GPOL#2186446, VOL 0, ISS 0

N-Phenyl Benzohydrazonoyl Halides as an Excellent

Precursor of Nitrile Imines for the Preparation of
Heterocyclic Compounds
Mohamed A. Elsayed, Korny A. Ali, Naglaa A. Abdel-Hafez, Ashraf M. Mohamed,
Abd-El-Galil E. Amr, Salwa F. Mohamed, and Jean-Marc Campagne

QUERY SHEET

This page lists questions we have about your paper. The numbers displayed at left are hyperlinked to
the location of the query in your paper.

The title and author names are listed on this sheet as they will be published, both on your paper and
on the Table of Contents. Please review and ensure the information is correct and advise us if any
changes need to be made. In addition, please review your paper as a whole for typographical and
essential corrections.

Your PDF proof has been enabled so that you can comment on the proof directly using Adobe
Acrobat. For further information on marking corrections using Acrobat, please visit https://
authorservices.taylorandfrancis.com/how-to-correct-proofs-with-adobe/

The CrossRef database (www.crossref.org/) has been used to validate the references.

AUTHOR QUERIES

Q1 Please check the author names, affiliations, and corresponding details have been
typeset correctly and correct if this is inaccurate.
Q2 The keywords “5” are maximum as per the journal style. Please edit accordingly.
Q3 Please provide the volume number and page range for reference “[8]”.
Q4 Please provide the caption for Scheme 1–63.
Q5 Please note that the ORCID section has been created from information supplied
with your manuscript submission/CATS. Please correct if this is inaccurate.
Q6 Please confirm the Scheme 63 as set in the proof are accurate.
Q7 Please provide the missing article title for all the references in the references list.
 POLYCYCLIC AROMATIC COMPOUNDS
https://doi.org/10.1080/10406638.2023.2186446

1
2
3 N-Phenyl Benzohydrazonoyl Halides as an Excellent Precursor
4 of Nitrile Imines for the Preparation of Heterocyclic
5
6 Compounds
7 a
8 Q5 Mohamed A. Elsayed , Korny A. Alia,b, Naglaa A. Abdel-Hafeza , Ashraf M. Mohameda,
a
9 Q5 Abd-El-Galil E. Amr , Salwa F. Mohameda, and Jean-Marc Campagnec
10 a
Applied Organic Chemistry Department, National Research Centre, Dokki, Egypt; bCenter of Excellence for
11 Advanced Science, Advanced Materials and Nanotechnology Group National Research Centre, Dokki, Egypt;
12 c
ICGM, Univ Montpellier, CNRS, ENSCM, Montpellier, France
13
14
ABSTRACT ARTICLE HISTORY
15 N-phenyl benzohydrazonoyl halide derivatives are important building Received 28 November 2022
16 blocks in the synthesis of a large number of heterocyclic compounds that Accepted 24 February 2023
17 include pyrazoles, pyridazine, etc. The main factor in the importance of
KEYWORDS
18 hydrazonyl halide is the easy release of the nitrile imine when treated in
Nitrile imine; pyrazoles;
19 an alkaline medium through the preparation process. Owing to the wide triazoles; thiazoles; spiro-
range of applications of these precursors, we will introduce a general over-
20 view for the synthesis and reactions of these types of compounds.
compounds; hydrazonoyl
21 Q2 halides

22
23
24
25 1. Introduction
26
27 N-heterocycles are priviledge substructures widely used in medicinal chemistry (59% of unique
28 small-molecule drugs contain a nitrogen heterocycle according to a 2014 study) thus revealing
29 much promise for industrial applications.1 The biological activity of hydrazonoyl halides as a
30 source for nitrile imines encouraged the scientist to synthesize these species. The pharmacology
31 of the hydrazonoyl halides generated from being bioactive in themselves and as a reagent to syn-
32 thesis of biologically active compounds2–10 have attracted the attention of researchers in this field
33 since the disclosure of the first hydrazonoyl halide by Fischer in 1882.11 Seminally developed by
34 Huisgen at the end of the 50’s,12 the use of nitriles imines (NIs) as 1,3-dipoles has emerged as a
35 valuable tool for the synthesis of a wide range of N-heterocycles as illustrated in Figure 1.13,14
36 Moreover, due to the potential formation of two mesomeric 1,3 dipoles, N- or C- regioisomers
37 adducts can be obtained thus extending the synthetic potential of this dipole. Due to their sub-
38 stantial reactivity, the species normally exist as a transient intermediate, generated in situ from a
39 suitable precursor before trapping with an appropriate partner. Hydrazonoyl halides have recently
40 appeared as an attractive source of NIs under mild conditions.15 The obective of this review is to
41 comprehensively cover these aspects and will be thus organized in two sections dealing with i)
42 the access to hydrazonoyl halides from differently diamino precursors (Section Synthesis of N-
43 phenyl benzohydrazonoyl halides); and ii) the use of these hydrazonoyl halides as NIs precursors
44 in the synthesis of N-heterocycles scaffolds (Section Reactions of N-phenyl benzohydrazonoyl hal-
45 ide). As generally observed with1,3-dipolar moieties, NIs chemistry is dominated by 1,3-dipolar
46 cycloadditions. Nonetheless, an additional aspect of these dipoles is their significant reactivity
47 with soft nucleophiles, such as thiols and carboxylic acids.16,17 All these points make the scope on
48
49 CONTACT Mohamed A. Elsayed abdelwahabchem86@gmail.com Applied Organic Chemistry Department, National
50 Q1 Research Centre, Dokki, Egypt
ß 2023 Taylor & Francis Group, LLC
51
 2 M. A. ELSAYED ET AL.

52
53
54
55
56
57
58
59
60
61
62
63
Figure 1. An overview of hydrazonoyl halides synthesis and their reactivity as NIs precursors in N-heterocycle synthesis.
64
65
66
67
68
69
70
71
72
73
74
75 Scheme 1.
76
77
78 the synthesis and reactions of hydrazonoyle halides the great challenge to scientist in the recent
79 years.
80
81
82 2. Synthesis of N-phenyl benzohydrazonoyl halides
83
84 The methods for the preparation of N-phenyl benzohydrazonoyl halide derivatives are discussed
85 in this section. We will first focus on the preparation of hydrazones (Shiff bases). Preparation of
86 hydrazonoyl halides via Schiff bases which were obtained from the reaction of the corresponding
87 carbonyl compound with hydrazines. Hydrazones are transformed into hydrazonoyl halides by
88 halogenation. Different methods for the preparation of N-phenyl benzohydrazonoyl halides are
89 performed, so we will show these methods in our review. Improving the yield one of the most
90 important factors in the synthetic methods so, increasing the yield is one of the important chal-
91 lenges in this review.
92
93
94 2.1. Halogenation of hydrazone derivatives
95 hydrazonoyl chloride 2 can be obtained by reaction of hydrazone 1 with phosphorous pentachlor-
96
ide in diethyl ether at 20
C for 1.5 h in yield 59% (Scheme 1).18,19 Alternatively, chlorination can
97
also be achieved using N-chlorosuccinimide and dimethylsulfide in dichloromethane at 78
C
98
99 for 2 h under an inert atmosphere (Scheme 1).20–22 Bromination of the corresponding N-acylphe-
100 nylhydrazines in acetic acid afforded hydrazonoyl bromides [ArNHN ¼ C(Br)Ar] 2 in yield 55%
101 (Scheme 1).18,23 The efficiency of this methods to prepare hydrazonoyl halide 2 is not good
102 because of the low yield obtained.
 POLYCYCLIC AROMATIC COMPOUNDS 3

103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120 Scheme 2.
121
122
123 2.2. Reaction of arylhydrazine with benzoyl chloride
124 A series of hydrazonoyl chlorides were prepared by the reaction of phenylhydrazines (4) with
125 benzoyl chloride derivatives (3) in pyridine in two steps. The first step, to a stirred solution of
126 phenylhydrazine derivatives 4 in pyridine, was slowly added benzoyl chloride in an ice bath for
127 20 min. Upon completion of the addition, the ice bath was removed, and the stirring was contin-
128 ued for another 15 h at r.t. to afford benzoyl phenylhydrazine in yields reached to 80%. In the
129
second step, a mixture of CCl4, Ph3P and benzoyl phenylhydrazine in acetonitrile was stirred at
130
r.t. for 6 h. After completion of the reaction, the solid was filtered and washed with diethyl ether
131
132 to afford hydrazonoyl chloride derivatives 2 in yields up to 50% (Scheme 2).19,24–27 The low yield
133 obtained from this method make it less preferable to synthesize hydrazonoyl halides.
134
135
136 2.3. Reaction of N-phenyl benzohydrazonic acid with chlorinating agents
137
138 The preparation process of hydrazonoyl chlorides 2 was achieved also in two steps starting from
139 phenyl hydrazine (4). At the first step, phenylhydrazine was reacted with benzoyl chloride in
140 pyridine at 20
C for 48 h to afford N-phenyl benzohydrazonic acid (5) with 55% yield. In the
141 second step, phosphorus pentachloride reacted with the N-phenyl benzohydrazonic acid (5) in
142 carbon tetrachloride to afford colorless crystals of N-phenyl benzohydrazonoyl chloride (3) in
143 32% yield (Scheme 3).28,29 As the previous methods, the very poor yield decrease the priority for
144 researchers to use it in the synthesis of hydrazonoyl halides.
145
146
147
148 2.4. From aryl azo alkenes
149
150 hydrazonyl chloride derivatives 2 was prepared with yields reached to 95% by treatment of the
151 aryl azo alkenes 6 with a solution of CuCl2.2H2O in acetone at 0
C. (Scheme 4).30 In contrast to
152 the other methods, using azo-compounds as starting materials afforded the corresponding hydra-
153 zonoyl halides in excellent yield.
 4 M. A. ELSAYED ET AL.

154
155
156
157
158
Scheme 3.
159
160
161
162
163
164
165
166
167
168
169 Scheme 4.
170
171
172
173
174
175
176
177
178
179
180
181
182 Scheme 5.
183
184
185 2.5. From benzyl alcohol
186 Benzyl alcohol was used as starting material for the preparation of N-phenyl benzohydrazonyl
187
chloride. Firstly, primary alcohols 8 were treated with DIB in the presence of TEMPO in CH2Cl2
188
at room temperature for 0.5 h under Argon atmosphere. Secondary, NH2NHR2 was added and
189
190 stirring continued at 60
C for 3 h. upon reaction completion, the solvent was evaporated to
191 obtain hydrazones. The formed hydrazones were treated with N-halosuccinimide in CH2Cl2 and
192 DMF in presence of decyl methyl sulfide at 78
C for 1 h and at room temperature for 3 h to
193 afford the corresponding N-phenyl benzohydrazonoyl halide derivatives 2 in 82% yield (Scheme
194 5).31 Benzyl alcohol is very good material to prepare hydrazonoyl halides because of the high
195 yield obtained.
196
197
198 2.6. From aromatic acids
199
Aromatic carboxylic acids are also valuable precursors for preparing N-phenyl benzohydrazonoyl
200
201 chloride derivatives in two steps. The first step, by treatment of the appropriate carboxylic acid
202 with thionyl chloride in toluene followed by the addition of aryl hydrazine in pyridine at 0
C. In
203 the second step, acetonitrile and tetrachlorocarbon and triphenylphosphine were added to give
204 compound 2 in yields 62–89% (Scheme 6).32
 POLYCYCLIC AROMATIC COMPOUNDS 5

205
206
207
208
209
210
211
212
213
214
215
216
217
218
219
220
221 Scheme 6.
222
223
224
225
226
227
228
229
230
231
232 Scheme 7.
233
234 Sersen and Gregan,33 reported the synthesis of N-phenyl benzohydrazonoyl chloride starting
235 from hydrazide in the same manner. N-substituted hydrazides were prepared by a nucleophilic
236 substitution reaction of 1-chloro-4-trifluoromethyl-2,6-dinitrobenzene (10) and the corresponding
237 hydrazides 11 (Scheme 6) in anhydrous dimethoxyethane with triethylamine for 2–3 h at room
238 temperature. The yields of these products were 74%–80%, after recrystallization. Treatment of the
239 new hydrazides 12 with thionyl chloride in boiling toluene gave 2 in 56–67% yields (Scheme 6).33
240 Owing to the low yield obtained, aromatic carboxylic acids is not good materials to synthesize
241 these species of hydrazonoyl halides. The biggest challenge will be how the scientists will try to
242 improve the methods for preparing hydrazonoyl halide with increasing the yield.
243
244
245 2.7. From trifluoroacetic acid
246
247 2,2,2-trifluoro-N-phenylacetohydrazonoyl chloride derivatives were disclosed by Tanaka et al in
248 198234 by halogenation of trifluoroacetaldehyde phenylhydrazone 14 which was generated in situ
249 from trifluoroacetaldehyde hydrate 13 and phenylhydrazine 5. Treatment of 14 with N-chloro-
250 and N-bromosuccinimide in dimethylformamide at room temperature afforded 15a and 15b in
251 71 and 74% yields, respectively (Scheme 7).
252 Similarly, Jasiniski et al prepared a series of hydrazonoyl bromide 15b starting with arylhydra-
253 zines 5 and trifluoroacetaldehyde hydrate (13). Condensation of 13 with 5 was carried out in the
254 presence of freshly activated molecular sieves, 4 Å in refluxed methanol, and after overnight heat-
255 ing at 75
C arylhydrazones 14 were isolated. Subsequent bromination of the azomethine group
 6 M. A. ELSAYED ET AL.

256
257
258
259
260
261
262
263
264
265
266
267
268
269
270
271
272 Scheme 8.
273
274
275
276
277
278
279
280
281
282
283
284 Scheme 9.
285
286
in 14 by using NBS, in a dry DMF solution, afforded desired hydrazonoyl bromide precursors
287
288 15b in fair to good yields of 50–75% (Scheme 8).35 The two method for preparing trifluoro-N-
289 phenylacetohydrazonoyl halide 15 by Tanaka and asiniski alternatively, gave aproximatly the
290 same yields.
291 Oh reported the synthesis of hydrazonoyl chloride 15a and the hydrazonoyl benzenesulfonate
292 15c. The acylation of 4-sulfonamidophenylhydrazine 16 with trifluoroacetic anhydride afforded
293 the trifluoroacetylated hydrazine 17. From 17, hydrazonoyl chloride 15a (an oil) or the hydrazo-
294 noyl benzenesulfonate 15c was obtained by slurring 17 in ethylacetate and cooled to 5–10 0C.
295 Benzenesulfonyl chlorid is added, followed by dropwise addition of N-methylmorpholine. The
296 reaction mixture is continued for 1 h at 5–10
C after which water is added and the mixture is
297 stirred for 0.5 h. the organic layer was extracted to afford 15 C (Scheme 9).36
298
299
300
301 3. Reactions of N-phenyl benzohydrazonoyl halide
302
303 N-phenyl benzoydrazonoyl halide derivatives have an important role in the synthesis of a large
304 number of heterocyclic compounds. The main factor in the importance of these species of hydra-
305 zonyl halides is the easily released Nitrile Imine when treated in an alkaline medium through the
306 preparation process.
 POLYCYCLIC AROMATIC COMPOUNDS 7

307
308
309
310
311
312
313
314 Scheme 10.
315
316
317
318
319
320
321
322
323
324
325
326
327
328
329
330
331
332
333
334
335
336 Scheme 11.
337
338
339 3.1. Synthesis of thiadiazine
340
341 The nitrile imine liberated from hydrazonoyl chloride 2 reacted with 2,5-dihydroxy-1,4-dithiane
342 (18), in the presence of triethylamine at room temperature for 8h to afford a white solid of thia-
343 diazine derivatives 19 in 95% yield (Scheme 10).37 This method give excellent yield.
344
345
346 3.2. Synthesis of pyrazole
347 Sibi et al reported the synthesis of a variety of chiral dihydropyrazoles scaffolds (Scheme 11). He
348 reported the highly regio- and enantioselective [3 þ 2] cycloadditions of hydrazonoyl halides 2a-d
349 to olefins 20a-h using 10 mol% chiral Lewis acid catalysts. The noncoordinating diisopropylethyl-
350
amine was used as a base initially. Ligand in combination with magnesium Lewis acids provided
351
cycloaddition product 21a-i in high yield and excellent enantioselectivity (Scheme 11). The reac-
352
353 tion was completely regioselective, with the carbon end of the dipole addition, C-adduct is favor
354 than N-adduct cycloaddition.38
355 The yield and regioselectivity is showed in Table 1. As shown in Table 1, all products gave
356 excellent yields and regioselectivity varies from 90 to 99% with different substituents entered. The
357 only exception was when R1 ¼ R4 ¼ H. In this case the yield was 82% and regioselectivity 79%.
 8 M. A. ELSAYED ET AL.

358 Table 1. Show the yield and regioselectivity of the products.

359 entry Dipole R1 R2 R3 R4 product yield(%)a ee(%)b
360 1 3a Me Ph Br H 21a 91 99
361 2
3
3a
3a
Et
Ph
Ph
Ph
Br
Br
H
H
21b
21c
93
95
99
97
362 4 3a 2-furyl Ph Br H 21d 94 99
363 5c 3a OBz Ph Br H 21e 97 96
364 6
7d
3a
3a
CO2t-Bu
CO2t-Bu
Ph
Ph
Br
Br
H
H
21f
21f
92
90
91
93
365 8 3a H Ph Br H 21g 82 79
366 9d 3a H Ph Br H 21g 95 84
367 10
11e
3b
3e
Me
Me
i-Pr
Ph
Br
H
H
H
21h
21i
98
92
99
95
368 12e 3e 3-Br-Ph Ph H H 21j 97 97
369 13 3d Me 4-Br-Ph Br H 21k 95 95
370 14
a
3d Me Ph OMe Br 21l 96 96
Isolated yield. bDetermined by chiral HPLC. cUpon treatment with NaBH4, the benzoate is cleaved to yield the corresponding
371 diol. dPerformed with 20 mol % Mg(NTf2)2-6. eEt3N as the base, 30 mol % Mg(NTf2)2-6, -20
C, 48 h.
372
373
374
375
376
377
378
379
380
381
382
383
384
385
386
387
388
389
390
391
392
393
394
395
396
Scheme 12.
397
398
399 Using the same method, Sibi et al enhanced the conditions of the reaction to obtain bis-pyra-
400 zole methanol 24 with good yields and a short time. When, Et3N is used to generate the nitrile
401 imine the reaction continued to 24 h, but reactions that use P1-t-Bu amine as base to generate the
402 nitrile imine were run for 2–4 h to give the desired product 24a-d (Scheme 12).39
403 As shown in the table, excellent yield was obtained when P1-t-Bu amine was used as a base. It
404 gave 94% yield in short time.
405 Hans et al described the synthesis of pyrazoline derivatives as a sole product via the addition
406 of hydrazonoyl chloride 2, smoothly to 1,2-oxazine 25 in diethyl ether with stirring for 48 h at r.t
407 affording the pyrazoline derivative as the solely isolated isomer (exo-selectivity) 26 in very good
408 yield 81% (Scheme 13).40
 POLYCYCLIC AROMATIC COMPOUNDS 9

409
410
411
412
413
414
415 Scheme 13.
416
417
418
419
420
421
422
423
424
425
426
427 Scheme 14.
428
429
430
431
432
433
434
435
436
437
438
439
440
441
442
443
444
445
446
447 Scheme 15.
448
449 Hamme and Dadiboyena et al found that when a-bromocinnamaldehyde (27) was used as the
450 alkene, pyrazole carboxaldehyde derivative (29) was the only isolated product (Scheme 14).
451
Pyrazole derivatives were obtained in 70–86% yield. The most probable driving force for the for-
452
mation of 29 is the creation of a stable aromatic system through the loss of HBr (Scheme 14).41
453
Yavari et al described studies on the development of new routes in heterocyclic synthesis. He
454
455 reported the reaction of hydrazonoyl chloride derivatives with acetylenic esters, in the presence of
456 triphenylphosphine, proceed via zwitterionic intermediates derived from triphenylphosphine and
457 acetylenic esters 30 with nitrile imine (generated in situe from the corresponding N-phenyl ben-
458 zohydrazonoyl chloride derivatives), which gave the N-adduct 3-aryl-1-phenyl-1H-pyrazoles (31)
459 in 83–92% yields (Scheme 15).42
 10 M. A. ELSAYED ET AL.

460
461
462
463
464
465
466
467
468
469
470
471
472 Scheme 16.
473
474
475
476
477
478
479
480
481
482
483
484
485
486
487
488
489
490 Scheme 17.
491
492
493 Jurij and Branko et al described the synthesis of pyrazole derivatives using hydrazonoyl chlor-
494 ide derivatives 2 and (E)-3-benzoyl amino-4-cyano-2-oxo-3-butene (32). The reactions were car-
495 ried out in boiling dichloromethane, in presence of triethylamine to obtain 5-acetyl-4-cyano-3-
496 aryl-1-phenyl-1H-pyrazoles (33) in good yields. (Scheme 16).43
497 Zhang and Ma et al studied the regioselective cycloaddition of hydrazonoyl chloride derivatives
498 2 as 1,3-dipoles, and isoxazolidinediones 35 as decarboxylated masked alkynyl dipolarophiles to
499 afford the corresponding pyrazole derivatives 36 (Scheme 17), in presence of potassium carbonate
500 in dichloroethane 2 ml at 90
C for 12 h. This method gave excellent regioselective control in pres-
501 ence of potassium carbonate as a base promoted [3 þ 2] cycloaddition reaction.44
502 Hafez et al reported the synthesis of some novel pyrazoles via 1,3-dipolar cycloaddition reac-
503 tion of hydrazonoyl chloride (2) and enamines. Enaminone 37 reacted with nitril imine (gener-
504 ated in situe from the corresponding hydrazonoyl chloride with TEA) in benzene at 20
C to give
505 pyrazole derivatives 38 in good yields (Scheme 18).45
506 Albar et al offered a versatile way for the regioselective synthesis of 2H-pyrazole derivatives via
507 the 1,3-dipolar cycloaddition of N-phenyl benzohydrazonoyl chloride (2) in sodium ethoxide and
508 unsymmetrical b-diketones (benzoyl acetone) to afford two pyrazole derivatives 41 and 42 in 9: 1
509
510
 POLYCYCLIC AROMATIC COMPOUNDS 11

511
512
513
514
515
516
517
518
519 Scheme 18.
520
521
522
523
524
525
526
527
528
529
530
531
532
533
534
535
536 Scheme 19.
537
538
539
540
541
542
543
544
545
546 Scheme 20.
547
548
549 ratio by lossing of water molecule (Scheme 19) in a similar manner to the cycloaddition of the
550 nitrilimides with a, b-unsaturated ketones and esters.46
551 Farag et al studied the regioselective synthesis of new pyrazole derivatives using hydrazonoyl
552 chloride (2) and enaminone in cycloaddition reaction. Enaminone 43 reacted with N-phenyl ben-
553 zohydrazonoyl chloride (2) in benzene and an equivalent amount of TEA under reflux for 2 h to
554 give pyrazole derivative 45 (Scheme 20) in 90% yield after recrystallization from EtOH/DMF.47
555 The yield obtained from this method is excellent comparing to the product yield obtained by
556 Hafez et al.
557 Gao et al described the cycloaddition of acetylenic sulfones to hydrazonoyl chloride (2) to
558 obtain pyrazoles derivatives. When acetylenic sulfones 46 reacted with hydrazonoyl chloride (2)
559 in N-ethyl-N, N-diisopropylamine In chloroform under refluxing temperature to give the
560
561
 12 M. A. ELSAYED ET AL.

562
563
564
565
566
567
568
569
570
571
572
573
574
575 Scheme 21.
576
577
578
579
580
581
582
583
584
585
586
587
588
589
590
591
592
593
594
595
596
597 Scheme 22.
598
599
corresponding pyrazole derivatives 47a, b with yields 70 and 67%, respectively (Scheme 21).48
600
601 The procedure gave good yields in chloroform as a solvent.
602 Kitane et al described a method for synthesis of pyrazole via cycloaddition of hydrazonoyl
603 chloride derivatives 2 with allyl derivatives 48 and 49. Position of HB and HA in both reagents
604 make the addition on the electrophilic carbon of hydrazonoyl halides choose the less hindrance
605 position of the alkene used. affect on the stereo and regioselectivity of the product The reaction
606 proceeds in benzene and triethylamine under refluxing conditions for 48 h to give pyrazole deriv-
607 atives 50 and 51, respectively in yields 60–80% of the isolated pure products (Scheme 22).49
608 Using the non-polar benzene as a solvent may enhanced the the yield of the product rather than
609 the chloroform used in Gao et al.
610 Bougrin et al developed a new method, he used catalyst with microwave assistance to obtain
611 the pyrazole derivatives. The author suggested that the best result of pyrazoline derivatives is
612 obtained in the case of indene 53, when hydrazonoyl chloride 2 and indene 53 with p-HAP300
 POLYCYCLIC AROMATIC COMPOUNDS 13

613
614
615
616
617
618
619
620
621
622
623
624
625
626
627
628
629
630
631
632
633 Scheme 23.
634
635
636
637
638
639
640
641
642
643
644
645
646
647
648
649 Scheme 24.
650
651
652
653
or p-HAP100 are used as catalysts. However, under the same conditions used for p-HAP300 and
654
655 p-HAP100, the catalyst KF/g-Al2O3 was more reactive. In his study, calcium hydroxyapatite sup-
656 port was used as a catalyst. 1,3-dipolar cycloaddition of hydrazonoyl chloride 2 on olefins deriva-
657 tives 52, 53 and 54 is readily catalyzed under solvent-free microwave irradiation and the
658 pyrazolines derivatives 55, 56, and 57 are obtained respectively in a few minutes with high yields
659 and 100% regioisomer ratio (Scheme 23).50
660 Sui et al. Reported cycloaddition of the nitrile imines, generated from the corresponding
661 hydrazonoyl chloride derivatives 2, to cycloalkanes 58 in toluene and TEA to give the dehydro-
662 genated precursors which underwent oxidation with choranil to provide the desired pyrazole
663 derivative 59 (Scheme 24).32
 14 M. A. ELSAYED ET AL.

664
665
666
667
668
669
670
671
672
673
674
675
676
677
678
679
680
681 Scheme 25.
682
683 Mahran et al synthesized pyrazole derivatives using hydrazonoyl chloride 2 and pyrimidine
684 derivatives 60, in the presence of sodium ethoxide in refluxing ethanol/DMF mixture. The mech-
685 anism of this reaction proceeds as shown in Scheme 25 by attack of active methylene of com-
686 pound 60 to electrophilic carbon of hydrazonoyl halide and subsequent dehydration to afforded
687 the corresponding phenylpyrazolo[3,4-c]pyrazolcyclopenta [4,5] thieno [2,3-d] pyrimidin-4-ones
688 derivative 61 (Scheme 25).51
689 Fuchi et al reported a solid-phase synthesis of pyrazoles via a regioselective 1,3-dipolar cyclo-
690 addition of hydrazonoyl chloride 2 to polymer-supported beta-(p-toluenesulfonyl) acrylate 62 to
691 give two new products. (62 generatyed in situe from the attachement of Fmoc-glycine (R ¼ H) to
692 the polymer-support amino resin and after removal of the Fmoc group (20% piperidine/CH2Cl2),
693 coupling of E-3-(p-toluenesulfonyl)- acrylic acid to polymer-supported amide (DIC/HOBt/DIEA)
694 to provide the resin 62) and subsequent beta-elimination of the toluene sulfonyl group in the
695 synthesis of pyrazole derivatives. The pyrazoline obtained under mild conditions of 1,3-Dipolar
696 cycloaddition on polymer-support at r.t. for 8 h. Subsequently, elimination of a p-toluenesulfonyl
697 group with DBU, followed by acid cleavage from the polymer-support (25% TFA/CH2Cl2)
698 afforded the desired pyrazoles 63 (C-adduct) and 64 (N-adduct) respectively (Scheme 26). The
699 isomer 63 was obtained as major product with highest selectivity 82% and highest purity 92%.52
700
701
702 3.3. Synthesis of triazole
703
704 Chen and Wu et al have prepared substituted triazole from hydrazonoyl chloride derivatives 2
705 using Nickel chloride which promoted the transformation of intramolecular nucleophilic add-
706 ition-elimination reaction. The reaction occurs in dioxane and a catalytic amount of triethylamine
707 under N2 atmosphere for 24 h at 80 or 120
C to afford 1,2,4-triazole derivatives 65 in up to 95%
708 yield (Scheme 27).53
709 Baouid and Compain et al promoted the reaction with more sterically hindrance hydrazonoyl
710 chloride derivatives 2 with 1,5-benzodiazepine derivatives 66. The reaction continued for two
711 days under stirring in benzene at room temperature. The cycloaddition reaction was found to
712 proceed regioselectively and give only the trans isomer as a stereoselective of bis-cyclo adducts 67
713 in yields vary from 33 to 60% (Scheme 28). The high yield 60% obtained in case of R1 ¼ H,
714 R2 ¼ Me, R3 ¼ H and X ¼ Cl but the lower yield 33% obtained when R3 ¼ Me.54
 POLYCYCLIC AROMATIC COMPOUNDS 15

715
716
717
718
719
720
721
722
723
724
725
726
727
728
729
730
731
732
733
734
735 Scheme 26.
736
737
738
739
740
741
742
743
744
745
746 Scheme 27.
747
748
749
750
751
752
753
754
755
756
757
758
759
760
761
762
763
764
765
Scheme 28.
 16 M. A. ELSAYED ET AL.

766
767
768
769
770
771
772
773
774
775 Scheme 29.
776
777
778
779
780
781
782
783
Scheme 30.
784
785
786 Su et al synthesized triazole derivatives by reaction of hydrazonoyl chloride derivatives with
787
nitriles catalyzed by ytterbium triflate [Yb(OTf)3]. The reaction was refluxed in dry chlorobenzene
788
and the addition of nitriles to the corresponding hydrazonoyl chloride derivatives in presence of
789
Yb(OTf)3. The most preferred conditions to be used in this reaction is 10 mol% of the catalyst
790
under reflux for 4 h to get the triazole derivatives 69 in yields reached to 85% (Scheme 29).55
791
Shawali et al reported the synthesis of the triazole moieties using hydrazonoyl chloride 2 and
792
6-amino-2-thiouracil 70 in TEA and refluxing dioxane for 10 h to give the corresponding Tri-azo-
793
lopyrimidine derivatives 71 in 70% yield (Scheme 30).56
794
Riyadh et al prepared triazolopyrimidine derivative 77 (Scheme 28) by reaction of azo phenyl
795
thiopyrimidine 72 with hydrazonoyl chloride 2 in refluxed dioxane and a catalytic amount of trie-
796
797 thylamine. The plausible mechanism of this reaction as shown in (Scheme 31) gave two possible
798 isomers 77 and 78. The spectral data and elemental analysis showed that only product 77 is in
799 favor because 13C NMR of C¼O group adjacent to nitrogen in pyrrole-type equal to d¼ 161–164
800 but for C¼O adjacent to nitrogen pyridine-type is at d ¼ 170–175. Since d value for the isolated
801 compound at 161–164 so, the structure 77 is approved with 72% yield.57
802 Mahran et al used 1,2,3,5,6,7-hexahydro-4H-cyclopenta[4, 5]thieno[2,3-d] pyrimidin-2, 4-
803 dithione (79) with hydrazonoyl chloride 2 to obtain the triazole ring. When a mixture of thiopyr-
804 imidine derivative and hydrazonoyl chloride (2) was added in sodium ethoxide solution and
805 drops of DMF under reflux for 6–8 h the corresponding triazolo pyrimidine derivative 80 was
806 obtained in 68% yield (Scheme 32).51
807 The three reported methods for preparation of condensed triazolopyrimidines by Shawali,
808 Riyadh and mahran et als showed the same product in regioselective reaction. The yield is aproxi-
809 matly identical. All this prove the structure of the new obtained product.
810 Paulvannan et al used different catalysts to reach the corresponding triazole moieties via cyc-
811 lization of 1,2,4-triazenes which obtained from the corresponding hydrazonoyl chloride 2 with
812 different amines and subsequent oxidation by different oxidizing agents such as NaClO,
813 Ca(ClO)2, Dess–Martin periodinane and Ley’s oxidizing agent (TPAP/NMO) to afford tri-substi-
814 tuted triazole derivatives 83 (Scheme 33). Investigation of the reaction with different primary
815 amines under condition A indicated that the substituent on the b-position of the amine 81 had a
816 significant impact on the yield (R1 ¼ Ph 69% yield; R1 ¼ CH2¼CH 51% yield; R1 ¼ 3-Pyr 47%
 POLYCYCLIC AROMATIC COMPOUNDS 17

817
818
819
820
821
822
823
824
825
826
827
828
829
830
831
832
833
834
835
836
837
838
839 Scheme 31.
840
841
842
843
844
845
846
847
848 Scheme 32.
849
850
851 yield; MeO2CHCH2CH2- 73% yield and R1 ¼ Ph(CH-)Ph 5% yield) (Scheme 33).58 Paulvannan
852 improved the conditions to reach the heist yields. under conditions B the yields were improved
853 with different catalysts as shown in Table 2 (Scheme 33).59
854 Al-Omair et al used 2-(methyl thio)-1H-benzo[d]imidazole and hydrazonoyl bromide to pre-
855 pare 1,3-disubstituted-1H-benzo[4, 5]imidazo[2,1-c][1, 2, 4]triazole (85) in yield of 80% (Scheme
856 34).60 S-Methyl benzimidazole 84 reacted with hydrazonoyl halide 2 in presence of triethyl amine
857 as base and chloroform for about 6 h reflux. This method give very good yield which make it
858 more preferable than the method reported by Shawali for synthesis of triazoles starting from dif-
859 ferent moieties of S-methyl as shown in Schemes 34 and 35.
860 Similarly, Shawali et al has selected to start with 3-thiomethyl-5-phenyl-1,2,4-triazole (86) and
861 hydrazonoyl chloride 2 to obtain 1H-[1, 2, 4] triazolo[3,4-c][1, 2, 4]triazole (87) in 75% yield
862 (Scheme 35).61 Shawali selected sodium ethoxide to form the nitrile imine which reacted with S-
863 methyl triazole derivative 86 in refluxing ethanol for 12 h to produce the trizole derivative 87 in
864 good yield.
865 Ito and Tanaka et al synthesized N-(phenylsulfonyl)benzohydrazonoyl chloride as a precoursor
866 for formation of 1,2,4-triazoles using N-substituted benzamidines, benzimidate and 2-
867
 18 M. A. ELSAYED ET AL.

868
869
870
871
872
873
874
875
876
877
878
879
880
881 Condition A : (a) 1.1 equiv. of 84, 1.1 or 2.2 equiv. of TEA, CH3CN, rt; 12 h; (b) 30% H2O2/sat KOH (90:10 v/v), CH3CN,
882 0°C to rt; (c) 1.2 equiv. of Ag2CO3, CH3CN, 2 h
883
884 Condition B : (a) 1.2 equiv. of 84, 1.2 equiv. of TEA (2.4 equiv. For R1= MeO2CCH2CH2), CH3CN, room temperature,
885 15 h; (b) 1.2 equiv. of Ag2CO3, CH3CN, 2 h; (c) NaClO, CH3CN, 24 h; (d) 2.0 equiv. of Ca(ClO)2, CH3CN, 24 h; (e) 1.5
886 equiv. of DMP, CH2Cl2, 3 h; (f) 0.2 equiv. of TPAP/1.5 equiv. of NMO, CH3CN, 3 h
887 Scheme 33.
888
889
890 Table 2. The yield of the products with different catalysts.
891 Yield
892 R Ag2CO3 NaClO Ca(ClO)2 Dess-Martin Periodinane TPAP/NMO
893 Ph 69 68 65 81 79
894 CH2 ¼ CH- 51 63 51 69 60
895 3-Pyr
MeO2C CH2 CH2
47
73
45
59
63
73
52
86
45
75
896
897
898
899
900
901
902
903
904
905
906
907
908
909
910
911
912
913
914 Scheme 34.
915
916
917
918
 POLYCYCLIC AROMATIC COMPOUNDS 19

919
920
921
922
923
924
925
926 Scheme 35.
927
928
929
930
931
932
933
934
935
936
937
938
939
940
941
942
943
944
945
946
947
948
949
950
951
952
953
954 Scheme 36.
955
956
957 aminopyridines or pyrimidines. They supposed that N-(phenylsulfonyl)benzohydrazonoyl chloride
958 has not the same function as 1,3-dipole for cycloaddition reaction of corresponding N-(phenyl)-
959 benzohydrazonoyl chloride because of the high electron withdrawing effect of phenyl sulfonyl
960 group so, amino hydrogen may be acidic and released easily by amidines. Also, the negative
961 charge on amino nitrogen is delocalized by phenyl sulfonyl group so, they dose not release Cl
962 to form 1,3-dipole and step by step mechanism involved followed by intramolecular cycloadd-
963 ition. When two moles of amidines 92 was added to one mole of hydrazonoyl chloride in THF at
964 room temperature for 2 h to give 1,2,4-triazole derivatives and traces of tetrazines 93 in more
965 cases (Scheme 36). The tautomeric structures of amidines make the nucleophilic attack of the
966 amidine on the imidoyl carbon of hydrazonoyl halide takes place in two ways (Scheme 36).62 The
967 yield of the reactions of 91 with benzamidines for these products changed as R and R/were
968 changed (Table 3).
969
 20 M. A. ELSAYED ET AL.

970 Table 3. Reaction of N-(phenylsulfonyl)benzohydrazonoyl chloride with benzamidines.

971 Ph-C=N-R
972 NHR/
973 Yield (%) of products
974 R R/ 90 92 91 MP of 91
C
975 Ph H trace 4 82
976 Ph Ph trace – 90 291–292
977 Ph Me 7 – 70
978 p-Cl-C6H4
p-Me-C6H4
H
H
4
trace
6
8
80
69
266–267
291–292
979 PhCH2 H 10 58 26 223–224
980 Et H 22 40 12 159–160
981 Me
H
H
H
16
20
37
49
16
–
248–250
982 Ph-C=NH 2 72 –
983
984 N=CHPh
985
986
987
988
989
990
991
992
993
994
995
996
997
998
999
Scheme 37.
1000
1001
1002
1003 Reaction of hydrazonoyl halide 88 with benzimidates proceeded analogously with the removal
1004 of the alkoxy group to give triazoles (Scheme 37). The yield of products for these reactions was
1005 displayed in Table 4.
1006 In the same manner, 2-aminopyridine and –pyrimidines reacted with hydrazonoyl halide 88 to
1007 give 3-phenyl-1,2,4-triazolo[4,3-a]pyridine and –pyrimidines in yields 54 and 42% respectively
1008 (Scheme 38).
1009
1010
1011
1012 3.4. Synthesis of thiadiazole
1013 Sobhy Gomha et al synthesized thiadiazole derivatives via reaction of ethylidene thiosemicarba-
1014
zone 96 with hydrazonoyl chloride 2 in refluxing dioxane and a catalytic amount of triethylamine
1015
for 5 h to give 1,3,4-thiadiazole 98 as the final product in 70% yield. The same product was
1016
1017 obtained by reaction of methyl 2-(1-(pyridin-4-yl) ethylidene)hydrazine carbodithioate (97) with
1018 3 in ethanol and triethylamine at room temperature for 2 h (Scheme 39).63 The yield in case of
1019 ethylidene thiosemicarbazone is good compared to the yield obtaind from reaction of carbodi-
1020 thioate derivative 97.
 POLYCYCLIC AROMATIC COMPOUNDS 21

1021 Table 4. 3,5-diphenyl-1,2,4-triazoles from benzimidates.

1022 Benzimidate
1023 R R/
Yield (%) of triazole

1024 H Et 92 (95)
1025 Ph Et 91(R ¼ Ph) (25)
91 (R ¼ Me)
1026 Me Me (33)

1027
1028
1029
1030
1031
1032
1033
1034
1035 Scheme 38.
1036
1037
1038
1039
1040
1041
1042
1043
1044
1045
1046
1047
1048
1049
1050 Scheme 39.
1051
1052
1053
1054
1055
1056
1057
1058
1059
1060 Scheme 40.
1061
1062
1063
1064
1065 Abdelhamid et al, reported the synthesis of thiadiazol moiety via reaction of 2-(1-(1H-indol-3-
1066 yl)ethylidene)hydrazine-1-carbothioamide (99) with hydrazonoyl chloride 3 in ethanolic triethyl-
1067 amine to give one isolable product 100 in 62% yield (Scheme 40).64
1068 Similarly, Abdelhamid group synthesized thiadiazole derivatives 102 by the reaction of hydra-
1069 zonoyl chloride 2 with appropriate methyl carbodithioates 101 in triethylamine and ethanol
1070 (Scheme 41). The newly synthesized products were obtained in 81–90% yields.65 The yield in this
1071 reaction is very good compared to the yield obtained for compound 100 in Scheme 40.
 22 M. A. ELSAYED ET AL.

1072
1073
1074
1075
1076
1077
1078
1079
1080
1081
1082
1083
1084
1085 Scheme 41.
1086
1087
1088
1089
1090
1091
1092
1093
1094
1095
1096
1097
1098
1099 Scheme 42.
1100
1101
1102
1103
1104
1105
1106
1107
1108 Scheme 43.
1109
1110
1111
1112
1113 Farag et al used cyanothioacetamide thiazoloantipyrine derivative 103 to afford thiadiazole
1114 moiety. Compound 103 reacted with hydrazonoyl chloride 2 in ethanolic triethylamine under
1115 reflux for 2 h to obtain thiadiazolo antipyrine derivative 104 in 75% yield (Scheme 42).66
1116 Similarly, Dawood et al reported the synthesis of thiadiazole derivative 106 via reaction of
1117 hydrazonoyl chloride 2 with cyano-2-(3-methyl benzofuran-2-yl) thioacetanilide (105) in etha-
1118 nolic triethylamine for 2 h under reflux to give the corresponding thiadiazolo-benzofurane deriva-
1119 tives 106 in 86% yield (Scheme 43).67 Better yield is obtained in this method than the yield
1120 obtained for thiadiazole derivative 104 from Farag group.
1121 Radwan et al described the synthesis of thiadiazole derivative 109 by reaction of (Z)-2-(1H-
1122 indole-2-carbonyl)-3-mercapto-3-(phenylamino)acrylonitrile (107) with phenylisothiocyanate in
 POLYCYCLIC AROMATIC COMPOUNDS 23

1123
1124
1125
1126
1127
1128
1129
1130 Scheme 44.
1131
1132
1133
1134
1135
1136
1137
1138
1139
1140
1141
1142
1143
1144
1145
1146
1147
1148
1149
1150
1151 Scheme 45.
1152
1153
1154
1155 DMF and potassium hydroxide to obain the corresponding potassium salt 108 which reacted
1156 with hydrazonoyl chloride 2 in refluxing ethanol and TEA to give 109. The reaction proceeded
1157
for 1 h under reflux in ethanolic triethylamine to afford the corresponding thiadiazole derivative
1158
109 in 69% yield (Scheme 44).68 Lower yield is obtained in this method. The yield in case of
1159
using benzofuran derivative 105 as starting material the better one compared to indole derivative
1160
107 and thiazole derivative 103.
1161
Abdelhamid et al used hydrazonoyl chloride 2 to prepare thiadiazole phenylthiocarbamate
1162
derivatives 113 and 117 by treatment of the thiocarbamate derivatives with hydrazonoyl chloride
1163
1164 2 in ethanolic triethylamine to afford the corresponding thiadiazole derivatives (Scheme 45).
1165 Treatment of methyl phenyl dithiocarbamate gave one isolable product identical in all spectra to
1166 obtained from the reaction of phenylthiourea with 2. Treatment of hydrazonoyl chloride with
1167 methyl phenylhydrazinedithiocarbamate 114 gave also one isolable product identical to 117
1168 (Scheme 45).69 The product 113 resulted from elimination of methanethiol or ammonia from the
1169 corresponding cycloadduct 112, which is formed from the hydrazone 111 or may also be formed
1170 through 1,3-dipolar cycloaddition of the nitrile imine to C¼S of methyl dithiocarbamate or phe-
1171 nylthiourea 110 (R ¼ SMe, NH2).
1172 Dawood et al used the thioacetanilide of benzofuran derivative with hydrazonoyl chloride 2 to
1173 reach thiadiazole moiety. The addition of thioacetanilide derivative 121 to hydrazonoyl chloride 2
 24 M. A. ELSAYED ET AL.

1174
1175
1176
1177
1178
1179
1180
1181
1182
1183
1184
1185
1186
1187
1188
1189
Scheme 46.
1190
1191
1192
1193
1194
1195
1196
1197
1198
1199
1200
1201
1202
1203
1204
1205
1206
1207
1208
1209
1210 Scheme 47.
1211
1212
1213
1214 in refluxing ethanolic TEA solution for 1 h afforded the desired thiadiazole derivative 123 in 63%
1215 yield (Scheme 46).70
1216 Dawood et al selected to start with 2-cyano-3-phenyl-2-pentenedinitrile (124) to react with
1217 hydrazonoyl chloride derivatives 2 to afford the corresponding thiadiazole derivative. When com-
1218 pound 124 reacted with phenyl isothiocyanate, in dimethylformamide, in the presence of potas-
1219 sium hydroxide, afforded the corresponding potassium salt which converted into 4-mercapto-2-
1220 phenyl-4-(phenylamino)buta-1,3-diene-1,1,3-tricarbo-nitrile(125) upon treatment with dilute
1221 hydrochloric acid. Treatment of 125 with N-phenyl benzohydrazonoyl chloride derivatives 3 in
1222 catalytic amount of ethanol and TEA under reflux for 3 h gave 1,3,4-thiadiazole derivatives 126 in
1223 65% yield (Scheme 47).71 The two procedures for Dawood et al to synthesize thiadiazole deriva-
1224 tives gave identical poor yields in nearly short time.
 POLYCYCLIC AROMATIC COMPOUNDS 25

1225
1226
1227
1228
1229
1230
1231
1232
1233
1234
1235
1236
1237
1238 Scheme 48.
1239
1240
1241
1242
1243
1244
1245
1246
1247
1248
1249
1250
1251
1252
1253
1254
1255
1256 Scheme 49.
1257
1258
1259 Similarly, Farag et al prepared thiadiazole derivative 129 by reaction of mercapto-2-furoylace-
1260 tonitril derivative 128 with hydrazonoyl chloride 2 and stirring overnight. A stirred solution of
1261 potassium hydroxide in dimethylformamide, 2-furoylacetonitrile 127 was added. After stirring for
1262 30 min, phenyl isothiocyanate was added to the reaction mixture. Stirring was continued for 6 h,
1263 then hydrazonoyl chloride 2, was added to the reaction mixture. The stirring was continued over-
1264 night. The precipitate was filtered off, washed with ethanol and recrystallised to afford the corre-
1265 sponding product The isolated product 129 was obtained in 84% yield (Scheme 48).72 Farag et al
1266 successed to get excellent yield in this method so, this method is preferred than the other meth-
1267 ods reported in Schemes 44, 46 and 47. to prepare thiadiazole derivatives.
1268 Ogurtsov et al described the synthesis of 5-methylene-1,3,4-thiadiazolines derivatives 131 by
1269 reaction of thiocarbonyl group of 5-chloro-1,2-dithiole-3-thione 130 with hydrazonoyl chloride
1270 derivatives via cycloaddition reaction followed with the opening of the dithiole ring with loss of
1271 sulfur to give 5-methylene-1,3,4-thiadiazolines 131 in yields 55–65% (Scheme 49). However, the
1272 addition of hydrazonoyl chloride derivatives 2 to dichlorodithiothione 132 gives unstable product
1273 dihydrotetrazine resulting from nitrile imine dimerization which could not be isolated from the
1274
1275
 26 M. A. ELSAYED ET AL.

1276
1277
1278
1279
1280
1281
1282
1283
1284
1285
1286
1287
1288 Scheme 50.
1289
1290
1291
1292
1293
1294
1295
1296
1297
1298
1299 Scheme 51.
1300
1301
1302
1303 reaction mixture. So, the subsequent addition of phenol or thiophenol to the reaction mixture
1304 gave 131 but with low yields (25% X ¼ S and 29% X ¼ O).73
1305
1306
1307 3.5. Synthesis of spiro cyclic compounds
1308
Li et al described a novel method for the preparation of spiro [indazole-5,30 -pyrazole] derivatives
1309
135 in [3 þ 2] cyclo addition by reaction of hydrazonoyl chloride 2 and 5-aryl methylidene-1-phe-
1310
nyl-1,5,6,7-tetrahydro-4H-indazol-4-ones (134) in TEA and benzene under reflux for 36 h to
1311
afford the corresponding spiro compound in 50–71% yields (Scheme 50).74
1312
Taheri et al reported the synthesis of Spiro cyclic compound using 1,3-dipolar cycloaddition
1313
1314 reactions. Treatment of 3-[3-methyl-5-thioxo-1H-1,2,4-triazol-4(5H)-ylimino]indolin-2-one (136)
1315 in acetonitrile and catalytic amount of TEA with hydrazonoyl chloride 2 afforded the new
1316 Spirocyclic derivatives 40 -[3-methyl-5-thioxo-1H-1,2,4-triazol4(5H)-yl]-20 ,50 -diphenyl-20 ,40 -dihydro
1317 Spiro(indolin-3,30 -[1, 2, 4]triazol)-2-one derivatives (137) in 89% yield (Scheme 51).75
1318 Fuchigami et al prepared spirocyclic compounds by the reaction of (E)-3- benzylidenechro-
1319 man-4-ones (138) and hydrazonoyl chloride 2 in dry benzene and TEA either at room tempera-
1320 ture or reflux (X ¼ S) to give 1,3,4-triarylspiropyrazole-5,30 -chroman-4-one derivatives 139
1321 (Scheme 52).76 The yield of the products is from 79–83%.
1322 Azizian et al used microwave irradiation to fast the 1,3-dipolar cycloaddition of hydrazonoyl
1323 chloride derivatives 2 to isatine imines. Spiroindole series were synthesized by the reaction of isa-
1324 tine imine 140 with hydrazonoyl chloride derivatives 2 in presence of the equivalent amount of
1325 TEA and N, N-dimethylacetamide (1 mL) for 5 min under irradiation (200 W) giving excellent
1326 yields of 141 (Scheme 53) compared to thermal heating for 6–10 h gave 20–30% yields. However,
 POLYCYCLIC AROMATIC COMPOUNDS 27

1327
1328
1329
1330
1331
1332
1333
1334
1335
Scheme 52.
1336
1337
1338
1339
1340
1341
1342
1343
1344
1345
1346
1347
1348
1349
1350
1351
1352
1353
1354
1355 Scheme 53.
1356
1357
1358
1359 the reaction gave very good yields at ambient temperature but in a very long time, 30 h. conven-
1360 tional heating reaction acetonitrile needed more than 30 h to complete the reaction. In both cases,
1361
spiro [3H-indole-3,50 (40 H)-[1, 2, 4]triazoline]-2-ones (141) were obtained.77
1362
Farag et al was found that 3-phenyl methylene-5-arylfuran-2(3H)-ones 142 are excellent build-
1363
ing blocks for the synthesis of a variety of spirocyclic compounds. Treatment of 3-aryliden-
1364
2(3H)-furanone derivatives 142 with hydrazonoyl chloride derivatives 2 in the catalytic amount of
1365
triethylamine in benzene under reflux, afforded the corresponding 1,2-diazaspiro[4]nona-2,8-
1366
diene-6-one derivatives 143 as a regioselective product identified by the spectral data in good
1367
1368 yields (Scheme 54).78 The reactions of 142 with nitrile imide generated insitue from the corre-
1369 sponding hydrznoyl halide 2 are regioselective and, in each case, only one regioisomer of 143
1370 with yields changed from 73 to 75%. The elemental analysis and spectral data confirmed the for-
1371 mation of structure 143.
1372 Similarly, Dawood et al reported the synthesis of spirocyclic compounds using another aryli-
1373 dine derivative by treatment of 3-(4-arylidene)-2,3-dihy-dro-4-oxo-thiopyrano[2,3-b]pyridine
1374 derivatives (145) with nitrile imine formed in situ from the effect of TEA on the corresponding
1375 hydrazonoyl chloride 2 in refluxing benzene for 20 h to afford regioselectively spiropyrazoline-
1376 5,30 -thiopyrano[2,3-b]pyridine derivatives 146 in 57 and 60% yields (Scheme 55). The spectral
1377 data provided support for the regioselective addition of the nitrilimine 2 to the benzyli-dene
 28 M. A. ELSAYED ET AL.

1378
1379
1380
1381
1382
1383
1384
1385
1386
1387
1388
1389
1390
1391
1392
1393 Scheme 54.
1394
1395
1396
1397
1398
1399
1400
1401
1402
1403
1404
1405
1406
1407
1408
1409
1410
1411
1412
1413 Scheme 55.
1414
1415
1416
olefinic moiety of compound 145 to give the spiropyrazoline-5,30 -thiopyrano[2,3-b]-pyridine
1417
1418 derivative 146 and the other regio isomer 147 not confirmed.79
1419 Pujol et al described the synthesis of new spirocyclic derivatives of pyrazolo-1,5-benzodiaze-
1420 pines 149 by 1,3-dipolar cycloaddition reaction of hydrazonoyl chloride derivatives 2 with pyra-
1421 zolo[1,5,4-ef][1, 5]benzodiazepin-6-thione (148) in triethylamine and benzene under reflux for
1422 24 h (Scheme 56). the condensation of hydrazonoyl chloride with pyrrolobenzodiazepine thione
1423 give only one product in 40–45% yield.80 As shown in Scheme 56 the yield is very poor in this
1424 procedure.
1425 Mishriky et al observed that the reaction occurs regioselectively via cycloaddition of two moles
1426 of hydrazonoyl chloride derivatives 2 to 2,6-bis(aryl methylidene)cyclohexanones (150) in dry
1427 benzene and TEA under reflux to form two spiro pyrazole ring attached to the base ring hexa-
1428 none either the same face giving rise to the cycloadducts 151 or from opposite face affording the
 POLYCYCLIC AROMATIC COMPOUNDS 29

1429
1430
1431
1432
1433
1434
1435
1436
1437
1438
1439 Scheme 56.
1440
1441
1442
1443
1444
1445
1446
1447
1448
1449
1450
1451
1452
1453
1454
1455
1456
1457
1458
1459
Scheme 57.
1460
1461
1462
1463
1464 isomeric products 152 in yield from 33–46% (Scheme 57).81 As shown in Scheme 57, the yield is
1465 very low with all derivative
1466 Kilishna et al used 4-Me-benzylidene-1-tetralone (153) to react with N-phenyl benzo hydrazo-
1467 noyl chloride (2) in dry chloroform under stirring for 40 h in presence of a catalytic amount of tri-
1468 methylamine to afford spiro[2-pyrazoline-5,20 -naphthalen]-10 -one derivatives 154 (Scheme 58).82
1469 Askri et al afforded a series of spiropyrazolines in good to excellent yields using microwave-
1470 assisted 1,3-dipolar cycloaddition of 1,3-bis(arylidene)-2-tetralones 155 to hydrazonoyl chloride
1471
derivatives 2 and Et3N in dichloromethane, under stirring in a microwave reactor at 80
C for
1472
15 min. The reaction afforded mono- and dispiropyrazolines (Scheme 59).
1473
The author studied the effect of p-substituent of the aryl group of dipolarophile and iminoni-
1474
1475 trile on the yield and regiochemical outcome (Table 5). From Table 5, according to the author
1476 study, we find the formation of mono-spiropyrazoline as a major product when the molar ratio
1477 of 1,3-dipole is 1.5 equivalent to the dienones.
1478 In contrast, the yield of the dispiropyrazoline increased with increasing the hydrazonoyl chlor-
1479 ide derivatives to 2 equivalent. Also, as shown in Table 5 the yield of mono and dispiropyrazoline
 30 M. A. ELSAYED ET AL.

1480
1481
1482
1483
1484
1485
1486
1487 Scheme 58.
1488
1489
1490
1491
1492
1493
1494
1495
1496
1497
1498
1499
1500
1501
1502
1503
1504
1505
1506 Scheme 59.
1507
1508
1509 Table 5. Stoichiometry-controlled synthesis of mono and dispiropyrazoline derivatives 169 and 168.
1510 166/167 with 1:1.5 molar ratio 166/167 with 1:3 molar ratio
1511
1512 (reaction time 15 min) (reaction time 30 min)
1513 Ar1 Ar2 a
ratio 157/156 b
yield (%) ratioa 157/156 yieldb (%)
1514 Ph Ph 90:10 85/7 10:90 10/75
1515 p-Me-C6H4
P-Meo-C6H4
Ph
Ph
86:14
83:17
73/14
82/14
14:86
17:83
18/73
14/82
1516 p-Cl-C6H4 Ph 90:10 77/11 10:90 11/77
1517 p-CN-C6H4 Ph 85:15 83/13 13:87 10/73
1518 Ph
p-Me-C6H4
p-Me-C6H4
p-Me-C6H4
87:13
82:12
73/10
70/13
12:82
10:90
13/70
14/77
1519 p-MeO-C6H4 p-Me-C6H4 90:10 77/14 10:90 10/75
1520 p-Cl-C6H4 p-Me-C6H4 90:10 75/10 16:84 11/72
1521 p-CN-C6H4 p-Me-C6H4 84:16 72/11 15:85 15/79
1522
a
The relative ratios were determined by analysis of the 1H NMR spectra of the crude reaction mixture. bIsolated yield after
purification by column chromatography on silica gel.
1523
1524
1525 is affected by the substituent present on each aromatic ring of both hydrazonoyl chloride deriva-
1526 tives and dipolarophiles.83
1527 Alizadeh et al developed an efficient method for the synthesis of spiro[indoline-3,20 -[1, 3,
1528 4]oxadiazol]-2-one derivatives by treatment of various isatins with hydrazonoyl chlorides in the
1529 presence of Et3N. This protocol has some advantages like using available starting materials, mild
1530
 POLYCYCLIC AROMATIC COMPOUNDS 31

1531
1532
1533
1534
1535
1536
1537
1538
1539
1540
1541
1542
1543
1544
1545
1546
1547
1548
1549
1550 Scheme 60.
1551
1552
1553
1554
1555
1556
1557
1558
1559
1560
1561
1562
1563
1564
1565
1566
1567
1568
1569 Scheme 61.
1570
1571
1572
1573
1574
reaction condition, relatively short reaction time, and high yields of product. Reaction of isatins
1575
1576 158 and hydrazonoyl chlorides 2 under the same condition gave the corresponding spirooxin-
1577 doles 159 in high yields (Scheme 60).24
1578 The mechanism of this reaction involves 1,3-Dipolar cycloaddition reaction of nitrile imine
1579 onto the C¼O group of isatin (156) to generate product 159 (Scheme 60).
1580 Similarly, nitrile imine was used as 1,3-dipole and reacted with acenaphthoquinone 160 and
1581 9,10-phenanthraquinone 162 to obtaine spirocompounds 161 and 163 in high yields (Scheme 61).24
 32 M. A. ELSAYED ET AL.

1582
1583
1584
1585
1586
1587
1588
1589
1590
1591
1592
1593
1594
1595
1596
1597
1598
1599
1600
1601
1602
1603 Scheme 62.
1604
1605
1606
1607
1608 Heimgartner et al reported the synthesis of spirocyclic 1,3,4-thiadiazole derivatives as a results
1609 of regio- and chemoselective (3 þ 2)-cycloaddition in good to excellent yields. The presence of the
1610 trifluoromethyl group (CF3-) is necessary to activate the nitrile imine for active trapping of the
1611 cyclopropenethione. As shown in Scheme 62, the required (3 þ 2)-cycloadducts 165 were sepa-
1612 rated as the major product in 64–86% yield. As shown, the substituent influenced both the yield
1613 and the stability of the obtained product. Thus, the electron-donating substituents resulted in
1614 lower yields, and for this reason, longer reaction times were needed for completion of the reac-
1615 tion. In contrast to 165a, the 4-methoxy derivative 165 g endured remarkable instability in CDCl3
1616 solution and decomposition at room temperature. Thioketone 164 cannot react with hydrazonoyl
1617 halide 2. The comparison of the reactivity of 15b and diphenyl nitrile imine generated in situe
1618 from 2 in base showed that the presence of the CF3 -group is necessary to accomplish sufficient
1619
electrophilicity in order to reach the (3 þ 2)-cycloadduct (Scheme 62).84
1620
1621
1622
1623
1624
1625 3.6. Synthesis of tetrazoles
1626
Bhagat et al present a study for the synthesis of tetrazoles using a polymer supported Fe-
1627
Phthalocyanine cross-linked with carboxyl functionalized benzimidazolium moiety
1628
1629 (PSFePcCFBM) explored as heterogenous photocatalyst, for regioselective synthesis of 1H-tetra-
1630 zoles from sodium azide and other afordable substrates. Azides acts as a nitrogen donor of tetra-
1631 zoles ring as well as it convert aldehyde into isocyanide as one of the nitrogen sources. The
1632 method showed good to excellent yields 67–91% under visible light irradiation (Scheme 63).85
 POLYCYCLIC AROMATIC COMPOUNDS 33

1633
1634
1635
1636
1637
1638
1639
1640
1641
1642
1643 Scheme 63.
1644 Q4
1645
1646
1647
1648
1649
1650
1651
1652
1653
1654
1655
1656
1657
1658
1659 Scheme 64. Mechanism of formation tetrazole.
1660 Q6
1661
1662
1663
1664
1665
1666
1667
1668
1669
1670
1671
1672
1673
1674
1675
1676
1677 structure of Fe-phthalocyanine catalyst (PsFePcCFBM)
1678 The results revealed that 8 h duration is enough for getting maximum yield of the product,
1679 only very slight improvement of the yield was achieved by increasing the time up to 10 h. Based
1680 on these observations, the molar ratio of the reactants was fixed as 1:1.5 and 8 h duration. From
1681 this study and observations, the yields in aromatic aldehyde was very high relevant to the ali-
1682 phatic aldehyde.
1683
 34 M. A. ELSAYED ET AL.

1684 The mechanism of regioselective formation of terazole induced Fe- catalyst support as shown
1685 in Scheme 64. The probable mechanism for the synthesis of 1-tetrazole involves the
1686 PSFePcCFBM promoted primary attack of azide on the aldehyde. In the succeeding step,
1687 PSFePcCFBM allowed photocatalytic excitation of intermediate resulting in 1,2-aryl radical migra-
1688 tion from carbon to nitrogen, followed by the elimination of N2 to provide the isocyanide inter-
1689 mediate. Lastly, this intermediate undertakes [3 þ 2] cycloaddition with azide to get
1690 compound 168.
1691
1692
1693 4. Conclusion
1694 Hydrazonoyl chloride are one of the most important versatile reagents used as building block spe-
1695 cies in heterocyclic chemistry. The reactivity of these species makes them participate in the syn-
1696 thesis of more biologically active compounds containing pyrazoles, thiadiazoles and triazines in
1697 addition to the ability to form spiro compounds. So, this review scope on the methods of prepar-
1698 ation and reactions of diphenyl hydrazonoyl halides.
1699
1700
1701 Disclosure statement
1702 No potential conflict of interest was reported by the authors.
1703
1704
1705 ORCID
1706 Naglaa A. Abdel-Hafez http://orcid.org/0000-0003-2211-8088
1707 Abd-El-Galil E. Amr http://orcid.org/0000-0002-1338-706X
1708
1709
1710 Q7 References
1711 1. (a) R. D. Taylor, M. MacCoss, and A. D. J. Lawson, Journal of Medicinal Chemistry 57 (2014): 5845–59. (b)
1712 E. Vitaku, D. T. Smith, and J. T. Njardarson, Journal of Medicinal Chemistry 57, no. 24 (2014): 10257–74.
1713 doi:10.1021/jm501100b. (c) M. Aldeghi, S. Malhotra, D. L. Selwood, and A. W. E. Chan, Chemical Biology &
1714 2.
Drug Design 83, no. 4 (2014): 450–61. doi:10.1111/cbdd.12260
M. Mohamed, L. Abu-Alola, O. Al-Zaidi, and H. Saad, International Journal of Communication 7 (2017):
1715 12–24.
1716 3. A. Sayed, S. Al-Shihry, and M. Gomaa, European Journal of Chemistry 5 (2014): 267–71.
1717 4. A. R. Sayed, Turkish Journal of Chemistry. 39 (2015): 600–9.
1718 5. L. D. Quin, and J. A. Tyrell, Fundamentals of Heterocyclic Chemistry: Importance in Nature and in the
1719 Synthesis of Pharmaceuticals (Hoboken, New Jersey: John Wiley& Sons, 2010).
6. N. Singh, R. Ranjana, M. Kumari, and B. Kumar, International Journal of Pharmaceutical and Clinical
1720 Research 8 (2016): 162–6.
1721 7. A. S. Shawali, T. A. Farghaly, S. M. M. Hussein, and A. Abdalla, Archives of Pharmacal Research 36 (2013):
1722 694–701.
1723 8. Salwa F. Mohamed, Dina H. Elnaggar, Mohamed A. Elsayed, Heba S. Abd-Elghaffar, Hana M. Hosny,
1724 Ashraf M. Mohamed, Eman M. H. Abbas, Thoraya A. Farghaly, and Raafat A. El-Awady, Polycyclic
1725 Q3 9.
Aromatic Compounds (2022)
N. A. Abdel Hafez, M. A. Elsayed, M. M. El-Shahawi, G. E. A. Awad, and K. A. Ali, Journal of Heterocyclic
1726 Chemistry 55, no. 3 (2018): 685–91.
1727 10. Korany A. Ali, N. A. Abdel Hafez, M. A. Elsayed, M. M. El-Shahawi, S. M. El-Hallouty, and A. E. Amr,
1728 Mini-Reviews in Medicinal Chemistry 18, no. 18 (2018): 717–27.
1729 11. E. Fisher, Liebigs Annalen 212 (1882): 316–39.
1730 12. R. Huisgen, M. Seidel, J. Sauer, J. W. McFarland, and G. Wallbillich, Journal of Organic Chemistry. 24
(1959): 892–3.
1731 13. (a) A. M. Farag, N. A. Kheder, and M. Budesinsky, Tetrahedron 53 (1997): 9293–300. (b) A. S. Shawali,
1732 A. M. Farag, H. A. Albar, and K. M. Dawood, Tetrahedron 49 (1993): 2761–6.
1733 14. A. M. Farag, A. S. Shawali, M. S. Algharib, and K. M. Dawood, Tetrahedron 50 (1994): 5091–8.
1734 15. G. Bertrand, and C. Wentrup, Angewandte Chemie International Edition 33 (1994): 527–45.
 POLYCYCLIC AROMATIC COMPOUNDS 35

1735 16. Z. Li, L. Qian, L. Li, J. C. Bernhammer, H. V. Huynh, J. S. Lee, and S. Q. Yao, Angewandte Chemie
1736 International Edition. 54 (2015): 12886–90.
17. (a) Y. Zhang, W. Liu, and Z. Zhao, Molecules 19 (2013): 306–15. (b) A. Herner, J. Marjanovic, T. M.
1737 Lewandowski, V. Marin, M. Patterson, L. Miesbauer, D. Ready, J. Williams, A. Vasudevan, and Q. Lin,
1738 Journal of the American Chemical Society. 138 (2016): 14609–15. (c) B. Vonh€oren, O. Roling, C. Buten, M.
1739 K€orsgen, H. F. Arlinghaus, and B. J. Ravoo, Langmuir 32 (2016): 2277–82. (d) C. Buten, S. Lamping, M.
1740 K€orsgen, H. F. Arlinghaus, C. Jamieson, and B. J. Ravoo, Langmuir 34 (2018): 2132–8. (e) C. Heiler, J.
1741 Offenloch, E. Blasco, and C. Barner-Kowollik, ACS Macro Letters. 6 (2017): 56–61.
1742 18. Karl Hemming, Abdul-Bassett N. Luheshi, Alan D. Redhouse, Robert K. Smalley, and J. Robin Thompson,
1743 Tetrahedron 49, no. 20 (1993): 4383–408.
19. Przemyslaw Wyrebek, and Stanislaw Ostrowski, Bulletin of the Chemical Society of Japan 85, no. 10 (2012):
1744 1167–74,78.
1745 20. Keith Livingstone, Sophie Bertrand, Alan R. Kennedy, and Craig Jamieson, Chemistry-A European Journal
1746 26, no. 46 (2020): 10591–7.
1747 21. Veera Reddy Yatham, Wacharee Harnying, Darius Kootz, J€ org-M. Neud€ orfl, Nils E. Schl€
orer, and Albrecht
1748 Berkessel, Journal of the American Chemical Society 138, no. 8 (2016): 2670–7.
1749 22. Yasar Dueruest, and Muhammet Yildirm, Monatshefte Fur Chemie 141, no. 9 (2010): 961–73.
1750 23.
24.
F. L. Scott, and J. B. Aylward, Tetrahedron Letters. (1965): 841.
Abdolali Alizadeh, and Leila Moafi, Helvetica Chimica Acta 99, no. 6 (2016): 457–61.
1751 25. Honglei Liu, Hao Jia, Bo Wang, Yumei Xiao, and Hongchao Guo, Organic Letters 19, no. 18 (2017): 4714–7.
1752 26. Zhenyan Guo, Hao Jia, Honglei Liu, Qijun Wang, Jiaxing Huang, and Hongchao Guo, Organic Letters 20,
1753 no. 10 (2018): 2939–43.
1754 27. Omid Khaledian, and Issa Yavari, Synthesis 52, no. 9 (2020): 1379–86.
1755 28. T. O. Burdyukova, A. Yu Fedorov, I. D. Grishin, Yu L. Kuznetsova, M. A. Lopatin, Yu B. Malysheva, E. Yu
Polozov, A. S. Vavilova, and E. A. Zaburdaeva, Russian Chemical Bulletin 69, no. 8 (2020): 1470–7.
1756 29. Chantal Ghiglieri-Bertez, Claude Coquelet, Alain Alazet, and Claude Bonne, European Journal of Medicinal
1757 Chemistry 22 (1987): 147–52.
1758 30. Orazio Attanasi, Paolo Battistoni, and Gabriele Fava, Canadian Journal of Chemistry 61 (1983): 2665–8.
1759 31. Eiji Kobayashi, and Hideo Togo, Synthesis 51, no. 19 (2019): 3723–35.
1760 32. (a) Vladimir V. Voronin, Maria S. Ledovskaya, Evgeniy G. Gordeev, Konstantin S. Rodygin, and
1761 Valentine P. Ananikov, Journal of Organic Chemistry 83, no. 7 (2018): 3819–28. (b) Zhihua Sui, Jihua Guan,
Michael P. Ferro, Kathy McCoy, Michael P. Wachter, William V. Murray, Monica Singer, Michele Steber,
1762 Dave M. Ritchie, and Dennis C. Argentieri, Bioorganic and Medicinal Chemistry Letters 10, no. 6 (2000):
1763 601–4.
1764 33. Frantisek. Serse
n, Fridrich. Gregan , Matus. Pesko, Dana. Dvoranova, Katarına. Kraľova, Zuzana.
1765 , and Jana. Donovalova, Molecules 20 (2015): 14139–54.
Matkovicova, Juraj. Gregan
1766 34. (a) K. Tanaka, S. Maeno, and K. Mitsuhashi, Chemistry Letters. (1982): 543–6. (b) K. Tanaka, S. Maeno, and
1767 K. Mitsuhashi, Journal of Heterocyclic Chemistry. 22 (1985): 565–8. (c) K. Tanaka, M. Kishida, S. Maeno,
1768 35.
and K. Mitsuhashi, Bulletin of the Chemical Society of Japan. 59 (1986): 2631–2.
Greta. Utecht, Andrzej. Fruzi nski, and Marcin. Jasi
nski, Organic & Biomolecular Chemistry 16, no. 8 (2018):
1769 1252–7. doi:10.1039/c7ob03126b
1770 36. Lynette M. Oh, Tetrahedron Letters 47 (2006): 7943–6.
1771 37. CN104844538, 2017. B; Location in patent: Paragraph 0031; 0056; 0059; 0060; 0061; 0062
1772 38. Mukund P. Sibi, Levi M. Stanley, and Craig P. Jasperse, Journal of the American Chemical Society 127, no.
1773 23 (2005): 8276–7. doi:10.1021/ja051650b
1774 39. Mukund P. Sibi, Levi M. Stanley, and Takahiro Soeta, Advanced Synthesis and Catalysis 348, no. 16-17
(2006): 2371–5.
1775 40. Elmar Schmidt, Hans-Ulrich Reissig, and Reinhold Zimmer, Synthesis 12 (2006): 2074–84.
1776 41. Sureshbabu Dadiboyena, Edward J. Valente, and Ashton T. Hamme, II, Tetrahedron Letters 51, no. 9 (2010):
1777 1341–3. doi:10.1016/j.tetlet.2010.01.017
1778 42. Issa. Yavari, Gholamhossein. Khalili, and Anvar. Mirzaei, Helvetica Chimica Acta 93 (2010): 277–80.
1779 43. Urska. Bratusek, Anton. Meden, Jurij. Svete, and Branko. Stanovnik, Arkivoc v (2003): 77–86.
1780 44. Yu-Chen Tian, Jun-Kuan Li, Fa-Guang Zhang, and Jun-An Ma, Advanced Synthesis and Catalysis 363, no. 8
(2021): 2093–7.
1781 45. Khadijah Mohamed Al-Zaydi, and Ebtisam Abdel Aziz Hafez, Journal of Chemical Research, Miniprint, no. 6
1782 (1999): 1621–33.
1783 46. Hassan A. Albar, Journal of Chemical Research, Miniprint, no. 3 (1999): 872–89.
1784 47. Ahmad M. Farag, Abdelrahman S. Mayhoub, Saber E. Barakat, and Ashraf H. Bayomi, Bioorganic and
1785 Medicinal Chemistry 16, no. 2 (2008): 881–9.
 36 M. A. ELSAYED ET AL.

1786 48. Detian Gao, Huimin Zhai, Masood Parvez, and Thomas G. Back, Journal of Organic Chemistry 73, no. 20
1787 (2008): 8057–68.
49. Abdelmejid Bahloul, Abdelfatah Sebban, Zainaba Dardari, Mohammed Boudouma, Said Kitane, Touria
1788 Belghiti, and Jean-Pierre Joly, Journal of Heterocyclic Chemistry 40, no. 2 (2003): 243–8.
1789 50. Atir, Mallouk, Bougrin, Soufiaoui, Laghzizil, Synthetic Communications 36, no. 1 (2006): 111–20.
1790 51. Asma M. Mahran, Khadiga M. Abu-Zied, and Wafaa A. Gad, Egyptian Journal of Chemistry 55, no. 2
1791 (2012): 191–200.
1792 52. Nobuhiro. Fuchi, Takayuki. Doi, and Takashi. Takahashi, Chemistry Letters 34, no. 3 (2005): 438–9.
1793 53. Shiying. Du, Zuguang. Yang, Jianhua. Tang, Zhengkai. Chen, and Xiao-Feng. Wu, Organic Letters 23 (2021):
2359–63.
1794 54. Khadija. Nabih, Abdesselam. Baouid, Aissa. Hasnaoui, Mohamed. Selkti, and Philippe. Compain, New
1795 Journal of Chemistry 27 (2003): 1644–8.
1796 55. Weike. Su, Dianwen. Yang, and Jianjun. Li, Synthetic Communications 35, no. 11 (2005): 1435–40.
1797 56. Mosselhi A. N. Mosselhi, Magda A. Abdallah, Thoraya A. Farghaly, and Ahmad S. Shawali, Monatshefte Fur
1798 Chemie 135 (2004): 211–22.
57. Sayed M. Riyadh, Journal of the Chinese Chemical Society 52 (2005): 545–51.
1799 58. K. Paulvannan, Tao Chen, and Ron Hale, Tetrahedron 56, no. 41 (2000): 8071–6.
1800 59. K. Paulvannan, Ron Hale, Daniel Sedehi, and Tao Chen, Tetrahedron 57, no. 48 (2001): 9677–82.
1801 60. M. A. Al-Omair, A. R. Sayed, and M. M. Youssef, Molecules 20, no. 2 (2015): 2591–610.
1802 61. A. S. Shawali, M. A. Abdallah, I. M. Abbas, and G. M. Eid, Journal of the Chinese Chemical Society 51, no. 2
1803 (2004): 351–7.
62. S. Ito, Y. Tanaka, A. Kakehi, and H. Miyazawa, Bulletin of the Chemical Society of Japan 50, no. 11 (1977):
1804 2969–72.
1805 63. Sobhi M. Gomha, Fathy M. Abdelrazek, Aly H. Abdelrahman, and Peter. Metz, Heterocycles 92, no. 5
1806 (2016): 954–67.
1807 64. Abdou O. Abdelhamid, Sobhi M. Gomha, and Saher M. Kandeel, Journal of Heterocyclic Chemistry 54
1808 (2017): 1529.
1809 65. Omer S. Abu-Team, Nora M. Rateb, and Abdou O. Abdelhamid, Phosphorus, Sulfur, and Silicon 178 (2003):
2363–71.
1810 66. Zaghloul E. Kandeel, Kamal M. Dawood, Eman A. Ragab, and Ahmad M. Farag, Heteroatom Chemistry 13,
1811 no. 3 (2002): 248–51.
1812 67. Kamal M. Dawood, Ahmad M. Farag, and Hatem A. Abdel-Aziz, Heteroatom Chemistry 18, no. 3 (2007):
1813 294–300.
1814 68. Mohamed A. A. Radwan, Eman A. Ragab, Nermin M. Sabry, and Siham M. El-Shenawy, Bioorganic &
1815 69.
Medicinal Chemistry 15 (2007): 3832–41.
Hussein F. Zohdi, Nora M. Rateb, Mohamed M. M. Sallam, and Abdou O. Abdelhamid, J. Chem. Research
1816 (S) (1998): 742–3.
1817 70. Kamal M. Dawood, Hassan. Abdel-Gawad, Eman A. Rageb, Mohey. Ellithey, and Hanan A. Mohamed,
1818 Bioorganic & Medicinal Chemistry 14, no. 11 (2006): 3672–80. doi:10.1016/j.bmc.2006.01.033
1819 71. Kamal M. Dawood, and Mohamed A. Raslan, Journal of Heterocyclic Chemistry 45 (2008): 137.
1820 72. Ahmad M. Farag, Kamal M. Dawood, and Hatem A. Abdel-Aziz, Journal of Chemical Research 12 (2004):
808–10.
1821 73. Vladimir A. Ogurtsov, Oleg A. Rakitin, Charles W. Rees, and Alexey A. Smolentsev, Mendeleev
1822 Communications. 15, no. 2 (2005): 55–6.
1823 74. Demin. Ren, Guoqiang. Kuang, and Xiaofang. Li, Chemistry of Heterocyclic Compounds 54, no. 12 (2018):
1824 1117–20.
1825 75. Atiye. Bazian, Milad. Taheri, and Haniyeh. Alavi, Russian Journal of General Chemistry 84, no. 3 (2014):
1826 76.
586–92.
Kamal M. Dawood, and Toshio. Fuchigami, The Journal of Organic Chemistry 70, no. 19 (2005): 7537–41.
1827 doi:10.1021/jo0507587
1828 77. Javad. Azizian, Saeed. Soozangarzadeh, and Khosrow. Jadidi, Synthetic Communications 31, no. 7 (2001):
1829 1069–73.
1830 78. Ahmad M. Farag, Yehya M. Elkholy, and Korany A. Ali, Journal of Heterocyclic Chemistry 45 (2008): 279.
1831 79.
80.
Kamal M. Dawood, Journal of Heterocyclic Chemistry 42 (2005): 221–5.
El Mostapha. Rakib, Mohammed. Benchidmi, El Mokhtar. Essassi, Abdelaziz El. Bouadili, Mostafa. Khouili,
1832 Jean M. Barbe, and M. Dolors Pujol, Heterocycles 53, no. 3 (2000): 571–7.
1833 81. A. S. Girgis, Y. A. Ibrahim, N. Mishriky, J. N. Lisgarten, B. S. Potterc, and R. A. Palmer, Tetrahedron 57
1834 (2001): 2015–9.
1835 82. R. Kilishna, D. Velmurugan, R. Murugesan, S. M. Shanmuga, and R. Raghunahan, Acta Cryst C55 (1999):
1836 1676–7.
 POLYCYCLIC AROMATIC COMPOUNDS 37

1837 83. Houda. Gazzeh, Sarra. Boudriga, Moheddine. Askri, Abderrahim. Khatyr, Michael. Knorr, Carsten.
1838 84.
Strohmann, Christopher. Golz, Yoann. Rousselin, and Marek M. Kubicki, RSC Advances. 6 (2016): 49868.
Greta Utecht-Jarzynska, Marcin Jasi nski, Kamil Swia˛tek, Grzegorz Mlosto
n, and Heinz Heimgartner,
1839 Heterocycles 101, no. 1 (2020): 251–62.
1840 85. Vijay Baburao. Khajone, Kamlesh Rudreshwar. Balinge, and Pundlik Rambhau. Bhagat, Catalysis Letters 151,
1841 no. 7 (2021): 1948–60.
1842
1843
1844
1845
1846
1847
1848
1849
1850
1851
1852
1853
1854
1855
1856
1857
1858
1859
1860
1861
1862
1863
1864
1865
1866
1867
1868
1869
1870
1871
1872
1873
1874
1875
1876
1877
1878
1879
1880
1881
1882
1883
1884
1885
1886
1887