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

603

The action of triphenylphosphine dichloride, generated from triphenylphosphine and hexachloroethane, on tertiary amines leads to phosphonium salts. Triethylamine is con-

verted into 351 and ethyldiisopropylamine

CH3 CH2

Ph3 PCl2

N CH2 CH3

CH3 CH2

gives a mixture of the salts 352 and 353391.

	H		+
		C	PPh3
	CH3 CH2
		C
	N		−
	CH3 CH2		H Cl

				(351)
	H3 C				+
		CH	H3 C	H	PPh3
	H3 C	N CH2 CH3		CH	C
	H3 C		H3 C
		CH		N	C
			H3 C
				CH	H
		CH3			Cl−
			H3 C
					(352)
					+
				H	PPh3

+H3 C H3 C H3 C

C

N

CH2 CH3

CH

(353)

Imidoylstannanes 355 are produced by the action of acylstannanes 354 on primary aliphatic and aromatic amines in the presence of 3 A˚ molecular sieves392.

R1COSnBu3 C R2NH2	! R1C(SnBu3)DNR2
(354)	(355)

Acetophenone reacts with the adduct of sulphur dioxide to dimethylamine to yield the red betaine 356 by way of an intermediate enamine393.

					+
			NMe2		NMe2	S
	HNMe2
PhCOCH3				Ph C
		Ph C	CH2		CH2 C	−
						S
					(356)

Bis(N,N-dialkylamino)trisulphides are formed by treatment of secondary amines with disulphur dichloride, followed by sulphuryl chloride and sodium sulphide, e.g.

604			G. V. Boyd
equation 119394.
S2Cl2			SO2Cl2
	S S		Na2S	S S S	NBu2	119
Bu2NH ! Bu2N			NBu2 ! Bu2N

An Arbuzov reaction of triethyl phosphite with N-chloroamines RNHCl (R D i-Pr, cyclohexyl or PhCH2), prepared from the corresponding amines and aqueous sodium hypochlorite, leads to the phosphoramides 357 with the elimination of ethyl chloride395.

(EtO)3P C RNHCl ! (EtO)2P(O)NHR C EtCl

(357)

A method for the preparation of olefins from primary amines is shown in equation 120. Treatment of 2-(4-bromophenyl)ethylamine (358) with acetic acid, acetic anhydride and sodium nitrite generates the nitroso amide 359, which decomposes to 4-bromostyrene in the presence of rhodium(II) acetate. The procedure is thus a mild, non-basic alternative to the classical Hofmann elimination of amines396,397.

			Ac
ArCH2 CH2 NH2		ArCH2 CH2 N	ArCH		CH2
			NO
(358)	(359)		(120)

Ar = Br

The deamination of primary amines RNH2 (R D C8H17, PhCH2, PhCHMe or PhCHDCHCH2) to the corresponding hydrocarbons is accomplished by conversion into the benzimidoyl chlorides, followed by reduction with tributyltin hydride in the presence of AIBN (equation 121)398.

C2[H]
RNH2 ! RNDC(Cl)Ph ! RH C PhCN C HCl	121

III. NITRO COMPOUNDS

The chemistry of nitroalkenes has been reviewed399 401 and an account of polynitro cage compounds, such as 1,3-dinitrocubane (360) and the trinitrobishomocubane 361, has appeared402.

A. Synthesis

Sodium perborate in acetic acid converts oximes into nitro compounds; thus acetophenone oxime yields 52% of PhCHMeNO2403. Nitroalkanes and nitroarenes are obtained from isocyanates and dimethyldioxirane (equation 122)404.

		Me	Me		(122)
		O	O
	RNCO			RNO2	(R = Bu, t-Bu, cyclohexyl, Ph)

12. Advances in the chemistry of amino and nitro compounds			605
	NO2		NO2
O2 N
		NO2
		O2 N
	O2 N NO2
(360)	(361)	(362)

The dinitrocubane 362 was prepared from the corresponding diisocyanate in this way404. In contrast, treatment of isocyanates with nitronium tetrafluoroborate and nitric acid yields N,N-dinitroalkylamines, e.g. BuN(NO2)2 from butyl isocyanate405. N- Nitrosodialkylamines are oxidized to the corresponding nitro amines by hydrogen peroxide in aqueous acetic acid, e.g. equation 123406.

Me2NNO ! Me2NNO2

123

3-Nitroalkenes are formed in the reaction of allyltrimethylsilanes with nitronium tetrafluoroborate in dichloromethane (equation 124)407.

				R
R	SiMe3	O2 N+BF4	−
				(124)
				NO2

Aliphatic and alicyclic ketones condense with primary nitroalkanes under the influence of N,N-dimethylethylenediamine to yield allylic nitro compounds as mixtures of geometrical isomers, e.g. equation 125408.

	O		CH2 NO2
	+ CH3 NO2	Et	Me	(125)
EtCH2	Me

H

The base-catalysed Michael addition of ˛,ˇ-unsaturated nitro compounds 363 to electron-deficient olefins 364 (R4 D Ac, CO2Me or CN) results in the formation of allylic nitro compounds 365; aldehydes give alcohols 366 in this reaction409.

Exposure of mixtures of alkenes, ceric ammonium nitrate, acetic acid and chloroform to ultrasound leads to ˛,ˇ-unsaturated nitroalkenes. A free-radical mechanism was proposed for this reaction (equation 126)410.

	NO2		NO2	NO2
+ NO2	Η		Η	−H+
		−
	− e		+
	Η		H

126

606		G. V. Boyd
R1	NO2			R1	NO2
	+	R4	DBU
R2	R3			R2	R3	R4
(363)	(364)				(365)
	H		R1	NO2
(363) + O	R4	R2			OH
				R3
				R4

(366)

N-Nitroamides 368 are produced by the rapid rearrangement of the imidoyl nitrates 367 formed in the reactions of imidoyl chlorides with silver nitrate. The transient nitrate esters were detected by NMR spectroscopy411.

	Cl			O	NO2		O	NO2
	C	N		C	N		C	N
Ar	1	Ar2	Ar	1	Ar2	Ar	1	Ar2
					(367)			(368)

Secondary aliphatic amines, such as diethylamine, pyrrolidine or piperidine, react with the electron-poor nitrate ester 2-(trifluoromethyl)-2-propyl nitrate (369) under neutral conditions to afford the corresponding N-nitro derivatives 370412.

F3CCMe2ONO2	C R2NH ! R2N NO2
(369)	(370)

The joint action of di-t-butyl nitroxide radicals and tetranitromethane on the hydrazine 371 in ether at room temperature yielded 75% of the N-nitroso compound 372, together with 10% of the dinitrohydrazone 373413.

1,1-Diiodo-2,2-dinitroethene (374), prepared by nitrating tetraiodoethene, condenses with all types of amines, e.g. propylamine, aniline and dimethylamine, to give the corresponding vicinal diamines 375414.

								NO2
MePhNNH2	+ But 2 NO	+ C(NO2 )4				MePhNNO + MePhNN		C
(371)					(372)			NO2
							(373)
I	I	O2 N		I		R1R2 NH	O2 N	NR1R2
C C		C	C				C	C
I	I	O2 N		I			O2 N	NR1R2
		(374)					(375)

12. Advances in the chemistry of amino and nitro compounds

607

B. Reactions

An extensive review on the use of nitroalkanes as alkyl anion synthons has appeared415.

1. Formation of oximes, nitrones, hydroxylamines, amines, etc.

The potassium salts of nitro compounds, such as 2-nitropropane, nitrocyclohexane and ethyl ˛-nitroacetate, are halogenated at the ˛-position by N-chloro- or N- bromosuccinimide, e.g. equation 127416.

	O2 N H		O2 N	O2 N Cl
			−
		KOH		(127)

K+

The fluorination of nitroalkanes has been described. A solution of acetyl hypofluorite, AcOF, is prepared by passing fluorine, diluted with nitrogen, into a cold suspension of hydrated sodium acetate in acetonitrile containing acetic acid. Adding a mixture of a nitroalkane and methanolic sodium methoxide yields the fluorinated nitroalkane, e.g. 1-fluoro-1-nitrocyclopentane from nitrocyclopentane417. A general method for alkylating nitroalkanes is exemplified by the reaction of the sodium nitronate 376 with the benzotriazole derivative 377 to yield 378418.

Me2 C−		N
		N
	+		Me2 CCH2 N
NO2		N	NO2
+
	Na	CH2	N
(376)		(377)	(378)

Chlorofluoronitronitrosomethane (380) was obtained by the decarboxylative nitrosation of chlorofluoronitroacetic acid (379)419.

Cl	NO2	Cl	NO2
C			C
F	CO2 H	F	NO
(379)			(380)

˛,ˇ-Unsaturated aldehydes are formed by acidic hydrolysis of the sodium salts of allylic nitro compounds (equation 128)420.

			+	O−
	NaOH				H2 SO4	RCH		CHCHO
RCH CHCH2 NO2		RCH CHCH	N
		Na+		O−

128

608	G. V. Boyd

Successive treatment of primary or secondary nitroalkanes with triethylamine and hexadecyltrimethylammonium permanganate affords aldehydes or ketones, respectively (e.g. equation 129). Hydroxyl groups and olefinic double bonds are not affected421.

CH2DCH(CH2)9NO2 ! CH2DCH(CH2)8CHO

129

Secondary nitroalkanes are oxidized to ketones by 3-chloro- or 4-nitrobenzoyl peroxide by way of their anions; thus MePhCHNO2 gives acetophenone in 92% yield422. The same reaction can be carried out with sodium chlorite in methylene chloride/aqueous sodium hydroxide/tetrabutylammonium hydrogen sulphate under phase-transfer conditions423. Nitrones 382 (R1 D H or Me; R2 D Me, CO2Me, CONHMe or CONMe2; R3 D t- Bu or Ph) are formed when the sodium salts 381 of nitroalkanes are treated with the appropriate nitroso compounds424.

R1	−		R3 NO	R1	+	R3
	C			C	N
R2	NO2			R2		O−
	Na+
	(381)			(382)
2-Butenylmagnesium	chloride	converts		aromatic nitro		compounds 383 (Ar D

2-MeC6H4, 2- or 4-ClC6H4 or 2,6-Me2C6H3) into the nitrones 384; aliphatic nitro compounds 385 (R D Pr or C5H11) yield allyl nitrones 386 in this reaction425.

ArNO2 + MeC

CHCH3

+

Ar

N

CMeCH

CH2

(383)

MgCl

O−

(384)

+

RCH2 NO2

RCH

N

CHMeCH

CH2

O−

(385)

(386)

Treatment of aromatic nitro compounds with allylmagnesium chloride, followed by 1.4 equiv. of LiAlH4(LAH) and a trace of palladium on charcoal affords hydroxylamines 387 (Ar D Ph, 4-ClC6H4, 2-FC6H4 or 3-MeOC6H4). If the amount of LAH is increased to 2.5 equiv. N-allylarylamines 388 result. 1-Nitrohexane and nitrocyclohexane react

analogously426.
ArN(OH)CH2CHDCH2	ArNHCH2CHDCH2
(387)	(388)

The reduction of nitroarenes to azoxy compounds ArNDN(O)Ar is promoted by bismuth trichloride/powdered zinc427. Aromatic amines are formed in excellent yields in the reduction of nitroarenes with BH3/NiCl2428 or nickel boride429. Acyl, ester, amide and cyano groups are not affected. Reaction of the nitro compounds RCH2NO2 (R D Ph, Bz

12. Advances in the chemistry of amino and nitro compounds

609

or MeO2C) with thionyl chloride and triethylamine generates nitrile oxides 389, which have been trapped in situ by various dipolarophiles. Dimethyl fumarate, for instance, yields the isoxazolines 390430.

										R
							CO2 Me			N
+
						O− +				O
R		C		N					MeO2 C
(389)							CO2 Me			CO2 Me
										(390)

Oximes 392 are produced when acetone solutions of nitroalkanes 391 (R D PhCH2, EtO2CCH2CH2, 1-cyclohexenyl etc.) are irradiated in the presence of triethylamine431.

RCH2NO2 ! RCHDNOH

(391)(392)

Nitromethane reacts with t-BuNHMgBr (prepared from ethylmagnesium bromide and t-butylamine in boiling THF) to give the oxime 393; nitroethane yields the analogue 394. The action of PhN(MgBr)2 on 2-methyl-2-nitropropane (395) results in the azoxy compound 396432.

			H
H3 CNO2 + ButNHMgBr				C NOH
			ButHN
				(393)
		Me			+
MeCH2 NO2		ButHN	C NOH	ButNO2	ButN			NPh
					O−
			(394)	(395)	(396)

Treatment of the nitronate salt 397 (from nitroethane and methanolic sodium methoxide) with benzene in the presence of trifluoromethanesulphonic acid gives acetophenone oxime, which is obtained mainly as the (E)-isomer 398433.

	−		H3 C	OH
		PhH		N
	H3 CCHNO2		C
	Na+		Ph
	(397)		(398)

Reduction of nitroalkanes RNO2 with samarium(II) iodide, obtained from samarium and 1,2-diiodoethane, yields either alkylhydroxylamines RNHOH or alkylamines RNH2, depending on the amount of the reagent434. The base-catalysed reaction of nitroalkanes with phenyl(vinyl) sulphoxide (399) yields the conjugate adducts 400, which fragment to allylic nitro compounds 401 on thermolysis435.

610

G. V. Boyd

O

O

R1

H

R1

CH2 CH2 S Ph

+ CH2

C

CH

S

Ph

C

R2

NO2

R2

NO2

(399)

(400)

R1

CH CH2

C

R2 NO2

(401)

Addition of nitroalkanes 402 (R D Me, Bu, Ph etc.) to methyl acrylate without a solvent in the presence of Amberlyst-21 gives good yields of the esters 403436. An analogous reaction with electrophilic acetylenes, e.g. dimethyl acetylenedicarboxylate, in the presence of potassium fluoride and tetrabutylammonium chloride yields adducts 404 as

mixtures of geometrical isomers437.

RCH2 NO2 +	CO2 Me
(402)

402 + MeO2 CC CCO2 Me

NO2

CH

R

CO2 Me

(403)

NO2 CO2 Me

CH

R H

MeO2 C

(404)

2. Reactions of aliphatic nitro compounds with nucleophiles

A review of the reaction of nitroalkanes RNO2 with carbon and heteroatom nucleophiles X to yield RX has appeared438. The nucleophilic displacement of a nitro group in benzylic and tertiary nitroalkanes by a thiophenyl group is exemplified in equation 130439.

	Me	SnCl4	Me
	C NO2 + Me3 SiSPh		C SPh	(130)
	Ph		Ph
			H
	H

A similar reaction occurs with electron-rich aromatic compounds, such as toluene or anisole, under tin(IV) chloride catalysis, e.g. equation 131:

CH2	CHCMe2NO2		ArH	SnCl4	CHCMe2Ar	131
		C		! CH2
	D				D

12. Advances in the chemistry of amino and nitro compounds

611

An intramolecular version of the process, 405 ! 406, and a novel replacement reaction using allyltrimethylsilane, 407 ! 408, were also reported440.

	Ph
	H NO2				Ph	H
	(405)			(406)
Me	CH CH2				Me
C	+ Me3 SiCH2 CH		CH2		C	CHCH2 CH2 CH CH2
H13 C6	NO2			H13 C6
(407)						(408)

1,4-Diketones are produced from nitroalkenes and the lithium enolates of ketones. Equation 132 shows the reaction of the enolate of 2-hexanone with 2-nitropropene in the presence of acetic anhydride. The resulting betaine 409, a greenish-blue liquid, is hydrolysed to the diketone by successive treatment with boron trifluoride and water441.

			H	H	Me			Me
		CH3		C	H2 C C
					NO2			N +
		C		C	Bu	O
	Bu	O	Bu	OLi				O −
						AcO
						(409)		(132)
								Me
					Bu	O		O

Reactions of aliphatic nitro compounds with nucleophiles have been reviewed442			444.
The oxidative reaction of nitronate anions, e.g.	410, with thiocyanate anions to
yield thiocyanates 411 proceeds by a ‘radical	radical-anion chain mechanism’

SRN1 (equation 133). Analogous replacements by azide, benzenesulphinate and 4- chlorobenzenethiolate have been reported445.

									−
				−			NO2			NO2
	− +Fe(III)								+Fe(III)
Me2 CNO2			Me2 CNO2	+ SCN		Me2 C				Me2 C
		−Fe(II)
							SCN			SCN
(410)
										(411) 133

612	G. V. Boyd

2-Bromo-2-nitropropane reacts with nitrobenzenethiolate anions ArS (Ar D 2- or 4-O2NC6H4) in diffuse daylight to give substitution products 412 and ‘dimers’ 413 (equation 134)446,447

Me2 C

NO2

NO2

SAr

NO2

Me2 C

NO2

−

A rS

(412)

Me2 C

(134)

Me2 C

NO2

Br

Br

−

Me2 C

NO2

Me2 C

(413)

The oxidative addition of hydroxide anion to nitroalkenes, e.g. (E)-2-nitro-2-butene, which leads to epoxides, proceeds by way of radical anions (equation 135)448.

H	NO2	KOH
		K3 [Fe(CN)6 ]
Me	Me

H	O− + O−		HO	NO2
O	N
		−e−
Me	Me		Me	Me

(135)

−H+

O−	NO2		H	O	NO2
Me	Me	−e−
			Me		Me

˛-Nitroazides result from successive treatment of potassium salts of nitroalkanes with potassium hexacyanoferrate and sodium azide. The products react further with sodium azide/potassium hexacyanoferrate to yield gem-diazides (equation 136)449.

					−	−
				+N3		NO2		NO2
Me2 CNO2 −
			Me2 CNO2			Me2 C		Me2 C
K	+					N3		N3

	−	(136)
	+N3
	N3
Me2 C
	N3

The nitronate anion 414 derived from phenylnorbornene reacts with benzenesulphinate, thiocyanate, nitrite or 4-chlorobenzenethiolate anions in the presence of Fe(III) by the SRN1 mechanism to give the norbornenes 415 (R D O2SPh, SCN, O2N, or SC6H4Cl-4, respectively). No cyclization occurred450.