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											593
	(		)n				O
				+ HNR1R2
O	N					R1R2 NC(CH2 )n +2 NHTos
					(296)
	Tos
	(295)
				O	SO2
			Et2 N		N
2 Et2 NCN + 2SO3				N					2HNR2	2Et2 NCONHSO2 NR2
						NEt2
											(298)
				S	O
				O2

(297)

Weakly nucleophilic amines such as 2,4-dinitroaniline are acylated in excellent yields by the mixed anhydride 301, prepared from the trimethylsilyl esters 299 (R D Me, i-Pr, t-Bu, PhCH2CH2, 2-MeC6H4 etc.) and 4-trifluoromethylbenzoic anhydride (300) under titanium(IV) catalysis:340

RCO2SiMe3 C(4-F3CC6H4CO)2O ! RCO O OC C6H4CF3 ! RCONHAr

(299)		(300)		(301)
Allylamines R1CHDCHCH2NR2R3 (R1			D	Me,	Pr	or Ph;	R2	D	Me,	Et	or
3	D				by carbon					in	the
Bu; R		Et, PhCH2 or Ph) are carbonylated					monoxide
presence	of	Pd(OAc)2/Ph2PCH2CH2CH2PPh2		to give		good yields of			the	amides

R1CHDCHCH2CONR2R3341 .

Heating mixtures of trifluoroacetic acid, a primary amine RNH2 (R D C6H13, PhCH2, PhCH2CH2, Ph, Ar or 1-C10H7), triphenylphosphine and triethylamine in carbon tetrachloride affords trifluoroacetimidoyl chlorides CF3CClDNR in yields of 80 90%. The corresponding bromides are produced in carbon tetrabromide342. 1-Cyanobenzotriazole is a safe and convenient synthon for the cyanide cation. It converts secondary amines (dioctylamine, dibenzylamine, pyrrolidine etc.) into N-cyano derivatives343. Secondary amines, e.g. dibutylamine and morpholine, yield N-nitrosoamines by the action of bromonitromethane. A proposed mechanism is shown in equation 107344.

R2 NH +

+

BrCH2 NO2

R2 NCH2 NO2

R2 N

CH2

R2 NCH2 ONO

NO2 −

−HCHO

R2 NNO

+

107

Trifluoroamine oxide

R2NH at

or below

F3 N O reacts with dialkylamines

0 °C to

give mixtures

of N-fluorodialkylamines

R2NF and

N-nitroso

compounds

R2N NO345. All types of secondary amines are converted into nitroamines R1R2NNO2 by treatment with ethylmagnesium bromide, followed by butyl nitrate346. N- (Arylaminosulphanyl)phthalimides, prepared from trimethylsilylamines as shown in

594	G. V. Boyd

equation 108, undergo a base-induced fragmentation at room temperature to yield transient thionitrosoarenes, which are trapped by 2,3-dimethylbuta-1,3-diene as Diels-Alder adducts and by 1-methylcyclohexene as ene products347,348.

	O	O
	ArNHSiMe3 + ClS N	ArNH S N
	O	O
	Me		O
	NAr	Me	−HN
	S	+	O
		Me
	Me		(108)
			NAr
		H	S
	CH2 HNAr
	+
	S

7. Protection of amines

Very high yields of N-t-butyloxycarbonylamines are obtained when solutions of hydrochlorides of primary or secondary aliphatic amines in methanol or ethanol are treated with di-t-butyl dicarbonate and ultrasound is applied until carbon dioxide is no longer evolved, e.g. equation 109. PhCH(OH)CHMeNHMe is acylated only at the nitrogen atom under these conditions349.

		O
	+	ButOC				+	ButOH + CO2
		ButOC	O
N	CO2 H				N	CO2 H	(109)
H		O			C
					O	OBut

The t-butyldiphenylsilyl group has been recommended for the protection of primary amines. The derivatives t-BuPh2SiNHR are stable under basic conditions and to chromatography and are unreactive towards alkylating and acylating agents. They are smoothly cleaved by the action of 80% acetic acid or 0.5 M hydrochloric acid at room temperature350. t-Butoxycarbonylamines react with the t-butyldimethylsilyl ester of trifluoromethanesulphonic acid to give silyl carbamates 302, which are decomposed to the free amines RNH2 by the action of tetrabutylammonium fluoride. Treatment of the carbamates with alkyl halides in the presence of tetrabutylammonium fluoride gives alkyl

12. Advances in the chemistry of amino and nitro compounds

595

carbamates, e.g. 303 with allyl bromide351,352.

RNHCO2 But + ButMe2 SiO2 SCF3 RNHCO2 SiMe2 But

(302)

RNHCO2 CH2 CH CH2

(303)

2-(Trimethylsilyl)ethanesulphonyl chloride, Me3SiCH2CH2SO2Cl, is useful for the protection of primary and secondary amines as sulphonamides, which are smoothly cleaved by fluoride ion353. Use of the triazene moiety as a protecting group for aromatic amines is illustrated in equation 110. The protected compounds react with s-butyllithium, followed by an electrophile E (carbon dioxide, acetophenone or trimethylsilyl chloride), to give, respectively, the corresponding carboxylic acid, alcohol or trimethylsilyl derivative, which are converted into the free amines by the action of nickel aluminium alloy in aqueous methanolic potassium hydroxide354.

(i)NaNO2 /HCl

(ii)Pyrrolidine

NH2	N N N
R	R

(i) s-BuLi
(ii) E	(110)

NH2	N N N
R	R
E	E

8. Formation of carbamates, ureas, isocyanates, etc.

The combined action of alkyl halides and carbon dioxide on aliphatic primary or secondary amines affords alkyl carbamates 304 or 305, respectively. The reactions are carried out in DMF355 or in the presence of a pentaalkylguanidine356.

R1NHCO2R3	R1R2NCO2R3
(304)	(305)

Primary aliphatic or aromatic amines RNH2 are converted into carbamates RNHCO2Et on treatment with carbon monoxide and di-t-butyl peroxide in the presence of palladium(II) chloride and copper(II) chloride357. Carbamic esters 304 and 305 are also obtained from aliphatic amines and ortho carbonates (R3O)4C358. Vinyl carbamates R12NCO2CHDCHR2 are produced from secondary aliphatic amines, acetylenes R2C CH (R2 D Bu or Ph) and carbon dioxide in the presence of ruthenium(III) chloride359.

Primary amines RNH2 (e.g. R D Bu) are converted into symmetrical ureas RNHCONHR at room temperature and atmospheric pressure by the action of

596	G. V.	Boyd
carbon monoxide in the presence	of a	catalyst prepared from montmorillonite,

di(pyridine)palladium(II) acetate and copper(II) chloride360. Ureas RNHCONHR are also produced when primary aliphatic or aromatic amines are heated under pressure with carbon dioxide and a trace of Ph3SbO/P4S10361. The photochemical carbonylation of allylamine at 20 atm mediated by dicobaltoctacarbonyl gave a mixture of pyrrolidin-2-one, N-allyl- 3-butenoamide and N,N0-diallylurea (equation 111)362.

NH2		+	N C
	N	O
			H O
				(111)
	H
		+	N C N
			H O H

Heating N,N0 -diphenylurea with amines (butylamine, cyclohexylamine, benzylamine, 2,6-diethylaniline or morpholine) in DMF in the presence of triethylamine yields unsymmetrical ureas, e.g. PhNHCONHBu from butylamine363. High yields of isocyanates RNCO are obtained in the reactions of primary aliphatic amines, carbon dioxide and triethylamine with phosphorus oxychloride364. Treatment of secondary amines with butyllithium, followed by carbon monoxide at 78 °C under atmospheric pressure, sulphur and an alkyl halide affords S-alkyl thiocarbamates, e.g. Et2NC(O)SCH2Ph from diethylamine and benzyl bromide. The key step in the sequence is the generation of the lithium thiocarbamate shown in equation 112365.

BuLi

S8

PhCH2

Br

CO

Et2 NC− Li+

Et2 NCS− Li+

Et2 NH

Et2 NCSCH2 Ph

(112)

O

O

O

Sequential treatment of tertiary amines containing N-methyl or N-benzyl groups with carbon disulphide and alkyl halides gives alkyl dithiocarbamates in good to excellent yields. Thus N-methylmorpholine, carbon disulphide and methyl iodide in THF gave 91% of compound 306366.

S

O

N CH3

O

N C

SMe

(306)

The conversion of symmetrical into unsymmetrical thioureas is exemplified by the formation of N-cyclohexyl-N0-phenylthiourea when N,N-diphenylthiourea is heated with cyclohexylamine and triethylamine in acetonitrile367. Carbonylation of lithium piperidide in the presence of tellurium generates the lithium carbamotellurate 307, which is trapped as the Te-ethyl carbamotellurate 308 by ethyl bromide368.

1,10-(Thiocarbonyldioxy)di(benzotriazole) 310, prepared by the action of thiophosgene on 1-(trimethylsilyloxy)benzotriazole 309, reacts with all types of primary amines at room temperature in the presence of triethylamine to give isothiocyanates 311 in 84 95% yields369.

12. Advances in the chemistry of amino and nitro compounds

597

CO

Te

N Li

O	O
N C	EtBr
	N C
TeLi	TeEt

(307)

(308)

N N

CSCl2

N OSiMe3

N N S N N

N OCO N

2

(309)

(310)

RNH2

N N

2 HO N

+

RNCS

(311)

Primary amines R1NH2 are converted into isothiocyanates by the action of carbon disulphide and alkyl halides R2X in the presence of DBU (equation 113)370.

	CS2		S
1	R2 X	1				(113)
R NH2		R N C			RNCS
		H	SR2 −R2 SH

9. Cyclization reactions

Heating amines RNH2(R D Pr, i-Pr, Bu, i-Bu, t-Bu, t-Bu or PhCH2) with ethyl 2- (hydroxymethyl)propenoate (312) in methanol affords the ˇ-lactams 313371,372.

	CH2 OH
CH2 OH
RNH2 + H2 C C	O
CO2 Et	N
	R
(312)	(313)

598 G. V. Boyd

Unstable 2,3-dialkyl-1,2-thiazetidine 1,1-dioxides 315 (R1 D Bu or C6H13; R2 D Et, i-Pr, t-Bu or PhCH2) are produced from the ethenesulphonyl fluorides 314 and primary amines373.

R1CH		CHSO F +	R2 NH		R	1	SO2
2			2
(314)							N
							R2
							(315)

The propargyl alcohol 316 reacts with carbon dioxide and aliphatic or aromatic primary amines RNH2 under tributylphosphine catalysis to yield 5,5-dimethyl-4-methylene- oxazolidin-2-ones 317374.

H
C			H2 C
C	+ CO2 + RNH2		NR
Me2 C			Me	O
OH			Me O
(316)		(317)

Cyclization of the N-(4-alkenyl)methylamines 318 (R1 D Me or Ph; R2 D H or Ph) under the influence of butyllithium gives the cis-pyrrolidines 319 stereoselectively375.

R1	CHR2		R1	N	CH2 R2
NH
Me				Me
(318)				(319)

The 2-vinylpyrrolidines 321 are formed in up to 99% diastereomeric excess by the ring closure of the allenic sulphides or sulphoxides 320 (R D PhS or PhSO), induced by silver(I) ions376.

C	CH2	CH2	HNR
NH		N		Me
Ph CH2 R		Ph CH2 R	O	N CO2 Me
(320)		(321)		(322)

Ultrasound irradiation of mixtures of amines RNH2 (R D PhCH2, Ph or Ar) and methyl pyruvate results in the 3-pyrrolin-2-ones 322377. The silver tetrafluoroborate-catalysed cyclization of the allenic amines 323 leads either to a pyrroline 324 or tetrahydropyridine 325, depending on the structure of the amine. The former is formed from 323 (R D H), the latter from 323 (R D Me)378.

12. Advances in the chemistry of amino and nitro compounds						599
			Me			Me
Me	H		Me			Me
C	C C	Me		Me
R	CMe2	CH	N	Me	N
H2 N	CH2	H			H
(323)			(324)		(325)

10. Formation of aminyl radicals

A review of the generation of aminyl radicals by photolysis and by metal-induced one-electron reductions of N-chloroamines has appeared379.

Aminyl radicals are produced by the sequence outlined in equation 114. The action of phosgene on the sodium salt of N-hydroxypyridine-2-thione yields the salt 326, which reacts with amines to give 327. The latter decompose to the radicals 328 on heating or irradiation380.

S			S				S
					R1R2 N
		O	+	+R1R2 NH
								N
+ − N			N		O
							O
Na O			O
			Cl−
			(326)				(327)
							(114)
				R1R2 N
				C	O			R1R2 N
							−CO2
				O			(328)

Treatment of 329, the N-butyl-N-4-pentenyl analogue of 327, with trifluoroacetic acid and t-butylthiolate radicals (from t-butylthiol) under irradiation with visible light gives the aminyl radical 330, which cyclizes to the pyrrolidine 331 and a t-butylthiolate radical is regenerated (equation 115). It is believed that the process involves, at least partially,

+

the aminium cation radical R1R2 NHž381.

	Bu	S		Bu
			N	NBu
	N
			+ ButS
	O		N
		O
	(329)		(330)	ButSH	(115)
				NBu
				+	ButS

CH3

(331)

600	G. V. Boyd

The carbamates 327 (R1 D R2 D Pr or Bu) react with t-butylthiol, malonic acid and ethoxyethylene under irradiation to yield the (ethoxyethyl)amines 333 via the radical cations 332. The N-allyl analogues 334 (R D Pr or PhCH2) cyclize to pyrrolidines 335382.

S

R1R2 N		1 2			1 2 +
	N	R R N			R R NH
				(332)
O	O
	(327)						OEt
				R1R2 NCH2 CH2 OEt
				(333)
				CH					Me
	CH2 CH CH2	CH2			CH2
	+	OEt
	NH	N +						R	N
R		R		CH2 CH					OEt
		H			OEt
		(334)							(335)

3-Hydroxy-4-methylthiazole-2(3H)thione carbamates, e.g. the cyclohexyl derivative 336, are precursors for monoalkylaminium cation radicals, which cannot be prepared from 2-thioxopyridinyloxycarbamates. The carbamate is obtained from 3-hydroxy-4- methylthiazole-2(3H)-thione and cyclohexyl isocyanate. When irradiated in the presence

of malonic acid and t-butyl hydrogen sulphide it yields the cyclohexylaminium cation

+

RNH2ž and thence cyclohexylamine383.

		S	S
S	S	O
NCO +		H	N
	N	N
HO		O	Me
		Me
		(336)
		But S
		H +
		+
		NH2

The N-4-pentenyl analogue 337 affords the radical cation 338, which cyclizes to 2- methylpyrrolidine, isolated as the N-benzoyl derivative 339 in high yield383.

A general method for the generation of aminyl radicals is by treatment of sulphenamides 340, prepared from secondary amines and N-benzenesulphenylphthalimide, with tributyltin hydride in the presence of AIBN (2,20 -azobisisobutyronitrile). The cyclopropyl derivative

	12. Advances in the chemistry of amino and nitro compounds							601
	S	S
	O						N	CH3
	N		+				C
N	O			N
						O	Ph
		Me		H2
	(337)		(338)				(339)

undergoes ring opening to the imine 341, whereas from the cyclopentyl analogue (equation 116)384.

O

N SPh + HNRMe PhS

	O
N		+H	NMe
	Me		(341)

N-methylcyclopentylamine is formed

	R	Bu3 Sn	R
	N		N
	Me		Me

	(340)	(116)
	N	+ H
		NHMe
		Me

11. Miscellaneous reactions
The high-pressure reaction of	N-methylpiperidine with 4-chloronitrobenzene
yields N-(4-nitrophenyl)piperidine	(equation 117); 2-chloronitrobenzene and chloro-

2,4-dinitrobenzene behave analogously. N-Methylpyrrolidine and 4-chloronitrobenzene afford a mixture of N-(4-nitrophenyl)pyrrolidine and the product 342 of ring scission (equation 118)385.

O2 N	Cl + Me N	O2 N	N
		−MeCl
			(117)
O2 N	Cl + Me N	O2 N	N
		Me	(118)
	+ O2 N
		N	(CH2 )4

+ Me

N

Cl−

(342)

602	G. V. Boyd
Di-2-pyridyl sulphite (343)	(from 2-pyridone and thionyl chloride in the presence

of triethylamine) transforms primary aliphatic and aromatic amines RNH2 into N- sulphinylamines RNDSDO and it dehydrates amides ArCONH2 to aryl cyanides, aldehyde oximes RCHDNOH (R D C8H17, 4-MeOC6H4 or PhCHDCH) to the cyanides RCN and N-alkyl- and N-arylformamides RNHCHO to isocyanides RNC. Aliphatic and aromatic

thioureas R1NHCSNHR2 yield carbodiimides R1NDCDNR2386 . The chemistry of di-2- pyridyl sulphite thus closely resembles that of 2-halogenopyridinium salts (Mukaiyama’s reagents)387 and triphenylphosphine/diethyl azodicarboxylate (Mitsunobu reagent)388.

O

S

N O O N

(343)

The perfluorinated amine 344 is cleaved by antimony pentafluoride to the imine 345 and the fluorocarbon 346389.

F3 C(CF2 )5

N F	F3 C(CF2 )4 CF		NF + F3 C(CF2 )4 CF3

F3 C(CF2 )5

(344)

(345)

(346)

In the presence of samarium(II) iodide, N-(2-iodobenzyl)dialkylamines 347 react with electrophiles at an ˛-carbon atom to yield deiodinated products by way of intermediate samarium compounds 348. Thus N-(2-iodobenzyl)diethylamine and pentan-3-one afford the hydroxy amine 349 and N-(2-iodobenzyl)pyrrolidine and propyl isocyanate give the amide 350390.

	R1		R1				R1
R2	I	R2	CH		R2		CH
	CH2			SmI2				E
	N		N			N
	CH2	+SmI2	CH2		E		CH2
		− HI
	(347)		(348)
	CH3
	CH2 I			CH3			CONHPr
Et	N			Et
				CHC
	CH2		Et N	OH Et			N CH2 Ph
				CH2 Ph
				(349)			(350)