, carbanions, and enamines giving the C-3 substituted derivatives (38) of rifamycin SV (117,120,121). Many of the derivatives show excellent antibacterial properties (109,118,122,123). The 3-cycHc amino derivatives of rifamycin SV also inhibit the polymerase of RNA tumor vimses (123,124). 

The original commercial source of E was extraction from bovine adrenal glands (5). This was replaced by a synthetic route for E and NE (Eig. 1) similar to the original pubHshed route of synthesis (6). Eriedel-Crafts acylation of catechol [120-80-9] with chloroacetyl chloride yields chloroacetocatechol [99-40-1]. Displacement of the chlorine by methylamine yields the methylamine derivative, adrenalone [99-45-6] which on catalytic reduction yields (+)-epinephrine [329-65-7]. Substitution of ammonia for methylamine in the sequence yields the amino derivative noradrenalone [499-61-6] which on reduction yields (+)-norepinephrine [138-65-8]. The racemic compounds were resolved with (+)-tartaric acid to give the physiologically active (—)-enantiomers. The commercial synthesis of E and related compounds has been reviewed (27). The synthetic route for L-3,4-dihydroxyphenylalanine [59-92-7] (l-DOPA) has been described (28). 

Numerous other methods are available for the preparation of amino derivatives, and these include direct synthesis (see Section 2.14.3.2) and more traditional transformations such as the Hofmann reaction. Aminopyrazine has been prepared from pyrazinamide (60G1807) and 2-aminoquinoxaline from the corresponding carboxamide (71JOC1158). The... 

A-Amino derivatives, e.g. (71), are converted to the corresponding NH compounds by nitrous acid and give acyl and alkoxymethylene derivatives with the usual reagents. 

There are two main classes here. Firstly, 5-substituted 4(6)-aminopyrimidines, e.g. the 5-ester (227), are reacted with esters in the presence of sodium (63CB1868), or with acetals in the presence of alkoxide (78KGS1549), to give pyrido[2,3-Keto esters give 6-ketones (229) (80USP4215216), whilst use of aminopyrimidine nitriles gives 7-oxo-5-amino derivatives (81USP4245094). 

The use of 2-substituted amino-3-aminopyridines (or corresponding 3-substituted amino-2-amino, 3-substituted amino-4-amino and 4-substituted amino-3-amino derivatives) gives the corresponding TV-substituted pyridopyrazinones with esters or alloxan, or with diketones gives quaternary salts such as (403) or their anhydro bases (404) e.g. 56CB2684, 78HCA2452). 

Aminofurans substituted with electron-withdrawing groups e.g. NO2) are known and 3-amino-2-methylfuran is a relatively stable amine which can be acylated and diazotized. 2-Amino-3-acetylfurans are converted into 3-cyano-2-methylpyrroles on treatment with aqueous ammonia. This transformation is a further illustration of the relative instability of the amino derivatives of five-membered ring heterocycles compared with anilines (Scheme 67) (781003821). 

These observations can be extrapolated to the pyrrole series the 2-amino derivatives are very unstable whereas 3-aminopyrroles appear to be more stable. 3-Amino-l-tritylpyr-role (162) appears to exist in solution exclusively in the imino-A -pyrroline form (163) (83JCS(P1)93). 2-Aminoindole (164) is unusual in that it exists mainly as the 3//-tautomer (165). 4-Alkylaminoindoles (166) undergo an unexpected rearrangement to 4-amino-1-alkylindoles (167) when heated with p-toluenesulfonic acid hydrate (82CC1356). 

Amination at an azole ring nitrogen is known for Af-unsubstituted azoles. Thus 4,5-diphenyl-1,2,3-triazole with hydroxylamine-O-sulfonic acid gives approximately equal amounts of the 1- (104) and 2-amino derivatives (105) (74AHC(16)33). Pyrazole affords (106) and indazole gives comparable amounts of the 1- and 2-amino derivatives. 

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