Patai S., Rappoport Z. 1996 The chemistry of functional groups. The chemistry of amino, nitroso, nitro and related groups / 0423 477

10. Hydrogen bonding and complex formation			453
	.....O	−
		O .....
H	+N	H
O		O

(84)

Intramolecular hydrogen bonding interactions may compete with hydrogen bonding with solvents. The electronic absorption spectra of 2-nitro-p-toluidine and 2-nitrophenol reveal203 (by the solvatochromic comparison method) that the intramolecular hydrogen bond of amines is retained even in strongly basic solvents, while the intramolecular hydrogen bond between the hydroxy and nitro groups in 2-nitrophenol is broken to form an intramolecular hydrogen bond even in poorly basic solvents.

Nitroenamines are affected by the isomerism204 shown in equilibrium 22. Compounds with primary (R1 D R2 D H) or secondary amino (R1 D H, R2 D alkyl) groups exist as mixtures of the intramolecularly hydrogen bonded Z and E forms, in an equilibrium (equation 22) depending on the solvent properties. The E form of a nitroenamine with a tertiary amino group is the more populated form.

	R	H				R	NO2
	C	C				C	C	(22)
	N	NO2				N	H
R	R				R	R
		Z					E
In the solid state,	intermolecular		and intramolecular				C HÐ Ð ÐO	hydrogen bonds

between nitro groups (or other oxygen-containing groups) and phenyl ring hydrogens are reported205. Intermolecular forces such as hydrogen bonds may cause twisting of the nitro group with respect to the phenyl ring plane of nitroaromatic derivatives206.

The crystallographic and spectroscopic investigations of 3-exo-6-exo-dichloro-5-endo- hydroxy-3-endo-nitrobicyclo[2.2.1]heptane-2-exo-carbonitrile (85), of 3-exo-chloro-6-exo- nitrobicyclo[2.2.1]heptan-2-exo-ol (86) and of 3-exo-chloro-6-exo-nitrobicyclo[2.2.1]- heptan-2-endo-ol (87) reveal that in 85 there is an intramolecular hydrogen bond between the hydroxy and nitro groups207, while in 86 linear hydrogen bonding occurs intermolecularly between the hydroxy and nitro groups, and in 87 the intermolecular hydrogen bonds are unsymmetrically bifurcated208. A bifurcated intramolecular hydrogen bond is also observed in the (2-nitrophenyl)hydrazone of benzophenone209 (88).

NC	Cl Cl		Cl
Cl	HO	NO2	NO2
OH	NO2		OH
(85)		(86)	(87)

454	Luciano Forlani

Ph Ph

C

N H

N

NO2

(88)

Crystal structures (by X-ray diffraction) indicate that the hydrogen of the N H group is involved in an intramolecular hydrogen bond with the ortho nitro group and there is also an interaction between the same hydrogen atom and the C C double bond of the phenyl ring (H/ interaction). When the nitro group is in the para position, the hydrogen bond is only with the CDC bond. This hydrogen bonding interaction is observed only in the solid phase and does not survive in solution.

The electronic effect of the nitro group bonded to the N-methyl group in anilines (89) is evaluated by canonical structure weights of p-nitro derivatives of benzene. The Hammett equation gives a value of C0.36 for the N(NO2)Me group in the para position: the usual strong electron-donating effect of the amino group is reverted by the electron-withdrawing ability of the nitro group210.

Me NO2

N

NO2

(89)

Some remarks about interactions between the nitro group and counter ions of anionic nucleophiles arise from the kinetic investigation of reactions of some 2-nitro-(1,3)- thiazoles and benzothiazoles toward nucleophiles211, where the nitro group is the leaving group, as shown in Scheme 10. The change of the counter ion in reactions with methoxide (LiC , NaC , KC ) indicates that the presence of ion pairs enhances the reaction rate, probably by interaction between the cation and the nitro group as illustrated by 90.

		M	+
	−	..
RO			..
				.
				O−
C		N (1−δ)+
δ +				O

(90)

10. Hydrogen bonding and complex formation			455
S		S
NO2 + RO−M+		OR + NO2 − M+
N		N

R = Me, t-Bu

M = Na, Li, K

SCHEME 10

Comparison of the nucleofugality of nitro and chloro groups (as leaving groups) indicates that the presence of hydrogen bonding between the leaving group and the solvent produces variations in the observed reactivities. Hydrogen bonds increase the rate of departure of the nitro group more than the rate of departure of halogens. With neutral nucleophiles (amines) both 2-nitrothiazole211 and 2-nitrobenzothiazole present autocatalytic kinetic behaviours212 which may be explained by the presence of an interaction between the heterocyclic substrate and the amine, in an equilibrium preceding the substitution reactions (equilibrium 23).

ArNO2 C HNC5H10	Kc	ArNO2ÐHNC5H10
			23

Here, HNC5H10 D piperidine; ArNO2 D 2-nitrothiazole, 2-nitrobenzothiazole; Kc D 0.19 and 0.29 (mol 1 dm3), respectively, at 25 °C in benzene.

B. Electron Donor Acceptor Complexes

Tetranitromethane produces strongly coloured electron donor acceptor (EDA) complexes with derivatives of the anthracene213, in dichloromethane. Specific irradiation of the charge transfer absorption band at > 500 nm produces a rapid fading of the colour of the solutions. From these solutions, adduct 91 is obtained (reaction 24); its structure is ascertained by X-ray crystallographic diffraction. 91 is derived from an anti-addition of fragments of tetranitromethane by a multistep pathway214.

H C(NO2 )3

+ C(NO2 )4		[EDA]	hν

O2 N H

(91)

(24)

The excitation of these complexes generates intimate ion pairs which are well suited for the quantitative study of ion-pair and radical-pair dynamics. The behaviour of the ion pairs generated by this method parallels the behaviour of ion pairs generated by usual solvolytic reactions215.

Nitration of naphthalene216, phenol derivatives217, dibenzofuran218 and 1,2,3,4- tetramethylbenzene219 occurs in a similar way, by charge-transfer excitation of complexes of naphthalene derivatives with N-nitropyridinium or tetranitromethane acceptors. The

456	Luciano Forlani

main products of reactions between 1,2,3,4-tetramethylbenzene and tetranitromethane are 92, 93 and 94. Transient cation radicals ArCH3Cž are spontaneously generated by excitation of the charge transfer complexes between methylbenzenes and tetranitromethane to afford side-chain nitration products220.

	Me	Me			Me
		Me	Me
	H	H		O2 N	Me
		NO2	NO2	H
	H	H		H	Me
		Me	Me
	(O2 N)3 C	(O2 N)3 C		(O2 N)3 C
	Me	Me			Me
	(92)	(93)			(94)

Aromatic nitro derivatives may act as electron acceptor molecules affording complexes with electron donor partners. This is the case of 1,3-dinitrobenzene which forms a 1:1 donor acceptor complex with tetrathiafulvalene221. These complexes are of interest in the field of electrical conductivity.

The reduction potential of nitroanilines decreases on increasing the solvent electron acceptivity for aprotic solvents. The first step of the electrochemical reduction of nitroanilines is the radical ArNO2 ž (the electron is mainly on the nitro group). When the amino group interacts with the solvent by forming a hydrogen bond, the sensitivity of the nitro group to solvent acceptivity is enhanced222.

1-(2,4,6-trinitrophenyl) propan 2-one 95 produces223 donor acceptor complexes with aromatic hydrocarbons (benzene, naphthalene, phenanthrene, pyrene) in carbon tetrachloride and in chloroform. These complexes have a donor:acceptor ratio of 1:1 and 2:1 when the donor is in excess; their practical utility (together with complexes with other electron acceptor partners)224 is for the separation (and the characterization) of polynuclear aromatic hydrocarbons from atmospheric pollutants or from hydrocarbon mixtures.

Intramolecular charge transfer in 4-nitropyridine N-oxide has been investigated by spectroscopic methods and by comparison with AM1 and MNDO semi-empirical methods to obtain the vibrational force field225. The results obtained indicate that protic solvents (water, methanol) favour the mesomeric form 97 which is also favoured in the crystal, by an internal interaction between the nitro and N-oxide groups226.

		−	−O	O−
	O	O
	CH2 COCH3	N +		N +
O2 N	NO2
		N +		N +
	NO2	O −		O
	(95)	(96)		(97)

10. Hydrogen bonding and complex formation

457

V. COVALENT COMPLEXES BETWEEN AMINES AND NITRO ACTIVATED

AROMATIC DERIVATIVES

-Anionic complexes (Meisenheimer complexes) between activated homocyclic and heterocyclic aromatic substrates and nucleophiles have been extensively investigated by different methods and detailed reviews and books are available227 231. The nitro group is frequently used to activate aromatic nucleophilic substitutions in both the homocyclic and heterocyclic aromatic series231, and consequently to stabilize the -complexes.

Among the reported -complexes, there are several involving amines in both zwitterionic (98) or anionic (99) forms230,232. The equilibrium between 98 and 99 is considered to shift towards the right owing to the presence of a base which acts as a catalyst, as shown in Scheme 11231 233, where B may be the same reacting amine, or another (non-nucleophilc) added base, such as a tertiary amine.

		+					NR1R2
	H	NHR1 R2				H
O2 N		NO2			O2 N		NO2
	−	+ B				−		+ BH+
	NO2					NO2
	(98)				(99)
R1 = H, R2 = alkyl, aryl
R1, R2	= alkyl
			SCHEME 11
When the	nucleophilic centre		is in		the starting		substrate, as in the case
of N,N0-dimethyl-N-picrylethylendiamine					(100), equilibrium 25			affords protonated
or unprotonated spiro-zwitterionic adduct 101 containing a diazolidine ring234.
			CH3
	CH3	NCH2 CH2 N				CH3 N	N	CH3
			H
	O2 N	NO2				O2 N		NO2
				− H +			−	(25)
		NO2					NO2
		(100)					(101)

Compound 102 is formed from 100 by a slow (but irreversible) process which competes with the formation of 101. 102 arises from the usual displacement of the nitro group by the second amino group.

In some unusual cases, the amino group bonded to activated substrates may be replaced by primary amines, as in the case of the reaction of 2,4-dinitronaphthalene derivatives235, illustrated by Scheme 12.

458	Luciano Forlani
R1	R2
	N			NHR
	NO2			NO2
	+ NH2 R			+ NHR1R2
	NO2			NO2
R1 = R2 = methyl, ethyl; R1 = n-butyl, R2 = methyl;
NR1 R2 = piperidino, R= methyl, ethyl, i-propyl
	SCHEME 12
	CH3
		N
	O2 N			N

CH3

NO2

(102)

In the case of N-(2,4-dinitrophenyl)piperidine, N-(2,4-dinitrophenyl)morpholine236, N-(2,4,6-trinitrophenyl)piperidine and N-(2,4,6-trinitrophenyl)morpholine237 the amino group is the leaving group with hydroxide ions, as shown by reaction 26. L (the leaving group) may be an N-piperidino or an N-morpholino group. These reactions are complicated by the formation of adducts in the unsubstituted positions of the phenyl ring.

	L			−O
O2 N	NO2	O2 N		NO2
	+ −OH			+ HL (26)
	NO2			NO2

The same displacement occurs in the hydrolysis of picrylimidazole238 (103). 103 reacts with n-butylamine in water239 to yield picric acid (from the reaction with water) and N-n- butyl-2,4,6-trinitroaniline. The dependence of kobs values (s 1 mol 1 dm3) on pH values indicates the presence (and importance) of equilibrium 27 on the reaction pathway of the

10. Hydrogen bonding and complex formation		459
	N
	N
O2 N	NO2

NO2

(103)

substitution reaction of the imidazole ring, which is the leaving group.

N			N
	H + H			H
N	N C4 H9		N	N C4 H9
O2 N	NO2	+	O2 N	NO2	(27)
	− H
	−			−
	NO2			NO2

Tertiary amines too are found to produce -complexes 104 with 1,3,5-trinitrobenzene and related compounds. Complexes 104 are studied by spectroscopic and kinetic methods. In the case of 1,8-diazabicyclo-[5,4,0]-undec-7-ene (DBU) and 1,5- diazabicyclo[4,3,0]non-5-ene (DBN), the delocalization of the positive charge of the nucleophile moiety in the usaturated system of DBN and DBU enhances the stability of the zwitterionic complex 105 and, of course, the nucleophilic power of these bases, as well as their basicity244.

For the system 1,3,5-trinitrobenzene/DBU, in toluene245, the formation of a molecular complex (probably donor acceptor-like) precedes the formation of 105 and produces a

H	+
	NR1R2 R3
O2 N	NO2
	−

NO2

(104)

NR1R2R3 D 1,8-diazabicyclo[2,2,2]octane240, quinuclidine240, 1,5-

diazabicyclo[4,3,0]non-5-ene240, 1,8-diazabicyclo[5,4,0]undec-7- ene240 242, pentaisopropylguanidine243

460	Luciano Forlani

N

+

H N

O2 N

NO2

−

NO2

(105)

particular kinetic feature (see Section VI.B). When 2,4,6-trinitrotoluene or other 1-alkyl- 2,4,6-trinitrobenzenes react with DBU or N,N,N0,N0 -tetramethylguanidine246, the proton abstraction from the side chain247 competes with zwitterionic complex formation248. In the case of the equilibrium between 1-nitro-1-(4-nitrophenyl)alkanes and DBU in acetonitrile249, the equilibrium of Scheme 13 of ion-pair formation 106 is followed by dissociation to free ions 107, as indicated by kinetic investigations.

	R							−
						R
O2 N	C H + DBU			O2 N		C		DBUH+
	NO2					NO2
			(106)
					R	−
	O2 N				C	+ DBUH+
					NO2

(107)

SCHEME 13

VI. NON-COVALENT INTERACTIONS BETWEEN AMINES AND NITRO

AROMATIC DERIVATIVES

In the literature, there are numerous reports regarding the interactions between amines and both electron and proton acceptors132, but less attention has been devoted to interactions between amines and aromatic electron acceptors, in particular when the substrate/amine system is a reacting system, as in the case of nucleophilic aromatic substitution (SNAr) reactions between amines and substrates activated by nitro or by other electron-withdrawing groups.

10. Hydrogen bonding and complex formation

461

A. Nature of the Complexes

The complexes involving molecules bearing the NH2, NHR groups are complicated by the possibility of the contemporaneous presence of different kinds of interactions, in particular electron donor acceptor and proton donor acceptor interactions. The complex 108 between diphenylamine and 2,4-dinitrotoluene250 is considered a charge transfer complex with a probable relevant hydrogen bonding interaction, as indicated by 1H NMR spectroscopic data251.

N

H

−O	+
	N	CH3
O
		NO2

(108)

In principle, aliphatic amines may interact as n electron donor molecules towards electron acceptor centres such as aromatic substrates, both homocyclic and heterocyclic, containing electron-withdrawing groups, usually nitro groups. These interactions are mainly electron donor acceptor (EDA) interactions, in which aromatic amines are considered n or/and electron donors.

In addition, there are two main kinds of hydrogen bonding interactions involving amines.

(i)Amines may interact with proton donors. Proton is a particular electron acceptor centre: the unshared electron pair of the nitrogen atom is responsible both for the strength of the hydrogen bond as well as for the basicity of the NR2 group (see Section II.B).

(ii)Protic amines, such as primary and secondary amines, are proton donor molecules in hydrogen bonding towards proton acceptor centres, as illustrated in 108.

A general method to investigate the presence of solute/solute interactions is based on the spectroscopic differences of the mixtures (i.e. of amines and of potential acceptors) from the solutions of the separate substances. When appropriate solutions of amines are mixed with solutions of electron acceptor substrates, an instantaneous colour development may be observed even if no reaction products are formed.

The extra absorbances observed by UV/VIS spectroscopy are due to equilibria which are quickly established after mixing, with the formation of non-covalent bonds and without (or before) reactions with covalent bond formations between the partners. The acidification of donor acceptor mixtures, return the absorbance values of the spectrum to the values of the separate compounds.

Electron donor acceptor complexes between amines and nitroarenes or other arenes bearing electron-withdrawing groups have been known for a long time. A crystalline solid complex between p-iodoaniline and 1,3,5-trinitrobenzene was investigated in 1943

by X-ray diffraction252. One of the interactions between these substances is between the amino group and the oxygen atoms of nitro groups, probably by weak hydrogen bonds.

The reactions between 2,4-dinitrohalogenobenzenes and X-substituted anilines in benzene produce the usual diphenylamines 109 by nucleophilic aromatic substitution reaction 28. The inspection of reaction mixtures by UV/VIS spectroscopy at ‘zero reaction

462	Luciano Forlani

time’ (i.e. before the formation of product of the substitution reactions 109) reveals253 the presence of an interaction between the substrate and the amine which is probably an electron donor acceptor complex with an absorption band in the visible region of the spectrum, as required by charge-transfer complexes. These interactions are indicated by equilibrium 29 and were studied quantitatively by Benesi Hildebrand treatment of UV/VIS spectroscopic data132 and confirmed by 1H NMR spectral data253.

		X
O2 N	L + H2 N
	NO2
	H	X	(28)
O2 N	N	+ HL
	NO2
L = F, Cl, Br.	(109)
		X
O2 N	L + H2 N	K c	MOLECULAR COMPLEX

(29)

NO2

L = F, Cl, Br.

The equilibrium 29 may refer to a single EDA complex; however, this is a simplification because several kinds of interaction may be operating: therefore the term ‘molecular complex’ may be more appropriate that the term ‘EDA complex’.

Some Kc values are reported in Table 1. In some cases, the Kc values reported agree with Kc values calculated from kinetic data obtained for reactions like 28, shown in Table 1. From these data, it is hard to distinguish whether the electronic interactions are n ! or ! .

A linear correlation between log Kc of equilibrium 29 and the x values of the Hammett equation gives a negative value 2.8 š 0.3 , which agrees with the electron donor ability of the amino group of substituted anilines253.

Complexation of electron acceptor substrates with aromatic solvents by electron donor acceptor complexes is an important way of understanding solvation and reactivity behaviours.

1-Fluoro-2,4-dinitrobenzene (FDNB) interacts with benzene253 (or other electron donor solvents) by equilibrium 30 (Kc D 0.018 mol 1 dm3 in CDCl3).

ArF	C	ArH		ArF ArH	30
				Ð

Apparent stability constants for interactions between 1-chloro-2,4-dinitrobenzene and benzene or mesitylene were found to be 0.76 and 0.96 (mol 1 dm3) respectively, and between 4-chloro-3-nitrotrifluoromethylbenzene and benzene or mesitylene the values were 0.96