Patai S., Rappoport Z. 1996 The chemistry of functional groups. The chemistry of amino, nitroso, nitro and related groups / 0533 626

which afford primary amines R1NH2 on hydrolysis or reduction24. Primary amines are produced from Grignard reagents and arenediazonium tetrafluoroborates, followed by reduction of the resulting azo compounds (equation 38)103.

Electrophilic amination reactions by means of oxaziridines have been reviewed105. Cyclohexylidenehydrazines 86 are formed from secondary amines such as diethylamine, dibutylamine and morpholine and the spirooxaziridine 85105.

NC

N,N-Dimethoxyamine is a source of the N-methoxynitrenium ion, which is generated by the action of boron trifluoride etherate. In the presence of dimethylsulphide the salt 87 is obtained; triphenylphosphine yields the analogue 88107.

+

8. Via >N C < synthons

The disilylamines 90, prepared from the chloro ethers 89 (R1 D Me or C6H13)+and

sodium bis(trisilylmethyl)amide function as synthetic equivalents of the (Me3Si)2NCH2 cation. They react with Grignard reagents R2MgBr (R2 D Me, i-Pr, cyclohexyl, Ph, PhCH2, CH2DCHCH2 or C3H7C C) to give the silylated amines 91, which are hydrolysed to the corresponding amine hydrochlorides 92 by dilute hydrochloric acid108,109.

R2 CH2 NH2 . HCl

(92)

Similarly, aminomethyl sulphides (from amines, formaldehyde and mercaptans) react with organolithium compounds to afford amines (equation 40)110,111.

The synthetic utility of benzotriazole derivatives as >N C< $ >NDC< synthons has been explored by Katritzky and his coworkers. The Mannich reaction of benzotriazole with primary aliphatic amines RNH2 and formaldehyde in an aqueous medium results in the formation of one or more of three types of product: BtCH2NHR, (BtCH2)2NR and (BtCH2NR)2CH2 [Bt D benzotriazol-1-yl (93)]112. Benzotriazole and aliphatic or aromatic aldehydes yield compounds 94113. The parent compound 1- hydroxymethylbenzotriazole reacts with aromatic amines to give secondary amines 95, primary aliphatic amines give the tertiary amines 96 and aqueous ammonium acetate at room temperature yields 97. The 1-benzotriazoles 98 are obtained from benzotriazole, aldehydes and aromatic amines114.

The products from benzotriazole, aldehydes and primary or secondary amines exist in the melt or in solution as equilibrium mixtures of 1- and 2-benzotriazolyl compounds, 99 and 100, whereas the solids are 1-benzotriazoles 99115. The equilibrium involves the resonance-stabilized aminomethyl cation and the delocalized benzotriazolide anion; it accounts for the ease with which the bond attached to the benzotriazole moiety is cleaved.

Heating the equilibrium mixture obtained from benzotriazole, an aldehyde RCH2CHO (R D Me, Et, Pr or Bu) and morpholine with sodium hydride in THF results in the

formation of an enamine with the elimination of sodium benzotriazolide and hydrogen (equation 41)115c.

The benzotriazole derivatives 101 (R1 D alkyl) formed from aliphatic aldehydes, benzotriazole and primary aromatic amines are reduced by lithium aluminium hydride or sodium borohydride to secondary amines 102, while Grignard reagents yield compounds of type 103116. The reaction has been used for the side-chain alkylation of 2-aminopyridine (equation 42) (direct alkylation occurs predominantly at the ring nitrogen atom).

(101)(103)

Numerous tertiary amines have been obtained from 104 (R1

R3 D alkyl) and sodium hydride or Grignard reagents (equation 43)116.

Bt CHR1NR2R3 ! CHR1R4NR2R3

(104)

The tertiary amines 96 react with organometallic compounds to afford disubstituted products 105117.

Bt CH2NR1CH2 Bt C 2R2M ! R2CH2NR1CH2R2

(96) (105)

Treatment of secondary amines 106 with hydroxymethylbenzotriazole yields 107, which forms tertiary amines 108 (Ar D Ph or 4-MeC6H4; R1, R2 D i-Pr, PhCH2 etc)118.

The benzotriazole 109 reacts with alkyl or allyl halides in the presence of bismuth(III) chloride and metallic aluminium to give the homoalkylated amines 110 in high yields119.

Bt CH2NMePh C RX ! RCH2NMePh

(109) (110)

The benzotriazole derivatives 111, obtained from benzotriazole, ethyl glyoxylate and secondary amines (diethylamine, pyrrolidine, piperidine or morpholine), furnish the amino esters 112 by the action of organozinc reagents R2ZnX (R2 D Me, Bu, PhCH2 or Ph)120.

Tertiary propargylamines 114 (R1 D H, Pr, i-Pr, C7H15 or Ph; NR22 D NMe2, NEt2, pyrrolidin-1-yl, piperidin-1-yl etc; R3 D C6H13, C8H17 or Ph) are formed from the benzotriazoles 113 and lithium acetylides121.

Hindered aliphatic aldehydes R1CHO (R1 D i-Pr or t-Bu) react with benzotriazole and anhydrous methanolic ammonia to yield the secondary amines 115, which are transformed into the phenylated amines 116 by the action of phenyllithium. Benzotriazole, aromatic aldehydes and ammonia give the imines 117, which react with lithium aluminium hydride to form dibenzylamines 118122.

PhLi

Bt CHR1NCHR1 Bt ! PhCHR1NCHR1Ph

Bt CHArNDCHAr ! ArCH2NHCH2Ar

(117) (118)

The ‘Reformatsky reaction’ of the benzotriazoles 119 (R1 D H, Pr, i-Pr or Ph; NR22 D

pyrrolidin-1-yl, piperidin-1-yl or morpholin-4-yl) with the bromo esters 120 (R3, R4 D H or Me) in the presence of zinc affords the ˇ-amino esters 121123.

Compounds 122, prepared from benzotriazole, p-dimethylaminobenzaldehyde and primary aromatic amines, are decomposed to the secondary amines 123 by sodium tetrafluoroborate124.

Bt CHNHAr CH2 NHAr

by condensation of the amine with benzotriazole and formaldehyde, followed by reaction of the products with Grignard reagents (equation 45)126.

1-(Benzotriazol-1-yl)-N-triphenylphosphorylidenemethylamine 125 and lithium amides LiNR1R2 (R1 D Ph, R2 D Me; NR1R2 D pyrrolidin-1-yl or morpholin-4-yl) afford the phosphoranes 126, which are converted into ˛-(arylideneamino)alkylamines 127 on treatment with aromatic aldehydes127.

The N-t-butylation of aromatic amines has been described. The benzotriazoles 128 (R1 D Pr, i-Pr or t-Bu; R2 D Ph, Ar or 2- or 3-pyridyl) react with hydrogen peroxide under

selenium dioxide catalysis to yield mixtures of amides 129 and rearranged formamides

130. The latter are formed almost exclusively from 128 (R1 D t-Bu). Hydrolysis yields N-t-butylarylamines128.

R1 CONHR2

(129)

Bt CHR1 NHR2

(130)

Symmetrical aminals, e.g. 132, are obtained from benzotriazoles such as 131 on treatment with piperidine129.

Compounds 133, prepared by the condensation of benzotriazole with aldehydes R1CHO (R1 D H, Pr or Ph) and N-octylaminoacetonitrile, react with sodium tetrafluoroborate to give the cyanomethyl derivatives 134. The latter are de-cyanomethylated by the action of copper(II) sulphate. Treatment of 133 with Grignard reagents affords the analogues 135 (R2 D Ph or PhCH2) and thence the secondary amines 136130.

ammonia furnish monoacylated aminals 138131.

Benzotriazole, secondary amines and ˛,ˇ-unsaturated aldehydes or ketones yield products which exist in solution as equilibrium mixtures of four possible isomers 139 142. Heating this mixture with sodium hydride produces dienamines132.

appeared140. These reactions proceed by dehydrogenation of intermediate -adducts; see, for example, the formation of 4-amino-3,6-dimethoxypyridazine (151)141.

method142. An amino group is introduced into the 2-position of 1,n-dinitronaphthalenes (n D 3 8)143 and various 5- and 8-nitroquinolines, such as 8-methyl-5-nitroquinoline and 6-chloro-8-nitroquinoline, have been aminated adjacent to the nitro group144. Pteridines are converted into alkylamino derivatives by the action of a solution of potassium permanganate in an alkylamine, e.g. equation 51145.

(152)

Photoamination of 7-methoxy-1,2-dihydronaphthalene in the presence of p- dicyanobenzene similarly affords the amine 153147 and 1-benzamido-9,10-anthraquinone reacts with butylamine under UV irradiation in air to yield 154148.

The photoamination of naphthalene, several substituted naphthalenes, anthracene and phenanthrene with ammonia, methylamine or benzylamine in aqueous acetonitrile in the presence of m-dicyanobenzene gave aminated dihydroarenes, e.g. 155. Secondary amines (dimethylamine and diethylamine) react less efficiently149. 9-Methoxyphenanthrene and

NH2

(153)

+H2 NBu

−2[H]

(154)

ammonia afforded 156 as a 75:25 mixture of cis- and trans-isomers, whereas with isopropylamine only the cis-adduct 157 was obtained150.

(157)

11. By reductive alkylation

The high-yield reductive methylation of numerous alkyl and arylamines and of dialkyland alkyl-arylamines with paraformaldehyde in the presence of zinc chloride and zinc borohydride has been reported (equation 52)151.

Refluxing a mixture of an aromatic amine ArNH2 and an aldehyde RCHO (R D Pr, PhCH2, Ph or 4-ClC6H4) in ethanol in the presence of sodium hydrogen telluride gives the alkylated amine ArNHCH2R in 22 95% yields152; secondary aliphatic amines react analogously153.