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

12. Advances in the chemistry of amino and nitro compounds	543
RCH2OH ! RCH2Br ! RCH2N3 ! RCH2NH2	20

Secondary amines are obtained from alcohols when the alcohol is treated with N- methyltosylamine in the presence of triphenylphosphine and diethyl azodicarboxylate56,57 and the tosyl group is then removed from the product 28 by treatment with sodium in liquid ammonia at 70 °C (equation 21)58.

ROH C MeNH Tos ! MeNR Tos ! MeNRH

21

(28)

Transition-metal- and enzyme-catalyzed alkylations of ammonia and amines with alcohols and diols have been reviewed59. RuCl2(PPh3)3 is a homogeneous catalyst for the reaction of long-chain terminal alcohols with secondary amines to give tertiary amines (equation 22)60.

Me(CH2)nOH C R2NH ! Me(CH2)nNR2n D 9, 13, 15, 17I R D Me, Et or Ph22

˛,ω-Diols react with secondary amines under ruthenium catalysis to yield diamines in high yields, e.g. equation 2361.

HOCH2 CH2 OH + 2HN NCH2 CH2 N (23)

The course of the condensation of ethylene glycol with secondary amines (Me2NH, Et2NH, pyrrolidine or morpholine) depends on the catalyst used. Triphenylphosphine complexes of ruthenium, e.g. RuCl2(PPh3)3, give hydroxyalkylamines while hydrated ruthenium(III) chloride yields diamines (equation 24)62.

HOCH2CH2NR2 HOCH2CH2OH ! R2NCH2CH2NR2 24

5. From epoxides, aziridines and oxetanes

Optically pure tri(hydroxyalkyl)amines 29 (R D Me, t-Bu, cyclohexyl or Ph) have been obtained from enantiomerically pure epoxides and methanolic ammonia63. Tetraphenylstibonium trifluoromethanesulphonate, SbPh4C CF3SO3 , catalyses the reaction of epoxides with amines, e.g. diethylamine or aniline, to yield 2-hydroxyalkylamines in quantitative yields (equation 25)64.

R
3	+ NH3				N(CH2 CHROH)3
O		(29)
Me
+	NHR1 R2				R1 R2 NCH2 CHMeOH	(25)

O

The lithium perchlorate-catalysed aminolysis of styrene oxide has been investigated. Amines of low nucleophilicity, such as aromatic amines, give almost exclusively products of type 30, sterically hindered amines (diisopropylamine, dicyclohexylamine etc.) give

544 G. V. Boyd

compounds 31 and unhindered aliphatic amines give mixtures. The first type of product is favoured when the reactions are conducted in acetone or ether, the second kind in protic

solvents such as ethanol

65

.

Alkanolamines 33 [R1

D

(S)-CHMePh, cyclohexyl, PhCH

,

2

2

(S)-CHMeCH

OSiPh

Bu etc; R

D

Ph, 2-ClC H

, 4-MeC H

or 4-O2NC6H4] result

2

2

6 4

6

4

1

66

.

from the reactions of arylethylene oxides 32 with the silylated amines R

NHSiMe3

Ph

R1 R2 NCHPhCH2 OH

R2

+ HNR1 R2

(30)

R1 NHCH2 CHR2 OH

O

R1 R2 NCH2 CHPhOH

O

(32)

(33)

(31)

The regioselective

ring-opening of epoxides 34

(R1

D

Me,

vinyl,

Ph etc.)

with

2

2

PbBr,

aminolead compounds R 3

PbNEt2, prepared from lithium diethylamide and R 3

gives good yields of the amino alcohols 3567.

R1

R2 NHCH2 CHR1OH

O

(34)

(35)

Catalysis of the aminolysis of epoxides by lanthanide triflates (ytterbium, neodymium and gadolinium trifluoromethanesulphonate) has been reported (e.g. equation 26)68.

C6 H13

		OH
+ HNPri2	Pri2 NCH2 CH	(26)

O

C6 H13

˛,˛-Dicyanoepoxides react with amines (isopropylamine, isobutylamine, piperidine or morpholine) to yield either open-chain ketones or amidinoepoxides, depending on the structure of the starting epoxide. The former type is formed from monoaryldicyanoepoxides, while the amidines result from ˇ,ˇ-disubstituted ˛,˛-dicyanoepoxides (equation 27)69.

Ar	CN	Ar	NR2	CN				Ar	NR2	CN
	CN	+ HNR2
						− HCN		H		O
O		H	OH CN
						− HCN + HNR2
				Ar	NR2		NR2

H O

12. Advances in the chemistry of amino and nitro compounds								545
Ph			CN		Ph	CN
			+ HNR2			NR2		(27)
Ph			CN		Ph
			O		O	NH
The regioselective	ring-opening of the chiral epoxides 36 (R1					D	Me, Pr or Ph) with
		2
aliphatic amines 37 (R			D t-Bu, PhCH2 or C6H13) in the presence of titanium tetraiso-

propoxide leads to mixtures of the amino alcohols 38 and 39, in which the former predominate70.

R1			R2 HN	OH
OH +	R2 NH2		R1
O				OH
(36)	(37)			(38)
			HO	OH
	+
			R1	NHR2
				(39)

The 1,2-diamines 41 (R D C6H13, PhCH2 or 4-MeOC6H4CH2) result from the action of trimethylamine N-oxide on the aziridine 40 in the presence of lithium iodide and Fe3(CO)1271.

Me
+	+		O−
	Me3 N				RNHCHMeCH2 NMe2
N
R
(40)				(41)

-Amino alcohols are produced by the reaction of primary or secondary amines (BuNH2, t-BuNH2, PhNH2, Et2NH or PhNHMe) with oxetane under the influence of ytterbium(III) trifluoromethanesulphonate (equation 28); 2-n-octyl- or 2-phenyloxetane afford only the isomers 42 (R3 D C8H17 or Ph)72.

+ R1 R2 NH			R1 R2 NCH2 CH2 CH2 OH	(28)
O
R1R2NCH2CH2CHR3OH
		(42)
6. From imines
Reductive coupling of imines 43 (R1		D Me, Ph or 2-pyridyl; R2		D Me, Pr, t-

Bu or PhCH2) in THF under the influence of a low-valent titanium species, produced by the action of magnesium amalgam on titanium(IV) chloride, gave the DL-diamines

546	G. V. Boyd
R1
NR2		R2 NHCHR1 CHR1 NHR2
H
(43)	(44)

44, accompanied by minor amounts of the corresponding meso-isomers and the amines R1CH2NHR273 .

Hydrogenation of imines, e.g. 45 48, with a chiral titanocene catalyst at 2000 psig gave the corresponding optically active secondary amines in high enantiomeric excess74. Imines are reduced to amines by trichlorosilane/boron trifluoride etherate in benzene75.

CH3	CH3
CH3	CH3
NCH2 Ph	NCH2 Ph
	CH3
(45)	(46)

Ph	Ph	N
N
(47)		(48)

The N-monomethylation of primary amines RNH2 (R D C8H17, C12H25, Ph, PhCH2CH2 etc.) has been accomplished in high yield by condensation with 3-methyl- 2-(methylthio)benzothiazolium iodide, followed by treatment of the resulting imine with methyl iodide or methyl tosylate to give the salts 49. The latter yield the products RNHMe by the action of butylamine (equation 29)76.

Me			Me
N +			N
SMe		RNH2	NR
S			S
	−
I

(29)

Me
N	+	R	R
	N		HN
S	X−	Me	Me
(49)

12. Advances in the chemistry of amino and nitro compounds

547

The iminofluorenes 50 are attacked by butyllithium at the nitrogen atom (‘azophilic attack’) to give the fluorenylamines 51, accompanied by products 52 of ‘carbophilic’ addition. The proportion of the two types depends on the nature of the group R: for R D Me or Bu there is almost exclusive azophilic reaction, for R D i-Pr 64% azophilic and 16% carbophilic attack and for R D Ph or 4-MeC6H4 23% azophilic and 70% carbophilic reaction77.

NR

N

Bu R

(50)

(51)

Bu NHR

(52)

A synthesis of fluorinated primary aliphatic amines based on a [1,3]-proton shift has been described. The carbonyl compounds RFCOR [RF D CF3, C2F6, C4F9, H(CF2)4, C6F5 etc.; R D H, Ph etc.] are condensed with benzylamine and the resulting imines 53 are treated with triethylamine or DBU to give rearranged imines 54. Acidic hydrolysis then gives the products78.

R				R		RF
F	+ H2	NCH2	Ph	F
				C N CH2 Ph
CO						R C N CHPh
R				R		H
				(53)	(54)

RF

R CNH2

H

A diastereoselective synthesis of vicinal diamines has been described79. The aldehydes 56 derived from chiral amino acids 55 were converted into the N-benzylimines 57 and the latter were treated with organometallic reagents R2M in the presence of cerium(III)

548	G. V. Boyd

chloride to give the adducts 59 selectively. It is proposed that the intermediate chelates 58 are attacked preferentially at the less shielded side. Complete debenzylation by hydrogenation in the presence of palladium dihydroxide gave the products 60. To reverse the direction of diastereoselectivity, the donor strength of the aldimine nitrogen atom was weakened by preparing the N-tosyl derivatives 61. Treatment of the latter with Grignard reagents R2MgX (R2 D Me, Et, Bu, Ph etc.) gave 90 94% of the non-chelation controlled adducts 62, which yielded the diamines 63.

H2 N

Bn2 N

Bn2 N

NBn

CO2 H

CHO

CH

R1

R1

R1

(55)

(56)

(57)

R2 M

R2

M

Bn2 N

NHBn

H2 N

NH2

Bn2 N

NBn

1

R2

1

R2

R1

R

R

H

(58)

(59)

(60)

(Bn = benzyl)

Bn2 N

NTos

+ TosN

S

O

Bn2 N

CHO

CH

− SO2

R1

R2

(56)

(61)

R2 MgX

Bn2 N

NHTos

H2 N

NH2

R1

R2

R1

R2

(62)

(63)

The sequence carbon radical ! imine ! amine is illustrated in equation 30. Irradiation of the pyridinethione 64 (R D cyclohexyl) with the light of a tungsten lamp generates the cyclohexyl radical 65, which was trapped as the imine 67 in the presence of the diazirine 66. The imine was finally hydrolysed to cyclohexylamine80.

12. Advances in the chemistry of amino and nitro compounds

549

				RCO2			R
		N	S				(65)
		O	O
		R				N	N
				+
							(30)
	(64)
						Ph	CF3
				(66)
	R			R
	N	N	N	N			Ph
						RN	RNH2
					− N2		CF3
	Ph	CF3	Ph	CF3
							(67)
	An efficient	primary	amine	synthesis via N-diisobutylaluminium imines has been

described. A cyanide R1CN (R1 D Bu, C8H17, Ph, 2-furyl or 2-thienyl) is treated with diisobutylaluminium hydride and the product is converted into the amine by reaction with an organomagnesium or organolithium compound R2M (R2 D Bu, t-Bu, allyl or benzyl) (equation 31)81.

		R1	Bui		R1
R1 CN			NAl	+ R2 M		NH2	(31)
					H
		H	Bui
					R2

The N-trimethylsilylimines 68 (R D t-Bu, Ph, 2-MeC6H4 or 2-BrC6H4), which are prepared by the reaction of non-enolizable aldehydes with lithium bis(trimethylsilyl)amide, followed by trimethylsilyl chloride, undergo pinacolic coupling induced by NbCl4 Ð 2THF to yield the vicinal diamines 69 as mixtures of DL- and meso-isomers, in which the former predominate. Another method for the preparation of 1,2-diamines is by the combined action of the niobium tetrachloride/tetrahydrofuran complex and tributyltin hydride on cyanides RCN (R D t-Bu, Ph, cyclopentyl or pent-4-en-1-yl) (equation 32)82.

RCH		NSiMe3		R	R
					CH CH
				H2 N	NH2
(68)					(32)
					(69)

RCN

550	G. V. Boyd

Aldimines are converted into diamines in up to 94% yields by heating with samarium(II) iodide in THF, followed by treatment with silica gel in methanol, e.g. equation 3383.

PhCH2NDCHPh ! PhCH2NHCHPhCHPhNHCH2Ph

33

The nitrophenylsulphenimine 71 is formed from the sulphenamide 70 and N- chlorosuccinimide in the presence of triethylamine. The imine reacts with Grignard compounds RMgBr to yield sulphenamides 72, which are cleaved by trifluoroacetic acid to the amino acids 73. Hence 71 functions as an electrophilic glycine equivalent84.

R

ButO CCH N

SAr

ButO CCH

N

SAr

t

O2 CCHNH SAr

2 2

2

Bu

H

(70)

(71)

(72)

HO2 CCHRNH2

(73)

Ar =

O2 N

7. By electrophilic amination

The N-amination of pyrazoles with hydroxylamine O-sulphonic acid in aqueous media at controlled pH allows the preparation of compounds with electron-withdrawing substituents85.

Electron-rich aromatic compounds, such as phenol, anisole and N,N-dimethylaniline, add to bis(2-trichloroethyl) azodicarboxylate under the influence of lithium perchlorate, boron trifluoride etherate or zinc chloride to yield para-substituted products 74, which are transformed into the anilines 75 by means of zinc and acetic acid86. Triflic acid (trifluoromethanesulphonic acid) catalyses the reactions of phenyl azide with benzene, toluene, chlorobenzene and naphthalene, to give N-arylanilines (equation 34)87.

ArH + Cl3 CCH2 O2 CN		NCO2 CH2 CCl3			ArN				NHCO2 CH2 Cl3		ArNH2
							CO2 CH2 CCl3
			(74)							(75)
		PhN3 + ArH					PhNHAr			(34)
				− N2

Treatment of benzene with trifluoromethanesulphonic acid, followed by trimethylsilyl azide, gives aniline in 94% yield. Toluene, o-xylene, mesitylene, chlorobenzene and

12. Advances in the chemistry of amino and nitro compounds

551

bromobenzene react analogously. The intermediate aminodiazonium triflate is a synthon

	for the nitrenium cation, NH2C (equation 35)88.
								+		C F3CSO3SiMe3
	Me3SiN3 C 2F3CSO3H ! H2N N2 F3CSO3
					+	!
	PhH	C	H2N		N2				PhNH2	35
							N	2

HC

Similarly, benzene and hydrazoic acid in the presence of a mixture of fluorosulphonic and trifluoromethanesulphonic acid give aniline quantitatively. From toluene 100% of a mixture of o-, m- and p-toluidines is obtained and bromobenzene yields 42% o- bromoaniline and 47% p-bromoaniline, Butyl azide gives N-butylarylamines under these conditions89. Photolysis of 1-aminoquinolinium perchlorate (76) in aromatic hydrocarbons (benzene, toluene, ethylbenzene or mesitylene) in the presence of 18-crown-6 affords arylamines, e.g. aniline and p-toluidine, by way of the nitrenium ion90; cf Reference 91.

+	−
H2 N ClO4

+

N ClO4 −

NH2

(76)

Lithium t-butyl N-tosyloxycarbamate, But O2CNTos LiC , is an electrophilic aminating agent for organometallic compounds RM (MeLi, BuLi, s-BuLi and PhCu) to give,

after hydrolysis, the protected amines RNHCO2But92 . Amines ArNH2 are produced in high yields in the reactions of organocopper compounds Ar2Cu(CN)Li2 derived from benzene, anisole, thiophen and pyridine with N,O-bis(trimethylsilyl)hydroxylamine Me3SiNHOSiMe3 (equation 36)93.

Me3 Si	+ Ar2 Cu(CN)Li2			H2	O
N O SiMe3							(36)
		Me3 SiNHAr				H2 NAr
H
Acylhydrazines R1CONHNHR2	(R1 D Ph or PhCH2; R2		D Bu, PhCH2 or Ph)

are produced by the action of hydroxamic acids R1CONHOH on the primary amines R2NH2 in the presence of tosyl chloride or 2-chloro-1-methylpyridinium chloride94. O- (Diphenylphosphinoyl)-N-arylhydroxylamines 77 (R D NO2, Ac, Tos or CN) react with N-methylaniline to afford the hydrazine derivatives 7895.

			O
R	NHO	P	Ph	+ HNMePh		R	NHNMePh
			Ph
	(77)						(78)
The	efficiencies of	O-(diphenylphosphinoyl)hydroxylamine					and hydroxylamine-O-

sulphonic acid as electrophilic aminating agents have been compared96. The conversion of

552	G. V. Boyd

Grignard reagents RMgX into the amines RNH2 succeeds with the former but fails with the latter. The two reagents gave comparable yields in the N-amination of pyridine and quinoline but for indole and carbazole the first was more effective. It was concluded that, in general, hydroxylamine-O-sulphonic acid was more versatile96. 1,2,3-Triazole reacts with hydroxylamine O-sulphonic acid in aqueous potassium hydroxide to yield a mixture of 53% 1-amino-1,2,3-triazole and 14% of the 2-amino isomer (equation 37)97.

HN	N	N	N	+	N	N
	N	H2 N	N		N	(37)
					NH2

Electrophilic aminations with O-substituted hydroxylamines H2NOAr and H2NOCOAr (Ar D mesityl or dinitromesityl) have been reviewed98. Numerous heterocycles have been transformed by the mesityl derivative 79 into the salts 80 and tertiary amines into 81. The action of O-(2,4-dinitrophenyl)hydroxylamine 82 [Ar D 2,4-(O2N)2C6H3] on aldehydes RCHO (R D C6H13, Ph, 4-MeOC6H4 and 4-O2NC6H4) results in oximes, which form nitriles under basic conditions99.

									R1	+
+ H2 NO3 SC6 H2 Me3			+				−		R2	NNH2
									R3	−O3 SC6 H2 Me3
N				N			O3 SC6 H2 Me3
					NH2
(79)							(80)			(81)
RCHO + H2 NOAr				RCH			NOAr		RCN
(82)

Organoboranes R2BH or R3B (R D C10H21, cyclohexyl or cyclooctyl etc.) react with hydroxylamine O-sulphonic acid or its mesityl derivative or with chloramine to form primary amines RNH2100,101.

The action of chloroamine and bromoamine on organometallic reagents has been reviewed102 and a comprehensive review of electrophilic aminations of carbanions has appeared103. Alkyl, alkenyl and aryllithium compounds are converted into tertiary amines

84 by	reaction with the mesityl compounds 83			(R	2	D	Me or Et; Ar	D	2, 4, 6-
	104
Me3C6H2) .		!
	R1Li C R22NOSO2Ar						R1R22N
	(83)		LiC OSO2Ar				(84)

O-(Diphenylphosphinoyl)hydroxylamine H2NOP(O)Ph2 and its N,N-dialkyl derivatives have been used for the amination of carbanions as well as of amines and sulphur and phosphorus nucleophiles103. Organic azides R1N3 (R1 D Tos, Ph3Si, PhSCH2, PhOCH2 and Me3SiCH2) and Grignard reagents R2MgX form triazene derivatives R1NDN NR2MgX,