The Open Bioactive Compounds Journal




ISSN: 1874-8473 ― Volume 7, 2019

Hydrazonoyl Halides: Their Versatile Biological Activities



Ahmad S.Shawalia, *, Nevien A.Samyb
a Department of Chemistry, Faculty of Science, University of Cairo, Giza, Egypt;
b Department of Dermatology, National Institute of Laser Enhanced Sciences, University of Cairo, Giza, Egypt

Abstract

The various biological activities namely anthelmintic, antiarthropodal, antiviral, antimicrobial, herbicidal, antisarcoptic, acaricidal, insecticidal and miticidal activities exhibited by the hydrazonoyl halides are surveyed. Also, the uses of such halides as pesticides, weed controlling and antihypertensive agents as well as lipoxygenase and cyclo-oxygenase inhibitors are presented. Furthermore, their contact dermatitis and phytotoxicity effects are pointed out in addition to their metabolic fate.

Keywords : Hydrazonoyl halides, biological activities, metabolism.


Article Information


Identifiers and Pagination:

Year: 2009
Volume: 2
First Page: 8
Last Page: 16
Publisher Id: TOBCJ-2-8
DOI: 10.2174/1874847300902010008

Article History:

Received Date: 21/10/2008
Revision Received Date: 10/11/2008
Acceptance Date: 2/12/2008
Electronic publication date: 29/1/2009
Collection year: 2009

Article Metrics:

CrossRef Citations:
0

Total Statistics:

Full-Text HTML Views: 1639
Abstract HTML Views: 1063
PDF Downloads: 236
ePub Downloads: 134
Total Views/Downloads: 3072

Unique Statistics:

Full-Text HTML Views: 687
Abstract HTML Views: 627
PDF Downloads: 163
ePub Downloads: 99
Total Views/Downloads: 1576
Geographical View

© Shawali and Samy; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.


* Address correspondence to this author at the Department of Chemistry, Faculty of Science, University of Cairo, Giza, Egypt; E-mail: as_shawali@yahoo.com





1. INTRODUCTION

Hydrazonoyl halides 1 are those compounds which have the characteristic function -C(X):NNH-, where X is a halogen group (e.g. Br or Cl). They are structurally related to hydrazonoic acids 2 in the same way as the imidoyl halides 3 are related to imidoic acids 4.

1, RC(X)=NNHR’ 2, RC(OH)=NNHR'

3, RC(X)=NR' 4, RC(OH)=NR'.

The first hydrazonoyl halide was described by Fisher shortly before the begining of the 20th century [1Fisher E. Uber die hydrazinverbindung Liebigs Ann 1882; 212: 316-40.
[http://dx.doi.org/10.1002/jlac.18822120303]
]. Since that time an increasing flow of work has appeared on the chemistry of such a class of compounds so that the output of published work recorded a peak of 261 papers and 53 patents in the eighties. The interest in the chemistry of such halides is a consequence of the fact that they undergo a wide variety of reactions which provide routes to a myriad of both heterocyclic and acyclic compounds. In addition, diverse biological activities such as anthelmintic, antiviral, antiarthropodal, antimicrobial, fungicidal, herbicidal, antisarcoptic, insecticidal, pesticidal, acaricidal, miticidal, etc., have been found to be associated with hydrazonoyl halides. In recent years, interest in the chemistry of this class of compounds has been renewed because of the development of novel synthetic routes and their use as versatile synthons for other compounds that found many applications in both industrial and pharmaceutical fields. At present there are ten review articles by Shawali et al. [2Shawali A S, Parkanyi C. Hydrazidoyl halides in synthesis of heterocycles J Heterocycl Chem 1980; 17: 833-54.
[http://dx.doi.org/10.1002/jhet.5570170501]
-1Fisher E. Uber die hydrazinverbindung Liebigs Ann 1882; 212: 316-40.
[http://dx.doi.org/10.1002/jlac.18822120303]
] covering the various aspects of the chemistry of such halides and their utility in synthesis of heterocycles, Another review by Butler and Scott outlined intermolecular and intramolecular substitution reactions of such halides [12Butler RN, Scott FL. Versatile reactive intermediates.Hydrazidic halides Chem Ind (London) 1970 1216-1221 Chem Abstr 1970; 73: 109379.]. In addition, an earlier summary dealing with the chemistry of these compounds had been incorporated by Ulrich in his review of imidoyl chlorides that appeared in 1968 [13Ulrich H. The Chemistry of Imidoyl Chlorides Hydrazidoyl halides 1968; Chapter 7: 173-89.]. No comprehensive review on the various biological activities of hydrazonoyl halides has appeared hitherto.

The goal of the present review is to bring to the reader’s attention the scope of the biological activities of hydrazonoyl halides. The literature is covered from 1968 up to mid of 2008. During this period more than 1750 articles and 150 patents making reference to the chemistry and applications of the title compounds have appeared. We hope that this review will stimulate the interest of both chemists and biologists in exploring further the chemistry of such compounds and their biological applications.

2. NOMENCLATURE

The nomenclature applied to hydrazonoyl halides has over the years been somewhat confusing. For example, the following compound was cited in literature under the names indicated below:

C6H5C(Cl)=NNHC6H5

α-Chlorobenzylidene phenylhydrazine

Benzoyl chloride N-phenylhydrazone

N-Phenyl benzhydrazidoyl chloride

α-Chlorobenzaldehyde phenylhydrazone

N-Phenyl benzenecarbohydrazonoyl chloride.

In this review, it is intended to adhere to the nomenclature rules adopted by Chemical Abstracts. According to the latter, the name of a given hydrazonoyl halide, in the absence of higher function or more preferred compound class, is derived from the parent acid by functional group replacement nomenclature. The suffixes appended to the names of molecular skeletons of carboxylic acid, hydrazonoic acid and the corresponding hydrazonoyl halide are as follows:



To illustrate the application of these rules of nomenclature, the following examples are given:

 CH3C(Br)=NNHC6H4NO2-4

 N-(4-Nitrophenyl) ethanehydrazonoyl bromide

 4-BrC6H4C(Cl)=NNHC6H5

 N-Phenyl 4-bromobenzenecarbohydrazonoyl chloride

 CH3COC(Cl)=NNHCOC6H5

 N-Benzoyl 2-oxopropanehydrazonoyl chloride

N-Phenyl furan-2-carbohydrazonoyl chloride

In the presence of other groups that have priority to hydrazonoic acid group, the hydrazonoyl halide is named as a hydrazono derivative of the parent compound and this is illustrated by the following two examples.

HOOC-C(Cl)=NNHC6H5

N-Phenylhydrazono-chloroacetic acid

C2H5OCO-C(Br)=NNHCONH2

Ethyl N-[(aminocarbonyl)hydrazono]bromoacetate

Also, when the hydrazonoyl halide residue (-C(X):NNH-) is a part of a more preferred class, it is named as halo derivative of the parent compound of such a class. For example, the halide (C6H5N=N-C(Cl)=NNHC6H5), as it belongs to the class of formazans (R-N=N-CH=NNHR') which is ranked highest of all nonfunctional nitrogen compounds, below imines but above nitrogen heterocycles, it is thus named as 3-chloro-1,5-diphenylformazan.

The various types of hydrazonoyl halides whose biological effects were explored are listed in Table 1.

Table 1


3. BIOLOGICAL ACTIVITIES

The patent literature contains a large number of hydrazonoyl halides that were reported to have various biological effects. Because of the diversity of structures covered, the discussion is presented according to the biological activity rather than chemical structure of the hydrazonoyl halide.

3.1 Contact Dermatitis

N-Phenyl benzenecarbohydrazonoyl chloride IA was reported to cause severe dermatitis in human [14Rothe A. Contact dermatitis from N-(a-chlorobenzylidene) phenylhydrazines Contact Dermatitis Chem Abstr 1988 108 162843c 1988; 18: 16-9.]. Out of 6 people, five-chemistry students were affected following a single contact. The clinical picture of the dermatitis was characterized by a biphasic course. Circumscribed slight lesions, developing usually within one day in directly affected areas were followed after 4 to 12 days by generalized widespread erythema and edema with papules and vesicles [14Rothe A. Contact dermatitis from N-(a-chlorobenzylidene) phenylhydrazines Contact Dermatitis Chem Abstr 1988 108 162843c 1988; 18: 16-9.].

IA, Ar-C(Cl)=NNHAr', Ar = Ar' =C6H5

3.2. Anthelmintic Activity

N-phenyl 4-methylbenzenecarbohydrazonoyl chloride IB was the first candidate of hydrazonoyl halides that proved effective against gastrointestinal nematodes and cestodes of ovines following a single oral dose of 30-50 mg/kg [15Kaugars G. Insecticidal acaricidal and anthelmintic benzoyl chloride phenylhydrazone derivatives Fr Demande, 2,103,533, May19, 1972; Chem Abstr 1973; 78: 29473c.-19Folz S D, Pax RA, Klei TR, et al. Development of a novel in vitro equine anthelmintic assay J Vet Pharmacol Ther 1988 11 177-182 Chem Abstr 1988; 109: 85599u.]. The sheep developed mild diarrhea and anorexia 10 days after treatment which lasted for 2-4 days, after which the sheep acquired their normal health. No ill signs were observed one week after treatment. N-(4-Chlorophenyl) 4-methoxybenzene-carbohydrazonoyl chloride IC has also been found to be an effective potent anthelmintic compound [20Perronnet J, Girault P, Grandadam JA. Anthelmintic N-(a-chloro-4'-methoxybenzylidene)-4-chlorophenylhydrazine FrDemade 275,566 Nov 30 1973 Chem Abstr 1974; 80: 70550e.].

IB 4-MeC6H4C(Cl)=NNHC6H5

IC 4-MeOC6H4C(Cl)=NNHC6H4Cl-4

In attempt to elucidate the relationship between structure and anthelmintic activity (SAR), Rector and coworkers [21Rector DL, Folz SD, Conklin RD, Nowakowski LH, Kaugars G. Structure-activity relationships in a broad-spectrum anthelmintic series.Acid chloride phenylhydraones. 1.Arylsubstitu-tions and chloride variations J Med Chem 1981; 24: 532-8.] prepared a series of thirty substituted N-phenyl benzenecarbohydrazonoyl chlorides I and evaluated their activity against three mouse helminths, Syphacia obvelata, Nematospiroides dubius and Hymenolepis nana. The dosage used was the highest dose (up to 7.5 mg / mouse / day) which did not elicit toxic effects on the mouse. The structural features required to give the superior anthelmintic activity in the series studied are meta- and/or para- halogen, alkoxy, alkyl, or alkylthio substituent(s) in the acid ring moiety. This is because any compound with an o-substituent in the acid ring residue was found to lack activity. Except for the N-(p-chlorophenyl), any substituent in the N-ring residue gave compounds with little or no activity. Multiple substitution in either ring decreases the activity. Also, the reported data revealed that there did not appear to be the detrimental ortho effect operating in the N-ring substitution as was apparent in the acid ring case.

The anthelmintic activity of other series of N-aryl and N-alkyl benzenecarbohydrazonoyl bromides IB (X= Br) and their chloride IB' (X = Cl) analogs were tested on mice infected with the nematode Nippostrongylus braziliensis [22Molodykh Zh V, Lisenkova AN, Buzykin BI, KitaevYu P. Athelmintic activity of some hydrazones Khim Farm Zh 1977 11 81-83 Chem Abstr 1977; 86: 165070m., 23Wing KD. Anthemintic N-alkyl-N,N'-diacylhydrazines: nonsteroidal ecdysone agonists S 524,333 Jun 13 1995 Chem Abstr 1995; 123: 313108e.]. The most active compound was N-(2-bromo-4-nitrophenyl) benzenecarbohdrazonoyl bromide IBc and the least active was N-(4-methylphenylsulfonyl) benzenecarbohydrazonoyl chloride IBd.

IBc C6H5C(Br)=NNHC6H3Br(NO2)-2,4

IBd C6H5C(Br)=NNHSO2C6H3Me-4

Other derivatives such as N-phenyl 4-methylthiobenzene-carbohydrazonoyl chloride IB and its N-(4-methylthio) benzenecarbohydrazonoyl chloride IC as well as N-(2,4-dibro-mophenyl) 4-methylthiobenzenecarbohydrazonoyl chloride ID were reported to be useful anthelmintics [24Kaugars G. Alkylthiobenzoic acid phenylhydrazides U S Patnt 414,932 Mar 29 1977 Chem Abstr 1977; 87: 5665b.].

IB-D ArC(Cl)=NNHAr'

Ar / Ar': B, 4-MeSC6H4 / Ph; C, Ph / 4-MeSC6H4;

D, 4-MeSC6H4 / 2,4-Br2C6H3

Also, N-phenyl derivatives of 4-methyl-, 4-nitro- and pentafluoro- benzenecarbohydrazonoyl chlorides as well as N-(2,4-dibromophenyl) benzenecarbohydrazonoyl chloride and N-(2,4,6-trichlorophenyl) 4-chlorobenzenecarbohydra-zonoyl chloride were reported to be useful anthelmintics [25Kaugars G, Germich EG. Benzoyl chloride phenylhydrazones against insects and mites US Patnt 417,540 Apr 12 1977 Chem Abstr 1977; 87: 22800.].

IB-D Ar-C(X)=NNHAr'

Ar / Ar': IB, C6H5 / 2,4-Br2C6H3;

ICa, 4-MeC6H4 / Ph; ICb, 4-O2NC6H4 / C6H5;

ICc, C6F5 / C6H5;

ID, 4-ClC6H4 / 2,4,6-Cl3C6H2

Moon et al.[26Moon MW, Kaugars G. Pyruvyl chloride phenylhydrazone anthemintic US Patnt 3 32,662 Jan 13 1976 Chem Abstr 1976; 84: 16001q.] synthesized a few N-aryl 2-oxopro-panehydrazonoyl chlorides VI in search of new anthelmintics. The results showed that N-(2,4-dichlorophenyl) derivative VIa (250 mg/Kg orally) was effective in sheep and N-(2-chloro-4-nitrophenyl) derivative VIb (30 mg/Kg orally) was effective in dogs.

VI CH3COC(Cl)=NNHAr

Ar: a, 2,4-Cl2C6H3; b, 2-Cl,4-O2NC6H3

Some N-aryl C-heteroarylmethanehydrazonoyl chlorides IV were also reported to be useful as anthelmintics [27Kaugars G. Halogen substituted pyridinealdehyde phenylhydrazones US Patnt 399,111, Oct 17 1972 Chem Abstr 1976; 84: 116001q., 28Kaugars G. Thiophenecarbonyl chloride phenylhydrazones US Patnt 309,703 May 07 1974 Chem Abstr 1976; 84: 116001q.].

IV Het-C(Cl)=NNHAr

Het: A, 2-furyl; B, 5-Br-2-(5-Br-furyl); C, 2-thienyl;

G, 3-pyridyl, M, 2-Cl-(pyrid-3-yl)

Ar: a, Ph; b, 2,4,6-Cl3C6H2

3.3. Antiarthropodal Activity

Several N-aryl benzenecarbohydrazonoyl chlorides I were reported active against anthropod pests and worms [29Kaugars G. Antianthropodal formulation U S Patnt 379,542 Apr 22 1975 Chem Abstr 1975; 83: 9553d.]. For example, N-(4-methylthiophenyl) benzenecarbohydrazonoyl chloride IB, N-phenyl 4-methylthiobenzenecar-bohydrazonoyl chloride ICa and its N-(2,4-dibromophenyl) analog ID [30Kaugars G. Alkylthio benzoyl chloride phenylhydrazones US Patnt 331,318 Jan 06 1976 Chem Abstr 1976; 84: 121494g.] and N-phenyl 3-trifluromethylbenzocar-bohydrazonoyl bromide ICb [31Kaugars G. a a a -Trifluoro-m-toluoyl chloride phenylhydrazone Ger Ofen 234,574 Jul 13 1972 Chem Abstr 1972; 76: 72258g.] were found useful for control of anthropodal pests such as insects, spiders, ticks and mites.

IB, Ph-C(Cl)=NNH C6H4-SMe-4

ICa, 4-MeSC6H4-C(Cl)=NNHPh

ICb, 3-F3CC6H4-C(Cl)=NNHPh

ID, 4-MeSC6H4-C(Cl)=NNH C6H3Br2-2,4

3.4. Antiviral Activity

A series of N-aryl 2-aryl-2-oxo-ethanehydrazonoyl bromides VII were tested as antiviral agents. The results showed that all compounds investigated succeeded to reduce the number of local lesions induced by tomato mosaic virus on detached Datura metel leaves [32Habib HM. The antiviral effect of some substituted a -keto hydrazidoyl chlorides Egypt J Microbiol 1987 22 129-142 Chem Abstr 1989; 110: 111581z.]. The order of activity was found to be Y/X: 4-Br / H = H / 4-Cl > H / 4-Me = 4-Me /H > H / 4-NO2. Analysis of the results obtained revealed that the activity of the studied compounds is more than that found for N-(4-nitrophenyl) benzenecarbohydrazonoyl bromide I. This result was considered to indicate that the presence of the 2-oxo group enhances the antiviral activity [32Habib HM. The antiviral effect of some substituted a -keto hydrazidoyl chlorides Egypt J Microbiol 1987 22 129-142 Chem Abstr 1989; 110: 111581z.].

VII YC6H4-CO-C(Br)=NNHC6H4X

Y/X: a, 4-Br / H; b, H / 4-Cl; c, H / 4-Me; d, 4-Me /H; e, H / 4-NO2

3.5. Antimicrobial Activity (Fungicidal and Bactericidal)

Twenty seven hydrazonoyl halides of types I, III and VI were examined for their toxicity, fungicidal, fungistatic and bactericidal activities. The fungicidal activity was found to depend on the acid residue R [33Molodykh ZhV, Buzykin BI, Kudrina MA, Sysoeva L. Antimicrobial activity of some arylhydrazones of acyl halides and arylhydrazides of carboxylic acids Khim Farm Zh 1980 14 33-42 Chem Abstr 1980; 93: 94943e.]. The toxicity of the studied halides I, III and VI in warm blooded animals decrease in the order of substituents H > 4-NO2 > 4-Cl > 4-Br > 2- or 3-NO2 [33Molodykh ZhV, Buzykin BI, Kudrina MA, Sysoeva L. Antimicrobial activity of some arylhydrazones of acyl halides and arylhydrazides of carboxylic acids Khim Farm Zh 1980 14 33-42 Chem Abstr 1980; 93: 94943e., 34Buzykin BI, Sysova LP, Molodykh ZhV, Kudrina MA, Neklesova ID, Kitaev Yu P. Acetyl chloride 4-bromophenyl- hydrazone possessing fungicidal and bactericidal properties USS 68610 Mar 07 1981 Chem Abstr 1981; 95: 42395z.].

I, YC6H4-C(X)=NNHC6H3R'R"-2,4

Y = H, 4-Br, 4-F, 4-Cl, 3-O2N, 4-O2N; X = Cl, Br

III, R-C(X)=NNHC6H3R'R"-2,4

R: Me, Et, Pr; X: Cl, Br

VI, MeCO-C(Cl)=NNHC6H3R'R"-2,4

R' = H, Br, O2N; R" = H, Br, Cl, O2N, H2NSO2

Dubenko et al. [35Dubenko RG, Granin EF, Konysheva VD, Gorbenko EF, Bazavova MI, Pel'kis PS. Fungicidal properties of arylhydazones of glyoxalic acid substituted derivatives Fiziol Akt Veshchestva 1981 13 33-37 Chem Abstr 1982; 96: 99275k.] reported that some N-aryl derivatives of, 2-oxo-2-phenylethanehydrazonoyl chlorides VII, 2-amino-2-oxoethanehydrazonoyl chlorides IX and cyanomethanehydrazonoyl chlorides XIII showed activity against wheat stem rust, phytophora infection of tomatoes and cucumber powdery mildew. Both systemic and contact activities were reported. Activities of these compounds were correlated with their structure.

VII PhCO-C(Cl)=NNHC6H4X

IX ArNHCO-C(Cl)=NNHC6H4X

XIII NC-C(Cl)=NNHC6H4X

X: a, H; b, Cl; c, Br; d, I; e, O2N; f, AcNHSO2; g, EtOCO

Also some N-aryl 2-oxopropanehydrazonoylchlorides VI were reported to be useful fungicides [36Draber W, Buechel KH, Hammann I, Frohberger PE. Pyruvamide 1-(phenylhydrazones) Ger Ofen 233,997 Oct 05 1972 Chem Abstr 1973; 78: 15844n.].

VI, CH3COC(Cl)=NNHAr; Ar = RR'C6H3,

R = H, 2-Cl, 2-Me, 3-F3C

R' = H, 2-, 3-, 4-Cl, 5-F3C, 6-Me, 4-O2N

3.6. Phytotoxicity Activity

Kukota et al. [37Kukota SN, Borisenko VP, Bodnar VN, Zhuravskaya NI, Lozinskii MO. Synthsis and phytotoxicity of arylhydrazones of substituted pyruvic and a,ß-dioxobutyric acids Fiziol Akt Veshchestva 1978 10 32-36 Chem Abstr 1979; 90: 6212a.] tested fifteen N-(4-substituted phenyl) 3-bromo-2-oxopropanehydrazonoyl bromides VI and their 3-pyridinio bromide analogs IV as plant growth regulators at 0.01, 0.001 and 0.0001 %. The N-(4-methylphenyl)-, N-(4-chlorophenyl)- and N-(4-nitrophenyl)- derivatives depressed the growth of roots, stalks and leaves of lettuce and Oats.

VI, BrCH2COC(Cl)=NNHC6H4X

IV, [C5H5N+-C(Cl)=NNH C6H4X] Br-

X = 4-Me, 4-Cl, 4-O2N

3.7. Herbicidal Activity

Kaugars and his coworkers [27Kaugars G. Halogen substituted pyridinealdehyde phenylhydrazones US Patnt 399,111, Oct 17 1972 Chem Abstr 1976; 84: 116001q., 28Kaugars G. Thiophenecarbonyl chloride phenylhydrazones US Patnt 309,703 May 07 1974 Chem Abstr 1976; 84: 116001q.] prepared two series of N-aryl hetarylcarbohydrazonoyl chlorides IV and indicated that they are primarily useful as herbicides.

IV, Het-C(Cl)=NNHAr

Het: A, 2-furyl, B, 2-(5-Br-furyl), C, 2-thienyl, D, 2-picolinyl,

E, nicotinyl, F, 4-pyridinyl

Ar = XC6H5-n; X: a, H, b, 2,4,6-Cl3

N-(2,4-Dichlorophenyl) propanehydrazonoyl chloride IIIa and its N-(2,4,6-trichlorophenyl) analog IIIb were reported to have, at 1Ib/acre, postemergence contact herbicidal activity against bread leaf weeds, and to a lesser degree against grasses [38Moon M W, Friedman A R, Steinhards A. Herbicidal activityof phenylhydrazones and related azo compounds J Agric Food Chem 1972 20 1187-1190 Chem Abstr 1973; 78: 39208j.]. Some other N-aryl (C2-4)alkane-hydrazonoyl chlorides IIIA were reported to be useful herbicides [39Kaugars G. Combating insects and mites using alkanoyl chloride phenylhydrazones U S Patnt 345,215, Jul 10 1973 Chem Abstr 1973; 79: 78412m.].

CH3CH2-C(Cl)=NNHAr

III, Ar: a, 2,4-Cl2C6H3; b, 2,4,6-Cl3C6H2

IIIA, R-C(Cl)=NNHC6H5-nXn

R = C2-4; X = H, 4-Cl, 2,4-Cl2, 4-Me

Also a series of N-aryl cyanomethanehdrazonoyl chlorides XIII was prepared and tested on lettuce and Oat cultured on agar [40Karabanov Yu V, Gershkovich A A, Lozinskii M O, Borisenko V P, Samolyuk L. Herbicidal activity of 1-halo-1-cyano-3-aryl-2,3-diaza-1-propenes Fiziol Akt Veshchestva 1974 6, 64-67 Chem Abstr 1975; 82: 165760d.]. Of these hydrazonoyl chlorides only N-(4-nitrophenyl)- and N-(2,4-dichlorophenyl)- derivatives XIIIa and XIIIb were reported to be the most effective herbicides, decreasing germination and inhibiting growth to the highest extent. Both compounds acted as herbicides at 0.0001% [40Karabanov Yu V, Gershkovich A A, Lozinskii M O, Borisenko V P, Samolyuk L. Herbicidal activity of 1-halo-1-cyano-3-aryl-2,3-diaza-1-propenes Fiziol Akt Veshchestva 1974 6, 64-67 Chem Abstr 1975; 82: 165760d.]. N-(4-methylphenyl) cyanomethanehydrazonoyl chloride XIIIc at 0.0001% was reported to stimulate lettuce stem growth to the highest extent [40Karabanov Yu V, Gershkovich A A, Lozinskii M O, Borisenko V P, Samolyuk L. Herbicidal activity of 1-halo-1-cyano-3-aryl-2,3-diaza-1-propenes Fiziol Akt Veshchestva 1974 6, 64-67 Chem Abstr 1975; 82: 165760d.].

XIII, NC-C(Cl)=NNHAr

Ar: a, 4-O2NC6H2; b, 2,4-Cl2C6H3; c, 4-MeC6H4

Twelve N-aryl alkanehydrazonoyl chlorides IIIA were also prepared and found useful as herbicides (e.g., against crabgrass, wild oats, yellow foxtail) [41Kaugars G. Weed control with substituted phenylhydrazones U S Patnt 3 70,505, Mar 11 1975 Chem Abstr 1975; 83: 78891z.]. N-(4-Chloro-phenyl) 2,2-dimethylpropanehydrazonoyl chloride IIIB was reported to exhibit the highest activity against crabgrass, wild oats and yellow foxtail [41Kaugars G. Weed control with substituted phenylhydrazones U S Patnt 3 70,505, Mar 11 1975 Chem Abstr 1975; 83: 78891z.].

IIIA, R-CX)=NNHAr, R = Et, Pr, Me2CH, Me3C

IIIB, (CH3)3C-C(Cl)=NNHC6H4Cl-4

Some other derivatives of N-Phenyl benzenecarbohydrazonoyl chloride I were prepared as useful herbicides [42Andree R, Luerssen K, Santel H J, et al. Preparation of benzhydrazidoyl halides as acaricides, insecticides and herbicides Ger OffenDE 400,591, Jul 15 1993; Chem Abstr 1993; 119: 133475f.]

I, XC6H4-C(Cl)=NNHC6H4Cl-2

X: alkyl, alkoxy, alkenyl, halo, CN, O2N

3.8. Antisarcoptic Activity

Strinadkin et al. [43Strinadkin P S, Buzykin B I, Gazetdinova N G, Sysoeva L P, Kitaev Yu P. Antisarcoptic activity of arylhydrazones of chloro(bromo)carboxylic acid anhydrides Fiziol Akt Veshchestva 1981765-67 Chem Abstr 1985; 103: 208842d.] reported that of the twenty derivatives of N-aryl substituted benzenecarbohydrazonoyl-, eth-anehydrazonoyl-, 3-pyridinecarbohydrazonoyl-, 4-pyridine-carbohydrazonoyl- and 2-oxopropane-hydrazonoyl halides I-VI, respectively N-(2-nitrophenyl) benzene-carbohydra-zonoyl chloride was the most effective as antisarcoptic. A single application (5-10 ml 0.05%) of such a chloride or 0.5% of N-(2,4-dibromophenyl) benzenecarbohydrazonoyl bromide I to rabbit's ears eradicated psoroptosis within 10 days.

I Ar-C(Cl)=NNHAr'

III CH3-C(Cl)=NNHAr

IV Het-C(Cl)=NNHAr

VI CH3CO-C(Cl)=NNHAr

Het: F, 4-Pyridyl G, 3-Pyridyl

Also, Buzykin et al. [44Buzykin B I, Strinadkin P S, Zabolotnyi K F, et al. Antisarcoptic activity and allergenic properties of arylhydrazones of acylhalogeniddes Fizio Akt Veshchestva 1990 22 20-24 Chem Abstr 1991; 115: 177380t.] studied the antisarcoptic activity of twenty one hydrazonoyl halides of types I, III and X against Psoroptos Cuniculi and reported that the activity of I increases with increasing electron donating properties of the substituent in the Ar’ group, 4-MeO > 4-Cl > 4-Br > 3-NO2 > 4-NO2 > 2-NO2. They found that one application of 0.05% of a 13.6% compositon emulsion of N-phenyl benzenecarbohydrazonoyl chloride Ia to rabbit ears 100% eradicated psoroptosis. LD50 of hydrazonoyl halides studied for mice was 0.4-13.5 ml/kg vc. a 0.5-10.9M LC50 for P. Cuniculi. Both N-(2-nitrophenyl) benzenecarbohydrazonoyl chloride Iband N-phenyl 4-bromobenzenecarbohydrazonoyl chloride Ic were strongly allergenic to rabbits.

I, Ar-C(Cl)=NNHAr'

Ar' = XC6H4; X = 4-MeO, 4-Cl, 4-Br, 3-NO2, 4-NO2, 2-NO2

III, HC(Cl)=NNHAr'

X, (RO)2PO-C(Cl)=NNHAr'

3.9. Acaricidal and Miticidal Activity

N-Phenyl 4-methylthiobenzenecarbohydrazonoyl chloride Ia, N-(4-methylthiophenyl) benzenecarbohydrazonoyl chloride Ib and N-(2,4-dibromophenyl) 4-methylthioben-zenecarbohydrazonoyl chloride Ic [24Kaugars G. Alkylthiobenzoic acid phenylhydrazides U S Patnt 414,932 Mar 29 1977 Chem Abstr 1977; 87: 5665b., 25Kaugars G, Germich EG. Benzoyl chloride phenylhydrazones against insects and mites US Patnt 417,540 Apr 12 1977 Chem Abstr 1977; 87: 22800., 45Hatzinikolis E N, Koutepas N G. Evaluation of acaricides against Tetranychus urticae koch (Acarina, Tetranychidae) Nea Agrotike Epiteor 1977 31 49-51 Chem Abstr 1977; 87: 48889v.] and N-(4-chlorophenyl) 3,3-dimethyl-2-oxopropanehydrazonoyl chloride VI [41Kaugars G. Weed control with substituted phenylhydrazones U S Patnt 3 70,505, Mar 11 1975 Chem Abstr 1975; 83: 78891z.] were reported to be useful as acaricides and miticides.

I Ar-C(Cl)=NNHAr'

VI Me3CCOC(Cl)=NNHC6H4Cl-4

Ar / Ar': a, H/ 4-MeSC6H4; b, 4-MeSC6H4 / H;

c, 4-MeSC6H4/2,4-Br2C6H3

Kaugars et al. [46Kaugars G, Germich E G. Benzoyl chloride phenylhydrazones as pesticides Ger Ofen 126 366 Jan 15 1970 Chem Abstr 1970; 72: 100323n., 47Kaugars G, Gemrich E G, Rizzo V L. Miticidal activity of benzoyl chloride phenylhydrazones J Agric Food Chem197321 647-650 Chem Abstr 1973; 79: 112347f.] screened seventy N-aryl benzenecarbohydrazonoyl chlorides I for miticidal activity and repellency, using the two-spotted spider miet. They reported that such activities depend to a large extent on the nature, position and number of substituents in either or both aromatic rings, the highest activity was shown by N-(2-chlorophenyl) derivatives of 4-chloro- and 4-bromo-benzenecarbohyd-razonoyl chlorides Ia,b and N-(3-trifluoromethyl) benzenecarbohydrazonoyl chloride Ic. Replacement of the hydrazone NH by N(CH3) decreased the activity [48Moon MW. The chlorination of aldehyde and ketone phenylhydrazones J Org Chem 1972; 37: 383-5.].

I Ar-C(Cl)=NNHAr'

Ar / Ar': a, 4-ClC6H4 / 2-ClC6H4H; b, 4-BrC6H4/ 2-ClC6H4; c, C6H5 / 3-F3CC6H4

Kaugers and Germrich [15Kaugars G. Insecticidal acaricidal and anthelmintic benzoyl chloride phenylhydrazone derivatives Fr Demande, 2,103,533, May19, 1972; Chem Abstr 1973; 78: 29473c., 49Kaugars G, Germich E G. Insecticidal and miticidal benzoyl chloride phenylhydrazones Ger Ofen 109,868 Oct 16 1969 Chem Abstr 1970; 72: 54978e.] indicated that N-aryl benzene-carbohydrazonoyl chlorides I are highly active as miticides. One of these compounds, namely N-(2,4,6-trichlorophenyl) benzenecarbohydrazonoyl chloride IB, has been extensively field tested and has been assigned the trade mark Banomite. The latter was reported to decrease significantly Texas citrus mite (Euteranychus banksi) eggs and adults [50Dean H A. Citrus mite control with certain acaricides J Rio Grande Val Hortic Soc 1974 28 122-130 Chem Abstr 1975; 83: 159083q.]. Other derivatives of benzenecarbohydrazonoyl chloride having methylthio group in either the C-phenyl or the N-phenyl groups were reported to be useful as acaricides [25Kaugars G, Germich EG. Benzoyl chloride phenylhydrazones against insects and mites US Patnt 417,540 Apr 12 1977 Chem Abstr 1977; 87: 22800.].

IB Ph-C(Cl)=NNHC6H2Cl3-2,4,6

Several other N-aryl alkanehydrazonoyl chlorides III were also reported to be useful as acaricides [39Kaugars G. Combating insects and mites using alkanoyl chloride phenylhydrazones U S Patnt 345,215, Jul 10 1973 Chem Abstr 1973; 79: 78412m., 51Boesch R. Phenylhydrazone derivatives Ger Ofen 226,783, Dec 13 1973 Chem Abstr 1974; 80: 70518a.].

III RC(Cl):NNHAr

R = Me, Et, n-Pr, i-Pr, t-Bu

Ar = 2,4-Cl2C6H3; 4-Cl,2-NO2C6H3, 2,4,6-Cl3C6H2

Also, N-phenyl methylthio-substituted benzenecarbohydrazonoyl chlorides IA,B were useful as acaricides [24Kaugars G. Alkylthiobenzoic acid phenylhydrazides U S Patnt 414,932 Mar 29 1977 Chem Abstr 1977; 87: 5665b., 52Kaugars G. Methylthio derivatives of benzoyl chloride phenylhydrazone Ger Ofen,134,482, Jan 27 1972; Chem Abstr 1972; 76: 112931e.].

IA,B RC6H4C(Cl):NNHC6H4R’

R/R’: 4-MeS / H, 4-Cl,2-MeS / H, H / 4-MeS, 4-MeS / 2,4-Br2

N-(2,4,6-Trichlorophenyl) benzenecarbohydrazonoyl chloride IB (banamite) was found more toxic (LC50 12 ppm) to the two spotted spider mite (Tetranychus urticae) than were nine of its potenrial metabolites. It inhibited rat liver monoamine oxidase at medium inhibitory concentrations (I50) of 4.7 x 10-5, 1.2 10-4 > 1.0 x10-3 and 1.4 x 10-3 M, respectively. Compounds relatively nontoxic to mites were usually ineffective monoamine oxidase inhibitors [53Knowles CO, Aziz SA. Toxicity of benzoyl chloride (2,4,6-trichlorophenyl)hydrazone (Banamite) and potential metabolites to twospotted spider mites and potency as inhibitors of rat liver monoamine oxidase Bull Environ Contam Toxicol 1974 12 158-160 Chem Abstr 1975; 82: 12245q.].

IB, Ph-C(Cl)=NNHC6H2Cl3-2,4,6

In another report [54Moon M W, Gemrich II E, Kaugers G G. Acaricidal activity of thioketal adducts of pyruvoyl chloride phenylhydrazone and related compounds J Agric Food Chem 1972 20 888-891 Chem Abstr 1972; 77: 9772n.], it was indicated that the acaricidal activity of the dithioketal of N-(2,4-dichlorophenyl) 2-oxopropanehydrazonoyl chlorides IVA against the 2-spotted spider mite (Tetranychus urticae) on lima bean plants depended on R group, and was in the descending order R: Me, Et, Ph, H and C5H11, that is the most active compound thus being the chloride IVAa. The thioketal IVAa was reported to be much more active than the corresponding ketal IVBa. Of the series IV, the most active halides were those having 3-F3C, 4-Brsubstituents in the N-aryl group.

Emmel et al. [55Emmel L, Henbach G. Acaricidal phenylhydrazones of dicarbonyl compounds Ger Ofen 217,761, Nov 04 1971 Chem Abstr 1972; 76: 33935f., 56Emmel L, Henbach G. Acaricidal phenylhydrazones of dicarbonyl compounds Ger Ofen 217,762 Apr 14 1971 Chem Abstr 1972; 76: 45971c.] prepared nineteen derivatives of ethyl N-arylhydrazonochloroacetates VIIIA and their methyl analogs VIIIB and used against red spiders on beans and apple trees. Also, N-(2,4-dibromophenyl) benzenehydrazonoyl bromide I was reported to be effective gave 100% control of houseflies in 48 h [57Noguchi T, Asada M, Ando M, Matsuda K, and Uchiyama Y. Insecticide-acaricide composition of the hydrazine series Japan at 702,326 Jan 24 1973 Chem Abstr 1974; 80: 11233f.].

VIII ROCOC(Cl):NNHC6H4X

I PhC(Br)=NNHC6H3Br2-2,4

R: A, Et; B, Me

X: H, 3-F3CO, 3-FCH2-CF2-O, 3-Cl2CH-CF2-O, 2-Me-4-Cl2CH-CF2-O

N-Phenyl and N-(2,4,6-trichlorophenyl) derivatives of 2-furyl-, 2-thienyl, 2- or 3-pyridyl- and 2-chloro-4-pyridyl- carbohydrazonoyl chlorides IV were also proved to have acaricidal activity [58Kaugars G. Pesticidal heterocyclic phenylhydrazone derivatives Ger Ofen 2 1972; 77: 5337q.].

IV Het-C(Cl)=NNHAr

Het: A, 2-furyl; B, 5-Br-2-furyl; C, 2-thienyl; G, 3-pyridyl;

H, 2-pyridyl; I, 2-Cl-4-pyridyl;

Ar: Ph, 2,4,6-Cl3C6H2

Also, eighteen N-aryl 2-oxopropanehydrazonoyl chlorides VI were prepared and found useful acaricides [36Draber W, Buechel KH, Hammann I, Frohberger PE. Pyruvamide 1-(phenylhydrazones) Ger Ofen 233,997 Oct 05 1972 Chem Abstr 1973; 78: 15844n.].

VI, CH3COC(Cl)=NNHC6H3RR'

R = H, 2-Cl, 2-Me, 2-Et R' = H, Me, Et

N-(4-Fluorophenyl) 2-chlorobenzenecarbohydrazonoyl chloride IC was prepared and reported to control totally Plutella maculipennis larvae on cabbage leaves when 0.01% concentration of it was used [42Andree R, Luerssen K, Santel H J, et al. Preparation of benzhydrazidoyl halides as acaricides, insecticides and herbicides Ger OffenDE 400,591, Jul 15 1993; Chem Abstr 1993; 119: 133475f.].

IC, 4-F-RnC6H4-nC(Cl)=NNHC6H5

R = alkyl, alkoxy, alkenyl, halo, CN, O2N; n = 0, 1-4

Also, thirty four alkanehydrazonoyl chlorides III, IV, IB and V were found useful as acaricides and insecticides [27Kaugars G. Halogen substituted pyridinealdehyde phenylhydrazones US Patnt 399,111, Oct 17 1972 Chem Abstr 1976; 84: 116001q., 28Kaugars G. Thiophenecarbonyl chloride phenylhydrazones US Patnt 309,703 May 07 1974 Chem Abstr 1976; 84: 116001q., 59Boesch R. Alkanoyl chlororide phenylhydrazones Ger Ofen 226,872 Dec 06 1973 Chem Abstr 1974; 80: 59659b.-64Draber W. a-Chloro- a -formylcarbonyl phenylhydrazones Ger Ofen 245,881 Mar 23 1972 Chem Abstr 1972; 77: 5147c.].

III, R-C(Cl)=NNHAr

R = CEmmel1-7 alkyl; Ar = 2-Cl-4-R”-5-R’C6H2: R’ = C1-4 alkoxy, CH2=CHCH2O, HC=CCH2O, or Cl, R” = Cl, Me or HC=CCH2O

IV, Het-C(Cl)=NNHAr;

Het: A, 2-furyl, B, 5-Bromo-2-furyl; C, 2-thienyl, D, picolinyl, E, nicotinyl; I, 2-Cl-4-pyridyl;

Ar: Ph, 2,4,6-Cl3C6H2

IB, PhC(Cl)=NNHC6H2Cl3-2,4,6

V, OCH-C(Cl)=NNHC6H3Cl2-3,4

3.10. Pesticides

N-Aryl 2-oxoethanehydrazonoyl chlorides V and their ketal and thioketal derivatives IV were reported to have strong pesticidal effects [65Draber W, Buechel K H, Hammann I, Unterstenhoefer G. Pesticidal glyoxyloyl chloride 1[(substituted phenyl)hydrazones] S Africa 9 0368, Jan 06 1970 Chem Abstr 1970; 73: 45130r.].

Kaugars et al. [46Kaugars G, Germich E G. Benzoyl chloride phenylhydrazones as pesticides Ger Ofen 126 366 Jan 15 1970 Chem Abstr 1970; 72: 100323n., 66Kaugars G, Germich E G. Benzoyl chloride phenylhydrazones as pesticides Ger Ofen 126,366, Jan 15 1970 Chem Abstr 1970; 72: 100323n.]reported that various substituted N-phenyl benzenecarbohydrazonoyl chlorides I have pesticidal properties.

I, Ar-C(Cl)=NNHAr'

N-Phenyl 3-trifluoromethylbenzenecarbohydrazonoyl chloride IAa was found by Kaugars et al. to be useful pesticide for controlling arthropods [31Kaugars G. a a a -Trifluoro-m-toluoyl chloride phenylhydrazone Ger Ofen 234,574 Jul 13 1972 Chem Abstr 1972; 76: 72258g.]. In addition, it was reported that N-phenyl 4-methylthiobenzenecarbohydrazonoyl chloride IAb and N-(4-methylthiophenyl) benzenecarbohydrazonoyl chloride IBa are useful for control of arthropodal pests such as insects, spiders, ticks and mites [63Hamed MS, Knowles CO. Penetration of pesticides into the bulb mite Rhizoglyphus echinopus Exp Appl Acarol19897 201-218 Chem Abstr 1989; 111: 169352n.].

IAa, 3-CF3C6H4-C(Cl)=NNHPh

IAb, 4-MeSC6H4-C(Cl)=NNHPh

IBa, Ph-C(Cl)=NNHC6H4SMe-4

3.11. Insecticidal Activity

Eighteen N-aryl 2-oxopropanehydrazonoyl chlorides VI were prepared and reported to be useful insecticides [36Draber W, Buechel KH, Hammann I, Frohberger PE. Pyruvamide 1-(phenylhydrazones) Ger Ofen 233,997 Oct 05 1972 Chem Abstr 1973; 78: 15844n.].

VI, MeCO-C(Cl)=NNHC6H3RR'

R: H, 2-Cl, 2-Me, 3-F3C

R': H, Me, Et

N-Phenyl and N-(2,4,6-trichlorophenyl) derivatives of 2-furan-, 2-thiophene-, 2-pyridine-, 3-pyridine- and 2-chloro-4-pyridine- carbohydrazonoyl chorides IV were found useful as insecticides because of their insect metamorphosis-inhibiting activity [27Kaugars G. Halogen substituted pyridinealdehyde phenylhydrazones US Patnt 399,111, Oct 17 1972 Chem Abstr 1976; 84: 116001q., 58Kaugars G. Pesticidal heterocyclic phenylhydrazone derivatives Ger Ofen 2 1972; 77: 5337q., 59Boesch R. Alkanoyl chlororide phenylhydrazones Ger Ofen 226,872 Dec 06 1973 Chem Abstr 1974; 80: 59659b.]. Tests on cabbage looper and three other insects were given.

IV Het-C(Cl)=NNHAr

Het: A, 2-furyl; C, 2-thienyl; G, 3-pyridyl; I, 2-Cl-4-pyridyl

Ar: Ph, 2,4,6-Cl3C6H2

N-Phenyl 2-substituted-propanehydrazonoyl chlorides of type IIIA and IIIB were also reported to be useful as insecticides because of their insect metamorphosis-inhibiting activity [41Kaugars G. Weed control with substituted phenylhydrazones U S Patnt 3 70,505, Mar 11 1975 Chem Abstr 1975; 83: 78891z., 67Moore JE. Insecticidal phenylhydrazone sulfides US Patent932,660 Jan 13 1976 Chem Abstr 1976; 84: 135317p.].

IIIA, Me-CH(SR)-C(Cl)=NNHPh

R = Me, Et, i-Pr, t-Bu, 4-ClC6H4

IIIB, R'C(Cl)=NNHAr

R': Et, Pr, Bu, i-Pr, t-Bu

Ar = XC6H4; X: H, 2-Me, 4-O2N, 4-Cl, 2,4-Cl2, 2,4,6-Cl3

In addition, substituted N-phenyl benzenecarbohydrazonoyl halides I and N-aryl (C2-4)-alkanehydrazonoyl chlorides III were reported to be useful as insecticides and miticides [25Kaugars G, Germich EG. Benzoyl chloride phenylhydrazones against insects and mites US Patnt 417,540 Apr 12 1977 Chem Abstr 1977; 87: 22800., 39Kaugars G. Combating insects and mites using alkanoyl chloride phenylhydrazones U S Patnt 345,215, Jul 10 1973 Chem Abstr 1973; 79: 78412m., 46Kaugars G, Germich E G. Benzoyl chloride phenylhydrazones as pesticides Ger Ofen 126 366 Jan 15 1970 Chem Abstr 1970; 72: 100323n., 49Kaugars G, Germich E G. Insecticidal and miticidal benzoyl chloride phenylhydrazones Ger Ofen 109,868 Oct 16 1969 Chem Abstr 1970; 72: 54978e., 66Kaugars G, Germich E G. Benzoyl chloride phenylhydrazones as pesticides Ger Ofen 126,366, Jan 15 1970 Chem Abstr 1970; 72: 100323n.]. For example N-(2,4-dibromophenyl) benzenecarbohydrazonoyl bromide 1 gave 100% control of houseflies in 48 h.

I, XC6H4-C(Cl)=NNHC6H4Y

X: H, 3-, 4-Me, 4-F, 2-, 3-, 4-Cl, 4-Br, 4-I, 2-Me, 4-i-Pr, 2,4-Cl2, 3,4-Cl2, 2,6-Cl2, 2,4-Cl(NO2), 3,4-Me(NO2), 3,4-Me2, 2,5-Me2, 3,5-Me2, F5

Y: 2,4-Br2, 2,5-Cl2. 2-Me, 4-Cl, 4-O2N,

III, R-C(Cl)=NNHAr

R = CnHn-1, n = 2,3,4

Furthermore, ketal, thioketal and dithioketal derivatives of N-aryl 2-oxopropanehydrazonoyl chlorides IVJ-L were reported to be useful insecticides for European red mites and double-spotted spider mites [65Draber W, Buechel K H, Hammann I, Unterstenhoefer G. Pesticidal glyoxyloyl chloride 1[(substituted phenyl)hydrazones] S Africa 9 0368, Jan 06 1970 Chem Abstr 1970; 73: 45130r., 68Moon MW. Insecticidal glyoxyloyl halide phenylhydrazones Ger Ofen 256,058 Jun 22 1972 Chem Abstr 1972; 77: 126648a.].

N-Phenyl and N-(4-methylthiophenyl) derivatives of benzenecarbohydrazonoyl chloride and its 2- and 4-methylthio analogs I were also reported to be useful as insecticides and acaricides [15Kaugars G. Insecticidal acaricidal and anthelmintic benzoyl chloride phenylhydrazone derivatives Fr Demande, 2,103,533, May19, 1972; Chem Abstr 1973; 78: 29473c., 24Kaugars G. Alkylthiobenzoic acid phenylhydrazides U S Patnt 414,932 Mar 29 1977 Chem Abstr 1977; 87: 5665b., 42Andree R, Luerssen K, Santel H J, et al. Preparation of benzhydrazidoyl halides as acaricides, insecticides and herbicides Ger OffenDE 400,591, Jul 15 1993; Chem Abstr 1993; 119: 133475f., 52Kaugars G. Methylthio derivatives of benzoyl chloride phenylhydrazone Ger Ofen,134,482, Jan 27 1972; Chem Abstr 1972; 76: 112931e.].

I, Ar-C(Cl)=NNHAr'

Ar = Ph, 2-MeSC6H4, 4-MeSC6H4

Ar' = Ph, 4-MeSC6H4

Kaugars prepared a series of N-aryl C-heteroaryl-methanehydrazonoyl chlorides IV and found that such halides are useful as insecticides [28Kaugars G. Thiophenecarbonyl chloride phenylhydrazones US Patnt 309,703 May 07 1974 Chem Abstr 1976; 84: 116001q., 60Kaugars G. Chloro substituted furfural phenylhydrazone US Patnt 321,261 Jun 28 1974 Chem Abstr 1976; 84: 116001q.].

IV, Het-C(Cl)=NNHC6H5-nCln

Het: A, 2-furyl, C, 2-thienyl, D, 2-pyridyl, G, 3-pyridyl, I, 4-pyridyl n = 1, 2, 3

Also, N-(2,4-dibromophenyl) benzenecarbohydrazonoyl bromide Ie was reported to be effective as insecticide as it gave 100% control of house flies in 48 hr [57Noguchi T, Asada M, Ando M, Matsuda K, and Uchiyama Y. Insecticide-acaricide composition of the hydrazine series Japan at 702,326 Jan 24 1973 Chem Abstr 1974; 80: 11233f.].

I, Ph-C(Br)=NNHC6H3Br2-2,4

In another report, it was indicated that the ketal derivatives of N-aryl 2-oxoethanehydrazonoyl chloride IV are effective insecticide [69Draber W, Buechel KH, Hammann I, Unterstenhofer G. Pesticidal a-halo-a-formyl carbonyl phenylhydrazones US Patent 366112Jan 18 1972 Chem Abstr 1972; 76: 140166c.].

Also, N-(4-chlorophenyl) 2,2-dimethylpropanehydrazonoyl chloride III was found useful as insecticide against housefly, cotton weevil and Mexaican beanbeetle [41Kaugars G. Weed control with substituted phenylhydrazones U S Patnt 3 70,505, Mar 11 1975 Chem Abstr 1975; 83: 78891z.].

III (CH3)3C-C(Cl)=NNHC6H4Cl-4

Also, several N-(2,4,6-trichlorophenyl) 2-alkylthioalkane-hydrazonoyl chlorides III were found to be useful as insecticides having morphogenic hormonal mimetic activity [70Moore JE. Insecticidal bisphenylhydrazone sulfides US Patnt 367,450 Feb 18 1975 Chem Abstr Chem Abstr 1975; 82: 139754k.-72Moore JE. Insecticidal bisphenylhydrazone sulfides S Patt 3n56,505 May 11 1976 Chem Abstr 1976; 85: 46220e.]. The bis-hydrazonoyl chlorides X1 were reported to have insecticidal activity against cabbage looper and alfafa weevil larvae [39Kaugars G. Combating insects and mites using alkanoyl chloride phenylhydrazones U S Patnt 345,215, Jul 10 1973 Chem Abstr 1973; 79: 78412m.].

The bis-hydrazonoyl chloride XII was reported to be useful insecticide for fertilizers [73Waheed A. Dow Chemical Co..4-\dichloro-N-[chloro-(2.4dichlorophenyl) methylene]benzenecarbohydrazonoyl chloride Jpn Kokai Tokkyo Koho 8098148 July 25 1980 Chem Abstr 1981; 94: 30332t.].

3.12. Weed Controlling Agents

Kaugars [41Kaugars G. Weed control with substituted phenylhydrazones U S Patnt 3 70,505, Mar 11 1975 Chem Abstr 1975; 83: 78891z.] indicated that tweleve N-aryl (C3-5)alkane hydrazonoyl chlorides III are useful as miticides, insecticides against housefly, cotton ball weevi, mexican bean beetle and as herbicides against crabgrass, wild oats and yellow foxtail.

III, R-C(Cl)=NNHAr; R = CnHn-1, n = 3,4, 5

In addition, Moon [74Moon MW. Controlling weeds with 1'-formyl-1'-halobenzenea- zomethanes U S Patnt 330,642, Aug 20 1974 Chem Abstr 1975; 82: 39582j.] prepared a series of 1'-formyl-4'-halobenzeneazamethanes VI and indicated that they are useful as weed controlling agents.

VI, RCOCR'(X)-N=N-Ar;

R = Lower alkyl, cycloalkyl, cycloalkoxy, haloalkyl, haloalkoxy

R' = Lower alkyl, cycloalkyl, Ph

X = Br, Cl

The hydrazonoyl chlorides VII, IX and XIII showed also activity against wheat stem rust, phytophora infection of tomatoes and cucumber powdery mildew [34Buzykin BI, Sysova LP, Molodykh ZhV, Kudrina MA, Neklesova ID, Kitaev Yu P. Acetyl chloride 4-bromophenyl- hydrazone possessing fungicidal and bactericidal properties USS 68610 Mar 07 1981 Chem Abstr 1981; 95: 42395z.].

VII, PhCO-C(Cl)=NNHAr IX, H2NCO-C(Cl)=NNHAr

XIII, NC -C(Cl)=NNHAr

In addition, the hydrazonoyl bromides VI were tested as plant growth regulators. They depressed the growth of roots, stalks and leaves of lettuce and oats [37Kukota SN, Borisenko VP, Bodnar VN, Zhuravskaya NI, Lozinskii MO. Synthsis and phytotoxicity of arylhydrazones of substituted pyruvic and a,ß-dioxobutyric acids Fiziol Akt Veshchestva 1978 10 32-36 Chem Abstr 1979; 90: 6212a.].

VI BrCH2COC(Br)=NNHC6H4X

X = 4-Me, 4-Cl, 4-NO2

3.13. Lipoxygenase and Cyclooxygenase Inhibitors

N-(2,4,6-Trichlorophenyl) benzenecarbohydrazonoyl chloride (banamite) IB was reported to be more toxic (LC50 12 ppm) to the twospotted spider mite (Tetranychus urticae) and it inhibits rat liver manoamine oxidase at median inhibitory concentrations [53Knowles CO, Aziz SA. Toxicity of benzoyl chloride (2,4,6-trichlorophenyl)hydrazone (Banamite) and potential metabolites to twospotted spider mites and potency as inhibitors of rat liver monoamine oxidase Bull Environ Contam Toxicol 1974 12 158-160 Chem Abstr 1975; 82: 12245q.]. Compounds relatively nontoxic to the mites were usually ineffective monoamine oxidase inhibtors

IB PhC(Cl)=NNHC6H2Cl3-2,4,6

4. METABOLIC FATE

The metabolism of the acaricide Banamite (N-(2,4,6-trichlorophenyl) benzenecarbohydrazonoyl chloride) was reported. It was indicated that it is metabolized slowly by the two-spotted spider mite (Tetranychus urticae). The major metabolites identified were benzaldehyde N-(2,4,6-trichloro-phenyl)hydrazone and benzoic N-(2,4,6-trichloro)hydrazide. Minor metabolites identified were 2,4,6-trichloroaniline, benzaldoxime, 2,4,6-trichlorophenylhydrazine and benzoic acid [61Knowles C O, Aziz S A. Metabolic fate of benzoyl chloride (2,4,6-trichlorophenyl)hydrazone (Banamite acaricide) in the twospoted spider mite J Econ Entomol 1974 67 574-576 Chem Abstr 1975; 82: 27198a.].

Also, the metabolism of one of the anthelmintic hydrazonoyl halides was studied in sheep and rats by Jaglan and coworkers [75Jaglan PS, Osline RE, Neff AW. Metabolic fate of p-toluoyl chloride phenylhydrazone (TCPH) in sheep.The nature of bound residues in erythrocytes J Agric Food Chem 1976 24 659-664 Chem Abstr 1976; 85: 116x.-79Jaglan PS. Identification of p-toluoyl chloride phenylhydrazone (TCPH) metabolites in the urine and feces of sheep J Agric Food Chem 19 208728a.]. For this purpose, the authors used 14C-(Phenylhydrazine) and 14C-(carboxy) labeled N-phenyl p-toluenecarbohydrazonoyl chloride (TCPH-I) and (TCPH-II), respectively. Ten days after a single oral therapeutic dose of 50 mg/kg, 93% of the radioactivity was recovered, 19% in urine and 74% in feces. The 14C residues were higher and persisted longer in blood and blood rich organs such as liver, lung, kidney and spleen compared to other tissues. The 14C residues were largely present in the hemoglobin. Such residues could neither be extracted into organic solvents nor separated from hemoglobin by dialysis, gel filtration or electrophoresis. Administration of TCPH-II resulted in a lower concentration of 14C in the blood. Most of the 14C residue in the blood was found in the plasma rather than in the erythrocytes which demonstrated that only the phenylhydrazine part of the molecule was bound to erythrocytes. Chromic acid oxidation of heme or globin from TCPH-I experiment produced 14C-benzoic acid. This finding was considered to indicate that the phenyl part of TCPH was bound to hemoglobin and that the carboxyl carbon of benzoic acid comes from heme or globin [75Jaglan PS, Osline RE, Neff AW. Metabolic fate of p-toluoyl chloride phenylhydrazone (TCPH) in sheep.The nature of bound residues in erythrocytes J Agric Food Chem 1976 24 659-664 Chem Abstr 1976; 85: 116x.].

In another report [76Jaglan PS, Gosline RE, Neff AW. Metabolic fate of p-toluoyl chloride phenylhydrazone (TCPH) in sheep The nature of bound residues in erythrocytes ACS Symp Ser 1976 178-179 Chem Abstr 1976; 85: 116489a.], it was indicated that both labels TCPH-I and TCPH-II cleared the gastrointestinal tract of treated sheep within ten days with the fecal radioactivity levels being 3-4 times greater than those for urine. Fractionation of blood from TCPH-I treated sheep showed that the majority of the radioactivity (66%) was associated with protein with erythrocytes having ten times the radioactivity of plasma. Although plasma levels were approximately equal for both TCPH-I and TCPH-II, 14C levels in erythrocytes from the form TCPH-I treatment were 15 times greater than with TCPH-II treatment suggesting cleavage of the molecule with only phenylhydrazine moiety being retained. Erythrocytic 14C was bound to hemoglobin [76Jaglan PS, Gosline RE, Neff AW. Metabolic fate of p-toluoyl chloride phenylhydrazone (TCPH) in sheep The nature of bound residues in erythrocytes ACS Symp Ser 1976 178-179 Chem Abstr 1976; 85: 116489a.].

An analytical procedure, to measure the level of phenyl groups incorporated in heme, based on their oxidation to benzoic acid, was developed to monitor the residues in treated animals [77Jaglan PS, Glen MW, Neff AW. Experiences in dealing with drug-related bound residues J Toxicol Environ Health 1977 2 815-826 Chem Abstr 1977; 87: 62570r.]. Relay metabolism in rats was studied by feeding sheep blood containing 14C residues from 14C-TCPH treatment. No retention of 14C residues in rat tissues was observed, which contrasted with the TCPH metabolism. A 90-day relay toxicity study in rats, which were fed dried blood from treated sheep containing up to 2000 times the potential exposure to residues in human diet, indicated no observable toxic responses. It was concluded tat these data support a tolerance of 6 ppm TCPH equivalents in blood [77Jaglan PS, Glen MW, Neff AW. Experiences in dealing with drug-related bound residues J Toxicol Environ Health 1977 2 815-826 Chem Abstr 1977; 87: 62570r.].

Furthermore, it was indicated that benzene was characterized as a volatile metabolite of p-toluic acid phenylhydrazide in rats. The relationship of benzene as the volatile metabolite of p-toluic acid phenylhydrazide and the phenyl groups bound to haemoglobin from treatment of sheep with 14C-(carboxy labeled) hydrazonoyl chloride (TCPH-I) was discussed [78Jaglan PS, Hornish RE. Identification of benzene asa volatile metabolite of p-toluic acid phenylhydrazide (TAPH) J Agric Food Chem 1977 25 963-964 Chem Abstr 1977; 87: 33616e.].

In an attempt to identify the metabolites of TCPH in the urine and feces of treated sheep, Jaglan and coworkers [79Jaglan PS. Identification of p-toluoyl chloride phenylhydrazone (TCPH) metabolites in the urine and feces of sheep J Agric Food Chem 19 208728a.] indicated that thin layer chromatography of ethyl acetate extracts of feces showed that about 12 % of the dose was present unchanged TCPH and < 2% as p-toluic acid phenylhydrazide (TAPH) and aniline. A major feal metabolite (27% of the dose) was characterized as 1-phenyl-1-acyl-2-p-tuolylhydrazine (where the acyl group was a mixture of stearyl, palmityl, myristyl and lauryl groups). Both TCPH and TAPH were not found in urine. Small amounts (< 1% of the dose) of p-toluic acid, α-ketoglutaric acid phenylhydrazone and pyruvic acid phenylhydrazone were also observed, based on cochromatography with synthetic compounds. The major urinary radioactivity (about 10 % of the dose) was characterized as p-methylhippuric acid, indicating molecular cleavage of TCPH [79Jaglan PS. Identification of p-toluoyl chloride phenylhydrazone (TCPH) metabolites in the urine and feces of sheep J Agric Food Chem 19 208728a.].

5. CONCLUSION

From the previous literature survey, it is clear that hydrazonoyl halides are very useful chemical-biology tools. In addition, we now have in hand an impressive number of biologically active candidates that can be used for treatment of various diseases. Less attention, however, was directed toward the synthesis and biology of C-alditolyl hydrazonoyl halides which are expected to have more penetrating power in the living cells. Further studies along this line may lead to products with better biological properties. For those who will be interested in exploring the chemistry and biology of such class of hydrazonoyl halides, the various review articles by one of the authors and mentioned in the introduction will be of help. In the light of the present review, there is every reason to believe that additional new and important biological applications of hydrazonoyl halides are just waiting to be discovered. It is hoped that this review will further stimulate interest in the biology of this class of organic compounds.

REFERENCES

[1] Fisher E. Uber die hydrazinverbindung Liebigs Ann 1882; 212: 316-40.
[http://dx.doi.org/10.1002/jlac.18822120303]
[2] Shawali A S, Parkanyi C. Hydrazidoyl halides in synthesis of heterocycles J Heterocycl Chem 1980; 17: 833-54.
[http://dx.doi.org/10.1002/jhet.5570170501]
[3] Shawali A S. Reactions of hydrazidoyl halides with sulfur compounds Heterocycles 1983; 20: 2239-85.
[http://dx.doi.org/10.3987/R-1983-11-2239]
[4] Shawali A S. Reactions of heterocyclic compounds with nitrilimines and their precursors Chem Rev 1993; 93: 2731-77.
[http://dx.doi.org/10.1021/cr00024a007]
[5] Shawali A S, Abdallah M A. The chemistry of heterocyclic hydraonoyl halides.Advances in Heterocyclic Chemistry Academic Press New York 1995; 63 : 277-338.
[6] Shawali A S, Elsheikh S M. Annelated 1,2,4,5-tetrazines J Heterocycl Chem 2001; 38: 541-59.
[http://dx.doi.org/10.1002/jhet.5570380301]
[7] Shawali A S, Mosselhi M A N. Hydrazonoyl halides.Useful building blocks for the synthesis of arylazoheterocycleshem J Heterocycl 2003; 40(3): 725-46.
[http://dx.doi.org/10.1002/jhet.5570400428]
[8] Shawali A S, Mosselhi M A N. The chemistry of thiohydrazonatesand theirutility in organic synthesis J Sulfur Chem 2005; 26(3): 267-303.
[http://dx.doi.org/10.1080/17415990500124586]
[9] Shawali A S, Edress M. Reactions of nitrilimines with heterocyclic amines and enamines.Convenient methodology for synthesisans and annulation of heterocycles Arkivoc 2006; ix: 292-365.
[10] Shawali A S, Sherief S A. The Chemistry of hydrazonates Curr Org Chem 2007; 11: 773-99.
[http://dx.doi.org/10.2174/138527207780831747]
[11] Shawali AS, Farghaly TA. Reactions of hydrazonoyl halides with heterocyclic thiones.Convenient methodology for heteroannultion synthesis of spiroheterocycles and heterocyclic ring transformation Arkivoc 2008; 18-64.
[http://dx.doi.org/10.3998/ark.5550190.0009.102]
[12] Butler RN, Scott FL. Versatile reactive intermediates.Hydrazidic halides Chem Ind (London) 1970 1216-1221 Chem Abstr 1970; 73: 109379.
[13] Ulrich H. The Chemistry of Imidoyl Chlorides Hydrazidoyl halides 1968; Chapter 7: 173-89.
[14] Rothe A. Contact dermatitis from N-(a-chlorobenzylidene) phenylhydrazines Contact Dermatitis Chem Abstr 1988 108 162843c 1988; 18: 16-9.
[15] Kaugars G. Insecticidal acaricidal and anthelmintic benzoyl chloride phenylhydrazone derivatives Fr Demande, 2,103,533, May19, 1972; Chem Abstr 1973; 78: 29473c.
[16] Kaugars G. Anthelmintic methods employing benzoyl chloride phenylhydrazones U S Patnt 332,661 Jan 13 1976 Chem Abstr 1976; 84: 99621x.
[17] Folz SD, Rector DL, Geng S. Efficacy of p-toluoyl chloride phenylhydrazone against gastrointestinal helminthes in ovines J Parasitol 1976 62 281-285 Chem Abstr 1976; 85: 40893e.
[18] Folz SD, Pax RA, Thomas EM, Bennett JL, Lee BL, Conder GA. Detecting in vitro anthelmintic effects with a micromotility meter Vet Parasitol 1987 24 241-250 Chem Abstr 1987; 107: 126379b.
[19] Folz S D, Pax RA, Klei TR, et al. Development of a novel in vitro equine anthelmintic assay J Vet Pharmacol Ther 1988 11 177-182 Chem Abstr 1988; 109: 85599u.
[20] Perronnet J, Girault P, Grandadam JA. Anthelmintic N-(a-chloro-4'-methoxybenzylidene)-4-chlorophenylhydrazine FrDemade 275,566 Nov 30 1973 Chem Abstr 1974; 80: 70550e.
[21] Rector DL, Folz SD, Conklin RD, Nowakowski LH, Kaugars G. Structure-activity relationships in a broad-spectrum anthelmintic series.Acid chloride phenylhydraones. 1.Arylsubstitu-tions and chloride variations J Med Chem 1981; 24: 532-8.
[22] Molodykh Zh V, Lisenkova AN, Buzykin BI, KitaevYu P. Athelmintic activity of some hydrazones Khim Farm Zh 1977 11 81-83 Chem Abstr 1977; 86: 165070m.
[23] Wing KD. Anthemintic N-alkyl-N,N'-diacylhydrazines: nonsteroidal ecdysone agonists S 524,333 Jun 13 1995 Chem Abstr 1995; 123: 313108e.
[24] Kaugars G. Alkylthiobenzoic acid phenylhydrazides U S Patnt 414,932 Mar 29 1977 Chem Abstr 1977; 87: 5665b.
[25] Kaugars G, Germich EG. Benzoyl chloride phenylhydrazones against insects and mites US Patnt 417,540 Apr 12 1977 Chem Abstr 1977; 87: 22800.
[26] Moon MW, Kaugars G. Pyruvyl chloride phenylhydrazone anthemintic US Patnt 3 32,662 Jan 13 1976 Chem Abstr 1976; 84: 16001q.
[27] Kaugars G. Halogen substituted pyridinealdehyde phenylhydrazones US Patnt 399,111, Oct 17 1972 Chem Abstr 1976; 84: 116001q.
[28] Kaugars G. Thiophenecarbonyl chloride phenylhydrazones US Patnt 309,703 May 07 1974 Chem Abstr 1976; 84: 116001q.
[29] Kaugars G. Antianthropodal formulation U S Patnt 379,542 Apr 22 1975 Chem Abstr 1975; 83: 9553d.
[30] Kaugars G. Alkylthio benzoyl chloride phenylhydrazones US Patnt 331,318 Jan 06 1976 Chem Abstr 1976; 84: 121494g.
[31] Kaugars G. a a a -Trifluoro-m-toluoyl chloride phenylhydrazone Ger Ofen 234,574 Jul 13 1972 Chem Abstr 1972; 76: 72258g.
[32] Habib HM. The antiviral effect of some substituted a -keto hydrazidoyl chlorides Egypt J Microbiol 1987 22 129-142 Chem Abstr 1989; 110: 111581z.
[33] Molodykh ZhV, Buzykin BI, Kudrina MA, Sysoeva L. Antimicrobial activity of some arylhydrazones of acyl halides and arylhydrazides of carboxylic acids Khim Farm Zh 1980 14 33-42 Chem Abstr 1980; 93: 94943e.
[34] Buzykin BI, Sysova LP, Molodykh ZhV, Kudrina MA, Neklesova ID, Kitaev Yu P. Acetyl chloride 4-bromophenyl- hydrazone possessing fungicidal and bactericidal properties USS 68610 Mar 07 1981 Chem Abstr 1981; 95: 42395z.
[35] Dubenko RG, Granin EF, Konysheva VD, Gorbenko EF, Bazavova MI, Pel'kis PS. Fungicidal properties of arylhydazones of glyoxalic acid substituted derivatives Fiziol Akt Veshchestva 1981 13 33-37 Chem Abstr 1982; 96: 99275k.
[36] Draber W, Buechel KH, Hammann I, Frohberger PE. Pyruvamide 1-(phenylhydrazones) Ger Ofen 233,997 Oct 05 1972 Chem Abstr 1973; 78: 15844n.
[37] Kukota SN, Borisenko VP, Bodnar VN, Zhuravskaya NI, Lozinskii MO. Synthsis and phytotoxicity of arylhydrazones of substituted pyruvic and a,ß-dioxobutyric acids Fiziol Akt Veshchestva 1978 10 32-36 Chem Abstr 1979; 90: 6212a.
[38] Moon M W, Friedman A R, Steinhards A. Herbicidal activityof phenylhydrazones and related azo compounds J Agric Food Chem 1972 20 1187-1190 Chem Abstr 1973; 78: 39208j.
[39] Kaugars G. Combating insects and mites using alkanoyl chloride phenylhydrazones U S Patnt 345,215, Jul 10 1973 Chem Abstr 1973; 79: 78412m.
[40] Karabanov Yu V, Gershkovich A A, Lozinskii M O, Borisenko V P, Samolyuk L. Herbicidal activity of 1-halo-1-cyano-3-aryl-2,3-diaza-1-propenes Fiziol Akt Veshchestva 1974 6, 64-67 Chem Abstr 1975; 82: 165760d.
[41] Kaugars G. Weed control with substituted phenylhydrazones U S Patnt 3 70,505, Mar 11 1975 Chem Abstr 1975; 83: 78891z.
[42] Andree R, Luerssen K, Santel H J, et al. Preparation of benzhydrazidoyl halides as acaricides, insecticides and herbicides Ger OffenDE 400,591, Jul 15 1993; Chem Abstr 1993; 119: 133475f.
[43] Strinadkin P S, Buzykin B I, Gazetdinova N G, Sysoeva L P, Kitaev Yu P. Antisarcoptic activity of arylhydrazones of chloro(bromo)carboxylic acid anhydrides Fiziol Akt Veshchestva 1981765-67 Chem Abstr 1985; 103: 208842d.
[44] Buzykin B I, Strinadkin P S, Zabolotnyi K F, et al. Antisarcoptic activity and allergenic properties of arylhydrazones of acylhalogeniddes Fizio Akt Veshchestva 1990 22 20-24 Chem Abstr 1991; 115: 177380t.
[45] Hatzinikolis E N, Koutepas N G. Evaluation of acaricides against Tetranychus urticae koch (Acarina, Tetranychidae) Nea Agrotike Epiteor 1977 31 49-51 Chem Abstr 1977; 87: 48889v.
[46] Kaugars G, Germich E G. Benzoyl chloride phenylhydrazones as pesticides Ger Ofen 126 366 Jan 15 1970 Chem Abstr 1970; 72: 100323n.
[47] Kaugars G, Gemrich E G, Rizzo V L. Miticidal activity of benzoyl chloride phenylhydrazones J Agric Food Chem197321 647-650 Chem Abstr 1973; 79: 112347f.
[48] Moon MW. The chlorination of aldehyde and ketone phenylhydrazones J Org Chem 1972; 37: 383-5.
[49] Kaugars G, Germich E G. Insecticidal and miticidal benzoyl chloride phenylhydrazones Ger Ofen 109,868 Oct 16 1969 Chem Abstr 1970; 72: 54978e.
[50] Dean H A. Citrus mite control with certain acaricides J Rio Grande Val Hortic Soc 1974 28 122-130 Chem Abstr 1975; 83: 159083q.
[51] Boesch R. Phenylhydrazone derivatives Ger Ofen 226,783, Dec 13 1973 Chem Abstr 1974; 80: 70518a.
[52] Kaugars G. Methylthio derivatives of benzoyl chloride phenylhydrazone Ger Ofen,134,482, Jan 27 1972; Chem Abstr 1972; 76: 112931e.
[53] Knowles CO, Aziz SA. Toxicity of benzoyl chloride (2,4,6-trichlorophenyl)hydrazone (Banamite) and potential metabolites to twospotted spider mites and potency as inhibitors of rat liver monoamine oxidase Bull Environ Contam Toxicol 1974 12 158-160 Chem Abstr 1975; 82: 12245q.
[54] Moon M W, Gemrich II E, Kaugers G G. Acaricidal activity of thioketal adducts of pyruvoyl chloride phenylhydrazone and related compounds J Agric Food Chem 1972 20 888-891 Chem Abstr 1972; 77: 9772n.
[55] Emmel L, Henbach G. Acaricidal phenylhydrazones of dicarbonyl compounds Ger Ofen 217,761, Nov 04 1971 Chem Abstr 1972; 76: 33935f.
[56] Emmel L, Henbach G. Acaricidal phenylhydrazones of dicarbonyl compounds Ger Ofen 217,762 Apr 14 1971 Chem Abstr 1972; 76: 45971c.
[57] Noguchi T, Asada M, Ando M, Matsuda K, and Uchiyama Y. Insecticide-acaricide composition of the hydrazine series Japan at 702,326 Jan 24 1973 Chem Abstr 1974; 80: 11233f.
[58] Kaugars G. Pesticidal heterocyclic phenylhydrazone derivatives Ger Ofen 2 1972; 77: 5337q.
[59] Boesch R. Alkanoyl chlororide phenylhydrazones Ger Ofen 226,872 Dec 06 1973 Chem Abstr 1974; 80: 59659b.
[60] Kaugars G. Chloro substituted furfural phenylhydrazone US Patnt 321,261 Jun 28 1974 Chem Abstr 1976; 84: 116001q.
[61] Knowles C O, Aziz S A. Metabolic fate of benzoyl chloride (2,4,6-trichlorophenyl)hydrazone (Banamite acaricide) in the twospoted spider mite J Econ Entomol 1974 67 574-576 Chem Abstr 1975; 82: 27198a.
[62] Gerson U, Aronowitz A. Spider mite webbing Part IV The effect of acaricides on spinning by the carmine spider mite Tetranychus cinnabarinus Pestic Sci 1981 12 211-214 Chem Abstr 1981; 95: 110100b.
[63] Hamed MS, Knowles CO. Penetration of pesticides into the bulb mite Rhizoglyphus echinopus Exp Appl Acarol19897 201-218 Chem Abstr 1989; 111: 169352n.
[64] Draber W. a-Chloro- a -formylcarbonyl phenylhydrazones Ger Ofen 245,881 Mar 23 1972 Chem Abstr 1972; 77: 5147c.
[65] Draber W, Buechel K H, Hammann I, Unterstenhoefer G. Pesticidal glyoxyloyl chloride 1[(substituted phenyl)hydrazones] S Africa 9 0368, Jan 06 1970 Chem Abstr 1970; 73: 45130r.
[66] Kaugars G, Germich E G. Benzoyl chloride phenylhydrazones as pesticides Ger Ofen 126,366, Jan 15 1970 Chem Abstr 1970; 72: 100323n.
[67] Moore JE. Insecticidal phenylhydrazone sulfides US Patent932,660 Jan 13 1976 Chem Abstr 1976; 84: 135317p.
[68] Moon MW. Insecticidal glyoxyloyl halide phenylhydrazones Ger Ofen 256,058 Jun 22 1972 Chem Abstr 1972; 77: 126648a.
[69] Draber W, Buechel KH, Hammann I, Unterstenhofer G. Pesticidal a-halo-a-formyl carbonyl phenylhydrazones US Patent 366112Jan 18 1972 Chem Abstr 1972; 76: 140166c.
[70] Moore JE. Insecticidal bisphenylhydrazone sulfides US Patnt 367,450 Feb 18 1975 Chem Abstr Chem Abstr 1975; 82: 139754k.
[71] Moore JE. Insecticidal phenylhydrazones sulfides US Patnt 367,449 Feb 18 1975 Chem Abstr 1975; 82: 139755m.
[72] Moore JE. Insecticidal bisphenylhydrazone sulfides S Patt 3n56,505 May 11 1976 Chem Abstr 1976; 85: 46220e.
[73] Waheed A. Dow Chemical Co..4-\dichloro-N-[chloro-(2.4dichlorophenyl) methylene]benzenecarbohydrazonoyl chloride Jpn Kokai Tokkyo Koho 8098148 July 25 1980 Chem Abstr 1981; 94: 30332t.
[74] Moon MW. Controlling weeds with 1'-formyl-1'-halobenzenea- zomethanes U S Patnt 330,642, Aug 20 1974 Chem Abstr 1975; 82: 39582j.
[75] Jaglan PS, Osline RE, Neff AW. Metabolic fate of p-toluoyl chloride phenylhydrazone (TCPH) in sheep.The nature of bound residues in erythrocytes J Agric Food Chem 1976 24 659-664 Chem Abstr 1976; 85: 116x.
[76] Jaglan PS, Gosline RE, Neff AW. Metabolic fate of p-toluoyl chloride phenylhydrazone (TCPH) in sheep The nature of bound residues in erythrocytes ACS Symp Ser 1976 178-179 Chem Abstr 1976; 85: 116489a.
[77] Jaglan PS, Glen MW, Neff AW. Experiences in dealing with drug-related bound residues J Toxicol Environ Health 1977 2 815-826 Chem Abstr 1977; 87: 62570r.
[78] Jaglan PS, Hornish RE. Identification of benzene asa volatile metabolite of p-toluic acid phenylhydrazide (TAPH) J Agric Food Chem 1977 25 963-964 Chem Abstr 1977; 87: 33616e.
[79] Jaglan PS. Identification of p-toluoyl chloride phenylhydrazone (TCPH) metabolites in the urine and feces of sheep J Agric Food Chem 19 208728a.

Endorsements



"It is an honor for us to publish our article in Open bioactive compound journal. The journal follows single blind peer review and plagiarism checking policy which is appreciable. I think soon your journal will attain high impact factor journals."


Zubair K. Labu
Department of Pharmacy, World University of Bangladesh, Bangladesh


Browse Contents




Webmaster Contact: info@benthamopen.net
Copyright © 2019 Bentham Open